GP symposium

2 April 2016

Dr Dinna Soon

Consultant Cardiologist, Department of Cardiology

Case presentation

• 76 years old male, chronic smoker, hypertension, previous MI

• 3/7 SOB and chest tightness

• BP : 170/90

• CVS- no murmur

• Chest -few wheeze

• ECG- sinus tachycardia, Q waves in anterior leads.

• CXR- ?Cardiomegaly, hyper inflated lungs, increased broncho- vascular markings.

• Normal initial lab results

Diagnostic Dilemma

• 1.ACS

• 2.Acute exacerbation of COPD

• 3. Acute PE

• 4. Acute Heart Failure (LVF)

Aspirin + Bronchodilator + Clexane + Diuretic

( ‘ABCD’ treatment)

More information…

• Orthopnoea, PND

• Cold peripheries, leg swelling, fine inspiratory crackles at lung bases , JVP elevated 6cm

• S3 Gallop

• BNP – markedly elevated

• ECHO- Dilated LV , severe LV systolic dysfunction- EF 20%

Organs that may be involved in development of shortness of breath

Biykem Bozkurt, and Douglas L. Mann Circulation.

2003;108:e11-e13

Lungs:

Asthma/COPD/Emphysema

Pneumonia

Pneumothorax

Cancer

Pulmonary embolism

Asbestosis/ systemic illness

(Rheumatoid arthritis)

Heart:

Heart failure

Angina equivalent

Systemic illness:

Anaemia

Hyperthroidism

Renal failure/liver failure

Nervous and

Musculoskeletal system:

Brain tumour/stroke

Muscle disorders

Heart Failure

• “A complex clinical syndrome that can result from any

structural or functional cardiac disorder that impairs the ability

of the ventricle to fill with or eject blood”

-American Heart Association and American College of Cardiology

Hunt SA et al.2009.Circulation.2009;119(14):e391-e479

Accuracy of Initial Evaluation Findings in Diagnosing Heart Failure

Ruling in Heart Failure

Michael K. Am Fam Physician.2012;85(12):1161-1168

Framingham Diagnostic Criteria for Heart Failure

• Paroxysmal nocturnal dyspnea/orthopnoea

• Neck vein distension

• Rales

• Cardiomegaly

• Acute pulmonary oedema

• S3 gallop

• Hepatojugular reflux

• Ankle edema

• Dyspnea on exertion

• Hepatomegaly

• Nocturnal cough

• Pleural effusion

• Tachycardia (>120 beats per

minute)

• Major Criteria • Minor Criteria

Heart failure is diagnosed when 2 major criteria or 1 major and 2 minor criteria are met

Patrick A. McKee et al. The Natural History of Congestive Heart Failure: The

Framingham Study.N Engl J Med 1971; 285:1441-1446

• To validate Framingham diagnostic criteria using echocardiography as the reference standard

to diagnose heart failure

• Framingham clinical criteria - very sensitive for systolic HF (92% compared with 89% for

diastolic HF) and moderately specific (79%)

• Absence of the Framingham clinical criteria rules out the diagnosis of HF

• However the presence of these criteria do not necessarily confirm the diagnosis, which may be

based in echocardiography Journal of Evaluation in Clinical Practice.2009;15(1):55-61

BNP & NT-pro BNP

• Secreted by atria and ventricles in response to stretching or increased wall tension1

• Normal BNP/NT-pro BNP effectively rules out HF2 (high negative predictive value)

No HF Further evaluation HF

BNP < 100 (NNV 96%) 100-400 > 400

NT-pro BNP <400 (NNP99%) 400-2000 >2000

Levels in pg/ml

1.Chen WC. Biomarkers in heart failure.Heart 2010;96(4):314-320

2.Balion C et al. Evid Rep Technol Assess 2006;(142) 1-147

3.Han-Na Kim et al. Natriuretic Peptide testing in HF.Circulation

2011;123: 2015-2019

WHO ARE AT RISK?

