CLINICAL DECISION MAKING - European Society of …...Chest Pain - M. Lettino, F. Schiele ... other...

CLINICAL DECISION MAKING TOOLKIT

Instant guidance for diagnosis, risk managementand treatment

2018 edition

The Clinical Decision Making Toolkit is produced by the Acute Cardiovascular Care Association (ACCA), developed and distributed through an educational grant from AstraZeneca. AstraZeneca was not involved in the development of this publication and in no way influenced its content.

ISBN: 978-2-9537898-7-4

The Acute Cardiovascular Care Association Clinical Decision-MakingTOOLKIT

Héctor Bueno, M.D., PhD., FESC Editor in Chief

Pascal Vranckx, M.D., PhD Associate Editor

The ACCA Toolkit is available through different platforms:

• Printed booklet, available at congresses where ESC-ACCA is represented

• Web-based pdf file downloadable at: www.escardio.org/ACCA

• Mobile application for smartphones/tablets available in both Apple & Googleplay stores

Héctor Bueno M.D., PhD., FESC Editor in Chief

The best care of patients with acute cardiovascular syndromes relies not only on specialists but also on systems of care that involve many non-cardiologists. Several of these syndromes require immediate diagnosis and decisions on treatment, some of them life-saving. Critical decisions must often be made quickly by professionals with different backgrounds and levels of expertise with limited resources. This poses a significant clinical challenge.

Against this background, the ACCA Clinical Decision-Making Toolkit was created as a comprehensive resource encompassing all aspects of acute cardiovascular care but structured as an easy-to-use instrument in environments where initial acute cardiovascular care is typically initiated. Comprehensive tables, clear diagrams and algorithms, based on the ESC clinical practice guidelines as well as in clinical experience should provide diagnostic and therapeutic guidance at a glance.

This 2018 Edition of the Clinical Decision Making Toolkit has been updated with the 2016 and 2017 ESC Guidelines, a chapter on secondary prevention was added and the chapter on acute heart failure benefited a major update. However, it does not replace textbooks and other sources of information that need to be consulted to reach an optimal management of these patients.

II

Preface

7 DAYS F R O M C A R D I A C E V E N TU N T I L P A T I E N T S T A B I L I S A T I O N

ICCUINTENSIVECARDIACCARE UNIT

CCUCORONARY CARE UNITPRE-HOSPITAL CARE

GENERALHOSPITAL

EMERGENCY ROOM

CARDIAC ARREST, STEMI, ACS, AHF, CARDIOGENIC SHOCK, ARRHYTHMIAS,VASCULAR SYNDROMES

List of Authors �� VI

CHAPTER 1: KEY SYMPTOMSChest Pain - M. Lettino, F. Schiele �� P. 2Dyspnea - C. Müller �� P. 9Syncope - R. Sutton �� P. 16

CHAPTER 2: ACUTE CORONARY SYNDROMESGeneral concepts - H. Bueno �� P. 24Non ST-segment elevation ACS - H. Bueno �� P. 29STEMI - P. Vranckx, B. Ibañez �� P. 34

CHAPTER 3: SECONDARY PREVENTION AFTER ACSGeneral secondary prevention strategies and lipid lowering - H. Bueno, S. Halvorsen �� P. 38Antithrombotic treatment - F. Costa, S. Halvorsen �� P. 41

CHAPTER 4: ACUTE HEART FAILUREWet-and-warm heart failure patient - V.P. Harjola, O. Miró �� P. 52Cardiogenic shock (wet-and-cold) - P. Vranckx, U. Zeymer �� P. 61

IV

Contents

CHAPTER 5: CARDIAC ARREST AND CPR - N. Nikolaou, L. Bossaert �� P. 71

CHAPTER 6: RHYTHM DISTURBANCESSupraventricular tachycardias and atrial fibrillation - J. Brugada �� P. 80Ventricular tachycardias - M. Santini, C. Lavalle, S. Lanzara �� P. 84Bradyarrhythmias - B. Gorenek �� P. 87

CHAPTER 7: ACUTE VASCULAR SYNDROMESAcute aortic syndromes - A. Evangelista �� P. 92Acute pulmonary embolism - A. Torbicki �� P. 102

CHAPTER 8: ACUTE MYOCARDIAL/PERICARDIAL SYNDROMES Acute myocarditis - A. Keren, A. Caforio �� P. 112Acute pericarditis and cardiac tamponade - C. Vrints, S. Price �� P. 117

CHAPTER 9: DRUGS IN ACUTE CARDIOVASCULAR CARE - A. de Lorenzo �� P. 121

Abbreviations �� P. 191References and copyright acknowledgments �� P. 199

V

Contents (Cont.)

Leo Bossaert Department of Medicine, University and University Hospital Antwerp, Antwerp, Belgium

Josep Brugada Department of Cardiology, Hospital Clinic Universitat de Barcelona, Barcelona, SpainHéctor Bueno Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),

and Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, SpainAlida Caforio Department of Cardiology, Padua University Medical School, Padua, ItalyFrancesco Costa Cardiovascular institute, Hospital Clínic, University of Barcelona, Barcelona, Spain

Department of Clinical and Experimental Medicine, University of Messina, Messina, ItalyArtur Evangelista Department of Cardiology, Hospital Universitario Vall d’Hebrón, Barcelona, SpainBulent Gorenek Department of Cardiology, Eskisehir Osmangazy University, Eskisehir, TurkeySigrun Halvorsen Department of Cardiology, Oslo University Hospital Ulleval and University of Oslo, Oslo, NorwayVeli-Pekka Harjola Division of Emergency Medicine, Department of Emergency Care and Services, Helsinki

University Hospital, FinlandBorja Ibañez Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),

and Department of Cardiology, University Hospital Fundación Jiménez Díaz, Madrid, Spain Andre Keren Heart Failure and Heart Muscle Disease Centre, Hadassah University Hospital,

Jerusalem, Israel

VI

List of Authors

Stefania Lanzara Department of Emergency, Ospedale Madre Giuseppina Vannini, Rome, ItalyCarlo Lavalle Department of Cardiology, Ospedale San Filippo Neri, Rome ItalyMaddalena Lettino Clinical Cardiology Unit, IRCCS Istituto Clinico Humanitas, Milano, ItalyAna de Lorenzo Pharmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, SpainÒscar Miró Emergency Department, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, SpainChristian Müller Department of Cardiology, University Hospital Basel, Basel,SwitzerlandNikolaos Nikolaou Departement of Cardiology, Konstantopouleio General Hospital, Athens, GreeceSusanna Price Consultant Cardiologist & Intensivist, Royal Brompton Hospital, London, United KingdomMassimo Santini Department of Cardiology, Ospedale San Filippo Neri, Rome, ItalyFrançois Schiele Department of Cardiology, University Hospital Jean-Minjoz, Besancon, FranceRichard Sutton Department of Cardiology, National Heart and Lung Institute Imperial College,

London, United Kingdom Adam Torbicki Department of Pulmonary Circulation and Thromboembolic Diseases, Centre of

Postgraduate Medical Education, ECZ Otwock, PolandPascal Vranckx Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Hasselt, BelgiumChristiaan Vrints Department of Cardiology, Antwerp University Hospital, Edegem, BelgiumUwe Zeymer Department of Cardiology, Herzzentrum Klinikum Ludwigshafen, Ludwigshafen, Germany

VII

List of Authors (Cont.)

CHAPTER 1

KEY SYMPTOMS

1.1 CHEST PAIN �� p.2 M. Lettino, F. Schiele

1.2 DYSPNEA �� p.9 C. Müller

1.3 SYNCOPE �� p.16 R. Sutton

P.1

1

1. Presentation

2. ECG

3. Troponin

4. Diagnosis

Reference: Roffi et al. Eur Heart J 2015; eurheartj.ehv320.

Low likelihood of Acute Coronary Syndrome

High likelihood of Acute Coronary Syndrome

NoncardiacOther

CardiacUA STEMINSTEMI

P.2

1.1Initial assessment of patients with CHEST PAIN

First call for chest pain Higher death risk / probability for ACS Lower death risk / probability for ACS

Arguments for vital risk

• Cardiorespiratory arrest, syncope/ loss of consciousness, neurological defect

• Dyspnea (see chapter 1.2 page 9)• Arrhythmias – tachycardia

• Normal consciousness• Normal breathing • Normal heart rhythm

Context, CV risk Age >40 years, previous CV disease(MI, stroke, PE), modifiable CV risk factors (smoker, HTN, hypercholesterolemia, diabetes), chronic CV treatment

• Age <40 years, • No previous CV disease• No CV risk factors• No chronic treatment

Chest Pain Medial/lateral thoracic pain, intense, with dyspnea

• Depends on position/palpation/ movements

• Variable intensity, short duration (<1 min)• Hyperthermia

Cardiac Ischemic Pain

Retro-sternal, constriction, jaw/cervical/arm/back irradiation, spontaneous, prolonged >20 min + dyspnea, sweating, lightheadedness, nausea

• Lateral, abdominal irradiation • No neuro-vegetative symptoms

P.3

1.1Factors to be considered in the evaluation

after the first call for CHEST PAIN

NoYes

Likelihood of ACS

High probability for ACS Low probability for ACS

Emergency transportwith trained medical team

ECG, decision for reperfusion,antithrombotics, immediate

transport to ED/CPU/ICCU/Cathlab(see chapter 2)

Emergency transportEmergency transportwith trained medical team

Hospital admissionto the ED/CPU

Emergency care: Resuscitation, hemodynamic or

rhythm restoration (see chapter 5)

Cardiology ward

Non-cardiology ward

Discharge afterprolonged observation

APPROACH AFTER FIRST CALL FOR OUT-OF-HOSPITAL CHEST PAIN

VITAL RISK? (see chapter 1.1 page 3)

P.4

1.1Approach after first call for out-of-hospital CHEST PAIN

NoYes

Likelihood of ACS

High probability for ACS Low probability for ACS

Emergency transportwith trained medical team

ECG, decision for reperfusion,antithrombotics, immediate

transport to ED/CPU/ICCU/Cathlab(see chapter 2)

Emergency transportEmergency transportwith trained medical team

Hospital admissionto the ED/CPU

Emergency care: Resuscitation, hemodynamic or

rhythm restoration (see chapter 5)

Cardiology ward

Non-cardiology ward

Discharge afterprolonged observation

APPROACH AFTER FIRST CALL FOR OUT-OF-HOSPITAL CHEST PAIN

VITAL RISK? (see chapter 1.1 page 3)

P.5

1.1

First medical contact Higher death risk / probability for ACS Lower death risk / probability for ACS

Hemodynamic, respiratory, neurological distress

• Cardiopulmonary arrest, hypotension, tachycardia, shock

• Dyspnea, hypoxemia, lung rales (Killip class >2)• ECG: ST-segment deviation

• Normal consciousness, no motion defects• Normal HR and BP• Normal breathing and SpO2,

no loss of pulse

Probability for ACS • Context, typical symptoms consistent with myocardial ischemia

• ECG changes• Hs cTn

• No CV risk, atypical symptoms, normal ECG

• Negative hs cTn only if onset of pain >3 hours (see chapter 2.1 page 24)

STEMI NSTE-ACS Uncertain diagnosis

(see chapter 2.1 page 24)

ECG criteria for STEMI ST depression or normal ECG

Normal ECG (repeat 12-lead ECG recording if symptoms persist/recur)

Other ST-segment abnormalities

Type of reperfusion

Time assessment

• Primary PCI or thrombolysis? Primary PCI if delay <120 min (preferably <90 min) or <60 min if onset of pain <120 min Consider age, anterior wall location

• Relevant times: Symptom onset, first medical contact (FMC). FMC → ECG/diagnosis; FMC → PCI; FMC → thrombolysis

• Primary PCI between 12-48 hours in patients with ongoing ischemia, symptoms or clinical/haemodynamic or electrical instability

• No reperfusion if delay >12 hours and stable, asymptomatic, without ST-segment elevation

P.6

1.1Factors to be considered in the evaluation

during the first medical contact for CHEST PAIN

Yes

Resuscitation, hemodynamic or respiratory support(see chapters 4 & 5)

Type of reperfusion (primary PCI or fibrinolysis)Record times (symptom onset, FMC)

High probability Low probability

No

FIRST MEDICAL CONTACT IN PATIENTS WITH CHEST PAIN (HOME-AMBULANCE)

Hemodynamic, respiratory or neurological distress?

ST-segment elevation

ECG <10 min → ACS ?

No ST-segment elevation butother ECG changes or persistent pain

Suspect ACS Uncertain diagnosis

No antithrombotic treatmentTransfer to a proximity centre

(with or without cath-lab)Start recommended medical therapy(including antithrombotic drugs)

Transfer to a centre with cath-lab

Non cardiovascular disease? • Sepsis• Acute respiratory distress• GI disease, bleeding, others

Acute cardiovascular disease other than ACS?• Acute aortic syndrome (see chapter 7)• Pulmonary embolism (see chapter 7)• Acute pericarditis (see chapter 8)• Acute heart failure (see chapter 4)

P.7

1.1First medical contact in patients with CHEST PAIN (home-ambulance)

• Diagnosis of NSTE-ACS (see chapter 2)• Acute aortic syndrome (see chapter 7)• Acute pulmonary embolism (see chapter 7)• Acute pericarditis (see chapter 8)• Acute heart failure (see chapter 4)• Aortic stenosis, hyperthrophic cardiomyopathy• Acute gastro-oesophageal disease• Acute pleuro-pulmonary disease• Acute psychogenic disorders

Repeat clinical and ECG examinationLaboratory: cTn, renal function, Hb,D-dimers Imaging: TTE, CT scanDiagnostic coronary angiography

Yes No

Yes No

MANAGEMENT OF PATIENTS WITH CHEST PAIN (EMERGENCY ROOM)

STEMI,NSTE-ACS with persistent pain,

Hemodynamic distress

No direct transfer to cath-lab → ED, Chest Pain Unit,

cardiology ward, other wards

Other CVD or No ACS

Resuscitation, hemodynamic or respiratory support(see chapters 4 & 5)

Direct transfer to cath-lab

Complicated NSTEMISTEMI (see chapter 2)

Hemodynamic, respiratory or neurological distress? P.8

1.1Management of patients with CHEST PAIN (emergency room)

DYSPNEA: DIFERENTIAL DIAGNOSIS

50% have ≥2 diagnoses, which may result in acute respiratory failure*!

• ECG • Chest X-ray • Blood count • cTn • BNP • Venous BG • D-dimers if suspicion of PE

Basic measures

• BP, HR, respiratory rate, SpO2 & temperature • Start oxygen to target SpO2 94-98% • Start i.v. line & monitor patient

Criteria for transfer to ICU (despite treatment for 30 minutes)

• Respiratory rate >35/min• SpO2 <85%

• SBP <90 mmHg • HR >120 bpm

Investigations:

Acute heartfailure

Acute coronary syndrome

Exacerbated COPDor other chronic

lung disease

Other causes, including• Asthma

• Severe sepsis • Tumor • Pneumothorax • Pleural effusion/ascites • Anxiety disorder • Anemia • Bronchitis • Metabolic acidosis • Neurologic disease

Pneumonia Pulmonaryembolism

* Defined as ≥1 criterion: • Respiratory rate ≥25/min • PaO2 ≤75 mmHg • SpO2 ≤92% in ambient air • PaCO2 ≥45 mmHg with arterial pH ≤7.35

Reference: Ray P et al. Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Critical Care (2006); 10 (3):R82.

P.9

1.2DYSPNEA: Diferential diagnosis

BASIC WORK-UP

• Positioning Keep head of bed elevated above level of legs• Oxygen Up to 12 l/min via rebreather mask, titrate oxygen saturation to 94%• Nitroglycerin 1-2 SL tablets or 2-3 patches 10 mg (1st choice). In pulmonary edema with severe shortness of breath: NTG drip 0.05% (100 mg in 200 ml) - Start with 25 µg/min = 3 ml/h, check BP after 5 and 10 min - Increase dose by 25 µg/min at a time as long as SBP >90 mmHg - Additional BP check 5 and 10 min after each increase in dosing - Check BP every 20 min once a steady drip rate is reached• Furosemide 40-120 mg i.v. (adjust based on kidney function and clinical findings; monitor creatinine)• Morphine 2 mg i.v. (preceeded by 10 mg i.v. metoclopramide PRN) if patient is in severe dyspnoea• Consider digoxin 0.5 (-1.0) mg i.v. in patients with atrial fibrillation• Anticoagulation Therapeutic dosing in ACS and atrial fibrillation: Enoxaparin 1 mg/kg body weight as 1st dose

Unstable after 30 minutes

CCU/ICU transfer Ward transfer

Stable after 30 minutes

• Chest X-ray (lung ultrasound)• Echocardiogram During admission (earlier if decompensated aortic stenosis or endocarditis are suspected)• Coronary angiography Emergent in patients with ACS; delayed in patients with suspected coronary artery disease

• Immediate 12-lead ECG, cardiac monitor, BP, respiratory rate, pulse oximetry• Clinical findings Most commonly: lower extremity edema, jugular venous distension, rales, work up for underlying cardiac disease and triggers• Laboratory findings Complete blood count, chemistries, cardiac enzymes, BNP, TSH, ABG as needed

P.10

1.2DYSPNEA: Acute heart failure (see chapter 4.1)

Reference: Ware L B and Matthay M A. Acute Pulmonary Edema. New Engl J Med (2005); 353:2788-2796.

BASIC WORK-UP

• Positioning Keep head of bed elevated above level of legs• Oxygen Up to 12 l/min via rebreather mask, titrate oxygen saturation to 94%• Nitroglycerin 1-2 SL tablets or 2-3 patches 10 mg (1st choice). In pulmonary edema with severe shortness of breath: NTG drip 0.05% (100 mg in 200 ml) - Start with 25 µg/min = 3 ml/h, check BP after 5 and 10 min - Increase dose by 25 µg/min at a time as long as SBP >90 mmHg - Additional BP check 5 and 10 min after each increase in dosing - Check BP every 20 min once a steady drip rate is reached• Furosemide 40-120 mg i.v. (adjust based on kidney function and clinical findings; monitor creatinine)• Morphine 2 mg i.v. (preceeded by 10 mg i.v. metoclopramide PRN) if patient is in severe dyspnoea• Consider digoxin 0.5 (-1.0) mg i.v. in patients with atrial fibrillation• Anticoagulation Therapeutic dosing in ACS and atrial fibrillation: Enoxaparin 1 mg/kg body weight as 1st dose

Unstable after 30 minutes

CCU/ICU transfer Ward transfer

Stable after 30 minutes

• Chest X-ray (lung ultrasound)• Echocardiogram During admission (earlier if decompensated aortic stenosis or endocarditis are suspected)• Coronary angiography Emergent in patients with ACS; delayed in patients with suspected coronary artery disease

• Immediate 12-lead ECG, cardiac monitor, BP, respiratory rate, pulse oximetry• Clinical findings Most commonly: lower extremity edema, jugular venous distension, rales, work up for underlying cardiac disease and triggers• Laboratory findings Complete blood count, chemistries, cardiac enzymes, BNP, TSH, ABG as needed

P.11

1.2

Priorities: 1. Vital signs 2. Diagnostic screening dependent upon clinical stratification

Hemodynamically unstable Hemodynamically stable

Intermediateprobability

Total score 2-6

Highprobability

Total score >6

Lowprobability

Total score <2

Outpatient management possible?→ Risk stratification

Initiate transfer to ICU

Immediate TTE (if available)

PE confirmed: Treatment(see chapter 7.2)

Resultinconclusive→ CT-angio

Rightventriculardysfunction

Wells criteria for PE: Score• Clinical signs and symptoms of deep vein thrombosis (DVT) + 3.0• No alternative diagnosis (or alternative diagnosis less likely than PE) + 3.0• Heart rate >100/min + 1.5• Immobilization or operation within the last 4 weeks + 1.5• Previous DVT or PE + 1.5• Hemoptysis + 1.0• Malignant tumor with treatment within the last 6 months or palliative care + 1.0

ABG, ECG, chest X-ray plus clinical assessment of PE probability (risk factors) plus monitoring

(see chapter 7.2)

P.12

1.2DYSPNEA: Acute pulmonary embolism (see chapter 7.2)

Copyright: Stein PD, Woodard PK, Weg JG, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. Am J Med (2006); 119:1048–55. - Goldhaber SZ. Pulmonary embolism. Lancet (2004); 363 (9417) 1295-1305. - Agnelli G and Becattini C. Acute Pulmonary Embolism. New Engl J Med (2010); 363:266-274.

Priorities: 1. Vital signs 2. Diagnostic screening dependent upon clinical stratification

Hemodynamically unstable Hemodynamically stable

Intermediateprobability

Total score 2-6

Highprobability

Total score >6

Lowprobability

Total score <2

Outpatient management possible?→ Risk stratification

Initiate transfer to ICU

Immediate TTE (if available)

PE confirmed: Treatment(see chapter 7.2)

Resultinconclusive→ CT-angio

Rightventriculardysfunction

Wells criteria for PE: Score• Clinical signs and symptoms of deep vein thrombosis (DVT) + 3.0• No alternative diagnosis (or alternative diagnosis less likely than PE) + 3.0• Heart rate >100/min + 1.5• Immobilization or operation within the last 4 weeks + 1.5• Previous DVT or PE + 1.5• Hemoptysis + 1.0• Malignant tumor with treatment within the last 6 months or palliative care + 1.0

ABG, ECG, chest X-ray plus clinical assessment of PE probability (risk factors) plus monitoring

(see chapter 7.2)

P.13

1.2

DYSPNEA: COPD EXACERBATION

• Verify diagnosis (DD: PE, acute heart failure, pneumothorax) • Oxygen administration → SpO2 target 88-92% (Beware of carbonarcosis: ABC after 1 h)

Definition: Known COPD and/or • Progressive dyspnea and/or • Change in quantitiy and color of sputum and/or • Heavy coughing

• COPD classification (GOLD)

• Etiology

• Hospitalisation indicated?

• Follow-up

• Evaluate ICU criteria• NIV indicated?

• Laboratory findings: Blood count, coagulation, ProCT, perhaps BNP, D-Dimers• Chest X-ray; ECG (exclusion of differential diagnoses)• Sputum cultures (always in case of hospitalisation or previousoutpatient antibiotic treatment)

• Oxygen therapy 2-(4) l; target saturation 90% • Salbutamol/ipratropium inhalations ≥4-6 x/d, if needed long-term inhalation• Systemic steroids prednisone 0.5 mg/kg of body weight for 5 days• Antibiotic treatment should be considered; always indicated in stage Gold IV• Physiotherapy

• History, clinical examination (blood pressure, pulse, oxygen saturation, vigilance)

Copyright: Leuppi JD et al. JAMA. 2013 Jun 5; 309(21):2223-31.

P.14

1.2DYSPNEA: COPD exacerbation

DYSPNEA: COMMUNITY-ACQUIRED PNEUMONIA

Objective: diagnostics, risk stratification & empirical immediate treatment <2(-4) hours

Definition

Complications

• Chest X-ray if dyspnea & cough • Laboratory workup clinical chemistry; BGA; procalcitonin• Sputum if patient admitted• Blood cultures (2x2) if patient admitted• Legionella antigen (urine) if Legionellosis suspected • Pneumococcus antigen (urine) if no other pathogen isolated

Risk stratification → manageable on an outpatient basis?- Pneumonia Severity Index- CURB-65

• Treatment; procalcitonin guided treatment• Consider outpatient treatment where PSI I-III or CURB65 0 or 1• Minimum 5-day course of treatment and afebrile for 48-72h, 7-10 days, 14 days where intracellular organisms (e.g. Legionella) are present

Copyrights: Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. (2007); 44 Suppl 2:S27-72. - Halm EA and Teirstein AS. Management of Community-Acquired Pneumonia New Engl J Med (2002); 347:2039-2045. - Woodhead M et al. Guidelines for the management of adult lower respiratory tract infections ERJ December 1, (2005); 26 (6) 1138-1180.

P.15

1.2DYSPNEA: Community-acquired pneumonia

Syncope is a transient loss of consciousness due to global cerebral hypoperfusion (usually, itself due to period of low blood pressure) characterised by rapid onset, short duration, spontaneous and complete recovery.

The differentiation between syncope and non-syncopal conditions with real or apparent LOC can be achieved in most cases with a detailed clinical history but sometimes can be extremely difficult. The following questions should be answered: • Was LOC complete? • Was LOC transient with rapid onset and short duration? • Did the patient recover spontaneously, completely and without sequelae? • Did the patient lose postural tone?

If the answers to these questions are positive, the episode has a high likelihood of being syncope. If the answer to one or more of these questions is negative, exclude other forms of LOC before proceeding with syncope evaluation.

Loss of Consciousness?

TLOCTrauma Not Trauma

• Accidental • Fall• Other abnormal mental state

No

No

Yes

Yes

• Coma• Intoxication

• Metabolic disturbance• Aborted sudden death

Transient, rapid onset,short time, self-terminating

Syncope Epilepsy Psychogenic

Reference: Sutton R. Clinical classification of syncope. - Prog Cardiovasc Dis. (2013); 55(4):339-44.

P.16

1.3SYNCOPE: Assessment of patients

with transient loss of conscioussness (TLOC)

Vasovagal syncope is diagnosed if syncope is precipitated by emotional distress or orthostatic stress and is associated with typical prodrome.

Situational syncope is diagnosed if syncope occurs during or immediately after specific triggers.

Orthostatic syncope is diagnosed when it occurs after standing up and there is documentation of orthostatic hypotension.

Arrhythmia related syncope is diagnosed by ECG when there is:

• Persistent sinus bradycardia <40 bpm in awake or repetitive sinoatrial block or sinus pauses >3 s • Mobitz II 2nd or 3rd degree AV block • Alternating left and right BBB • VT or rapid paroxysmal SVT • Non-sustained episodes of polymorphic VT and long or short QT interval • Pacemaker or ICD malfunction with cardiac pauses

Cardiac ischemia related syncope is diagnosed when syncope presents with ECG evidence of acute ischemia with or without myocardial infarction.

Cardiovascular syncope is diagnosed when syncope presents in patients with prolapsing atrial myxoma, severe aortic stenosis, pulmonary hypertension, pulmonary embolus or acute aortic dissection.

Reference: Moya A et al. Eur Heart J(2009) 30, 2631–2671 (1).

P.17

1.3SYNCOPE: Diagnostic criteria (1)

Diagnostic criteria with initial evaluation

Patients with suspected syncope presenting to ED or clinic

“Uncertain” or unexplained syncope Certain diagnosis of syncope

Risk stratification

High risk Intermediate risk Low risk

Observation UnitHome if stable,

Admit to hospitalif evidence of high risk

HomeOutpatient SMU

referral

Outpatient SMU for diagnosis, treatment and follow-up as appropriate

Hospital admissionInpatient SMU

Initiate therapyInpatient SMU, outpatient SMU orpersonal physician as appropriate

Copyright: Sutton R, Brignole M, Benditt DG. Key challenges in the current management of syncope. Nat Rev Cardiol. (2012 ); (10):590-8.

Once syncope is considered to be the likely diagnosis, risk stratification is required to determine further management. P.18

1.3SYNCOPE: Evaluation and risk stratification of patients

with suspected syncope

Carotid sinus massage Orthostatic Hypotension

Indications• CSM is indicated in patients >40 years with syncope

of unknown aetiology after initial evaluation;• CSM should be avoided in patients with previous MI,

TIA or stroke within the past 3 months and in patients with carotid bruits (except if carotid Doppler studies excluded significant stenosis)

Recommendations: Active standing Indications• Manual intermittent determination with

sphygmomanometer of BP supine and, when OH is suspected, during active standing for 3 min is indicated as initial evaluation;

• Continuous beat-to-beat non-invasive pressure measurement may be helpful in cases of doubt

Diagnostic criteria• CSM is diagnostic if syncope is reproduced in presence

of asystole longer than 3 s and/or a fall in systolic BP >50 mmHg

Diagnostic criteria• The test is diagnostic when there is a symptomatic

fall in systolic BP from baseline value ≥20 mmHg or diastolic BP ≥10 mmHg or a decrease in systolic BP to <90 mmHg;

• The test should be considered diagnostic when there is an asymptomatic fall in systolic BP from baseline value ≥20 mmHg or diastolic BP >10 mmHg or a decrease in systolic BP to <90 mmHg

Reference: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (2).

P.19

1.3SYNCOPE: Diagnostic criteria (2)

Diagnostic criteria with provocation maneuvers

Treatment of reflex syncope Treatment of orthostatic hypotension

• Explanation of the diagnosis, provision of reassurance and explanation of risk of recurrence are in all patients

• Isometric PCM are indicated in patients with prodrome• Cardiac pacing should be considered in patients with dominant

cardioinhibitory CSS• Cardiac pacing should be considered in patients with frequent recurrent reflex

syncope, age >40 years and documented spontaneous cardioinhibitory response during monitoring

• Midodrine may be indicated in patients with VVS refractory to lifestyle measures• Tilt training may be useful for education of patients but long-term benefit depends

on compliance• Cardiac pacing may be indicated in patients with tilt-induced cardioinhibitory

response with recurrent frequent unpredictable syncope and age >40 after alternative therapy has failed

• Triggers or situations inducing syncope must be avoided as much as possible• Hypotensive drugs must be modified or discontinued• Cardiac pacing is not indicated in the absence of a documented cardioinhibitory

reflex• Beta-adrenergic blocking drugs are not indicated• Fluid consumption and salt in the diet should be increased

• Adequate hydration and salt intake must be maintained

• Midodrine should be administered as adjunctive therapy if needed

• Fludrocortisone should be administered as adjunctive therapy if needed

• PCM may be indicated • Abdominal binders and/or support

stockings to reduce venous pooling may be indicated

• Head-up tilt sleeping (>10°) to increase fluid volume may be indicated

• Triggers or situations inducing syncope must be avoided as much as possible

• Hypotensive drugs administered for concomitant conditions must be discontinued or reduced

Copyright: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (3).

P.20

1.3Treatment according to type of SYNCOPE (1)

Treatment of arrhythmic syncope

Cardiac Pacing• Pacing is indicated in patients with sinus node disease in

whom syncope is demonstrated to be due to sinus arrest (symptom-ECG correlation) without a correctable cause

• Pacing is indicated in sinus node disease patients with syncope and abnormal CSNRT

• Pacing is indicated in sinus node disease patients with syncope and asymptomatic pauses >3 sec. (with possible exceptions of young trained persons, during sleep and in medicated patients)

• Pacing is indicated in patients with syncope and 2nd degree Mobitz II, advanced or complete AV block

• Pacing is indicated in patients with syncope, BBB and positive EPS

• Pacing should be considered in patients with unexplained syncope and BBB

• Pacing may be indicated in patients with unexplained syncope and sinus node disease with persistent sinus bradycardia itself asymptomatic

• Pacing is not indicated in patients with unexplained syncope without evidence of any conduction disturbance

Catheter ablation• Catheter ablation is indicated in patients with symptom/

arrhythmia ECG correlation in both SVT and VT in the absence of structural heart disease (with exception of atrial fibrillation)

• Catheter ablation may be indicated in patients with syncope due to the onset of rapid atrial fibrillation

Antiarrhythmic drug therapy• Antiarrhythmic drug therapy, including rate control drugs,

is indicated in patients with syncope due to onset of rapid atrial fibrillation

• Drug therapy should be considered in patients with symptom/ arrhythmia ECG correlation in both SVT and VT when catheter ablation cannot be undertaken or has failed

Implantable Cardioverter Defibrillator (ICD) • ICD is indicated in patients with documented VT

and structural heart disease• ICD is indicated when sustained monomorphic VT is induced

at EPS in patients with previous myocardial infarction• ICD should be considered in patients with documented VT

and inherited cardiomyopathies or channelopathies

Copyright: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (4).

P.21

1.3Treatment according to type of SYNCOPE (2)

CHAPTER 2

ACUTE CORONARY SYNDROMES

2.1 GENERAL CONCEPTS �� p.24 H. Bueno

2.2 NON ST-SEGMENT ELEVATION ACS �� p.29 H. Bueno

2.3 ST-SEGMENT ELEVATION MI (STEMI) �� p.35 P. Vranckx, B. Ibañez

2

hs-cTn<ULNhs-cTn>ULN

ACUTE CORONARY SYNDROMES: DIAGNOSIS

CHEST PAIN or symptoms sugestive of myocardial ischemia

ECG

ST elevation(persistent)

Repolarization not interpretable(i.e. LBBB, pacemaker...)

ST/T abnormalities Normal ECG

STEMI

Pain resolves with nitroglycerin 1st hsTn

NSTEMI Unstable Angina Work-up

differential diagnoses

Pain onset >6 h Pain onset <6 h

Re-test hs-cTn (3h later)See next page for 1 h rule-in & rule-out algorithm

hs-cTnno change

∆ hs-cTn(1 value >ULN)

hs-cTn >x5 ULNor

clinicaldiagnosis

clear

Potential noncardiac

causes for abnormal Tn

ConsiderSTEMI

Yes

No

References: Roffi M. Eur Heart J 2016; 37:267-315. Ibañez B. Eur Heart J 2018; 39:119-177.

P.24

2.1ACUTE CORONARY SYNDROMES: Diagnosis (1)

Suspected NSTEMI

Other0h≥D ng/l

or≥

ObserveRule-out Rule-in

hs-cTnT (Elecsys)*

hs-cTnl (Architect)*

hs-cTnl (Dimension Vista)*

0-1h E ng/l0h<A ng/l

0h<B ng/l and

0-1h<Cng/l

A

5

2

0,5

B

12

5

5

C

3

2

2

D

52

52

107

E

5

6

19

oror

• NSTEMI can be ruled-out at presentation, if hs-cTn concentration is very low• NSTEMI can be ruled out by the combination of low baseline levels and the lack of a relevant increase within 1 h• NSTEMI is highly likely if initial hs-cTn concentration is at least moderately elevated or hs-cTn concentrations

show a clear rise within the first hour

Reference: Roffi M. Eur Heart J 2016; 37:267-315.

*Cut-off levels are assay-specific.

P.25

2.1ACUTE CORONARY SYNDROMES: Diagnosis (2)

0-1 H Rule-in & rule out test for NSTEMI

Causes of chest pain Not related to ACS

Causes of troponin elevationNot related to ACS

Primary cardiovascular• Acute pericarditis, pericardial effusion• Acute myocarditis• Severe hypertensive crisis• Stress cardiomyopathy (Tako-Tsubo syndrome)• Hypertrophic cardiomyopathy, aortic stenosis • Severe acute heart failure • Acute aortic syndrome (dissection, hematoma)• Pulmonary embolism, pulmonary infarction• Cardiac contusion

Primary cardiovascular• Acute myo(peri)carditis• Severe hypertensive crisis• Pulmonary edema or severe congestive heart failure• Stress cardiomyopathy (Tako-Tsubo syndrome)• Post- tachy- or bradyarrhythmias• Cardiac contusion or cardiac procedures

(ablation, cardioversion, or endomyocardial biopsy)• Aortic dissection, aortic valve disease or hypertrophic cardiomyopathy• Pulmonary embolism, severe pulmonary hypertension

Primary non-cardiovascular• Oesophageal spasm, oesophagitis, Gastro

Esophageal Reflux (GER)• Peptic ulcer disease, cholecystitis, pancreatitis• Pneumonia, bronchitis, asthma attack• Pleuritis, pleural effusion, pneumothorax• Pulmonary embolism, severe pulmonary

hypertension• Thoracic trauma• Costochondritis, rib fracture • Cervical / thoracic vertebral or discal damage• Herpes Zoster

Primary non-cardiovascular• Renal dysfunction (acute or chronic)• Critical illness (sepsis, repiratory failure…)• Acute neurological damage (i.e. stroke, subarachnoid hemorrhage)• Severe burns (affecting >30% of body surface area)• Rhabdomyolysis• Drug toxicity (chemotherapy with adriamycin, 5-fluorouracil,

herceptin, snake venoms…)• Inflammatory or degenerative muscle diseases• Hypothyroidism• Infiltrative diseases (amyloidosis, hemochromatosis, sarcoidosis)• Scleroderma

P.26

2.1ACUTE CORONARY SYNDROMES: Differential diagnosis (1)

ST-segment elevation Negative T waves

Fixed• LV aneurysm• LBBB, WPW, hypertrophic cardiomyopathy, LVH• Pacemaker stimulation• Early repolarisation (elevated J-point)Dynamic• Acute (myo)pericarditis• Pulmonary embolism• Electrolyte disturbances (hyperkalemia)• Acute brain damage (stroke, subarachnoid haemorrhage)• Tako Tsubo syndrome

• Normal variants, i.e. women (right precordial leads), children, teenagers

• Evolutive changes post myocardial infarction

• Chronic ischemic heart disease• Acute (myo)pericarditis,

cardiomyopathies• BBB, LVH, WPW• Post-tachycardia or

pacemaker stimulation• Metabolic or ionic disturbances

ST-segment depression Prominent T waves

Fixed• Abnormal QRS (LBBB, WPW, pacemaker stimulation…)• LVH, hypertrophic cardiomyopathy• Chronic ischemic heart disease

• Normal variants, i.e. early repolarisation

• Metabolic or ionic disturbances (i.e. hyperkalemia)

• Acute neurological damage (stroke, subarachnoid haemorrhage)

Dynamic • Acute (myo)pericarditis• Acute pulmonary hypertension• Electrolyte disturbances (hyperkalemia)• Intermitent LBBB, WPW, pacing• Post-tachycardia / cardioversion

• Severe hypertensive crisis• Drug effects (digoxin)• Shock, pancreatitis• Hyperventilation• Tako Tsubo syndrome

P.27

2.1ACUTE CORONARY SYNDROMES: Differential diagnosis (2)

Causes of repolarisation abnormalities in the ECG not related to ACS

2ECG

(<10 min)

3Diagnosis /

Risk assessment

4Medical

Treatment

5InvasiveStrategy

STEMI (see chapter 2.3)

Thrombolysisfor STEMI if

primary PCI nottimely available

PrimaryPCI

1Clinical

Evaluation

NSTE ACS(see chapter 2.2)

ACS unclear(Rule out ACS) (see chapter 1.1)

No ACS

Chest Pain Unit

• Clinical presentation (BP, HR)

• ECG presentation

• Past history

• Ischemic risk (i.e. GRACE, TIMI scores)

• Bleeding risk (i.e. CRUSADE score)

• Additional information (labs, imaging...) optional

Anti-ischemictherapy

Antiplatelettherapy

Anticoagulation

Emergent<2 hours

Urgent2-24 hours

Early24-72 hours

No /Elective

Quality ofchest pain

Clinicalcontext

Probabilityof CAD

Physicalexamination

GENERAL APPROACH TO THE PATIENT WITH CHEST PAIN / SUSPECTED ACS

ECG

Rule out noncardiac causes

P.28

2.1GENERAL APPROACH

to the patient with chest pain/suspected ACS

Ischemic risk

GRACE risk score TIMI risk score

Predictive Factors• Age• HR*

• SBP*

• Creatinine (mg/dl)*• Killip class*• Cardiac arrest*• ST-segment deviation• Elevated cardiac markers

OutcomesIn-hospital, 6-month, 1-year and 3-year mortality1-year death/MI

Predictive Factors• Age 65 years • At least 3 risk factors for CAD • Significant (>50%) coronary stenosis• ST deviation • Severe anginal symptoms (>2 events in last 24h)• Use of aspirin in last 7 days • Elevated serum cardiac markers

OutcomeAll-cause mortality/new or recurrent MI/severe recurrent ischemia requiring urgent revascularisation at 14 days

* At admission.

50

40

30

20

10

0 70 90 110 130 150 170 190 210

GRACE Risk Score

Probability of all-cause mortality from hopital discharge to 6 months (%)

50

40

30

20

10

00-1 2 3 4 5 >=6

TIMI Risk Score

Risk of 14 days events (%)

Risk calculation http://www.gracescore.org/WebSite/WebVersion.aspx

Risk calculation http://www.timi.org/index.php?page=calculators

P.29

2.2NON ST-SEGMENT ELEVATION ACS: Risk stratification (1)

Bleeding risk

CRUSADE risk score

Predictive Factors• Sex• HR*

• SBP*

• Creatinine (mg/dl)*• Baseline hematocrit*• GFR: Cockcroft-Gault*• Diabetes• Prior vascular disease• Signs of congestive heart failure*

OutcomeIn-hospital major bleeding

Copyrights: Eagle KA et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month post-discharge death in an international registry. JAMA. (2004); 291(22):2727-33. - Antman EM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. (2000); 284(7):835-42. - Subherwal S, et al Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation (2009); 119(14):1873-82.

* At admission.

50

40

30

20

10

00 20 40 60 80 100

CRUSADE Bleeding Score

Probability of in-hospital major bleeding(%)

Risk calculationwww.crusadebleedingscore.org

P.30

2.2NON ST-SEGMENT ELEVATION ACS: Risk stratification (2)

Initial treatment*• Nitrates• Morphine• Oxygen (if SpO2 <90%)

One of the following: • Fondaparinux • Enoxaparin • UFH • Bivalirudin

Aspirin + one of: • Ticagrelor • Prasugrel • Clopidogrel

Optionally: • GP IIb/IIIa inhibitors • Cangrelor

• Nitrates• Beta-blockers• Calcium antagonists

• Statins• ACE inh. (or ARB)• Aldosterone inhibitors

Pharmacologicaltreatment*

Anti ischemictreatment

Antithrombotictherapy

Anticoagulation Antiplatelets

PCICABG

Other preventivetherapies

Myocardialrevascularisation

*For more information on individual drug doses and indications,

SEE CHAPTER 3 SECONDARY PREVENTION AFTER ACS & CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE

P.31

2.2NON ST-SEGMENT ELEVATION ACS: Treatment (1)

General overview

Very-high-risk criteria

• Haemodynamic instability or cardiogenic shock• Recurrent or ongoing chest pain refractory to medical treatment• Life-threatening arrhythmias or cardiac arrest• Mechanical complications of MI• Acute heart failure• Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation

High-risk criteria • Rise or fall in cardiac troponin compatible with MI• Dynamic ST- or T-wave changes (symptomatic or silent)• GRACE score >140

Intermediate-risk criteria

• Diabetes mellitus• Renal insufficienty (eGFR <60 ml/min/1.73 m2)• LVEF <40% or congestive heart failure• Early post-infarction angina• Prior PCI• Prior CABG• GRACE risk score >109 and <140

Low-risk criteria • Any characteristics not mentioned above


P.32


Risk criteria mandating invasive strategy in NSTE-ACS

Symptoms Onset

PCI centre

Very high

ImmediateInvasive (<2 hr)

Early invasive(<24 hr)

Invasive(<72 hr)

High

Intermediate

Immediate transfer to PCI centre

Same-day transfer

Transfer

Transfer optional Ris

k st

rati

fica

tion

The

rape

utic

stra

tegy

Low

EMS or Non–PCI centre

First medical contact NSTE-ACS diagnosis

Very high

High

Intermediate

Low

Non-invasivetesting if appropriate


P.33


Timing and strategy for invasive management

0

24 hours

10 min

90 min

2 hours

Str

ateg

y cl

ock

ECG STEMI diagnosis

Time to PCI?

≤120min

Primary PCIstrategy

Fibrinolysisstrategya

Bolus offibrinolyticb

Transferto PCI centre

Meet reperfusioncriteria?

No Yes

Routine PCI strategy

RescuePCI

>120min

Alert & transferto PCI centre

Wire crossing(reperfusion)

≥120

min

60-9

0m

in

Reference: Ibañez B. Eur Heart J 2018; 39:119-177.

STEMI Treatment (1):Reperfusion strategy

a If fibrinolysis is contra-indicated, direct for primary PCI strategy regardless of time to PCI.b 10 min is the maximum target delay time from STEMI diagnosis to fibrinolytic bolus administration, however, it should be given as soon as possible after STEMI diagnosis (after ruling out contra-indications).

P.34

2.3

AspirinLoading

Prasugrel or ticagrelor loading(clopidogrel as alternative)

Aspirinmaintenance

Prasugrel or ticagrelor maintenance(clopidogrel as alternative)

Oxygen when SpO2 <90%

High dose statin(e.g. atorvastatin 80 mg or rosuvastatin 40 mg)

Oral β-blocker

ACE inhibitor

Mineralocorticoid receptor antagonist(if LVEF <40% and heart failure)

i.v. Beta-blocker

i.v. Opioids/tranquilizer

DURING PCI: radial access, UFH (enoxaparin/bivalirudin as alternatives)

STEMIdiagnosis

Wire crossing(reperfusion)

HospitalAdmission

HospitalDischarge


P.35

2.3STEMI Treatment (2):Medical management of patients treated with primary PCI

Aspirinloading

Clopidogrelloading

Fibrinolysis bolus Enoxaparin

Aspirinmaintenance

Clopidogrelmaintenance

Oxygen when SpO2 <90%

i.v. Opioids/tranquilizer

High dose statin(e.g. atorvastatin 80 mg or rosuvastatin 40 mg)

Oral β-blocker

ACE inhibitor

Mineralocorticoid receptor antagonist(if LVEF <40% and heart failure)

STEMIdiagnosis

HospitalAdmission

HospitalDischarge

10min

Coronary angiography ± PCI(2-24h)


P.36

2.3STEMI Treatment (3):Medical management of patients treated with fibrinolysis

CHAPTER 3

SECONDARY PREVENTION AFTER ACS

3.1 GENERAL SECONDARY PREVENTION STRATEGIES AND LIPID LOWERING �� p.38 H. Bueno, S. Halvorsen

3.2 ANTITHROMBOTIC TREATMENT �� p.41 F. Costa, S. Halvorsen

P.37

3

Acute Coronary Syndrome

Re-evaluate lifestyle, control of risk factors, psychosocial factors and adherance to therapy

Adjustment of secondary prevention therapies. Consider polypill, if needed


Aspirin + P2Y12

inhibitor(12 months)

Consider addingEzetimibe*

PCSK9 inhibitor*

Considerdose adjustmentConsider ARNI*

Consider SGLT2 inhibitor*GLP-1 agonists*

Lipidlowering

High intensitystatin therapy

BP/LVD/HF control

ACEI / ARB*,Beta-blockers*,

MRA*

Glucosecontrol

MetforminInsulin*

Hospitalization

• Risk factor control (e.g.weight control, smoking cessation,blood pressure and lipid control)• Diet/nutritional counseling• Physical activity counseling/excercise training• Psychosocial management,sex advice• Vocational advice

Plan and scheduleCardiac Rehabilitation

Educationand counselling

Cardioprotective drugsin secondary prevention

Reinforce educationPsychosocial support

1- Acute care • Drug therapy • Coronary revascularisation2- Cardiovascular risk assessment (e.g. concealed and uncontrolled risk factors)3- Initiate secondary prevention and set treatment goals

After Discharge

CardiacRehabilitation

programme

After 12 monthsconsider*:Ticagrelor60 mg bid

Anticoagulation?**

P.38

3.1SECONDARY PREVENTION STRATEGIES after ACS

Acute Coronary Syndrome

Re-evaluate lifestyle, control of risk factors, psychosocial factors and adherance to therapy

Adjustment of secondary prevention therapies. Consider polypill, if needed


Aspirin + P2Y12

inhibitor(12 months)

Consider addingEzetimibe*

PCSK9 inhibitor*

Considerdose adjustmentConsider ARNI*

Consider SGLT2 inhibitor*GLP-1 agonists*

Lipidlowering

High intensitystatin therapy

BP/LVD/HF control

ACEI / ARB*,Beta-blockers*,

MRA*

Glucosecontrol

MetforminInsulin*

Hospitalization

• Risk factor control (e.g.weight control, smoking cessation,blood pressure and lipid control)• Diet/nutritional counseling• Physical activity counseling/excercise training• Psychosocial management,sex advice• Vocational advice

Plan and scheduleCardiac Rehabilitation

Educationand counselling

Cardioprotective drugsin secondary prevention

Reinforce educationPsychosocial support

1- Acute care • Drug therapy • Coronary revascularisation2- Cardiovascular risk assessment (e.g. concealed and uncontrolled risk factors)3- Initiate secondary prevention and set treatment goals

After Discharge

CardiacRehabilitation

programme

After 12 monthsconsider*:Ticagrelor60 mg bid

Anticoagulation?**

Reference modified from Cortés-Beringola A. Eur J Prev Cardiol 2017; 24(3 suppl): 22-28.

* When individually indicated and without specific contraindications. - ** Rivaroxaban 2.5 mg bid pending approval for indication in chronic CAD.

P.39

3.1

Potential strategies to optimize secondary prevention therapy after ACS

• Participation in a comprehensive, multi-disciplinary cardiac rehabilitation programme after hospital discharge

• Coordination with primary care provider (and other specilaists) in therapeutic plan and objectives

• Re-check and reinforce advise on all lifestyle changes (diet, physical activity, smoking cessation…) during follow-up visits

• Check and optimise doses of all indicated secondary prevention drugs

• Use of specialist support, nicotine replacement therapies, varenicline, and/or bupropion individually or in combination for patients who do not quit or restart smoking

• Use of ezetimibe and/or a PCSK9 inhibitor in patients who remain at high risk with LDL-cholesterol >70 mg/dl despite apropriate diet and maximally tolerated doses of statins

• Use of a polypill or combination therapy in patients with suboptimal adherence to drug therapy

P.40

3.1After ACS: POTENTIAL STRATEGIES

TO OPTIMIZE SECONDARY PREVENTION THERAPY

PCI

Stable CAD

DES/BMS or DCB BRS DES/BMS or DCB

High Bleeding Risk

6mo DAPTClass I A1

1mo DAPT Class IIb C

3mo DAPT Class IIa B

≥12mo DAPTClass IIa C

12mo DAPTClass I A

6mo DAPTClass IIa B

>12mo DAPTClass IIb B

DAPT >6moClass IIb A

High Bleeding Risk

ACS

No

1mo

3mo

6mo

12mo

30mo

Yes No

or

Yes

A C

A C

A C

A C 2

A P A Tor

A C 3

A CA P A T

or A C 4

A PA T

A T

Treatmentindication

Device used

Time

A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260.

P.41

3.2ANTITHROMBOTIC TREATMENT:

Dual antiplatelet therapy duration in patients with ACS (1)

Medical Treatment Alone

Stable CAD ACS

No indicationfor DAPT unlessconcomitant orprior indication

overrides

Stable CAD

No indicationfor DAPT unlessconcomitant orprior indication

overrides

12mo DAPTClass I C

6mo DAPTClass IIa C

>12mo DAPTClass IIb C

High Bleeding Risk

CABG

No

1mo

3mo

6mo

12mo

30mo

Yes

ACS

High Bleeding Risk

No YesTime

or

A C 3

A CA P A T

or

A CA PA T

A T

12mo DAPTClass I C

>1mo DAPTClass IIa C

>12mo DAPTClass IIb C

orA C

3A CA T

or A CA T

Treatmentindication

Device used

A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260.

P.42


Dual antiplatelet therapy duration in patients with ACS (2)

CLOPIDOGREL

Ticagrelor LD (180 mg)24h after last prasugrel dose

Prasugrel LD (60 mg)24h after last ticagrelor dose

Prasu

grel

LD (60 m

g)

irres

pecti

ce of

prior

clop

idogr

el

timing

and d

osing

Clopido

grel

LD (600 m

g)

24h afte

r last

pras

ugrel

dose

Ticagrelor LD (180 mg)

irrespectice of prior clopidogrel

timing and dosing

Clopidogrel LD (600 mg)

24h after last ticagrelor dose

Ticagrelor LD (90 mg b.i.d.)24h after last prasugrel dose


Prasu

grel

MD (10 m

g q.d.

)

24h afte

r last

clopid

ogrel

dose

Clopido

grel

MD (75 m

g q.d.

)

24h afte

r last

pras

ugrel

dose

Tricagrelor MD (90 mg b.i.d.)

24h after last clopidogrel dose



ACCUTE SETTINGALWAYS RELOAD

CLOPIDOGREL

CHRONICSETTING

PRASUGREL TICAGRELOR


Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.

P.43


Switching between P2Y12 inhibitors for DAPT after ACS (1)

CLOPIDOGREL

Ticagrelor LD (180 mg)24h after last prasugrel dose


Prasu

grel

LD (60 m

g)

irres

pecti

ce of

prior

clop

idogr

el

timing

and d

osing

Clopido

grel

LD (600 m

g)

24h afte

r last

pras

ugrel

dose

Ticagrelor LD (180 mg)

irrespectice of prior clopidogrel

timing and dosing



Ticagrelor LD (90 mg b.i.d.)24h after last prasugrel dose


Prasu

grel

MD (10 m

g q.d.

)

24h afte

r last

clopid

ogrel

dose

Clopido

grel

MD (75 m

g q.d.

)

24h afte

r last

pras

ugrel

dose

Tricagrelor MD (90 mg b.i.d.)

24h after last clopidogrel dose



ACCUTE SETTINGALWAYS RELOAD

CLOPIDOGREL

CHRONICSETTING



Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.

P.44


Switching between P2Y12 inhibitors for DAPT after ACS (2)

P.45


Risk scores validated for DAPT duration decision-making

PRECISE-DAPT score DAPT score

Time of use At the time of coronary stenting After 12 months of uneventful DAPT

DAPT duration strategies assessed

Short DAPT (3-6 months)vs. Standard/long DAPT (12-24 monts)

Standard DAPT (12 months) vs. Long DAPT (30 months)

Score calculation HB Age ≥75 65 to <75 <65

Cigarette smokingDiabetes mellitusMI at presentationPrior PCI or prior MIPaclitaxel-eluting stentStent diameter <3 mmCHF or LVEF <30%Vein graft stent

— 2 pt— 1 pt0 pt

+ 1 pt+ 1 pt+ 1 pt+ 1 pt+ 1 pt+ 1 pt

+ 2 pt+ 2 pt

WBC

Age

CrCl

Prior Bleeding

ScorePoints

Score range 0 to 100 points — 2 to 10 points

Decision making cut-off

Score ≥25 → Short DAPTScore <25 → Standard/long DAPT

Score ≥2 → Long DAPTScore <2 → Standard DAPT

Electronic calculator www.precisedaptscore.com www.daptstudy.org

DUAL THERAPY strategy:

TRIPLE THERAPY strategy:

STEP

2:

Trea

tmen

t ty

peST

EP 3

:Tr

eatm

ent

dura

tion

STEP

1:Pa

tient

risk

asse

ssm

ent

BR>IR

DUAL (12 mo.) OAC alone

OAC alone

OAC alone

TRIPLE (for 1 mo.)

TRIPLE (up to 6 mo.)DUAL(up to 12 mo.)

DUAL (up to 12 mo.)

BR<IR

• NOAC* (preferable) - Apixaban 5 mg b.i.d. (reduce to 2.5 mg b.i.d. (1) - Dabigatran 110 mg b.i.d. (preferable while on DAPT) or 150 mg b.i.d. - Edoxaban 60 mg q.d. (reduce to 30 mg q.d. (2)

- Rivaroxaban 20 mg q.d. (reduce to 15 mg q.d. (3) or 15 mg (may be considered DAPT/SAPT)or• VKA dose ajusted: consider maintaining INR in the lower part of the recommended target range (e.g. 2.0-2.5 for AF and MV in aortic position, 2.5-3.0 for MV in mitral position)

OAC:• Clopidogrel 75 mg q.d. (preferable)*or

• Aspirin 75-100 mg q.d.

SAPT:

• Clopidogrel 75 mg q.d.and

• Aspirin 75-100 mg q.d.

DAPT:

• HIGH RISK OF BLEEDING?High HAS-BLED: Hypertension, abnormal liver/renal function, prior stroke, bleeding diathesis, labile INR if on VKA, age >65, drugs(e.g. NSAIDs or antiplatelets), alcohol abuse, ABC score: Age, Biomarkers (GDF-15, hs cTnT, Hb) and Clinical history of prior bleeding• HIGH RISK OF RECURRENT CORONARY ISCHEMIC EVENTS?ACS at presentation, prior ST, stenting of last remaining vessel, CrCL <60 ml/min, ≥3 stents implanted or lesions treated,bifurcation with 2 stents, overall stentlengh >60 mm, treatment of CTO

TRIPLETHERAPY

(If High BR Low IR)

(If High BR High IR)or

(If Low BR High IR)

DUALTHERAPY

Reference adapted from Valgimigli M et al. Eur Heart J. 2018;39:213-260.

* In case of selecting dual therapy immediately after stent implantation clopidogrel should be selected as single antiplatelet agent. Aspirin should however be administered at the time of the intervention.

(1) Age ≥80 years, body weight ≤60 kg or serum creatinine level ≥1.5 mg/dL. (2) CrCl of 30–50 ml/min, body weight ≤60 kg, concomitant use of verapamil, quinidine or dronedarone. (3) CrCl 30-49 ml/min.

P.46

3.2ANTITHROMBOTIC TREATMENT in patients with concomitant

indication for DAPT and chronic oral anticoagulation (1)

SURGERY

Minimal delay for P2Y12 interruption Days after surgery

CLOPIDOGREL

PRASUGREL

TICAGRELOR

CLOPIDOGREL

PRASUGREL(2)

TICAGRELOR(2)

ASPIRIN(1)

//••••••9••••••8••••••7••••••6••••••5••••••4••••••3••••••2••••••1•••••• 0••••••••••••••••••1-4

STOP

STOP

STOP

= Expected average platelet function recovery(1) Decision to stop aspirin throughout surgery should be made on a single case basis taking into account the surgical bleeding risk

(2) In patients not requiring OAC

Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.

P.47


Management of DAPT after ACS in patients with indication for surgery

LIFE-THREATENING BLEEDINGe.g. massive overt genitourinary,respiratory or upper/lowergastrointestinal bleeding,active intracranial, spinalor intraocular haemorrhage,or any bleeding

STOP ALL ANTITHROMBOTIC MEDICATIONSand reverse OAC. Once bleeding has ceased, re-evaluate the needfor DAPT or SAPT, preferably with the P2Y12 inhibitorespecially in case of upper GI bleeding

CONTINUE DAPT a , CONTINUE OAC c

CONTINUE DAPT, CONTINUE OAC Consider skipping one single next pill

CONSIDER STOPPING DAPTand continue with SAPT, preferably with the P2Y12 inhibitorespecially in case of upper GI bleeding. Once bleeding has ceased,re-evaluate the need for DAPT or SAPTa

CONSIDER STOPPING OACor even reversal until bleeding is controlled, unless prohibitive thrombotic risk(i.e. mechanical heart valve in mitral position, cardiac assist device )b-c-d

Reinitiate treatment within one week if clinically indicated.If Bleeding persist despite treatment, or treatment is not possibleCONSIDER STOPPING ALL ANTITHROMBOTIC MEDICATIONS

CONSIDER STOPPING DAPTand continue with SAPT, preferably with the P2Y12 inhibitorespecially in caseof upper GI bleeding Reinitiate DAPT as soon as deemed safea

CONSIDER STOPPING OACor even reversal until bleeding is controlled, unless very high thrombotic risk(i.e. mechanical heart valves, cardiac assist device, CHA2DS2-VASc ≥4 ).b-c-d

Reinitiate treatment within one week if clinically indicated.

SEVERE BLEEDINGe.g. severe genitourinary,respiratory or upper/lowergastrointestinal bleeding

MODERATE BLEEDINGe.g. genitourinary, respiratoryor upper/lower gastrointestinalbleeding with significant bloodloss or requiring transfusion

MILD BLEEDINGe.g. not self resolving epistaxis,moderate conjunctival bleeding,genitourinary or upper/lowergastrointestinal bleedingwithout significant blood loss,mild haemoptysis

TRIVIAL BLEEDING e.g. skin bruising or ecchimosis,self-resolving epistaxis, minimal conjunctival bleeding

ANTITHROMBOTIC TREATMENTMANAGEMENT DURING BLEEDING

Active bleeding and unstable hemodynamicputting patient’s life immediately at risk?

Hospitalization required? Hb loss >5 g/dl

Hb loss <5 g/dl

Significant blood loss (>3 g/dl) ?

Requires medical interventionor further evaluation?

Yes

Yes

Yes

Yes

No

No

No

No

Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.

a Consider shortening DAPT duration or switching to less potent P2Y12 inhibitor (i.e. from ticagrelor/prasugrel to clopidogrel), especially if recurrent bleeding occurs b Reinitiate treatment within one week if clinically indicated. For Vitamin-K antagonist consider a target INR of 2.0-2.5 unless overriding indication (i.e. mechanical heart valves or cardiac assist device) for NOAC consider the lowest effective dose. - c In case of triple therapy consider downgrading to dual therapy, preferably with clopidogrel and OAC. - d If patients on dual therapy, consider stopping antiplatelet therapy if deemed safe.

P.48


Management of acute bleeding after ACS

Acute upper GI haemorrhage in patient using antiplatelet agent(s) (APT)

Upper GI endoscopy demonstrates a nonvariceal source of bleeding (e.g. peptic ucler bleed)

High risk endoscopic stigmata identified(Forrest classification* Ia, Ib, IIa, IIb)

APT used for secondary prophylaxis(known cardiovascular disease)

Patients on low dose ASA alone• Resume low-lose ASA by day 3 following in dex endoscopy• Second-look endoscopy at the discretionof the endoscopist may be considered

Paptients on dual antiplatelet therapy (DAPT)• Continue low dose ASA without interruption• Early cardiology consultation for recommendationof second resumption/ continuation of second APT• Second-look endoscopy at the discretion of the endoscopoist may be considered

APT used for secondary prophylaxis(known cardiovascular disease)

Patients on low dose ASA alone• Continue low-dose ASA without interruption

Paptients on dual antiplatelet therapy (DAPT)• Continue DAPT without interruption

Low risk endoscopic stigmata identified(Forrest classification* IIc, III)

*The Forrest classification in defined as follows: Ia spuring hemorrhage, Ib oozing hemorrhage, IIa nonbleeding visible vessel, IIb an adherent clot, IIc flat pigmented spot, and III clean base ucler.

Reference: Halvorsen et al. Eur Heart J 2017; 38: 1455-62.

P.49


Management of antiplatelet therapy after acute GI bleeding

CHAPTER 4

ACUTE HEART FAILURE

4.1 WET-AND-WARM HEART FAILURE PATIENT �� p.52 V.P. Harjola, O. Miró

4.2 CARDIOGENIC SHOCK (WET-AND-COLD) �� p.61 P. Vranckx, U. Zeymer

4

Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.

WARM-DRY WARM-WET

COLD-DRY COLD-WET

HYPOPERFUSION (+)Cold sweaty extremities, Oliguria,

Mental confusion, Dizziness,Narrow pulse pressure

HYPOPERFUSION (-)

CONGESTION (-) CONGESTION (+)Pulmonary congestion, orthopnoea/paroxismal,

nocturnal dyspnoea, peripheral (bilateral) oedema, jugular venous dilatation, congested hepatomegaly,

gut congestion, ascites, hepatojugular reflux

Clinical profiles of patients with acute heart failure based on the presence/absence of congestion and/or hypoperfusion

Hypoperfusion is not synonymous with hypotension, but often hypoperfusion is accompanied by hypotension.

P.52

4.1Clinical profiles of patients with acute heart failure

Reference: McMurray JJ et al. Eur Heart J (2012); 33:1787-847.Ponikowski P et al. Eur J Heart Fail. 2016; 18:891-975.

1 Symptoms: Dyspnea (on effort or at rest)/breathlessness, fatigue, orthopnea, cough, weight gain/ankle swelling.

2 Signs: Tachypnea, tachycardia, low or normal blood pressure, raised jugular venous pressure, 3rd/4th heart sound, rales, oedema, intolerance of the supine position.

3 Cardiovascular risk profile: Older age, HTN, diabetes, smoking, dyslipidemia, family history, history of CVD.

4 Precipitants/causes that need urgent management (CHAMP): Acute coronary syndrome. Hypertensive emergency. Rapid arrhythmias or severe bradyarrhythmia/conduction disturbance. Mechanical causes. Pulmonary embolism.

5 Differential diagnosis: Exacerbated pulmonary disease, pneumonia, pulmonary embolism, pneumothorax, acute respiratory distress syndrome, (severe) anaemia, hyperventilation (metabolic acidosis), sepsis/septic shock, redistributive/hypovolemic shock.

FACTORS TRIGGERING ACUTE HEART FAILURE

• Acute coronary syndrome• Tachyarrhythmia (e.g. atrial fibrillation, ventricular tachycardia)• Excessive rise in blood pressure• Infection (e.g. pneumonia, infective endocarditis, sepsis).• Non-adherence with salt/fluid intake or medications• Toxic substances (alcohol, recreational drugs)• Drugs (e.g. NSAIDs, corticosteroids, negative inotropic

substances, cardiotoxic chemotherapeutics)• Exacerbation of chronic obstructive pulmonary disease• Pulmonary embolism• Surgery and perioperative complications• Increased sympathetic drive, stress-related cardiomyopathy• Metabolic/hormonal derangements (e.g. thyroid dysfunction,

diabetic ketosis, adrenal dysfunction, pregnancy and peripartum related abnormalities)

• Cerebrovascular insult• Acute mechanical cause : myocardial rupture complicating

ACS (free wall rupture, ventricular septal defect, acute mitral regurgitation), chest trauma or cardiac intervention, acute native or prosthetic valve incompetence secondary to endocarditis, aortic dissection or thrombosis

P.53

4.1ACUTE HEART FAILURE: Diagnosis and causes (2)

Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8): 891-975. DOI: 10.1002/ejhf.592.

Patient with suspected AHF

1. Cardiogenic shock ?Urgent phase after

first medical contact

Immediate stabilizationand transfer to ICU/CCU

Immediate initiationof specific treatement

Indentification of acute aeticology :C = Acute Coronary syndromeH = Hypertension emergencyA = ArrhythmiaM = Acute Mechanical causeP = Pulmonary embolism

Diagnostic work-up to confirm AHFClinical evaluation to select optimal management

Immediate phase(initial 60-120 minutes)

Circulatory support• pharmacological• mechanical

Ventilatory support• oxygen• non-invasive positivepressure ventilation (CPAP, BiPAP)• mechanical ventilation

2. Respiratory failure ?

YesNo

No

No

Yes

Yes

P.54

4.1Initial management of a patient with ACUTE HEART FAILURE

After 60-90 min

In hospital

Pre-hospital or emergency room

Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17:544-58.

Conventional oxygen therapy

Conventionaloxygen therapy

Intolerance

Weaning

CPAP

CPAP

FAILURE

PS-PEEP

SUCCESS

SIGNIFICANT HYPERCAPNIAAND ACIDOSIS

NORMAL pHAND pCO

2

Intubation

Intubation

RESPIRATORY DISTRESS?SpO2 <90%, RR>25,

Work of breathing, orthopnea

"PERSISTENT" RESPIRATORY DISTRESS?

Upright position

No Yes

Yes

Venous/Arterial blood gases

No

Room air

P.55

4.1ACUTE HEART FAILURE: Airway (A) and breathing (B)

Oxygen therapy and ventilatory support in acute heart failure

INSTRUMENTATION & INVESTIGATIONS: Intravenous line (peripheral/central) and BP monitoring (arterial line in shock and severe ventilatory/gas-exchange disturbances)Laboratory measures • Cardiac markers (troponin, BNP/NT-proBNP/MR-proANP) • Complete blood count, electrolytes, creatinine, urea, glucose,

inflammation, TSH • Consider arterial or venous blood gases, lactate, D-dimer

(suspicion of acute pulmonary embolism) Standard 12-lead ECG • Rhythm, rate, conduction times? • Signs of ischemia/myocardial infarction? Hypertrophy? Echocardiography a) Immediately in haemodynamically unstable patients b) Within 48 hours when cardiac structure and function are either not known or

may have changed since previous studies

Ventricular function (systolic and diastolic)? Estimated left-and right-side filling pressures? Lung ultrasound? Presence of valve dysfunction (severe stenosis/insufficiency)? Pericardial tamponade?

ACTIONS:

Rule in/out acute heart failure

as cause of symptoms and signs

Determine clinical profile

Start as soon as possible treatment of both heart failure and the factors identified

as triggers

Establish cause

C - CIRCULATION*

HR (bradycardia [<60/min], normal [60-100/min], tachycardia [>100/min]), rhythm (regular, irregular), SBP (very low [<90 mmHg], low, normal [110-140 mmHg], high [>140 mmHg]), and elevated jugular pressure should be checked.

P.56

4.1ACUTE HEART FAILURE: Initial diagnosis (CDE)

References: Mebazaa A et al. Intensive Care Med. (2016); 42(2):147-63; Mueller C et al. Eur Heart J Acute Cardiovasc Care. (2017); 6(1):81-6.

D – DISABILITY DUE TO NEUROLOGICAL DETERIORATION • Normal consiousness/altered mental status?

Measurement of mental state with AVPU (alert, visual, pain or unresponsive) or Glasgow • Coma Scale: EMV score <8 Consider endotracheal intubation and mechanical ventilation • Anxiety, severe dyspnea? Consider cautious administration of morphine 2 mg i.v. bolus,

preceded by antiemetic as needed

E – EXPOSURE & EXAMINATION • Temperature/fever: central and peripheral • Weight • Skin/extremities: circulation (e.g. capilary refill), color • Urinary output (<0.5 ml/kg/hr) Consider inserting indwelling catheter;

the benefits should outweigh the risks of infection and long-term complications

P.57

4.1

Patient with AHF

Bedside assessment to identify haemodynamic profiles

"DRY" patient

"WET" and "COLD" patient

Systolic blood pressure <90 mmHg

"WET" patient

No(5% of all AHF patients)

Yes(95% of all AHF patients)

Yes No

Yes No

Yes

No

PRESENCE OF CONGESTIONa?

ADEQUATE PERIPHERAL PERFUSION?

"DRY" and "COLD"Hypoperfused, hypovolemic

"DRY" and "WARM"Adequately perfused

≈ Compensated

• Inotropic agent• Consider vasopressor in refractory cases• Diuretic (when perfusion corrected)• Consider machanical circulatory support if no response to drugs

• Vasodilators• Diuretics• Consider inotropic agent In refractory cases• Vasodilator

• Diuretic• Diuretic• Vasodilator• Ultrafiltration (consider if diuretic resistance)

Consider fluid challengeConsider inotropic agent if still hypoperfusedAdjust oral therapy

"WET" and "WARM"patient (typically elevatedor normal systolic blood

pressure)

Vascular type-fluid redistribution

Hypertension predominates

Cardiac type-fluid accumulation

Congestion predominates

P.58

4.1ACUTE HEART FAILURE: Management of patients with acute heart

failure based on clinical profile during an early phase

Patient with AHF

Bedside assessment to identify haemodynamic profiles

"DRY" patient

"WET" and "COLD" patient

Systolic blood pressure <90 mmHg

"WET" patient

No(5% of all AHF patients)

Yes(95% of all AHF patients)

Yes No

Yes No

Yes

No

PRESENCE OF CONGESTIONa?

ADEQUATE PERIPHERAL PERFUSION?

"DRY" and "COLD"Hypoperfused, hypovolemic

"DRY" and "WARM"Adequately perfused

≈ Compensated

• Inotropic agent• Consider vasopressor in refractory cases• Diuretic (when perfusion corrected)• Consider machanical circulatory support if no response to drugs

• Vasodilators• Diuretics• Consider inotropic agent In refractory cases• Vasodilator

• Diuretic• Diuretic• Vasodilator• Ultrafiltration (consider if diuretic resistance)

Consider fluid challengeConsider inotropic agent if still hypoperfusedAdjust oral therapy

"WET" and "WARM"patient (typically elevatedor normal systolic blood

pressure)

Vascular type-fluid redistribution

Hypertension predominates

Cardiac type-fluid accumulation

Congestion predominates

a Symptoms/signs of congestion: orthopnoea, paroxysmal nocturnal dyspnoea, breathlessness, bi-basilar rales, abnormal blood pressure response to the Valsalva maneuver (left-sided); symptoms of gut congestion, jugular venous distension, hepatojugular reflux, hepatomegaly, ascites, and peripheral oedema (right-sided).

For more information on individual drug doses and indications,

SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE

Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.

P.59

4.1

No acute heart failure

MONITORINGDyspnea (VAS, RR), BP, SpO2, HR and

rhythm, urine output, peripheral perfusion

REASSESSMENTClinical, biological and psychosocial parameters by trained nurses

Observation unit (<24h)

Discharge home

Ward (cardiology, internal medicine, geriatrics)

Rehabilitation program

Visit to cardiologist <1-2 weeks

Palliative care hospitals

ICU/CCU

Confirmed acute heart failure

DIAGNOSTIC TESTS

OBS

ERVA

TIO

N U

P TO

120

min

ADM

ISSI

ON

/DIS

CHA

RGE

Risk stratification: ensure patientis at low risk before direct dischargeRisk stratification: ensure patient

is at low risk before direct discharge

TREATMENT OBJECTIVES to prevent organ dysfunction:Improve symptoms, maintain SBP >90 mmHg and peripheral

perfusion, mantain SpO2 >90% (see table in pages 63-64)

Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17: 544-58 and Miró Ò et al. Ann Intern Med (2017); 167:698-705.

P.60

4.1ACUTE HEART FAILURE: Management of acute heart failure

Normotension/Hypertension

Hypotension Low heart rate Potassium Renal impairment

<100 >90 mmHg

<90 mmHg

<60≥50 bpm

<50 bpm ≤3.5 mmol/L

>5.5 mmol/L

Cr <2.5,eGFR >30

Cr >2.5,eGFR <30

ACE-I/ARB Review/increase

Reduce/ stop

Stop No change

No change

Review/increase

Stop Review Stop

Beta-blocker No change Reduce/ stop

Stop Reduce Stop No change

No change

No change

No change

MRA No change No change

Stop No change

No change

Review/increase

Stop Reduce Stop

Diuretics Increase Reduce Stop No change

No change

Review/ No change

Review/ increase

No change

Review

Sacubitril/Valsartan

Review/increase

Stop Stop No change

No change

Review/increase

Stop Review Stop

Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.

Management of oral therapy in AHF in the first 48 hours P.61

ACUTE HEART FAILURE: Treatment (C) and preventive measures 4.04.1

Normotension/Hypertension

Hypotension Low heart rate Potassium Renal impairment

<100 >90 mmHg

<90 mmHg

<60≥50 bpm

<50 bpm ≤3.5 mmol/L

>5.5 mmol/L

Cr <2.5,eGFR >30

Cr >2.5,eGFR <30

Other vasodilators (nitrates)

Increase Reduce/stop

Stop No change

No change

No change

No change

No change

No change

Other heart rate slowing drugs (amiodarone, non-dihydropyridine CCB, ivabradine)

Review Reduce/stop

Stop Reduce/stop

Stop Review/stop(*)

No change

No change

No change

Thrombosis prophylaxis should be started in patients not anticoagulated.(*) Amiodarone.

Management of oral therapy in AHF in the first 48 hours

Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.

P.62

ACUTE HEART FAILURE: Treatment (C) and preventive measures (Cont.) 4.1

Hemodynamic criteria to define cardiogenic shock

• Systolic blood pressure <80 to 90 mmHg or mean arterial pressure 30 mmHg lower than baseline

• Severe reduction in cardiac index: <1.8 l/min/m2 without support or <2.0 to 2.2 l/min/m2 with support

• Adequate or elevated filling pressure: Left ventricular end-diastolic pressure >18 mmHg or Right atrial pressure >10 to 15 mmHg

Clinical condition defined as the inability of the heart to deliver an adequate amount of blood to the tissues to meet resting metabolic demands as a result of impairment of its pumping function.

Cardiogenic shock is equal to wet-cold phenotype. The clinical signs of hypoperfusion are listed in page 65. In addition, blood lactate is typically elevated above 2 mmol/L.

P.63

4.2CARDIOGENIC SHOCK: Definition

LV pump failure is the primary insult in most forms of CS, but other parts of the circulatory system contribute to shock with inadequate compensation or additional defects P.64

4.2CARDIOGENIC SHOCK: Causes

This protocol should be initiated as soon as cardiogenic shock/end organ hypoperfusion is recognised and should not be delayed pending intensive care admission.

EARLY TRIAGE & MONITORINGStart high flow O2 Establish i.v. access

• Age: 65–74, ≥75• Heart rate >100 beats per minute• Systolic blood pressure <100 mmHg• Proportional pulse pressure ≤25 % (CI <2.2 l/min/m2)• Orthopnea (PCWP >22 mmHg)• Tachypnea (>20/min), >30/min (!)• Killip class IV • Clinical symptoms of tissue hypoperfusion/hypoxia:

- cool extremities - decreased urine output (urine output <40 ml/h) - decreased capillary refill or mottling - alteration in mental status

INITIAL RESUSCITATION• Arterial and a central venous

catheterization with a catheter capable of measuring central venous oxygen saturation

• Standard transthoracic echocardiogram to assess left (and right) ventricular function and for the detection of potential mechanical complications following MI

• Early coronary angiography in specialized myocardial intervention centre when signs and/or symptoms of ongoing myocardial ischemia (e.g. ST-segment elevation myocardial infarction).

• CORRECT: hypoglycemia & hypocalcemia,• TREAT: sustaned arrhythmias: brady- or tachycardia• Isotonic saline-fluid challenge - 200-300 ml

over 30 min period to achieve a central venous pressure of 8 to 12 mmHg or until perfusion improves (with a maximum of 500 ml)

• CONSIDER NIMV for comfort (fatigue, distress) or as needed: - To correct acidosis - To correct hypoxemia

• INOTROPIC SUPPORT (dobutamine, levosimendan and/or vasopressor support)

TREATMENT GOALS • a mean arterial pressure of 60 mmHg or above, • a mean pulmonary artery wedge pressure of 18 mmHg or below, • a central venous pressure of 8 to 12 mmHg, • a urinary output of 0,5 ml or more per hour per kilogram of body weight • an arterial pH of 7.3 to 7.5 • a central venous saturation (ScvO2) ≥70% (provided SpO2 ≥93%

and Hb level ≥9 g/dl)

In persistent drug-resistant cardiogenic shock,consider mechanical circulatory support

0 min

5 min

15 min

60 min

EMER

GEN

CY

DEP

AR

TMEN

T

CA

RD

IAC

INTE

NS

IVE

CA

RE

UN

ITP.65

4.2CARDIOGENIC SHOCK: Initial triage and management

Ventilator modeTidal Volume goalPlateau Pressure goalAnticipated PEEP levelsVentilator rate and pH goalInspiration: Expiration timeOxygenation goal: • PaO2

• SpO2

Pressure assist/controlReduce tidal volume to 6-8 ml/kg lean body weight≤30 cm H2O5-10 cm H2O12-20, adjusted to achieve a pH ≥7.30 if possible1:1 to 1:2

50-80 mmHg>90%

Predicted body weight calculation: • Male: 50 + 0.91 (height in cm - 152.4) • Female: 45.5 + 0.91 (height in cm - 152.4)

Some patients with CS will require increased PEEP to attain functional residual capacity and maintain oxygenation, and peak pressures above 30 cm H2O to attain effective tidal volumes of 6-8 ml/kg with adequate CO2 removal.

For more informations on individual drug doses and indications:



P.66

4.2CARDIOGENIC SHOCK: Treatment and ventilator procedures

CARDIOGENIC SHOCK: MANAGEMENT FOLLOWING STEMI

Assess volume statusTreat sustained arrhythmias: brady - or tachy -Consider mechanical ventilation for comfort (during PCI) and/or as needed: • to correct acidosis • to correct hypoxemiaInotropic support (dobutamine and/or vasopressor support)

Signs (ST-segment elevation or new LBBB)and/or clinical symptoms of ongoing

myocardial ischemia

Early coronary angiography± Pulmonary artery catheter± IABP in selected patientsin a specialised Myocardial

Intervention Centre

PCI ± stentingof the culprit lesion

CABG+ correct mechanical complications

Pump failureRV, LV, both

Sho

rt-t

erm

mec

hani

cal

circ

ulat

ory

supp

ort

AorticdissectionPericardialtamponade

• Acute severe mitral valve regurgitation • Ventricular septum rupture • Severe aortic/mitral valve stenosis

Operating theater ± coronary angiography

Emergency echocardiography± Tissue doppler imaging

± Color flow imagingNo

NSTEACS,Delayed CSYes

P.67

4.2CARDIOGENIC SHOCK: management following STEMI

72-hrs

2-weeks

1-month ...

Left ventricular support BiVentricular support

Partial support

IABP Impella 2.5 Tandem-heart

Impella 5.0 ImplantableECMOLevitronix

Full support

Level of support

Pulmonary support

P.68

4.2CARDIOGENIC SHOCK:

Mechanical circulatory support, basic characteristics

Different systems for mechanical circulatory support are available to the medical community. The available devices differ in terms of the insertion procedure, mechanical properties, and mode of action. A minimal flow rate of 70 ml/kg/min, representing a cardiac index of at least 2.5 L/m2, is generally required to provide adequate organ perfusion. This flow is the sum of the mechanical circulatory support output and the remaining function of the heart.

The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock

Type Support Access

Intra-aortic balloon pump

Balloon counterpulsation

Pulsatile flow <0.5 L Arterial: 7.5 French

Impella Recover LP 2.5 CP LP 5.0

Axial flow Continuous flow <2.5 L <4.0 L <5.0 L

Arterial: 12 FrenchArterial: 14 FrenchArterial: 21 French

Tandemheart

Centrifugal flow

<5.0 L

Continuous flow

<5.0 L

Venous: 21 FrenchArterial: 15-17 French

Venous: 15-29 FrenchArterial: 15-29 French

Cardiohelp

(www.save-score.com).

P.69

4.2

Monsieurs KG, et al. European Resuscitation Council Guidelines for Resuscitation 2015. Section 1 Executive Summary. Resuscitation 2015; 95C:1-80, DOI:10.1016/j.resuscitation.2015.07.038

CHAPTER 5 CARDIAC ARREST AND

CARDIOPULMONARY RESUSCITATIONN. Nikolaou, L. Bossaert

5

THE CHAIN OF SURVIVAL

P.71

OUT OF HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT

VICTIM COLLAPSES

Victim respondsVictim unresponsive

Leave victim as foundFind out what is wrong

Reassess victim regularly Shout for helpOpen airway

Assess breathing

Not breathing normally

Call for an ambulanceStart CPR 30:2

Send or go for an AED

As soon as AED arrives

Start AED,listen to and follow voice prompts

AED Assesses rhythm

AED not available

30 chest compressions: 2 rescue breaths

Continue until victim starts to wake up: to move, open eyes, and breathe normally

No shock advised

Immediately resume CPR 30:2 for 2 min

Shock advised

1 shock

Immediately resumeCPR 30:2 for 2 min

Breathing normally

Put victim in recovery positionand call for an ambulance

Approach safelyCheck response

P.72

5OUT OF HOSPITAL CARDIAC ARREST:

Assessment of a collapsed victim and initial treatment

OUT OF HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT

VICTIM COLLAPSES

Victim respondsVictim unresponsive

Leave victim as foundFind out what is wrong

Reassess victim regularly Shout for helpOpen airway

Assess breathing

Not breathing normally

Call for an ambulanceStart CPR 30:2

Send or go for an AED

As soon as AED arrives

Start AED,listen to and follow voice prompts

AED Assesses rhythm

AED not available

30 chest compressions: 2 rescue breaths

Continue until victim starts to wake up: to move, open eyes, and breathe normally

No shock advised

Immediately resume CPR 30:2 for 2 min

Shock advised

1 shock

Immediately resumeCPR 30:2 for 2 min

Breathing normally

Put victim in recovery positionand call for an ambulance

Approach safelyCheck response

P.73

5

IN-HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT

Collapsed/sick patient

Shout for HELP & assess patient

YesNo

Assess ABCDERecognise & treat

oxygen; monitoring, i.v. access

Call resuscitationteam

CPR 30:2with oxygen and airway adjuncts

Call resuscitation teamif appropriate

Apply pads/monitorAttempt defibrillation

if appropriate

Handover to resuscitation teamAdvanced Life Supportwhen resuscitation team arrives

Signs of life?

P.74

5IN-HOSPITAL CARDIAC ARREST:

Assessment of a collapsed victim and initial treatment

IN-HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT

Collapsed/sick patient

Shout for HELP & assess patient

YesNo

Assess ABCDERecognise & treat

oxygen; monitoring, i.v. access


CPR 30:2with oxygen and airway adjuncts

Call resuscitation teamif appropriate

Apply pads/monitorAttempt defibrillation

if appropriate

Handover to resuscitation teamAdvanced Life Supportwhen resuscitation team arrives

Signs of life?

P.75

5

IN-HOSPITAL CARDIAC ARREST: ADVANCED LIFE SUPPORT

Unresponsiveand not breathing

normally ?

Assessrhythm

CPR 30:2Attach defibrillator/monitor

Minimise interruptions

DURING CPR• Ensure high-quality chest compressions• Minimise interruptions to compressions• Give Oxygen• Use waveform capnography• Continuous chest compressions when advanced airway in place• Vascular access (intravenous, intraosseous) • Give adrenaline every 3-5 min• Give amiodarone after 3 shocks• Correct reversible causes

REVERSIBLE CAUSES • Hypoxia• Hypovolaemia• Hypo-/hyperkalaemia/metabolic• Hypothermia

• Thrombosis• Tamponade - cardiac• Toxins• Tension pneumothorax


Shockable(VF/Pulseless VT)

1 ShockReturn of

spontaneous circulation

IMMEDIATE POST CARDIACARREST TREATMENT

Immediately resume:CPR for 2 min


Non-shockable(PEA/Asystole)


Minimise interruptions • Use ABCDE approach• Aim for SaO2 94-98%• Aim for normal PaCO2

• 12-lead ECG• Treat precipitating cause• Temperature control / Therapeutic hypothermia

CONSIDER• Ultrasound imaging• Mechanical chest compressions to facilitate transfer/treatment• Coronary angiography and PCI• Extracorporeal CPR

P.76

5IN-HOSPITAL CARDIAC ARREST: Advanced life support

IN-HOSPITAL CARDIAC ARREST: ADVANCED LIFE SUPPORT

Unresponsiveand not breathing

normally ?

Assessrhythm

CPR 30:2Attach defibrillator/monitor


DURING CPR• Ensure high-quality chest compressions• Minimise interruptions to compressions• Give Oxygen• Use waveform capnography• Continuous chest compressions when advanced airway in place• Vascular access (intravenous, intraosseous) • Give adrenaline every 3-5 min• Give amiodarone after 3 shocks• Correct reversible causes

REVERSIBLE CAUSES • Hypoxia• Hypovolaemia• Hypo-/hyperkalaemia/metabolic• Hypothermia

• Thrombosis• Tamponade - cardiac• Toxins• Tension pneumothorax


Shockable(VF/Pulseless VT)

1 ShockReturn of

spontaneous circulation

IMMEDIATE POST CARDIACARREST TREATMENT



Non-shockable(PEA/Asystole)


Minimise interruptions • Use ABCDE approach• Aim for SaO2 94-98%• Aim for normal PaCO2

• 12-lead ECG• Treat precipitating cause• Temperature control / Therapeutic hypothermia

CONSIDER• Ultrasound imaging• Mechanical chest compressions to facilitate transfer/treatment• Coronary angiography and PCI• Extracorporeal CPR

P.77

5

Give adrenaline and amiodaroneafter 3rd shock

Adrenaline: 1 mg i.v.(10 ml 1:10,000 or 1 ml 1:1000)

repeated every 3-5 min(alternate loops)

given without interrupting chest compressions

Amiodarone 300 mg bolus i.v.

Second bolus dose of 150 mg i.v.if VF/VT persists

followed by infusion of900 mg over 24 h

Adrenaline: 1mg i.v. (10 ml 1:10,000 or 1 ml 1:1000)given as soon as circulatory access is obtained

Repeat every 3-5 min (alternate loops)Give without interrupting chest compressions

IN-HOSPITAL CARDIAC ARREST: DRUG THERAPY DURING ADVANCED LIFE SUPPORT

Cardiac Arrest

Non-shockable rhythm

Shockable rhythm(VF, pulseless VT)

P.78

5IN-HOSPITAL CARDIAC ARREST:

Drug therapy during advanced life support

CHAPTER 6

RHYTHM DISTURBANCES

6.1 SUPRAVENTRICULAR TACHYCARDIAS AND ATRIAL FIBRILLATION �� p.80 J. Brugada

6.2 VENTRICULAR TACHYCARDIAS �� p.84 M. Santini, C. Lavalle, S. Lanzara

6.3 BRADYARRHYTHMIAS �� p.87 B. Gorenek

6

QRS morphology similar to QRS morphologyin sinus rhythm?

QRS morphology similar to QRS morphologyin sinus rhythm?

YES

QRS complex <120 msec

Supraventr.Tachycardia

QRS complex >120 msec

Supraventr.Tachycardia

+ BBB



Fascicular Tachycardiaor SVT with

aberrant conduction

Ventricular Tachycardia or SVT with

aberrant conduction



AFconductingover AVN

AF + BBBor

AF + WPW

AF+

WPW

IrregularVentricular Tachycardia

Variable QRSmorphology

NO YES NO

TACHYARRHYTHMIAS: DIAGNOSTIC CRITERIA

Tachycardia >100 beats/min

IrregularRegular

P.80

6.1TACHYARRHYTHMIAS: Diagnostic criteria

• Concordant precordial pattern (all leads + or all leads –)• No RS pattern in precordial leads • RS pattern with beginning of R wave to nadir of S wave >100 msec

Consider SVT using

the AV node (AVNRT, AVNT)

Atrial flutteror atrial

tachycardiaVentricular

Tachycardia Ventricular

Tachycardia Ventricular

Tachycardia

Consider Sinus tachycardia

or non properadministrationof adenosine

(too slow, insufficient dose, etc)

Typicalmorphologyin V1 & V6

More As than Vs

More Vs than As

WideQRS complex

NarrowQRS complex

Regular tachycardia

Vagal maneuversor

i.v. adenosine

No changeTachycardia terminates

AV relation changes

P.81

6.1TACHYARRHYTHMIAS: Diagnostic maneuvers

Hemodynamicallynon-stable

Immediate electricalcardioversion

No termination

Hemodynamicallystable

Vagal maneuversand/or i.v. Adenosine

Less than 48 hourssince initiation

ANDhemodynamically stable

CardioversionElectrical or pharmacologicalusing oral or i.v. flecainide

(only in normal heart)or i.v. vernakalant

Anticoagulationis initiated using i.v. heparine

Hemodynamically non-stable

Immediate electricalCardioversion

If no cardioversionis considered: rate control

using betablockers orcalcium antagonists,together with proper

anticoagulation, if required

Narrow QRScomplex tachycardia

Reconsider diagnosis: sinus tachycardia,atrial tachycardia

If no evidence:Intravenous verapamil

Wide QRScomplex tachycardia

Reconsider the diagnosis of Ventricular Tachycardia even

if hemodynamically stable

Do not administerverapimil

More than 48 hours ORunknown time of initiation,

ANDPatient chronically anticoagulated

ORa TEE showing no thrombus

Electrical or pharmacological Cardioversion

Termination

TACHYARRHYTHMIAS: THERAPEUTIC ALGORITHMS (1)

Regular Supraventricular Tachycardias with or without bundle branch block

Irregular and narrow QRS complexTachycardia

Hemodynamicallynon-stable

Immediate electricalcardioversion

No termination

Hemodynamicallystable

Vagal maneuversand/or i.v. Adenosine

Less than 48 hourssince initiation

ANDhemodynamically stable

CardioversionElectrical or pharmacologicalusing oral or i.v. flecainide

(only in normal heart)or i.v. vernakalant

Anticoagulationis initiated using i.v. heparine



If no cardioversionis considered: rate control

using betablockers orcalcium antagonists,together with proper

anticoagulation, if required

Narrow QRScomplex tachycardia

Reconsider diagnosis: sinus tachycardia,atrial tachycardia

If no evidence:Intravenous verapamil

Wide QRScomplex tachycardia

Reconsider the diagnosis of Ventricular Tachycardia even

if hemodynamically stable

Do not administerverapimil

More than 48 hours ORunknown time of initiation,

ANDPatient chronically anticoagulated

ORa TEE showing no thrombus

Electrical or pharmacological Cardioversion

Termination


Regular Supraventricular Tachycardias with or without bundle branch block

Irregular and narrow QRS complexTachycardia

P.82

6.1TACHYARRHYTHMIAS: Therapeutic algorithms (1)



If no cardioversion is considered:rate control using betablockers orcalcium antagonists (only if VT and

AF+WPW is excluded), togetherwith proper anticoagulation

if required

Less than 48 hours since initiationAND

hemodynamically stable

Cardioversionelectrical or pharmacologicalusing oral or i.v. flecainide

(only in normal heart)or i.v. amiodarone

Anticoagulationis initiated using i.v. heparin

More than 48 hoursor unknown initiation,

ANDpatient chronically anticoagulated

or a TEE showing no thrombus

Electrical or pharmacologicalCardioversion


Irregular and wide QRS complex Tachycardia

P.83

6.1TACHYARRHYTHMIAS: Therapeutic algorithms (2)

VENTRICULAR TACHYCARDIAS: DIFERENTIAL DIAGNOSIS OF WIDE QRS TACHYCARDIA

EKG signs of atrio-ventricular dissociationRandom P waves unrelated to QRS complexesCapture beats / fusion beats / second degree V-A block

1st Step

2nd Step

3rd Step

Concordant pattern in precordial leadsNo RS morphology in any of the precordial leads

An interval >100 ms from the beginning of theQRS complex to the nadir of S in a precordial lead

Morphology in precordial leads

RBBB morphology LBBB morphology

Morphologyin aVR lead

Initial R wave

Initial R waveor q >40 msec

V1: qR, R, R’V6: rS,QS

V1: rsR’, RSR’V6: qRs

Aberrant conduction

V6: R V1: rS; R >30 ms,S nadir >60 ms,notching of the

S wave

V6: qR, QS

Yes

Yes

Yes

No

No

No

Yes

No

No

No

No

Yes

Yes

Yes

Notch in thedescendingQ wave limb

Vi/Vt ≤1

VT

VT

Aberrant conduction

VT

P.84

6.2VENTRICULAR TACHYSCARDIAS:

Diferential diagnosis of wide QRS tachyscardias

VENTRICULAR TACHYCARDIAS: DIFERENTIAL DIAGNOSIS OF WIDE QRS TACHYCARDIA

EKG signs of atrio-ventricular dissociationRandom P waves unrelated to QRS complexesCapture beats / fusion beats / second degree V-A block

1st Step

2nd Step

3rd Step

Concordant pattern in precordial leadsNo RS morphology in any of the precordial leads

An interval >100 ms from the beginning of theQRS complex to the nadir of S in a precordial lead

Morphology in precordial leads

RBBB morphology LBBB morphology

Morphologyin aVR lead

Initial R wave

Initial R waveor q >40 msec

V1: qR, R, R’V6: rS,QS

V1: rsR’, RSR’V6: qRs

Aberrant conduction

V6: R V1: rS; R >30 ms,S nadir >60 ms,notching of the

S wave

V6: qR, QS

Yes

Yes

Yes

No

No

No

Yes

No

No

No

No

Yes

Yes

Yes

Notch in thedescendingQ wave limb

Vi/Vt ≤1

VT

VT

Aberrant conduction

VT

P.85

6.2

MANAGEMENT OF WIDE QRS TACHYCARDIAS

Hemodynamic Tolerance

Stable

Regular rhythmIrregular rhythm

Vagal maneuverand/or

i.v. adenosine (push)

Differential Diagnosis

Interruption orslow down HR

Yes

YesNo

No

DifferentialDiagnosis

(see chapter 6.1page 81)

SVT

AF with aberrant ventricular conduction • β-blockers• i.v.• Verapamil or diltazem Pre excited AF • Class 1 AADs Polymorphic VT • Amiodarone

Amiodarone 150 mg i.v.(can be repeated up to

a maximum dose of 2.2 g in 24 h) Synchronised cardioversion

With pulsePulseless

Non-stable

• Sedationor analgesia

• Synchronised cardioversion 100 to 200 J (monophasic)or 50-100 J (biphasic)

ACLS Resuscitation algorithm

• Immediate high- energydefibrillation (200 J biphasicor 360 monophasic)• Resume CPR and continue according to the ACLS algorithm

Drugs used in the ACLS algorithm

• Epinephrine 1 mg i.v./i.o.(repeat every 3-5 min)• Vasopressin 40 i.v./i.o. • Amiodarone 300 mg i.v./i.o. once then consider an additional150 mg i.v./i.o. dose• Lidocaine 1-1.5 mg/kg first dosethen 0.5-0-75 mg/kg i.v./i.o.for max 3 doses or 3 mg/kg• Magnesium loading dose 1-2 gr i.v./i.o. for torsade des pointes

P.86

6.2Management of wide QRS TACHYSCARDIAS

Sinus node dysfunction Atrioventricular (AV) blocks

• Sinus bradycardia: It is a rhythm that originates from the sinus node and has a rate of under 60 beats per minute

• Sinoatrial exit block: The depolarisations that occur in the sinus node cannot leave the node towards the atria

• Sinus arrest: Sinus pause or arrest is defined as the transient absence of sinus P waves on the ECG

• First degree AV block: Atrioventricular impulse transmission is delayed, resulting in a PR interval longer than 200 msec

• Second degree AV block: Mobitz type I (Wenckebach block): Progressive PR interval prolongation, which precedes a nonconducted P wave

• Second degree AV block: Mobitz type II: PR interval remains unchanged prior to a P wave that suddenly fails to conduct to the ventricles

• Third degree (complete) AV block: No atrial impulses reach the ventricle

P.87

6.3BRADYARRHYTHMIAS: Definitions and diagnosis

• Rule out and treat any underlying causes of bradyarrhythmia• Treat symptomatic patients only



Temporary transvenous pacing

Be Careful! • Complications are common! • Shall not be used routinely • Use only as a last resource when chronotropic drugs are insufficient • Every effort should be made to implant a permanent pacemaker

as soon as possible, if the indications are established.

Indications limited to: • High-degree AV block without escape rhythm • Life threatening bradyarrhythmias, such as those that occur during interventional

procedures, in acute settings such as acute myocardial infarction, drug toxicity.

P.88

6.3BRADYARRHYTHMIAS: Treatment (1)

Permanent pacemaker is indicated in the following settings:

• Documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms • Symptomatic chronotropic incompetence • Symptomatic sinus bradycardia that results from required drug therapy for medical conditions

Permanent pacemaker is not recommended in the following settings:

• Asymptomatic patients • Patients for whom the symptoms suggestive of bradycardia

have been clearly documented to occur in the absence of bradycardia • Symptomatic bradycardia due to nonessential drug therapy

P.89


Pacemaker therapies in sinus node dysfunction

Permanent pacemaker therapy is indicated in the following settings regardless of associated symptoms:

• Third-degree AV block • Advanced second-degree AV block • Symptomatic Mobitz I or Mobitz II second-degree AV block • Mobitz II second-degree AV block with a wide QRS or chronic bifascicular block • Exercise-induced second- or third-degree AV block • Neuromuscular diseases with third- or second-degree AV block • Third- or second-degree (Mobitz I or II) AV block after catheter ablation or valve surgery

when block is not expected to resolve

Permanent pacemaker is not recommended in the following settings:

• Asymptomatic patients • Patients for whom the symptoms suggestive of bradycardia have been clearly documented

to occur in the absence of bradycardia • Symptomatic bradycardia due to nonessential drug therapy

P.90


Pacemaker therapies in atrioventricular blocks

CHAPTER 7

ACUTE VASCULAR SYNDROMES

7.1 ACUTE AORTIC SYNDROMES �� p.92 A. Evangelista

7.2 ACUTE PULMONARY EMBOLISM �� p.102 A. Torbicki

7

Classic aortic dissectionSeparation of the aorta media with presence

of extraluminal blood within the layers of the aortic wall.The intimal flap divides the aorta into two lumina, the true and the false

Penetrating aortic ulcer (PAU)Atherosclerotic lesion penetrates

the internal elastic lamina of the aorta wall

Aortic aneurysm rupture (contained or not contained)

Intramural hematoma (IMH)Aortic wall hematoma with no entry tear and no two-lumen flow

P.92

7.1ACUTE AORTIC SYNDROMES: Concept and classification (1)

Types of presentation

DeBakey’s Classification• Type I and Type II dissections both originate in the ascending aorta

In type I, the dissection extends distally to the descending aorta In type II, it is confined to the ascending aorta

• Type III dissections originate in the descending aorta

Stanford Classification• Type A includes all dissections involving the ascending

aorta regardless of entry site location• Type B dissections include all those distal to the

brachiocephalic trunk, sparing the ascending aorta

Time course• Acute: <14 days• Subacute: 15-90 days• Chronic: >90 days

Copyright: Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: Part II: therapeutic management and follow-up. Circulation (2003); 108(6),772-778.

Adapted with permission from Nienaber CA, Eagle KA, Circulation 2003;108(6):772-778. All rights reserved.

De Bakey

Stanford

Type I

Type A

Type II

Type A

Type III

Type B

P.93

7.1ACUTE AORTIC SYNDROMES: Concept and classification (2)

Anatomic classification and time course

SYMPTOMS AND SIGNS SUGGESTIVE OF AAS

• Abrupt and severe chest/back pain with maximum intensity at onset

• Pulse/pressure deficit - Peripheral or visceral ischemia - Neurological deficit

• Widened mediastinum on chest X -ray• Risk factors for dissection• Other

- Acute aortic regurgitation - Pericardial effusion - Hemomediastinum/hemothorax

DIFFERENTIAL DIAGNOSIS

• Acute coronary syndrome (with/without ST-segment elevation)

• Aortic regurgitation without dissection• Aortic aneurysms without dissection• Musculoskeletal pain• Pericarditis• Pleuritis• Mediastinal tumours• Pulmonary embolism• Cholecystitis• Atherosclerosis or cholesterol embolism

P.94

7.1ACUTE AORTIC SYNDROME:

Clinical suspicion and differential diagnosis

Copyright: Hiratzka et al. 2010 Guidelines on Thoracic Aortic Disease. Circulation. (2010) ; 121: page-310 (fig 25 step 2).

Consider acute aortic dissection in all patients presenting with:

• Chest, back or abdominal pain• Syncope• Symptoms consistent with perfusion deficit (central nervous system, visceral myocardial or limb ischemia)

Pre-test risk assessment for acute aortic dissection

• Marfan’s syndrome• Connective tissue disease• Family history of aortic disease• Aortic valve disease• Thoracic aortic aneurysm

• Perfusion deficit: - Pulse deficit - SBP differential - Focal neurological deficit• Aortic regurgitation murmur• Hypotension or shock

Chest, back or abdominal paindescribed as:

Abrupt at onset, severe in intensity, and ripping/sharp or stabbing quality

High-risk conditions High-risk pain features High-risk exam features

P.95

7.1General approach to the patient

with suspected ACUTE AORTIC SYNDROME

Laboratory tests To detect signs of:

Red blood cell count Blood loss, bleeding, anaemia

White blood cell count Infection, inflammation (SIRS)

C-reactive protein Inflammatory response

ProCalcitonin Differential diagnosis between SIRS and sepsis

Creatine kinase Reperfusion injury, rhabdomyolysis

TroponinIorT Myocardial ischaemia, myocardial infarction

D-dimer Aortic dissection, pulmonary embolism, thrombosis

Creatinine Renal failure (existing or developing)

Aspartate transaminase / alanine aminotransferase Liver ischaemia, liver disease

Lactate Bowel ischaemia, metabolic disorder

Glucose Diabetes mellitus

Blood gases Metabolic disorder, oxygenation

Reference: Eur Heart J 2014; eurheartj.ehu281.

P.96

7.1Laboratory tests required for patients

with ACUTE AORTIC dissection

a STEMI can be associated with AAS in rare cases.

b Pending local availability, patient characteristics, and physician experience.

c Proof of type-A AD by the presence of flap, aortic regurgitation, and/or pericardial effusion.

d Preferably point-of-care, otherwise classical.

e Also troponin to detect non–ST-segment elevation myocardial infarction.

Flowchart for decision-making based on pre-test sensitivity of acute aortic syndrome. Reference: Eur Heart J 2014; eurheartj.ehu281.

ACUTE CHEST PAIN

High probability (score 2-3)or typical chest pain

Medical history + clinical examination + ECG STEMIa: see ESC guidelines169

HAEMODYNAMIC STATEUNSTABLE

Low probability (score 0-1)TTE + TOE/CT°

STABLE

AASconfirmed

AASexcludedConsideralternatediagnosis

D-dimers d,e + TTE + Chest X-ray TTE

Consideralternatediagnosis

No argumentfor AD

Signsof AD

Widenedmedia- stinum

DefiniteType A -AD c

Inconclusive

Refer on emergencyto surgical team andpre-operative TOE

CT (or TOE)

AASconfirmed

Consideralternatediagnosisrepeat CT

if necessaryAAS

confirmedConsideralternatediagnosis

CT (MRI or TOE)b

P.97

7.1ACUTE CHEST PAIN

Aortic dissection • Visualization of intimal flap• Extent of the disease according to the aortic anatomic segmentation• Identification of the false and true lumens (if present)• Localization of entry and re-entry tears (if present)• Identification of antegrade and/or retrograde aortic dissection• Identification grading, and mechanism of aortic valve regurgitation• Involvement of side branches• Detection of malperfusion (low flow or no flow)• Detection of organ ischaemia (brain, myocardium, bowels, kidneys, etc.)• Detection of pericardial effusion and its severity• Detection and extent of pleural effusion• Detection of peri-aortic bleeding• Signs of mediastinal bleeding

Intramural haematoma

• Localization and extent of aortic wall thickening• Co-existence of atheromatous disease (calcium shift)• Presence of small intimal tears

Penetrating aortic ulcer

• Localization of the lesion (length and depth)• Co-existence of intramural haematoma• Involvement of the peri-aortic tissue and bleeding• Thickness of the residual wall

In all cases • Co-existence of other aortic lesions: aneurysms, plaques, signs of inflammatory disease, etc.

P.98

7.1Details required from imaging in ACUTE AORTIC dissection

ACUTE AORTIC SYNDROMES MANAGEMENT: GENERAL APPROACH

ACUTE AORTIC DISSECTION

Type A(Ascending aorta

involvement)

Type B(No ascending

aorta involvement)

Uncomplicated

Medical treatment

Open Surgery with/without Endovascular

Therapy

Endovascular Therapy or

Open Surgery(TEVAR)

Complicated(malperfusion,

rupture)

P.99

7.1ACUTE AORTIC SYNDROMES MANAGEMENT: General approach

1 • Detailed medical history and complete physical examination (when possible)

2 • Standard 12-lead ECG: Rule-out ACS, documentation of myocardial ischemia

3 • Intravenous line, blood sample (CK, cTn, myoglobin, white blood count, D-dimer, hematocrit, LDH)

4 • Monitoring: HR and BP

5 • Pain relief (morphine sulphate) (see chapter 4)

6 • Noninvasive imaging (see previous page)

7 • Transfer to ICU



P.100

7.1ACUTE AORTIC SYNDROMES: Initial management

URGENT SURGERY (<24h)

Emergency Surgery

Graft replacement of ascending aorta +/- arch with/without aortic valve or aortic root

replacement/repair (depending on aortic regurgitationand aortic root involvement)

ACUTE AORTIC SYNDROMES: SURGICAL MANAGEMENT

TYPE A ACUTE AORTIC DISSECTION TYPE B ACUTE AORTIC DISSECTION

• Haemodynamic instability (hypotension/shock) • Tamponade• Severe acute aortic regurgitation• Impending rupture• Flap in aortic root• Malperfusion syndrome

Elective/individualisedSurgery

• Non-complicated intramural hematoma• Comorbidities• Age >80 years

Definitive diagnosis

COMPLICATEDdefined as:

by clinical presentation and imaging

• Impending rupture • Malperfusion • Refractory HTN • SBP (<90 mmHg) • Shock

UNCOMPLICATEDdefined as:No features

of complicateddissection

MEDICALMANAGEMENT

and imagingsurveillance protocol• On admission• At 7 days• At discharge• Every 6 months thereafter

MEDICALMANAGEMENT

andTEVAR

MEDICALMANAGEMENT

and OPEN SURGERY

REPAIRif TEVAR

contraindicated

Yes No

P.101

7.1ACUTE AORTIC SYNDROMES: Surgical management

Diagnostic algorithm

as for suspected high-risk PE

Diagnostic algorithm as for suspected not high-risk PE

Assess clinical risk (PESI or SPESI)

RV function (echo or CT) a

Laboratory testing b

Intermediate risk

PE confirmed

Consider further risk stratificaiton

PESI Class III-IVor sPESI ≥ I

PESI Class I-IIor sPESI = 0

PE confirmed

Both positive One positiveor both negative

Clinical suspicion

Shock / hypotension?NoYes

P.102

7.2Risk-adjusted management strategies

in ACUTE PULMONARY EMBOLISM

Reference: Eur Heart J 2014; 35:3033-3073.

a If echocardiography has already been performed during diagnostic work-up for PE and detected RV dysfunction, or if the CT already performed for diagnostic work–up has shown RV enlargement (RV/LV (left ventricular) ratio ≥0.9, a cardiac troponin test should be performed except for cases in which primary reperfusion is not a therapeutic option (e.g. due to severe comorbidity or limited life expectancy of the patient).

b Markers of myocardial injury (e.g. elevated cardiac troponin I or T concentrations in plasma), or of heart failure as a result of (right) ventricular dysfunction (elevated natriuretic peptide concentrations in plasma). If a laboratory test for a cardiac biomarker has already been performed during initial diagnostic work-up (e.g. in the chest pain unit) and was positive, then an echocardiogram should be considered to assess RV function, or RV size should be (re)assessed on CT.

c Patients in the PESI Class I-II, or with sPESI of 0, and elevated cardiac biomarkers or signs of RV dysfunction on imaging tests, are also to be classified into the intermediate-low risk category. This might apply to situations in which imaging or biomarker results become available before calculation of the clinical severity index. These patients are probably no candidates for home treatment.

d Thrombolysis, if (and as soon as) clinical signs of haemodynamic decompensation appear; surgical pulmonary embolectomy or percutaneous catheter-directed treatment may be considered as alternative options to systemic thrombolysis, particularly if the bleeding risk is high.

e Monitoring should be considered for patients with confirmed PE and a positive troponin test, even if there is no evidence of RV dysfunction on echocardiography or CT.

f The simplified version of the PESI has not been validated in prospective home treatment trials; inclusion criteria other than the PESI were used in two single-armed (non-randomized) management studies.

Intermediate-high risk Intermediate-low risk

A/C; monitoringconsider rescue

reperfusiondHospitalization A/C e

Consider early discharge and home treatment if feasible f

Primary reperfusion

High-risk Low riskc

P.103

7.2

CARDIOVASCULARSymptoms/Signs

including but not limited to:

Shock? orSBP <90 mmHg?

orSBP fall by >40 mmHg?

persisting >15 min, otherwise unexplained

RESPIRATORYSymptoms/Signs

including but not limited to:

ACUTE PULMONARY EMBOLISM: DIAGNOSIS

YES NO

Dyspnea

• Chest pain (angina)• Syncope • Tachycardia• ECG changes• NT-proBNP ↑• Troponin ↑

• Chest pain (pleural)• Pleural effusion• Tachypnea• Hemoptysis• Hypoxemia• Atelectasis

Suspectacute

PE

Management algorithmfor UNSTABLE patients

Management algorithmfor initially STABLE patients

Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 638 - figure 66.1.

P.104

7.2ACUTE PULMONARY EMBOLISM: Diagnosis

MANAGEMENT ALGORITHM FOR UNSTABLE PATIENTS WITHSUSPECTED ACUTE PULMONARY EMBOLISM

CT angiography immediately availableand patient stabilised

Primary PA reperfusion

Primary PA reperfusion not justified

patient stabilised

No further diagnostictests feasible

Right heart,pulmonary artery or

venous thrombi?

Echocardiography(bedside)

CT*

Angio

RV pressure overload

CUS

No Yes

Yes

Yes positive

negative

No

TEE

Search for other causes

* Consider also pulmonary angiography if unstable patient in hemodynamic lab.


P.105

7.2Management algorithm for unstable patients

with suspected ACUTE PULMONARY EMBOLISM

Shock or hypotension YES

Contraindications for thrombolysis

No Relative Absolute

Primary PAreperfusion strategy

Thrombolysis

Low- dose transcatheterthrombolysis /

clot fragmetation

Surgical orPercutaneous catheter

embolectomy(availability/experience)

Supportive treatment i.v. UFH, STABILISE SYSTEMIC BLOOD PRESSURE, CORRECT HYPOXEMIA

P.106

7.2ACUTE PE: Management strategy for initially unstable patients

with confirmed high risk pulmonary embolism

MANAGEMENT ALGORITHM FOR INITIALLY STABLE PATIENTS WITHSUSPECTED ACUTE PULMONARY EMBOLISM

Low or intermediate“PE unlikely“

positive

negative D-dimer

CT angiography

negative positivenegative

Confirm by CUSV/Q scan or angiography

positive

CT angiography

CUS

CUSpositive

High or“PE likely“

Anticoagulationnot justified

Anticoagulationrequired

Anticoagulationnot justified

Anticoagulationrequired

Asses clinical (pre-test) probalility


P.107

7.2Management algorithm for initially stable patients

with suspected ACUTE PULMONARY EMBOLISM

Markers for myocardial injury Positive Positive Negative

Markers for RV overload Positive Positive Negative

Clinical risk assessment score (PESI)

Positive (class III-V) Positive (class III-V) Negative (class I-II)

Suggested initial anticoagulation

UFH i.v./LMWH s.c.LMWH/Fonda/apixaban/

rivaroxabanapixaban/rivaroxaban

STRATEGYMonitoring (ICU)*

rescue thrombolysisHospitalisation**

(telemonitoring)Early

discharge***

* When all markers are positive. - ** When at least one marker is positive. - *** When all markers are negative.



P.108

7.2Suggested management strategy for initially stable patients

with (non-high risk) confirmed PE

Key drugs for initial treatment of patients with confirmed PE

Uns

tabl

e

Alteplase (rtPA) (intravenous) 100 mp/2h or 0.6 mp/kg/15 min (max 50 mp)

Urokinase (intravenous) 3 million IU over 2h

Streptokinase (intravenous) 1.5 million IU over 2h

Unfractionated heparin (intravenous) 80 IU/kg bolus + 18 IU/kg/h

Sta

ble

Enoxaparine (subcutaneous) 1 mp/kg BID or 1.5 mp/kg QD

Tinzaparin (subcutaneous) 175 U/kg QD

Fondaparinux (subcutaneous) 7.5 mp (50-100 kg of body weight)5 mp for patients <50 kg, 10 mp for patients >100 kg

Rivaroxaban (oral) 15 mp BID (for 3 weeks, then 20 mp QD)

Apixaban (oral) 10 mg bid (for 7 days, than 5 mg bid)



P.109

7.2PULMONARY EMBOLISM: Pharmacological treatment

CHAPTER 8

ACUTE MYOCARDIAL/PERICARDIAL SYNDROMES

8.1 ACUTE MYOCARDITIS �� p.112 A. Keren, A. Caforio

8.2 ACUTE PERICARDITIS AND CARDIAC TAMPONADE �� p.117 C. Vrints, S. Price

8

CAUSES OF MYOCARDITIS

MYOCARDITIS (WHO /ISFC): Inflammatory disease of the myocardium diagnosedby established histological, immunological and immunohistochemical criteria.

INFECTIOUS TOXICIMMUNE-MEDIATED

• Viral• Bacterial• Spirochaetal• Fungal • Protozoal• Parasitic• Rickettsial

• Drugs • Heavy Metals• Hormones, e.g. catecholamines (Pheochromocytoma)• Physical agents

• Allergens: Tetanus toxoid, vaccines, serum sickness, Drugs• Alloantigens: Heart transplant rejection• Autoantigens: Infection-negative lymphocytic, infection-negative giant cell, associated with autoimmune or immune oriented disorders

P.112

8.1ACUTE MYOCARDITIS: Definition and causes

Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (15).

Clinical presentationswith or without ancillary findings Diagnostic criteria

• Acute chest pain (pericarditic or pseudo-ischemic)• New-onset (days up to 3 months) or worsening

dyspnea or fatigue, with or without left/right heart failure signs

• Palpitation, unexplained arrhythmia symptoms, syncope, aborted sudden cardiac death

• Unexplained cardiogenic shock and/or pulmonary oedema

I. ECG/Holter/stress test features: Newly abnormal ECG and/or Holter and/or stress testing, any of the following: • I to III degree atrioventricular block, or bundle branch block,

ST/T wave changes (ST elevation or non ST elevation, T wave inversion), • Sinus arrest, ventricular tachycardia or fibrillation and asystole,

atrial fibrillation, frequent premature beats, supraventricular tachycardia• Reduced R wave height, intraventricular conduction delay

(widened QRS complex), abnormal Q waves, low voltage

II. Myocardiocytolysis markers: Elevated cTnT/cTnI

III. Functional/structural abnormalities on echocardiography• New, otherwise unexplained LV and/or RV structure and function

abnormality (including incidental finding in apparently asymptomatic subjects): regional wall motion or global systolic or diastolic function abnormality, with or without ventricular dilatation, with or without increased wall thickness, with or without pericardial effusion, with or without endocavitary thrombi

IV. Tissue characterisation by CMR: Edema and/or LGE of classical myocarditic pattern

Ancillary findings which support the clinical suspicion of myocarditis

• Fever ≥38.1°C within the preceding 30 days • A respiratory or gastrointestinal infection• Previous clinically suspected or biopsy proven

myocarditis• Peri-partum period• Personal and/or family history of allergic asthma• Other types of allergy• Extra-cardiac autoimmune disease • Toxic agents• Family history of dilated cardiomyopathy, myocarditis

P.113

8.1ACUTE MYOCARDITIS: Diagnostic criteria (1)

Diagnostic criteria for clinically suspected myocarditis

One or more of the clinical presentations shown in the Diagnostic Criteria* with or without Ancillary Features*

ANDOne or more Diagnostic Criteria from different categories (I to IV)*

OR

when the patient is asymptomatic, two or more diagnostic criteria from different categories (I to IV)*

in the absence of:

1) angiographically detectable coronary artery disease2) known pre-existing cardiovascular disease or extra-cardiac causes that could explain the syndrome

(e.g. valve disease, congenital heart disease, hyperthyroidism, etc.)

Suspicion is higher with higher number of fulfilled criteria*

Endomyocardial biopsy is necessary to:

1) confirm the diagnosis of clinically suspected myocarditis, 2) identify the type and aetiology of inflammation,

and 3) provide the basis for safe immunosuppression (in virus negative cases).

Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (16).

*SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE

P.114

8.1ACUTE MYOCARDITIS: Diagnostic criteria (2)

Acute myocarditis should be clinically suspected in the presence of:

Hemodynamically stable Preserved LV function

No eosinophiliaNo significant rhythm or conduction disturbances

Not associated with systemic immune disease*

General supportive therapy

General supportive therapyImmunosuppression if

unresponsive and virus negative EMB

Hemodynamically unstable,decreased LV function, cardiogenic shock

Pharmacological and, if needed,mechanical circulatory support (ECMO, LVAD/Bi-VAD,

bridge to heart transplant or to recovery)

Lymphocytic Giant cell, eosinophilic,sarcoidosis (acute decompensation)

Immunosuppressionif infection-negative EMB

History, Physycal examination; ECG; Echocardiogram; Laboratory tests (Troponin, CRP, ESR, blood cell count, BNP); CMR; If available, serum cardiac autoantibodies

Clinically suspected myocarditis

Consider coronary angiography and EMB

No coronary artery disease

*If myocarditis is associated with systemic immune disease exacerbation, therapy overlaps with treatment of the background disease (usually immunosuppression).

P.115

8.1ACUTE MYOCARDITIS: Diagnostic and management protocol

• Patients with a life-threatening presentation should be sent to specialised units with capability for hemodynamic monitoring, cardiac catheterisation and expertise in endomyocardial biopsy.

• In patients with hemodynamic instability a mechanical cardio-pulmonary assist device may be needed as a bridge to recovery or to heart transplantation.

• Heart transplant should be deferred in the acute phase, because recovery may occur, but can be considered for hemodynamically unstable myocarditis patients, including those with giant cell myocarditis, if optimal pharmacological support and mechanical assistance cannot stabilise the patient

• ICD implantation for complex arrhythmias should be deferred until resolution of the acute episode, with possible use of a lifevest during the recovery period.

Reference: Caforio ALP et al. Eur Heart J. 2013 Jul 3 (18).

P.116

8.1Management of patients

with life-threatening ACUTE MYOCARDITIS

DIAGNOSIS (≥ 2 of the following):

• Chest pain (pleuritic) varying with position• Pericardial friction rub• Typical ECG changes (PR depression and/or diffuse concave ST-segment elevation)• Echocardiography: new pericardial effusion

Yes

Myopericarditis if:↑ TroponinEchocardiography: ↓ LV-function

Acutepericarditis

Equivocal or no

Consider cardiac

MRI

Delayedenhancementpericardium

Consider alternative diagnoses

P.117

8.2ACUTE PERICARDITIS: Diagnosis

ACUTE PERICARDITIS: MANAGEMENT

Acute pericarditis

High-risk features?

• Fever >38°C • Subacute onset • Anticoagulated • Trauma • Immunocompromised • Hypotension • Jugular venous distension • Large effusion

Other causes

• Post cardiac injury syndrome• Post cardiac surgery• Post MI: Dressler syndrome• Uremic• Neoplastic• Collagen vascular diseases (e.g. SLE)• Bacterial• Tuberculous

Yes

Hospital admissionStable

Ibuprofen + colchicineFurther testing for underlying etiology

Tamponade?

Pericardiocentesis

No

Most frequent cause:Viral pericarditis

Outpatient treatment

Aspirin 800 mgor Ibuprofen 600 mg BID - 2 weeks

If persisting or recurrent chest pain :Add colchicine 0.5 mg once (<70 kg)or 0.5 mg BID (≥70 kg) for 3 monthsAvoid corticosteroids!

P.118

8.2ACUTE PERICARDITIS: Management

CARDIAC TAMPONADE: DIAGNOSIS AND MANAGEMENT

Tamponade ?

Tamponade

Echocardiographywith respirometer

• Presence of a moderate to large pericardial effusion

• Diastolic collapses of right atrium and right ventricle

• Ventricular interdependence

• Increased tricuspid and pulmonary flow velocities (>50%) with decreased mitral and aortic flow velocities (>25%) during inspiration (predictive value >90%)

Physical examination• Distended neck veins• Shock• Pulsus paradoxus• Muffled heart sounds

ECG• Sinus tachycardia• Microvoltage QRS• Electrical alternans

Cardiac catheterization Early• Right atrial pressure ↑• Loss of X-descent

Late• Aortic pressure ↓• Pulsus paradoxus• Intracardiac diastolic pressure equilibration

Percutaneouspericardiocentesis & drainage

Consider surgical drainageAvoid PEEP ventilation

Not performed in routineP.119

8.2CARDIAC TAMPONADE: Diagnosis and management

CHAPTER 9

DRUGS IN ACUTE CARDIOVASCULAR

CAREAna de Lorenzo

P.121

9

Drug Indications Dose Dose adjustments Comments

Asp

irin Primary (not universally approved)

and secondary cardiovascular disease prevention

LD (if ACS): 150-300 mg oralMD: 75-100 mg oral QD

-

Major contraindications: GI bleeding-active peptic ulcer

Tica

grel

or

ACS (all patients at moderate-to-high risk of ischaemic events, e.g. elevated cardiac troponins)

LD: 180 mg oralMD: 90 mg oral BID -

Major contraindications: previous intracerebral hemorrhage, severe hepatic impairment, strong CYP3A4 inhibitors

Secondary prevention 1-3 years post-MI

MD: 60 mg oral BID-

Pra

sugr

el ACS with planned PCI LD: 60 mg oralMD: 10 mg oral QD

MD: 5 mg QD weight <60kg

Contraindication: previous stroke/TIA Prasugrel is generally not recommended in elderly, and if positive benefit/risk 5 mg is recommended

DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.

P.122

Oral antiplatelets 9


Clo

pido

grel

ACS + PCI or medical management (patients who cannot receive ticagrelor or prasugrel) and in ACS patients at high bleeding risk (e.g. patients who require oral anticoagulation)

LD: 300-600 mg oralMD: 75 mg oral QD

-

Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and oral anticoagulants

STEMI + fibrinolysis <75 years

LD: 300 mg oralMD: 75 mg oral QD

-

Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and oral anticoagulants

STEMI + fibrinolysis ≥75 years

LD: 75 mg oral MD: 75 mg oral QD

-

Secondary prevention >12 months post coronary stenting

MD: 75 mg oral QD-


P.123

Oral antiplatelets (Cont.) 9


Abc

ixim

ab

Adjunct to PCI for bailout situations or thrombotic complications

LD: 0.25 mg/Kg i.v. MD: 0.125 μg/Kg/min i.v. (max: 10 μg/min) for 12h

-

Contraindications:

Active internal bleeding - History of CVA within 2 years - Bleeding diathesis - Preexisting thrombocytopenia - Recent (within 2 months) intracranial or intraspinal surgery or trauma - Recent (within 2 months) major surgery - Intracranial neoplasm, arteriovenous malformation, or aneurysm - Severe uncontrolled hypertension - Presumed or documented history of vasculitis - Severe hepatic failure or severe renal failure requiring haemodialysis - Hypertensive retinopathy

Ept

ifib

atid

e

ACS treated medically or with PCI

LD: 180 μg/Kg i.v. (at a 10 min interval)If STEMI and PCI: add a second 180 mcg/kg i.v. bolus at 10 minMD: 2 μg/Kg/min i.v. infusion

Reduce infusion dose to 1 μg/kg/min if CrCl 30-50 ml/min

Contraindications:

Bleeding diathesis or bleeding within the previous 30 days - Severe uncontrolled hypertension - Major surgery within the preceding 6 weeks - Stroke within 30 days or any history of hemorrhagic stroke - Coadministration of another parenteral GP II b/III a inhibitor - Severe renal impairment or dependency on renal dialysis - History of intracranial disease - Clinically significant hepatic impairment - Thrombocytopenia - Prothrombine time >1.2 times control or INR ≥2


P.124

Intravenous antiplatelets 9


Tiro

fiba

n

ACS treated medically or with PCI

LD: 25 μg/Kg i.v. over 5 minMD: 0.15 μg/Kg/min i.v. Infusion to 18 hours

CrCl <30 ml/min: decrease 50% bolus and infusion dose

Contraindications:

A history of thrombocytopenia following prior exposure

Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month

Can

grel

or

All patients undergoing PCI(elective + ACS)immediate onset + rapid offset (platelet recovery in 60min)

IV Bolus of 30 μg/Kg+ IV infusion of 4 μg/kg/min for at least 2 hours from start of PCI

-

Major contraindications:

Significant active bleeding or stroke

Transition to oral P2Y12 inhibitors variable according to type of agent


P.125

Intravenous antiplatelets (Cont.) 9


War

fari

n A

ceno

coum

arol Treatment and

prophylaxis of thrombosis

INR goal of 2-3 (INR: 2.5-3.5 for mechanical mitral valve prostheses or double valve replacement)

Assessing individual risks for thromboembolism and bleeding

-

Api

xaba

n

Prevention of stroke and systemic embolism in NVAF

5 mg oral BID 2.5 mg oral BID1) when at least 2 of the following characteristics: age ≥80, Cr >1.5 mg/dl or weight <60Kg2) when CrCl 15-29 ml/min

Contraindicated if CrCl <15 ml/min or severe hepatic impairmentTreatment of DVT and PE 10 mg oral BID for the first

7 days followed by 5 mg oral BID

-

Prevention of recurrent DVT and PE

2.5 mg oral BID

-


P.126

Oral anticoagulants and antagonists 9


Dab

igat

ran


150 mg oral BID 110 mg BID (if age ≥80, increased bleeding risk or concomitant use of verapamil)

Contraindicated if CrCl <30 ml/min or severe hepatic impairment

Active clinically significant bleeding

Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole and dronedarone

Treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days and prevention of recurrent DVT and PE in patients who have been previously treated

Edox

aban


60 mg oral QD 30 mg oral QD 1) when CrCl 15-50 ml/min2) weight <60Kg3) concomitant use of the following P-glycoprotein inhibitors: ciclosporin, dronedarone, erythromycin, or ketoconazole.

Edoxaban can be initiated in patients who may require cardioversion. Treatment should be started at least 2 hours before cardioversionTreatment of DVT and

PE and prevention of recurrent DVT and PE

60 mg oral QD


P.127

Oral anticoagulants and antagonists (Cont.) 9


Riv

arox

aban


20 mg oral QD CrCl <50 ml/min: 15 mg QD Contraindicated if CrCl <15 ml/min or hepatic disease associated with coagulopathy and clinically relevant bleeding risk

Rivaroxaban can be initiated in patients who may require cardioversion

Treatment should be started at least 4 hours before cardioversion

Treatment of DVT and PE and prevention of recurrent DVT and PE

15 mg oral BID for the first 3 weeks followed by 20 mg QD

Reduce the maintenance dose to 15 mg QD if bleeding risk outweighs the risk for recurrent DVT and PE (not formally approved)

Prevention of atherothrombotic events

2.5 mg oral BID-

Anticoagulant antagonists

Idar

uciz

umab

Specific reversal agent for dabigatran

5g i.v. over 5 to 10 min

Another 5g dose if prolonged clotting times and:- recurrence of clinically

relevant bleeding- if potential re-bleeding

would be life-threatening- second emergency

surgery/urgent procedure

-

Dabigatran treatment can be re-initiated 24h after administration of idarucizumab, other antithrombotic therapy at any time

Relevant coagulation parameters are aPTT, dTT or ECT


P.128



Anticoagulant antagonists

Phy

tom

enad

ione

(V

itam

in K

)

Reversal for vitamin K antagonists

Patients with asymptomatic high INR with or without mild haemorrhage

Anticoagulant INR Oral Vitamin K i.v. Vitamin K

Warfarin

5-9 1-2.5 mg or 2-5 mg for a rapid reversal (additional dose of 1-2 mg if INR remains high after 24h)

0.5-1 mg

>9 2.5-5 mg (up to 10 mg) 1 mg

Acenocoumarol5-8 1-2 mg 1-2 mg

>8 3-5 mg 1-2 mg

Severe or life-threatening haemorrhage

Anticoagulant Situation i.v. Vitamin K Concomitant treatment

Warfarin

Severe haemorrhage

5-10 mg CCP or FFP

Life-threatening 10 mg CCP, FFP or rFVIIa

AcenocoumarolSevere haemorrhage

5 mg CCP, FFP or rFVIIa

P.129




UFH

NSTE-ACS LD: 4,000 IU i.v. MD: 1,000 IU/h i.v. Target aPTT: 50-70s or 1.5 to 2.0 times that of control to be monitored at 3, 6, 12 and 24h

Monitoring for heparin-induced thrombocytopenia (HIT)

Dose-independent reaction

STEMI Primary PCI: 70-100 IU/Kg i.v. when no GP-IIb/IIIa inhibitor is planned. 50-60 IU/Kg i.v. bolus with GP-IIb/IIIa inhibitors - Fibrinolysis/No reperfusion: 60 IU/kg i.v. bolus (max: 4,000 IU) followed by an i.v. infusion of 12 IU/kg (max: 1,000 IU/h) for 24-48h

Target aPTT: 50-70s or 1.5 to 2.0 times that of control to be monitored at 3, 6, 12 and 24h

Treatment of DVT and PE

80 IU/Kg i.v. bolus followed by 18 IU/Kg/h

According to aPTT, thromboembolic and bleeding risk

Fond

apar

inux

NSTE-ACS 2.5 mg QD s.c. up to 8 days or hospital discharge - Acute bacterial endocarditis

Severe hepatic impairment: caution advised

Contraindicated if CrCl <20 ml/min

Contraindicated for DVT/PE treatment if CrCl <30 ml/min

STEMI Fibrinolysis/No reperfusion: 2.5 mg i.v. bolus followed by 2.5 mg QD s.c. up to 8 days or hospital discharge

-


5 mg QD s.c. (<50kg); 7.5 mg QD s.c. (50-100kg); 10 mg QD s.c. (>100kg)

If >100Kg and CrCl 30-50 ml/min: 10 mg followed by 7.5 mg/24h s.c.

Prevention of VTE 2.5 mg QD s.c. CrCl 20-50 ml/min: 1.5 mg QD s.c.

P.130


Parenteral anticoagulants 9


Biv

alir

udin

PCI for NSTE-ACS 0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which may be continued for up to 4h post PCI as clinically warranted and further continued at a reduced infusion dose of 0.25 mg/kg/h for 4-12h as clinically necessary

Patients undergoing PCI with CrCl 30-50 ml/min should receive a lower infusion rate of 1.4 mg/kg/h

No change for the bolus dose

Contraindicated if CrCl <30 ml/min

Active bleeding or increased risk of bleeding, severe uncontrolled hypertension, subacute bacterial endocarditis

PCI for STEMI 0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which should be continued for up to 4h after the procedureAfter cessation of the 1.75 mg/kg/h infusion, a reduced infusion dose of 0.25 mg/kg/h may be continued for 4-12h

PCI for elective cases

0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which may be continued for up to 4h post PCI as clinically waranted


P.131

Parenteral anticoagulants (Cont.) 9


Eno

xapa

rin

NSTE-ACS 30 mg i.v. + 1 mg/kg s.c. BID If >75 years: no LD and MD 0.75 mg/Kg BID s.c.CrCl <30 ml/min: no LD and MD 1 mg/Kg QD s.c.If >75 years and CrCl <30 ml/min: no LD and 0.75 mg/Kg QD s.c.

Monitoring for HIT

Anti Xa monitoring during treatment with LMWH might be helpful in pregnancy, extreme body weights and renal impairment

STE-ACS Primary PCI: 0.5 mg/Kg i.v. bolusFibrinolysis/No reperfusion:

a) Age <75 years: 30 mg i.v. bolus followed by 1 mg/Kg BID s.c. until hospital discharge for a max of 8 days The first two doses should not exceed 100 mg

b) Age >75 years: no bolus; 0.75 mg/Kg BID s.c. - The first two doses should not exceed 75 mg

In patients with CrCl <30 ml/min: regardless of age, the s.c. doses are given once daily


1 mg/Kg s.c. BID or 1.5 mg/Kg s.c. QD CrCl <30 ml/min: 1 mg/Kg/24h s.c.

Prevention of VTE 40 mg s.c. QD CrCl <30 ml/min: 20 mg s.c. QD


P.132



Tinz

apar

in Prevention of VTE 3,500 IU s.c. QD (moderate risk)4,500 IU s.c. QD (high risk)

-Monitoring for HIT

Anti Xa monitoring during treatment with LMWH might be helpful in pregnancy, extreme body weights and renal impairment

Dalteparin: In cancer patients, dose of 200 IU/kg (max: 18,000 IU)/24h for 1 month, followed by 150 IU/kg/24h for 5 months After this period, vitamin K antag or a LMWH should be continued indefinitely or until the cancer is considered cured


175 IU/Kg s.c. QD -

Dal

tepa

rin

Prevention of VTE 2,500 IU s.c. QD (moderate risk)5,000 IU s.c. QD (high risk)

-


200 IU/Kg QD or 100 IU/Kg BID s.c. Anti Xa monitoring if renal impairment

Arg

atro

ban Anticoagulant in

patients with HITInitial i.v. infusion dose: 2 μg/kg/min (not to exceed 10 μg/kg/min)Patients undergoing PCI: 350 μg/kg i.v. followed by 25 μg/kg/min i.v.

Renal and hepatic impairment: caution advised

Monitored using aPTT goal:

1.5 to 3.0 times the initial baseline value

PCI: ACT goal: 300-450s


P.133


Drug Indications DoseDose

adjustmentsComments

Str

epto

kina

se (S

K)

STEMI <12 hours 1.5 million units over 30-60 min i.v. -

Absolute contraindications to fibrinolytics:

Previous intracranial haemorrhage or stroke of unknown origin at any time

Ischaemic stroke in the preceding 6 months

Central nervous system damage or neoplasms or atrioventricular malformation

Recent major trauma/surgery/head injury (within the preceding 3 weeks)

Gastrointestinal bleeding within the past month

Known bleeding disorder (excluding menses)

Aortic dissection

Non-compressible punctures in the past 24h (e.g. liver biopsy, lumbar puncture)

Treatment of PE 250,000 IU as a LD over 30min, followed by 100,000 IU/h over 12-24h

-

Alt

epla

se (t

PA)

STEMI <12 hours 15 mg i.v. bolus:0.75 mg/kg over 30 min (up to 50 mg) then0.5 mg/kg over 60 min i.v. (up to 35 mg)

-

Treatment of PE Total dose of 100 mg: 10 mg i.v. bolus followed by 90 mg i.v. for 2h

If weight <65 Kg: max dose <1.5 mg/kg


P.134

Fibrinolytics 9


adjustmentsComments

Ret

epla

se

(rt-

PA)

STEMI <12 hours 10 units + 10 units i.v. bolus given 30 min apart


Absolute contraindications to fibrinolytics:

Previous intracranial haemorrhage or stroke of unknown origin at any time

Ischaemic stroke in the preceding 6 months

Central nervous system damage or neoplasms or atrioventricular malformation

Recent major trauma/surgery/head injury (within the preceding 3 weeks)

Gastrointestinal bleeding within the past month

Known bleeding disorder (excluding menses)

Aortic dissection

Non-compressible punctures in the past 24h (e.g. liver biopsy, lumbar puncture)

Tene

ctep

lase

(T

NK-

tPA

)

STEMI <12 hours Single i.v. bolus over 10 seconds:

30 mg if <60kg35 mg if 60 to <70kg40 mg if 70 to <80kg45 mg if 80 to <90kg50 mg if ≥90kg -


P.135

Fibrinolytics (Cont.) 9


Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm

Ate

nolo

l

NSTE-ACS LD: 25-100 mg oral MD: 25-100 mg QD

Elderly: start at a lower doseCrCl 15-35 ml/min: max dose 50 mg/day; CrCl <15 ml/min: max dose 25 mg/day

Only if normal LVEF

STEMI 25-100 mg QD,titrate as tolerated up to 100 mg QD only if no LVSD or CHF

Car

vedi

lol NSTE-ACS LD: 3.125-25 mg oral

MD: 3.125-25 mg BID Caution in elderly and hepatic impairment

Preferred if LVSD/HF

STEMI 3.125-6.25 mg BID, titrated as tolerated up to 50 mg BID

Bis

opro

lol NSTE-ACS LD: 1.25-10 mg oral

MD: 1.25-10 mg QDCaution in renal or hepatic impairment Preferred if LVSD/HF

STEMI 1.25-5 mg QD, titrate as tolerated up to 10 mg QD


P.136

Antiischemic drugs 9


Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm

Met

opro

lol NSTE-ACS LD: 25-100 mg oral

MD: 25-100 mg BIDCaution in hepatic impairment Preferred if LVSD/HF

STEMI 5-25 mg BID, titrate as tolerated up to 200 mg QD

Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina

Ver

apam

il ACS LD: 80-120 mg oralMD: 80-240 mg TID-QD

Caution in elderly, renal or hepatic impairment

Contraindicated if bradycardia, HF, LVSD

Dilt

iaze

m ACS LD: 60-120 mg oralMD: 60-300 mg TID-QD

Caution in elderly and hepatic impairment



P.137

Antiischemic drugs (Cont.) 9


Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina

Am

lodi

pine ACS LD: 5-10 mg oral, MD: 5-10 mg QD Caution in hepatic impairment Contraindicated

if hypotension

Nitrates

Nit

rogl

ycer

in

i.v.

ACS If intolerant or unresponsive to nitroglycerin s.l. 5 μg/min - Increase by 5 mcg/min q 3-5 min up to 20 μg/min

If 20 mcg/min is inadequate, increase by 10 to 20 μg/min every 3 to 5 min

Max dose: 400 μg/min

-

Contraindicated if severe hypotension and co-administration with phosphodiesterase inhibitors

The most common adverse effects are headache and dizziness

i.v. nitroglycerin requires NON-PVC containers

spra

y Angina 1-2 puff s.l. every 5 min as needed, up to 3 puffs in 15 min -

subl

ingu

al

tabl

et

Angina 0.3 to 0.6 mg s.l. or in the buccal pouch every 5 min as needed, up to 3 doses in 15 min -


P.138



Isos

orbi

de m

onon

itra

te Angina 5-10 mg BID with the two doses given 7h apart (8am and 3pm) to decrease tolerance development - then titrate to 10 mg BID in first 2-3 days Extended release tablet: Initial: 30-60 mg given in the morning as a single dose Titrate upward as needed, giving at least 3 days between increases Max daily single dose: 240 mg

-

Contraindicated if severe hypotension and co-administration with phosphodiesterase inhibitors

The most common adverse effects are headache and dizziness

Isos

orbi

de

dini

trat

e Angina Initial dose: 5 to 20 mg orally 2 or 3 times/dayMD: 10 to 40 mg orally 2 or 3 times a dayExtended release: 40 to 160 mg/day orally

-

Nit

rogl

ycer

in

tran

sder

mal

p

atch

Angina 0.2 to 0.4 mg/h patch applied topically once a day for 12 to 14h per day; titrate as needed and tolerated up to 0.8 mg/h -


P.139



Other antiishemic drugs

Ivab

radi

ne Stable angina 5-7.5 mg oral BID Caution in elderly and CrCl <15 ml/min Contraindicated if severe hepatic impairment

Ran

olaz

ine

Stable angina Initial dose: 375 mg oral BIDAfter 2-4 weeks, the dose should be titrated to 500 mg BID and, according to the patient’s response, further titrated to a recommended max dose of 750 mg BID

Use with caution in renal and hepatic impairment, CHF, elderly, low weight

Contraindicated if CrCl <30 ml/min, concomitant administration of potent CYP3A4 inhibitors, moderate or severe hepatic impairment

Trim

etaz

idin

e

Stable angina Modified-release: 35 mg oral BID Caution in elderly and 30 <CrCl <60 ml/min

Contraindicated in parkinson disease, parkinsonian symptoms, tremors, restlessleg syndrome, movement disorders, severe renal impairment


P.140



Statins: Primary or secondary prevention of cardiovascular disease For secondary prevention, start with high doses initiated early after admission and downtitrate if side effects. Target LDL-C levels <70 mg/dl

AtorvastatinLDL-C reduction

<30% 30-40% 40-50% >50%

Simva 10 mg

Simva 20-40 mg

Simva/ezet 20/10 mg

Simva/ezet 40/10 mg

Lova 20 mg

Ator 10 mg

Ator 20-40 mg

Ator 40-80 mg

Prava 10-40 mg

Rosu 5 mg Rosu 10 mgRosu 20-40 mg

Pita 1 mg Pita 2 mg Pita 4 mg

Fluva 20-40 mg

Fluva 80 mg

-

Contraindicated in patients with active liver disease or with unexplained elevation of liver function enzyme levels

RosuvastatinCrCl <30 ml/min: start 5 mg QD, max: 10 mg QD

PitavastatinCrCl 30-59 ml/min: start 1 mg QD, max 2 mg/day; CrCl 10-29 ml/min: not defined

SimvastatinSevere renal impairment: start 5 mg QPM

FluvastatinCaution in severe renal impairment

PravastatinSignificant renal impairment: start 10 mg QD

LovastatinCrCl <30 ml/min: caution if dose >20 mg QD


P.141

Lipid lowering drugs 9


Others

EzetimibeHypercholesterolaemia 10 mg oral QD Avoid use if moderate-severe

hepatic impairment-

FenofibrateHyperlipidemia 48-160 mg oral QD

May adjust dose q 4-8 weeks

CrCl 50-90 ml/min: start 48-54 mg QD

Contraindicated if CrCl <50 ml/min or hepatic impairment

Gemfibrozil

Hyperlipidemia 900-1,200 mg/day oral

-

Contraindicatedif severe renal impairment or hepatic dysfunctionStatins may increase muscle toxicity: avoid concomitant use


P.142

Lipid lowering drugs (Cont.) 9


PCSK9 Inhibitors

Evolocumab

Hypercholesterolaemia and mixed dyslipidaemia Homozygous familial hypercholesterolaemia

140 mg s.c. every 2 weeks or 420 mg every month

Homozygous familial hypercholesterolaemia: 420 mg s.c every month Up-titrate to 420 mg every 2 weeks if a response is not achieved

-

Most common side effects:

Nasopharingitis, upper respiratory tract infection, headache and back pain

Alirocumab

Hypercholesterolaemia and mixed dyslipidaemia

Start dose: 75 mg s.c. every 2 weeks

If a larger LDL-C reduction (>60%) is required, the start dose could be 150 mg every 2 weeks, or 300 mg every 4 weeks

The dose can be individualised based on LDL-C level, goal of therapy, and response. Max dose: 150 mg once every 2 weeks

Most common side effects:

Upper respiratory tract signs and symptoms, pruritus and injection site reactions

P.143


Lipid lowering drugs (Cont.) 9


ACEI

Cap

topr

il

HF Start: 6.25 mg oral TID Target dose: 50 mg TID

CrCl >50 ml/min: 75-100% of the normal doseCrCl 10-50 ml/min: 25-50%CrCl <10 ml/min: 12.5%

Check renal function, electrolytes, drug interactions


History of angioedema, known bilateral renal artery stenosis, pregnancy (risk)

HTN Start: 12.5 mg oral BID Target dose: 25-50 mg TID Max 450 mg/day

Ena

lapr

il HF, HTN Start: 2.5 mg oral BID Target dose: 10-20 mg BID

CrCl 30-80 ml/min: start 5 mg/dayCrCl 10-30 ml/min: start 2.5 mg/day

Lisi

nopr

il

HF Start: 2.5-5.0 mg oral QD Target dose: 20-35 mg QD

CrCl 31-80 ml/min: start 5-10 mg/day CrCl 10-30 ml/min: start 2.5-5 mg/day CrCl <10 ml/min: start 2.5 mg/day

HTN 10-20 mg oral QD Max: 80 mg QD


P.144

Heart failure & hypertension 9


Per

indo

pril HF Start: 2 mg oral QD

Target dose: 8 mg QDCrCl >60 ml/min: start 4 mg/dayCrCl 31-60 ml/min: start 2 mg/dayCrCl 15-30 ml/min: start 2 mg every other dayCrCl <15ml/min: 2 mg on the day of dialysis




HTN Start: 4 mg QDMax dose: 8 mg QD

Ram

ipri

l HF, HTN Start: 2.5 mg oral QDTarget dose: 5 mg BID

CrCl <40 ml/min: start 1.25 mg QD, max 5 mg/dayCaution in elderly and hepatic impairment

Tran

dola

pril

HF Start: 0.5 mg oral QDTarget dose: 4 mg QD

CrCl <30 ml/min or severe hepatic impairment: start 0.5 mg

HTN 2-4 mg oral QD CrCl <30 ml/min or severe hepatic impairment: start 0.5 mg


P.145

Heart failure & hypertension (Cont.) 9


ARB

Can

desa

rtan

HF, HTN Start: 4-8 mg oral QDTarget dose: 32 mg QD

If renal or hepatic impairment: start 4 mg/day

If ACEI is not tolerated




Losa

rtan

HF Start: 50 mg oral QDTarget dose: 150 mg QD

CrCl <20 ml/min: 25 mg QDCaution if hepatic impairment

HTN 50-100 mg oral QD CrCl <20 ml/min: 25 mg QDCaution if hepatic impairment

Vals

arta

n HF Start: 40 mg oral BIDTarget dose: 160 mg BID

If mild-moderate hepatic impairment: max dose 80 mg/day

HTN 80-160 mg QD If mild-moderate hepatic impairment: max dose 80 mg/day


P.146



Neprilysin inhibitor/ARB

Sac

ubit

ril/

Val

sart

an

Symptomatic chronic HF with reduced ejection fraction

Start: 49 mg/51 mg oral BID Target dose: 97 mg/103 mg BID

Do not initiate if K >5.4 mmol/l or SBP <100 mmHg Start dose of 24 mg/26 mg BID if SBP 100-110 mmHg or CrCl 30-60 ml/min

Do not co-administer with an ACEI or ARB. It must not be started for at least 36 hours after discontinuing an ACEI

Contraindicated if history of angioedema related to ACEI or ARB

Hereditary or idiopathic angioedema

Concomitant use with aliskiren if diabetes mellitus or renal impairment

Severe hepatic impairment, biliary cirrhosis and cholestasis


P.147



Beta-blockers: Check 12 - lead ECG

Car

dios

elec

tive

(1)

Ate

nolo

l HTN Start: 25 mg oral QD Usual dose: 50-100 mg QD

CrCl 10-50 ml/min: decrease dose 50% CrCl <10 ml/min: decrease dose 75%

Major contraindications: asthma, 2nd or 3rd degree AV block

Bis

opro

lol

HF Start: 1.25 mg oral QD Target dose: 10 mg QD

CrCl <20 ml/min: max dose 10 mg QD Hepatic impairment: avoid use

HTN Start: 2.5-5 mg oral QD Usual dose: 5-10 mg QD Max dose: 20 mg QD

Met

opro

lol

HF Start: 12.5-25 mg oral QD Target dose: 200 mg QD

Hepatic impairment: start with low doses and titrate gradually

HTN 100-400 mg QD Max dose: 400 mg QD


P.148



Beta-blockers: Check 12- lead ECG

Car

dios

elec

tive

(2

)

Neb

ivol

ol

HF Start: 1.25 mg oral QD Target dose: 10 mg QD

Renal impairment or elderly: start dose 2.5 mg QD, titrate to 5 mg QD Hepatic impairment: contraindicated

Major contraindications: asthma, 2nd or 3rd degree AV block

HTN Start: 2.5 mg oral QD Usual dose: 5 mg QD

Non

-car

dios

elec

tive

Car

vedi

lol

HF Start: 3.125 mg oral BID Target dose: 25-50 mg BID

Caution in elderly Contraindicated if hepatic impairment

HTN Start: 12.5 mg oral QD Usual dose: 25 mg QD and max dose: 25 mg BID or 50 mg QD


P.149



Other vasodilators

Am

lodi

pine

HTN Start: 5 mg oral QD, increase after 1-2 weeksMax: 10 mg/day

Elderly or secondary agent: start 2.5 mg QD Hepatic impairment: start 2.5 mg QD

Contraindicated if cardiogenic shock, 2nd or 3rd degree AV block, severe hypotension

Nife

dipi

ne

HTN Extended-release form: Start 20 mg oral BID or TID Max: 60 mg BID


Ver

apam

il HTN Immediate-release form: Dose: 80-120 mg oral TID; Start: 80 mg TID; Max: 480 mg/day

Start 40 mg oral TID in elderly or small stature patients



P.150



Loop diuretics

Furo

sem

ide HF 20-40 mg i.v. bolus, continuous

100 mg/6h (adjust based on kidney function and clinical findings; monitor creatinine)

Anuria: contraindicated Cirrhosis/ascites: caution advised

-

HTN 10-40 mg oral BID

Tors

emid

e HF 10-20 mg oral or i.v. QD Hepatic impairment: initial dose should be reduced by 50% and dosage adjustments made cautiously -

HTN 5 mg oral or i.v. QD Max 10 mg QD


P.151



Thiazides

Chl

orth

alid

one

HF 50-100 mg oral QD MD: 25-50 mg QD

Elderly: max dose 25 mg/day CrCl <25 ml/min: avoid use -

HTN Start 12.5-25 mg oral QD; Max: 50 mg/day

Elderly: max dose 25 mg/day CrCl <25 ml/min: avoid use -

Hyd

roch

loro

thia

zide HF 25-200 mg oral/day CrCl <25 ml/min: avoid use

Hepatic impairment: caution advised -

HTN Start 12.5-25 mg oral QD MD: may increase to 50 mg oral as a single or 2 divided doses

CrCl <25 ml/min: avoid use Hepatic impairment: caution advised

-

Inda

pam

ide HTN Start 1.25 mg PO QAM x4weeks,

then increase dose if no response Max: 5 mg/day

CrCl <25 ml/min: avoid use Hepatic impairment: caution advised

-


P.152



Aldosterone-antagonists

Spi

rono

lact

one HF Start 25 mg oral QD

Target dose: 25-50 mg QDCrCl <10 ml/min, anuria or acute renal impairment: contraindicated Severe hepatic impairment and elderly: caution advised

Check renal function, electrolytes, drug interactionsProduces gynecomastiaHTN 50-100 mg/day oral

Epl

eren

one HF Start 25 mg oral QD

Target dose: 50 mg QDElderly: caution advised CrCl <50 ml/min: contraindicated

Check renal function, electrolytes, drug interactionsMajor contraindications: strong CYP3A4 inhibitors

HTN 50 mg oral QD-BIDMax: 100 mg/day

Others

Ivab

radi

ne HF 5-7.5 mg oral BID Caution in elderly and CrCl <15ml/min

Contraindicated if severe hepatic impairment


P.153



Levo

sim

enda

n HF/cardiogenic shock

LD: 6 to 12 μg/kg i.v. over 10 min (given only if immediate effect is needed) followed by 0.05 to 0.2 μg/kg/min as a continuous infusion for 24h

Avoid use if CrCl <30 ml/min or severe hepatic impairment

Calcium sensitizer and ATP-dependent potassium channel opener

Milr

inon

e

HF/cardiogenic shock

50 μg/kg i.v. in 10-20 min, continuous 0.375-0.75 μg/kg/min

Renal: Same bolus. Adjust infusion: CrCl 50 ml/min: start 0.43 μg/kg/min CrCl 40 ml/min: start 0.38 μg/kg/min CrCl 30 ml/min: start 0.33 μg/kg/min CrCl 20 ml/min: start 0.28 μg/kg/minCrCl 10 ml/min: start 0.23 μg/kg/minCrCl 5 ml/min: start 0.20 μg/kg/min

Phosphodiesterase inhibitor

Caution if atrial flutter

Hypotensive drug

Isop

rena

line/

Is

opro

tere

nol Cardiogenic

shock0.5-5 μg/min (0.25-2.5ml of a 1:250,000 dilution) i.v. infusion

-

ß1, ß2 agonist

Contraindicated in patients with tachyarrhythmia, tachycardia or heart block caused by digitalis intoxication, ventricular arrhythmias which require inotropic therapy, angina pectoris, recent ACS, hyperthyroidism

Bradyarrhythmias Bolus: 20-40 μg i.v.Infusion: 0.5 μg/min of 2 mg/100 ml normal saline

ß ef

fect


P.154

Inotropics & vasopressors 9


Dob

utam

ine Cardiogenic

shock2-20 μg/kg/min i.v.

-

ß1, a1/ß2 agonist

Increases contractility with little effect on heart rate and blood pressure. Reduces pulmonary and systemic VR, PCP

Dop

amin

e Cardiogenic shock

Dopaminergic effect: 2-5 μg/Kg/min i.v.ß effect : 5-15 μg/Kg/min i.v.a effect : 15-40 μg/Kg/min i.v.

-

ß, a, dopaminergic agonist

Increases BP, PAP, heart rate, cardiac output and pulmonary and systemic VR

More arrhythmogenic than dobutamine and noradrenaline

Nor

adre

nalin

e Cardiogenic shock

0.05-0.2 μg/kg/min i.v. titrate to effect

-

a 1, ß1 agonist

Increases BP and PAP

Little arrhythmogenic

ß ef

fect

a ef

fect


P.155

Inotropics & vasopressors (Cont.) 9


Group I

Pro

cain

amid

e i.v

.

AF (termination); stable VT (with a pulse)

15-18 mg/kg i.v. over 60min, followed by infusion of 1-4 mg/min

Reduce LD to 12 mg/kg in severe renal impairmentReduce MD by one-third in moderate renal impairment and by two-thirds in severe renal impairmentCaution in elderly and asthma

Hypotension (negative inotropic agent)

Lupus-like syndrome

Contraindicated if myasthenia gravis, AV block, severe renal impairment

Lido

cain

e i.v

.

Pulseless VT/VF

1-1.5 mg/kg i.v./i.o. bolus (can give additional 0.5-0.75 mg/kg i.v./i.o. push every 5-10 min if persistent VT/VF, max cumulative dose = 3 mg/kg), followed by infusion of 1-4 mg/min

1-2 mg/min infusion if liver disease or HF

Contraindicated if advanced AV block, bradycardia,

hypersensitivity to local anesthetics

Caution in HF, renal impairment and elderly

May cause seizures, psychosis

Stop if QRS widens >50%

Stable VT (with a pulse)

1-1.5 mg/kg i.v. bolus (can give additional 0.5-0.75 mg/kg i.v. push every 5-10 min if persistent VT, max cumulative dose = 3 mg/kg), followed by infusion of 1-4 mg/min


P.156

Antiarrhythmics 9


Group I

Flec

aini

de

i.v.

SVT, ventricular arrhythmias

2 mg/kg (max 150 mg) i.v. over 30 minThis may be followed by an infusion at a rate of 1.5 mg/kg/h for 1 h, reduced to 0.1-0.25 mg/kg/h for up to 24h, max cumulative dose = 600 mg

Severe renal impairment: caution advised

Contraindicated if cardiogenic shock, recent MI, 2nd or 3rd degree AV block

Pro

pafe

none

i.v

.

PSVT, ventricular arrhythmias

LD: 0.5-2 mg/kg i.v. direct over aminimum of 3-5minMD: 0.5-2.5 mg/kg i.v. direct q8h (max 560 mg/day) or continuous infusion up to 23 mg/h

May need to reduce dose in renal or hepatic failure

Contraindicated if unstable HF, cardiogenic shock, AV block, bradycardia, myasthenia gravissevere hypotension,bronchospastic disorders, Brugada syndrome


P.157

Antiarrhythmics (Cont.) 9


adjustmentsComments

Group II

Ate

nolo

l i.v

.

Arrhythmias 2.5 mg i.v. over 2.5 min every 5 min(max 10 mg)

Caution in elderly and/or severe renal impairment

Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, unstable HF

Met

opro

lol

i.v.

Arrhythmias 2.5-5 mg i.v. over 5min, may repeat every 5 min (max 15 mg)

Caution if severe hepatic impairment

Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, unstable HF

Pro

pran

olol

i.v

.

Arrhythmias Initially given as slow i.v. boluses of 1 mg, repeated at 2 min intervals (max: 10 mg in conscious patients and 5 mg if under anesthesia) -

Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, asthma, unstable HF


P.158



adjustmentsComments

Group III

Am

ioda

rone

i.v

.

AF (termination) 5 mg/Kg i.v. over 30min, followed by infusion of 1 mg/min for 6h, then 0.5 mg/min

-Reduce infusion rate if bradycardia, AV block, hypotension

Bolus should be avoided if hypotension or severe LV dysfunction

Highly vesicant agent

Stable VT (with a pulse)

150 mg i.v. over 10 min followed by infusion of 1 mg/min for 6h, then 0.5 mg/min

-

Pulseless VT/VF 300 mg bolus i.v. (can give additional150 mg i.v. bolus if VF/VT persists) followed by infusion of 900 mg over 24h

-

Dro

neda

rone Paroxysmal

or persistent AF prevention

400 mg oral BID

-

Contraindicated if severe renal or liver dysfunction, LVSD, symptomatic HF, permanent AF, bradycardia… (multiple contraindications)


P.159



adjustmentsComments

Group IV

Dilt

iaze

m

i.v.

PSVT; AF (rate control) 0.25 mg/kg i.v. over 2 min (may repeat with 0.35 mg/kg i.v. over 2 min), followed by infusion of 5-15 mg/h

Hepatic impairment: caution advised -

Ver

apam

il i.v

.

PSVT; AF (rate control) 2.5-5 mg i.v. over 2 min (may repeat up to max cumulative dose of 20 mg); can follow with infusion of 2.5-10 mg/h -

Contraindicated if AF+WPW, tachycardias QRS (except RVOT-VT), fascicular VT, bronchospasm, age >70 years

Antidote: - LVD: Calcium gluconate, dobutamine

- Bradycardia/AV block: Atropine, Isoproterenol

Ade

nosi

ne

i.v.

Rapid conversion to a normal sinus rhythm of PSVT including those associated with accessory by-pass tracts (WPW syndrome)

Rapid i.v. boluses separated by 2 min: 6 mg → 6 mg → 12 mg

-

Contraindicated if sick sinus syndrome, second or third degree Atrio-Ventricular (AV) block (except in patients with a functioning artificial pacemaker), chronic obstructive lung disease with evidence of bronchospasm (e.g. asthma bronchiale), long QT syndrome, severe hypotension; decompensated states of heart failure - Adenosine can cause AF


P.160



adjustmentsComments

Others

Mag

nesi

um

sulfa

te

VT-Torsades de Pointes

Bolus: 1-2g i.v./i.o. over 5 minPerfusion: 5-20 mg/min i.v.

Caution if severe renal failure

Contraindicated if myasthenia gravis

Ver

naka

lant

Conversion of recent onset AF

3 mg/kg i.v. over 10 min

If AF persists, a second 10min-infusion of 2 mg/kg, 15 min later may be administered

-

Contraindicated if ACS within the last 30 days, severe aortic stenosis, SBP <100 mmHg, HF class NYHA III/IV, severe bradycardia, sinus node dysfunction or 2nd or 3rd degree heart block, prolonged QT at baseline, use of i.v. antiarrhythmics (class I and class III) within 4h prior to, as well as in the first 4h after, vernakalant administration


P.161



Benzodiazepines: Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment. Benzodiazepines may induce anterograde amnesia. Discontinuation: dosage should be reduced slowly

Short-acting benzodiazepines

Alp

razo

lam

Moderate or severe anxiety or anxiety associated with depression

250-500mcg oral TID as short as possible, increasing if required to a total of 3 mg daily

Elderly or debilitating disease: 250mcg BID or TID and gradually increased if needed and tolerated

Renal impairment or mild-moderate hepatic impairment: caution

Contraindicated if myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic insufficiency

Lopr

azol

am

Insomnia 1 mg oral at bedtime. This may be increased to 1.5 mg or 2 mg if necessary

Frail, debilitated or elderly: start with half a tablet. Max dose: 1 mg

Chronic pulmonary, insufficiency, cerebrovascular disease and chronic renal or hepatic impairment: caution

Contraindicated if acute pulmonary insufficiency, severe respiratory insufficiency, myasthenia gravis, phobic or obsessional states and sleep apnoea syndrome, monotherapy in depression or anxiety associated with depression and chronic psychosis and alcohol intake

P.162


Sedatives and neuropsychiatric drugs 9



Lora

zepa

m o

ral

Severe anxiety

Premedication before surgery

Anxiety: 1-4 mg oral in divided doses

Insomnia: 1-2 mg oral before retiring

Premedication before surgery: 2-3 mg oral the night before operation 2-4 mg oral 1-2h before the procedure

Elderly: may respond to lower doses

Renal or hepatic impairment: lower doses may be sufficient

Contraindicated if acute pulmonary insufficiency, respiratory depression, sleep apnoea, obsessional states, severe hepatic insufficiency, myasthenia gravis

Lora

zepa

m in

ject

ion Pre-operative

medication, acute anxiety states, acute excitement or acute mania, status epilepticus

Premedication: 0.05 mg/Kg

By the i.v. route the injection should be given 30-45 min before surgery

By the i.m. route the injection should be given 1-1.5h before surgery

Acute anxiety: 0.025-0.03 mg/kg i.v./i.m. Repeat 6 hourly

Status epilepticus: 4 mg i.v.

P.163


Sedatives and neuropsychiatric drugs 9



Lorm

etaz

epam

ora

l Short-term treatment of insomnia

0.5-1.5 mg oral before retiring. The initial dosage may be increased to 2 mg in individual cases if this proves necessary

Elderly: may respond to lower doses

Chronic respiratory insufficiency: a lower dose is recommended

Severe renal impairment: caution

Contraindicated if myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, acute intoxication with alcohol, hypnotics, analgesics or psychotropic drugs, severe liver insufficiency

Mid

azol

am o

ral

Insomnia DOSE / DOSE ADJUSTMENTS: 7.5-15 mg oral at bedtime

COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered

P.164


Sedatives and neuropsychiatric drugs (Cont.) 9



Mid

azol

am in

ject

ion

(1)

Short-acting sleep-inducing drug

DOSE / DOSE ADJUSTMENTS:

Indications Adults <60 y Adults ≥60 y/debilitated or chronically ill

Conscious sedation i.v. Initial dose: 2-2.5 mg Titration doses: 1 mg Total dose: 3.5-7.5 mg

i.v Initial dose: 0.5-1 mg Titration doses: 0.5-1 mg Total dose: <3.5 mg

Anaesthesia premedication

i.v. 1-2 mg repeatedi.m. 0.07-0.1 mg/kg

i.v. Initial dose: 0.5 mg Slow uptitration as needed

i.m. 0.025-0.05 mg/kg



P.165



Mid

azol

am in

ject

ion

(2)

Short-acting sleep-inducing drug

DOSE / DOSE ADJUSTMENTS:

Indications Adults <60 y Adults ≥60 y/debilitated or chronically ill

Anaesthesia induction i.v. 0.15-0.2 mg/kg (0.3-0.35 without premedication)

i.v. 0.05-0.15 mg/kg (0.15-0.3 without premedication)

Sedative component in combined anaesthesia

i.v. Intermittent doses of 0.03-0.1 mg/kg or continuous infusion of 0.03-0.1 mg/kg/h

i.v. Lower doses than recommended for adults <60 years

Sedation in ICU i.v. LD: 0.03-0.3 mg/kg in increments of 1-2.5 mg MD: 0.03-0.2 mg/kg/h


P.166




adjustmentsComments

Long-acting benzodiazepines

Bro

maz

epam

Insomnia, short-term treatment of anxiety or panic attacks

1.5-3 mg oral up to TID

If a severe condition: 6-12 mg oral BID or TID

Elderly or hepatic impairment: lower doses are recommended

Contraindicated if myasthenia gravis, severe hepatic impairment, severe respiratory insufficiency, sleep apnoea syndrome

Clo

baza

m

Anxiety, adjunctive therapy in epilepsy

Anxiety: 20-30 mg oral daily in divided doses or as a single dose given at night. Doses up to 60 mg daily have been used in severe anxiety

Epilepsy: starting dose of 20-30 mg oral per day, increasing up to a max of 60 mg daily

Elderly: lower doses may be used

Chronic or acute severe respiratory insufficiency, renal or hepatic impairment: lower doses are recommended

Contraindicated if history of drug or alcohol dependence, myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment

P.167




adjustmentsComments


Clo

naze

pam

Epileptic disease and seizures

Oral: Initial dose not to exceed 1 mg/day; MD: 4-8 mg

i.v.: 1 mg by slow injection or slow infusion. Repeat dose if needed (1-4 mg are usually sufficient)

Elderly: initial dose should not exceed 0.5 mg/day

Chronic pulmonary insufficiency, renal or mild-moderate hepatic impairment: may require lower doses

Contraindicated if acute pulmonary insufficiency, severe respiratory insufficiency, sleep apnoea syndrome, myasthenia gravis, severe hepatic insufficiency, coma or in patients known to be abusing pharmaceuticals, drugs or alcohol

Clo

raze

pate

ora

l Anxiety, insomnia

5-30 mg oral at bedtime or in divided doses

Elderly, renal and hepatic impairment: lower doses may be required

Contraindicated if myasthenia gravis, severe decompensated respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment

Caution if alcohol deprivation, give thiamine before administering glucose containing i.v. fluids

P.168




adjustmentsComments


Clo

raze

pate

in

ject

ion

Agitation, confusion, aggressiveness, premedication, tetanus, alcoholism

Agitation, confusion, aggressiveness: 20-200 mg/day, i.m./i.v. followed by oral therapy

Premedication: 20-50 mg/day i.m./i.v. Alcoholism: 50-100 mg every 3-4h

Benign tetanus (without tracheostomy) 120-500 mg/day i.v.

Malignant tetanus (with tracheostomy and assisted ventilation): 500-2,000 mg/day i.v.

Elderly, renal and hepatic impairment: lower doses may be required

Contraindicated if myasthenia gravis, severe decompensated respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment

Caution if alcohol deprivation, give thiamine before administering glucose containing i.v. fluids

Ch

lord

iaze

pox

ide Anxiety,

muscle spasm, symptomatic relief of acute alcohol withdrawal

Anxiety: starting dose 5 mg/day oral: usual dose up to 30 mg in divided doses increasing to a max of 100 mg/day, in divided doses, adjusted on an individual basis

Insomnia associated with anxiety: 10-30 mg oral at bedtime

Muscle spasm: 10-30 mg/day oral in divided doses

Alcohol withdrawal: 25-100 mg, repeated if necessary, in 2-4h

Elderly and/or debilitated patients, renal or hepatic impairment: dosage should not exceed half the adult dose

Contraindicated if acute pulmonary insufficiency, sleep apnoea, respiratory depression, phobic and obsessional states, chronic psychosis, severe hepatic impairment, myasthenia gravis

P.169




adjustmentsComments


Dia

zepam

(1)

Anxiety 5-30 mg oral daily in divided doses or 10 mg i.v. or i.m. and repeated after an interval of not less than 4h

0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg

Elderly and debilitated patients: half of the recommended dose

Hepatic impairment and severe renal impairment: a lower dose is recommended

Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyriaInsomnia associated

with anxiety5-15 mg oral before retiring

Cerebral palsy 5-60 mg oral daily in divided doses

Upper motor neuronic spasticity

5-60 mg oral daily in divided doses

P.170




adjustmentsComments


Dia

zepam

(2

)

Muscle spasm 5-15 mg oral daily in divided doses or

10 mg i.v. or i.m. and repeated after after an interval of not less than 4h

0.5 mg/Kg rectal. Dose can be repeated every 4-12h. Max 30 mg



Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyria

Tetanus 0.1-0.3 mg/Kg i.v. and repeated every 1-4h; alternatively, a continuous infusion of 3-10 mg/kg/24h may be used.

0.5 mg/kg rectal. Dose can be repeated every 4-12h. Max 30 mg

P.171


9Sedatives and neuropsychiatric drugs (Cont.)


adjustmentsComments


Dia

zepam

(3

)

Epilepsy 2-60 mg oral daily in divided doses

or 10-20 mg i.v.or i.m. The dose can be repeated if necessary after 30-60min. If indicated, this may be followed by slow i.v. infusion (max total dose 3 mg/kg over 24h)

or 0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg



Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyria

Alcohol withdrawal 5-20 mg oral, repeated if necessary in 2-4h

0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg

Delirium tremens: 10-20 mg i.v. or i.m.

Premedication before surgery

5-20 mg oral

P.172





Flur

azep

am

Insomnia 15 mg oral at bedtime.

If severe insomnia: 30 mg oral but residual effects on awakening are more frequent at this dose

Elderly, chronic pulmonary insufficiency, renal or hepatic impairment: lower dose is recommended

Contraindicated if myasthenia gravis, severe pulmonary insufficiency, respiratory depression, phobic or obsessional states, chronic psychosis, sleep apnoea, severe hepatic insufficiency

Other sedatives

Clo

met

hia

zole

(1) Management of

restlessness and agitation in the elderly

192 mg (1 capsule) oral TID Elderly, renal impairment, gross liver damage, decreased liver function, sleep apnoea and chronic pulmonary insufficiency: caution

Contraindicated if acute pulmonary insufficiency

Alcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short term use

Severe insomnia in the elderly

192-384 mg oral (1-2 capsules) at bedtime

P.173




Other sedatives

Clo

met

hia

zole

(2

) INDICATIONS: Alcohol withdrawal INITIAL DOSE : 2-4 capsules oral, if necessary repeated after some hoursDay 1: first 24h: 9-12 capsules, divided into 3 or 4 doses

Day 2: 6-8 capsules, divided into 3 or 4 doses

Day 3: 4-6 capsules, divided into 3 or 4 doses

Days 4-6: A gradual reduction in dosage until the final dose

Administration for more than 9 days is not recommended

Elderly, renal impairment, gross liver damage, decreased liver function, sleep apnoea and chronic pulmonary insufficiency: caution

Contraindicated if acute pulmonary insufficiencyAlcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short term use

Dex

med

etom

idin

e Sedation of adult ICU patients

Switch to dexmedetomidine: initial i.v. infusion rate of 0.7 mcg/kg/hTitrate upwards to achieve desired level of sedation, range 0.2-1.4 mcg/kg/hMax dose: 1.4 mcg/kg/hMax duration: 14 days

Caution if hepatic impairment, impaired peripheral autonomic activity, pre-existing bradycardiaFrail patients: a lower starting infusion rate should be considered

The drug provides analgesia and does not cause respiratory depression. Associated with a lower prevalence of ICU delirium compared to benzodiazepines. Primary adverse effects are dose-related bradycardia and hypotension.Dexmedetomidine should not be administered by loading or bolus dose

P.174




Other sedatives

Dox

yla

min

e

Insomnia 12.5-25 mg oral at bedtime Max duration: 7 days

Renal and hepatic impairment: caution

Contraindicated if hypersensitive to other antihistaminesCaution if: asthma, narrow angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloric/duodenal obstruction, bladder neck obstruction, concurrent use with MAOIs

Mel

aton

in Insomnia in patients ≥55 years

2 mg oral at bedtimeMax duration: 13 weeks

Renal impairment: cautionHepatic impairment: not recommended

Do not use in patients with autoimmune diseasesDo not crush or chew tablets

Pro

pof

ol

Sedation during intensive care

Initiate at 5 mcg/Kg/min i.v. (0.3 mcg/Kg/h) and titrate to achieve sedation goals by 5 mcg/Kg/min every 5 minMaintenace rates of 5-50 mcg/Kg/min may be requiredAvoid prolonged infusions >50 mcg/Kg/min

Elderly: rate of infusion should be reduced. Rapid bolus administration is not indicated in this group of patients

Rapid onset (1-2 min) and short duration (3-5 min or longer if prolonged infusion)Avoid loading doses because of the risk of hypotensionMonitor blood lipid levels, blood pressurePropofol has no analgesic properties

P.175




Other sedatives

Zol

pide

m Insomnia 10 mg oral at bedtime

Max duration: 4 weeks

Elderly, debilitated patients, hepatic impairment: initial dose 5 mg

Contraindicated if obstructive sleep apnoea, myasthenia gravis, severe hepatic insufficiency, acute and/or severe respiratory depression

Zop

iclo

ne Insomnia 7.5 mg oral at bedtime

Max duration: 4 weeks

Elderly, hepatic or renal impairment: initial dose 3.75 mg

Contraindicated if myasthenia gravis, severe sleep apnoea syndrome, severe respiratory or severe hepatic insufficiency

P.176




adjustmentsComments

Neuroleptics: Extrapyramidal symptoms and neuroleptic malignant syndrome may occur with all neuroleptics. Elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated

Typical neuroleptics

Chlo

rpro

maz

ine

Schizophrenia and other psychoses

Oral: Initially 25 mg TID or 75 mg at bedtime increasing by daily amounts of 25 mg to an effective MD (75-300 mg daily, some patients may require up to 1g)

I.M.: 25-50 mg every 6-8h

Elderly (schizophrenia, nausea and vomiting): start with ⅓ - ½ usual adult dose

Contraindicated if liver or renal dysfunction, epilepsy, Parkinson, hypothyroidism, cardiac failure, phaeochromocytoma, agranulocytosis myasthenia gravis, prostate hypertrophy, history of narrow angle glaucoma

Caution in patients with risk factor for stroke, seizures, cardiovascular disease or a family history of QT prolongation

Intractable hiccup Oral: 25-50 mg TID or QD

I.M.: 25-50 mg and if this fails 25-50 mg by slow i.v. infusion

Nausea and vomiting in terminal illness

Oral: 10-25 mg every 4-6h

I.M.: 25 mg initially then 25-50 mg every 3-4h until vomiting stops, then change to orally

P.177




adjustmentsComments


Flu

phen

azin

e

Schizophrenia and other psychoses

Patients without previous exposure of fluphenazine: start 12.5 mg i.m Next dose depends on patient’s response (12.5-100 mg)

When administered as maintenance therapy, a single injection may be effective for up to 4weeks or longer

Elderly (over 60): a lower dose is recommended

Liver and renal disease: caution

Contraindicated if comatose states, marked cerebral atherosclerosis, liver failure, renal failure, phaeochromocytoma, severe cardiac insufficiency, severely depressed states, existing blood dyscrasias

Caution if arrythmias, Parkinson, narrow angle glaucoma, thyrotoxicosis, hypothyroidism, epilepsy, myasthenia gravis, prostatic hypertrophy, severe respiratory disease

P.178





Hal

oper

idol

ora

l (1)

Schizophrenia, psychoses and mania

Acute phase: 2-20 mg/day oral as a single dose or in divided doses

Chronic phase: 1-3 mg oral TID, may be increased up to 20 mg/day in divided doses, depending on the response

Max daily dose: 20 mg

DOSE ADJUSTMENTS:

Elderly: start with half the dosage stated for adults and adjusted according to the results if necessary

COMMENTS: Contraindicated if comatose states, CNS depression, Parkinson, lesions of the basal ganglia, clinical significant cardiac disorders, QT interval prolongation, history of ventricular arrhythmia or Torsades de pointes, clinically significant bradycardia, 2nd or 3rd degree heart block, uncorrected hypokalaemia and use of other QT prolonging drugs

Caution if renal failure, liver disease, epilepsy, hyperthyroidism, phaeochromocytoma

Bioavailability from the oral route is about 60% of that from the i.m. route and readjustment of dose may be required i.v. haloperidol can be associated with QT prolongation and torsades de pointes

Psychomotor anti-agitation

Acute phase: Moderate symptomatology 1.5-3.0 mg oral BID or TID

Severe symptomatology/resistant patients 3-5 mg oral BID or TID

Chronic phase: 0.5-1 mg oral TID, may be increased to 2-3 mg TID, if required, MD: gradually reduced to the lowest effective MD

Max daily dose: 20 mg

P.179





Hal

oper

idol

or

al (

2)

Gilles de la Tourette syndrome, severe tics, intractable hiccup

Starting dose 1.5 mg oral TID adjusted according to responseA daily MD of 10 mg may be required in Gilles de la Tourette syndromeMax daily dose: 20 mg

DOSE ADJUSTMENTS:Elderly: start with half the dosage stated for adults and adjusted according to the results if necessary

COMMENTS: Contraindicated if comatose states, CNS depression, Parkinson, lesions of the basal ganglia, clinical significant cardiac disorders, QT interval prolongation, history of ventricular arrhythmia or Torsades de pointes, clinically significant bradycardia, 2nd or 3rd degree heart block, uncorrected hypokalaemia and use of other QT prolonging drugs

Caution if renal failure, liver disease, epilepsy, hyperthyroidism, phaeochromocytoma

Bioavailability from the oral route is about 60% of that from the i.m. route and readjustment of dose may be required i.v. haloperidol can be associated with QT prolongation and torsades de pointes H

alop

erid

ol in

ject

ion

Rapid control of the symptoms of hostility, aggression, hyperactivity, disruptive and violent behaviour, confusion, emotional withdrawal, hallucinations and delusions associated with acute and chronic schizophrenia, mania, and hypomania, and organic brain syndrome Nausea and vomiting

Initial doses of 2-10 mg i.m.Depending on the response of the patients, subsequent doses may be given every 4-8h up to a max of 18 mg/day

P.180





Lev

om

epro

mazin

e

Management of pain, restlessness or distress in terminally ill patient

12.5-25 mg i.m. or i.v. injection. In cases of severe agitation, up to 50 mg may be used, repeated every 6-8hor25-200 mg/day by continuos s.c. infusionor12.5-50 mg oral every 4-8h

Elderly: caution Caution if liver dysfunction or cardiac disease, bradycardia or 2nd or 3rd degree heart block, risk of QT interval prolongation

Psychiatric conditions

Bed patients: initially the total daily dose 100-200 mg oral, usually divided into 3 doses, gradually increased to 1g daily if necessary

Per

icya

zine

Anxiety, psichiatric conditions

Severe conditions: Initially 75 mg/day oral in divided doses. Titrate according to patient response at weekly intervals; MD: max dose 300 mg/dayMild or moderate conditions: Initially 15-30 mg/day oral divided in two doses, with a larger dose being given in the evening

ElderlySevere conditions: Initially 15-30 mg/day in divided doses Mild or moderate conditions: start 5-10 mg/day. Half or quarter the normal adult dose may be sufficient as MD

Caution if liver or renal dysfunction, epilepsy, Parkinson, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostrate hypertrophy, history of narrow angle glaucoma, agranulocytosis, risk of QT interval prolongationDiscontinue if unexplained fever

P.181





Per

ph

enazin

e

Anxiety, psichiatric conditions, nausea and vomiting, intractable hiccup

DOSE: 4 mg oral TID. Titrate according to patient response. Max daily dose: 24 mg

DOSE ADJUSTMENTS: Elderly: one quarter or one half of the recommended adult dosage

COMMENTS: Contraindicated if leucopenia, or in association with drugs liable to cause bone marrow depression, or to patients in comatose states - Caution if liver disease, severe respiratory disease, renal failure, epilepsy, Parkinson, history of narrow angle glaucoma, hypothyroidism, myasthenia gravis, phaeochromocytoma, prostatic hypertrophy, risk of QT interval prolongation

Pim

ozid

e

Schizophrenia, other psychoses

DOSE: Chronic schizophrenia: 2-20 mg oral daily, with 2 mg as a starting dose

This may be increased according to response and tolerance

Other psychoses: an initial dose of 4 mg oral daily which may then be gradually increased, if necessary, according to response, max 16 mg daily

DOSE ADJUSTMENTS: Elderly: half the normal starting dose

Caution if hepatic, renal impairment or phaeochromocytoma

COMMENTS: Contraindicated if risk of QT interval prolongation, known uncorrected hypokalaemia, hypomagnesaemia, clinically significant cardiac disorders, clinically significant bradycardia, severe central nervous system depression, depression, Parkinson, concomitant use with CYP3A4 or CYP2D6 inhibiting drugs, serotonin uptake inhibitors

P.182





Trif

luoper

azin

e Anxiety, depressive symptoms, agitation, nausea and vomiting

Low dosage: 2-4 mg/day oral, given in divided doses, according to the severity of the patient’s condition

High dosage: 5 mg oral BID, after a week this may be increased to 15 mg/day. If necessary, further increases of 5 mg may be made at three-day intervals

DOSE ADJUSTMENTS: Elderly: starting dose should be reduced by at least half

COMMENTS: Contraindicated if comatose patients, existing blood dyscrasias or known liver damage, uncontrolled cardiac decompensation

Caution if CV disease , Parkinson, risk of QT interval prolongation

Zu

clopen

thix

ol

Acute psychoses 50-150 mg i.m., repeated if necessary after 2-3 days

Some patients may need an additional injection between 1-2 days after the first injection

Max accumulated dosage: 400 mg

DOSE ADJUSTMENTS: Elderly, renal or hepatic impairment: caution, a lower dose may be necessary

COMMENTS: Contraindicated if circulatory collapse, depressed level of consciousness

Caution if Parkinson, epilepsy, risk of QT interval prolongation, cardiac disease, or arrhythmias, narrow angle glaucoma, myasthenia gravis, prostatic hypertrophy, hypothyroidism, hyperthyroidism, phaeochromocytoma

P.183




Atypical neuroleptics: 3 differences with typical neuroleptics: the risk of extrapyramidal symptoms is lower, tardive dyskinesia is reduced and the ability to block serotonin-2 receptors is present. Atypical neuroleptics have been associated with new-onset diabetes and metabolic syndrome

Am

isulp

ride

Schizophrenia For acute psychotic episodes: 400-800 mg/day oral In individual cases, the daily dose may be increased up to 1,200 mg/day

Doses should be adjusted individually

Administered QD at oral doses up to 300 mg, higher doses BID

Elderly: caution

CrCl 30-60 ml/min: reduce to a half

CrCl 10-30 ml/min: reduce to a third

Contraindicated if concomitant prolactin-dependent tumours, phaeochromocytoma, combination with levodopa

Caution if epilepsy, risk of QT interval prolongation

Ase

nap

ine Severe manic

episodes associated with bipolar type I disorder

5 mg s.l. BID The dose can be increased to 10 mg BID based on individual clinical response and tolerability

Elderly, moderate hepatic impairment: caution

Caution if Parkinson, risk of QT interval prolongation, seizures

Do not use in severe hepatic impairment or CrCl <15ml/min

Do not chew or swallow tablets

P.184




Atypical neuroleptics

Ari

pipr

azol

e

Schizophrenia, manic episodes in bipolar type I disorder

Oral: 10-15 mg QD with a MD of 10-30 mg QDi.m.: Recommended initial dose: 9.75 mg Dose range: 5.25-15 mgA second injection may be administered 2h after the first injection, on the basis of individual clinical status and no more than three injections should be given in any 24h periodMax daily dose: 30 mg/day

Caution if elderly, severe hepatic impairment

Orodispersible tablet should be placed in the mouth, it will rapidly disperse in salivaCaution if known CV disease, history of QT prolongation, epilepsy, concomitant administration of potent CYP3A4 or CYP2D6 inhibitors

Ola

nza

pine

Psichiatric conditions

Schizophrenia: recommended starting dose 10 mg/day orally

Manic episode: Starting dose 15 mg QD oral in monotherapy or 10 mg QD in combination therapy. Then, adjust dose according to response: 5-20 mg/day

Elderly, renal or hepatic impairment: consider a lower starting dose (5 mg/day)

Contraindicated if risk of narrow-angle glaucomaCaution if Parkinson, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongationOrodispersible tablet should be placed in the mouth, it will rapidly disperse in saliva

P.185





Pal

iper

idon

e

Schizophrenia, schizoaffective disorder

6 mg oral QD, administered in the morning. Some patients may benefit from lower or higher doses within the recommended range of 3-12 mg QD (6-12 mg for schizoaffective disorder)

Caution if elderly patients with dementia with risk factors for stroke

Mild renal impairment: initial dose 3 mg QD (max 6 mg)

Moderate-severe renal impairment: initial dose 1.5 mg QD (max 3 mg)

CrCl <10 ml/min: not recommended

Caution if severe hepatic impairment, seizures, Parkinson, risk of QT interval prolongation, low leukocyte and/or neutrophil counts for any reason, known CV disease, cerebrovascular disease or conditions that predispose the patient to hypotension

Do not chew, divide, or crush

Take it the same way with regard to meals

P.186




adjustmentsComments


Quet

iapi

ne

Schizophrenia IRF: Total daily dose for the first 4 days is: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4), then 150-750 mg/day Administered in 2 divided doses PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2 MD: 400-800 mg/day

DOSE ADJUSTMENTS: Elderly, hepatic impairment: caution, a lower dose may be necessary

COMMENTS: Contraindicated if concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone

Caution if low leukocyte and/or neutrophil counts for any reason, history of seizures, cerebrovascular disease, cardiovascular disease, risk of QT interval prolongation

It could be used if Parkinson disease

PRF: tablets should not be split, chewed or crushed

Moderate-severe manic episodes in bipolar disorder

IRF: Total daily dose for the first 4 days is: 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3) and 400 mg (Day 4) Further dosage adjustments up to 800 mg/day Administered in 2 divided doses PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2 MD: 400-800 mg/day

Depression in bipolar disorders

IRF: Total daily dose for the first 4days is: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4) The recommended daily dose is 300 mg Administered at bedtimePRF: Total daily dose for the first 4 days is: 50 mg oral (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4) Recommended daily dose: 300 mg

Major depressive episodes

PRF: 50 mg on Day 1 and 2, and 150 mg on Day 3 and 4 at bedtimeMax dose 300 mg/day

P.187





Ris

peri

done

(1)

Schizophrenia Start 2 mg/day oral (QD or in 2 divided doses)

The dosage may be increased on the 2nd day to 4 mg

MD: 4-6 mg

Elderly: 0.5 mg BID

Caution if renal or hepatic impairment

Caution if known cardiovascular disease, low leukocyte and/or neutrophil counts for any reason, Parkinson, risk of QT interval prolongation

Orodispersable tablet: place the tablet on the tongue

Manic episodes in bipolar disorder

Start with 2 mg oral QD

Dosage adjustments, if needed, should occur at intervals of not less than 24h and in dosage increments of 1 mg/day. Max daily dose 6 mg

Elderly: start with 0.5 mg BID

This dosage can be individually adjusted with 0.5 mg BID increments to 1-2 mg BID


Persistent aggression in patients with moderate to severe Alzheimer’s dementia

Start with 0.25 mg oral BID

This dosage can be individually adjusted by increments of 0.25 mg BID, not more frequently than every other day, if needed. Optimum dose is 0.5 mg BID for most patients


P.188





Ris

peri

done

(2) Conduct disorder ≥50kg: starting dose 0.5 mg oral QD

This dosage can be individually adjusted by increments of 0.5 mg QD not more frequently than every other day, if needed. Optimum dose is 1 mg QD for most patients<50kg: starting dose 0.25 mg oral QD This dosage can be individually adjusted by increments of 0.25 mg QD not more frequently than every other day, if needed. Optimum dose is 0.5 mg QD


Caution if known cardiovascular disease, low leukocyte and/or neutrophil counts for any reason, Parkinson, risk of QT interval prolongationOrodispersable tablet: place the tablet on the tongue

Sulp

irid

e

Acute and chronic schizophrenia

Starting dose: 400-800 mg oral daily, given as one or two tablets twice daily (morning and early evening)Predominantly positive symptons: starting dose of at least 400 mg oral BID, increasing if necessary up to a max of 1,200 mg BIDPredominantly negative symptoms respond to doses below 800 mg oral daily, a starting dose of 400 mg BID is recommendedPatients with mixed positive and negative symptoms: 400-600 mg oral BID

Renal impairment: caution

Contraindicated if phaeochromocytoma and acute porphyria, concomitant prolactin-dependent tumours, association with levodopa or antiparkinsonian drugsCaution if Parkinson, epilepsy, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongation

P.189





Tia

prid

e

Behavioral disorders in dementia patients

Starting dose 50 mg oral/i.m./i.v. BID, increasing if necessary to 100 mg TID

Max dose 400 mg/day

Elderly: caution

CrCl 30-60 ml/min: 75% of the normal dose

CrCl 10-30 ml/min: 50% of the normal dose

CrCl <10 ml/min: 25% of the normal dose

Contraindicated if phaeochromocytoma, concomitant prolactin-dependent tumours, association with levodopa or antiparkinsonian drugs

Caution if epilepsy, Parkinson, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongation

Huntington’s disease 1,200 mg/day oral/i.m./i.v. divided in 3 doses

Progressive reduction to a MD

Zip

rasi

done

Schizophrenia

Bipolar type I disorder

Initial dose 40 mg oral BID with food Then, dose may be increased to 60-80 mg BID

Max dose 80 mg BID

Elderly, renal or hepatic impairment: caution, a lower dose may be necessary

Contraindicated if known history of QT prolongation, decompensated heart failure, recent MI

It could the parenteral drug of choice for patients with Parkinson disease

Acute treatment of agitation in schizophrenia

10-20 mg i.m. administered as required up to a max dose of 40 mg/day

Doses of 10 mg may be administered every 2h

P.190



APTT = Activated partial thromboplastin timeAB = Airway and breathingABG = Arterial blood gasAADs = Antiarrhythmic drugsAAS = Acute aortic syndromeACEI = Angiotensin converting enzyme inhibitorACLS = Advanced cardiovascular life supportACS = Acute coronary syndromeACT = Activated clotting timeAD = Aortic DissectionAED = Automated external defibrillator AF = Atrial fibrillationAo = Aortic aPTT = Activated partial thromboplastin timeARB = Angiotensin receptor blockersAS = Aortic stenosisAV = Atrioventricular AVN = Atrioventricular nodeAVNRT = Atrioventricular nodal re-entrant

tachycardiaAVNT = Atrioventricular nodal tachycardiaBID = Twice a dayBBB = Bundle branch block

BLS = Basic life support BNP = Brain natriuretic peptideBP = Blood pressureCABG = Coronary artery bypass graftingCAD = Coronary artery diseaseCath Lab = Catheterisation laboratoryCCB = Calcium channel blockers CCU = Coronary care unitCHF = Congestive heart failureCMR = Cardiovascular magnetic resonanceCOPD = Chronic obstructive pulmonary diseaseCPAP = Continuous positive airway pressure CPR = Cardiopulmonary resuscitationCr = Creatinine blood level (mg/dL)CrCl = Creatinine clearanceCS = Cardiogenic shockCSM = Carotid sinus massage CSNRT = Corrected sinus node recovery timeCSS = Carotid sinus syndromeCT = Computed tomographyCT-angio = Computed tomography angiographycTn = Cardiac troponinCUS = Compression venous ultrasound

P.191

Abbreviations

CV = CardiovascularCVA = Cerebrovascular accident CXR = Chest X-rayDAPT = Dual antiplatelet therapyDD = Dyastolic dysfunctionDM = Diabetes mellitusdTT = Diluted thrombin time DVT = Deep vein thrombosis ECG = ElectrocardiogramECT = Ecarin clotting time ED = Emergency department EG = ElectrogramseGFR = Estimated glomerular filtration rate

(ml/min/1.73 m2) EMB = Endomyocardial biopsyEMS = Emergency medical servicesEPS = Electrophysiological study ERC = European Resuscitation CouncilESR = Erythrocyte sedimentation rate ETT = Exercice treadmill testing FFP = Fresh frozen plasmaFMC = First medical contact

GER = Gastroesophageal refluxGFR = Glomerular flow rateGI = GastrointestinalGP = GlycoproteinHb = haemoglobinHF = Heart failureHIT = Heparin-induced thrombocytopeniaHOCM = Hypertrophic obstructive cardiomyopathy HTN = Hypertension HR = Heart ratehsTn = High-sensitive troponinIABP = Intra-aortic balloon pump ICC = Intensive cardiac careICCU = Intensive cardiac care unitICD = Implantable cardioverter defibrillatorIHD = Ischemic heart diseaseIMH = Intramural hematomaIRF = Immediate-release formulationISFC = International Society and Federation

of Cardiologyi.o. = Intraosseous IV = Invasive ventilation

P.192

Abbreviations (Cont.)

i.v. = IntravenousKD = Kidney diseaseLBBB = Left bundle branch blockLD = Loading doseLGE = Late gadolinium enhancement LMWH = Low-molecular weight heparinLOC = Loss of consciousness LV = Left ventricularLVD = Left ventricular dysfunctionLVEF = Left ventricular ejection fraction LVH = Left ventricular hypertrophyLVSD = Left ventricular systolic dysfunctionMCS = Mechanical circulatory support MD = Maintenance doseMDCT = Computed tomography with >4 elementsMI = Myocardial infarctionMRA = Mineralocorticoid receptor antagonistMRI = Magnetic resonance imagingMvo = Microvascular obstructionNIV = Non-invasive ventilationNOAC = New oral anticoagulantsNSAID = Non-steroidal anti-inflammatory drugs

NSTE-ACS = Non ST-segment elevation acute coronary syndrome

NSTEMI = Non ST-segment elevation myocardial infarction NTG = NitroglycerinNT-proBNP = N-terminal pro brain natriuretic

peptideNVAF = Non-valvular atrial fibrillationNYHA = New York Heart AssociationOH = Orthostatic hypotensionPAP = Pulmonary arterial pressurePAU = Penetrating aortic ulcer PCI = Percutaneous coronary interventionPCM = Physical counter-measures PCP = Pulmonary capillary pressurePE = Pulmonary embolismPEA = Pulmonary endarterectomyPEEP = Positive end expiratory pressurePPC = Prothrombin complex concentratePR = Pulmonary regurgitationPRECISE-DAPT = PREdicting bleeding Complications

In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy

P.193


PRF = Prolonged-release formulationProCT = ProcalcitoninPRN = Pro re nata PS-PEEP = Pressure support-positive end-

expiratory pressure PSVT = Paroxysmal supraventricular tachycardiaQD = Once a dayQPM = Every eveningrFVIIa = Recombinant factor VIIartPA = Recombinant tissue plasminogen activatorRV = Right ventricularRVOT-VT = Right ventricular outflow tract

ventricular tachycardiaSBP = Systemic blood pressures.c = SubcutaneousSIRS = systemic inflammatory response syndrome SLE = Systemic lupus erythematosusSMU = Syncope management unitsSTE-ACS = ST-segment elevation acute

coronary syndromeSTEMI = ST-segment elevation myocardial

infarction

SVT = Supraventricular tachycardiaSpo2 = Oxygen saturation TEE = Transesophageal echocardiographyTEVAR = Thoracic endovascular aortic repair TIA = Transient ischemic attack TID = Three times a dayTLOC = Transient loss of consciousnessTOE = Transoesopageal echocardiographyTSH = Thyroid-stimulating hormone TTE = Transthoracic echocardiographyUA = Unstable anginaUFH = Unfractionated heparinULN = Upper limit of normalVF = Ventricular fibrillationVR = Vascular resistanceVT = Ventricular tachycardia VTE = Venous thromboembolismVVS = Vasovagal syncopeWBC = white blood cell count WHO = World Health OrganizationWPW = Wolff-Parkinson-White

P.194


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P.195

Notes

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P.196

Notes

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Reproduced With permission of Oxford University Press (UK) © European Society of Cardiology

Habib G, et al. 2015 ESC Guidelines for the management of infective endocarditis. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv319.

Priori, SG, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv316 .

Adler Y, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv318 .

Roffi M, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv320 .

Erbel R, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. European Heart Journal Aug 2014, DOI: 10.1093/eurheartj/ehu281 .

Konstantinides SV, et al. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. European Heart Journal Nov 2014, 35 (43) 3033-3073; DOI: 10.1093/eurheartj/ehu283.

Lip GYH, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). European Heart Journal Dec 2014, 35 (45) 3155-3179; DOI: 10.1093/eurheartj/ehu298.

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References and copyright acknowledgments (Cont.)

Windecker S, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization. European Heart Journal Oct 2014, 35 (37) 2541-2619; DOI: 10.1093/eurheartj/ehu278.

Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. European Heart Journal (2013); July 3. DOI: 10.1093/eurheartj/eht210.

McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. European Heart Journal (2012) DOI: 10.1093/eurheartj/ehs104.

Steg G, James SK Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal (2012); DOI: 10.1093/eurheartj/ehs215.

Steg PG, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal Oct 2012, 33 (20) 2569-2619; DOI: 10.1093/eurheartj/ehs215.

Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, et al. ESC Guidelines for the diagnosis and management of syncope. European Heart Journal (2009); DOI:10.1093/eurheartj/ehp298.

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This is a publication of the Acute Cardiovascular Care Association (ACCA), a branch of the European Society of Cardiology. Its content reflects the opinion of the authors based on the evidence available at the time it was written and does not necessarily imply an endorsement by ACCA or the ESC.

The guidance suggested in the Clinical Decision Making Toolkit does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.

Some content, illustrations/tables/figures were inspired and/or adapted from ESC Guidelines and other existing sources, with permission granted by the original publishers.

AcknowledgementsWe are indebted to all the authors for their commitment and for the strong effort to synthesise their wide scientific knowledge and clinical experience into simple algorithms and schemes using the aim to help clinicians in everyday clinical practice in the easiest possible manner as the main driver of their work.

The support of this initiative by the ACCA board members was essential to launch this initiative as was the hard work of the ESC staff to make this project move forward.

January 2018

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