Risk Factors for Heart Failure

• Coronary artery

disease

• Hypertension (LVH)

• Valvular heart disease

• Alcoholism

• Infection (viral)

• Diabetes

• Congenital heart defects

• Other:

– Obesity

– Age

– Smoking

– Obstructive Sleep Apnea

Evaluation for IHD

• Warranted in patients with HF, especially if angina is present, given that

CAD is the cause for HF in approximately two-thirds of the patients1

• Coronary angiography has been shown to improve symptoms and

survival in patients with angina and reduced ejection fraction 2

1.Ghoerghiade M et al. Chronic HF in US: a manifestation of CAD.

Circulation.1998;97(3):282-289

2.Hunt SA et al.2009 focused update incorporated into the ACC/AHA

2005 guidelines for diagnosis and management of HF in

adults.Circulation.2009;119(14):e391-e479

MK et al. American

Family

Physician.2012;85(12):11

61-1168

Identify alternative/reversible

causes and treat Suspected Heart Failure

Framingham criteria not met

OR

Normal BNP

Referral and approach to care NICE (UK) GUIDELINES

• Refer patients to the specialist multidisciplinary heart failure team in the

following situations:

• Initial diagnosis of heart failure

• Management of severe heart failure (NHYA III-IV)

• Heart failure not responding to treatment

• Heart failure due to valve disease

• Patient who is pregnant or planning to get pregnant

NICE UK 2010 Chronic HF in adults

TREATMENT

Entresto: enhancement of natriuretic and other vasoactive peptides, with simultaneous RAAS suppression

Current therapies are unable to fully address neurohormonal imbalance

in Heart Failure:

ENTRESTO is a new alternative to an ACEI or ARBs in patients with HFrEF1

1. McMurray et al. Eur J Heart Fail 2013;15:1062–73

Figure references: Levin et al. N Engl J Med 1998;339:321–8 Nathisuwan & Talbert. Pharmacotherapy

2002;22:27–42

Kemp & Conte. Cardiovascular Pathology 2012;365–71

Schrier & Abraham. N Engl J Med 2009;341:577–85

SNS

RAAS

Vasoconstriction Blood pressure

Sympathetic tone Aldosterone Hypertrophy

Fibrosis

Ang II AT1R

HF SYMPTOMS &

PROGRESSION

INACTIVE

FRAGMENTS

NP system

Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy

NPRs NPs

Epinephrine

Norepinephrine α1, β1, β2

receptors

Vasoconstriction RAAS activity

Vasopressin Heart rate

Contractility

Neprilysin

inhibitors

RAAS inhibitors

(ACEI, ARB, MRA)

β-blockers

ENTRESTO

NEJM SEP 2014. 371;11

20 21 20 % reduction in

CV death or HF

hospitalization

P<0.001

% reduction in HF

hospitalization

P<0.001

% reduction in

CV mortality

P<0.001

PARADIGM-HF: Efficacy of ENTRESTO over Enalapril

% reduction in all-cause mortality

p<0.001 16

LCZ696 superior to enalapril in reducing

symptoms and physical limitations of HF

(indicated by KCCQ score)

KCCQ, Kansas City Cardiomyopathy Questionnaire

Impact of ENTRESTO in improving QoL in HF Patients

Death imputed as zero. The analysis included all patients with at least one KCCQ data point

Significantly fewer patients treated with Entresto had a 5-point deterioration in KCCQ

scores at Month 8, compared with enalapril and the effect was consistent for all sub-

domains of KCCQ; also the effect was consistent at Months 8, 12 and 24.1

Summary

• Heart failure is primarily a clinical diagnosis.

• The initial evaluation of patients with SOB/suspected HF should include a

history and physical examination, laboratory assessment, CXR and ECG.

ECHO can confirm the diagnosis.

• A displaced cardiac apex, a third heart sound, and CXR findings of

pulmonary venous congestion or interstitial edema are good predictors to

rule in the diagnosis of HF

• Systolic heart failure can be effectively ruled out with a normal B-type

natriuretic peptide or N-terminal pro-B-type natriuretic peptide level

• Systolic heart failure can be effectively ruled out when Framingham

criteria are not met.

• Current treatments (beta-blocker, ACEi/ARB, MRA) mainly focus on

blocking the detrimental effects of neurohormonal activation, and largely

ignore the physiological compensatory effect of the natriuretic peptide

system.

• Inhibition of neprilysin (ARNI) results in an increase in the activity of

natriuretic peptides and other vasoactive peptides that can potentially

exert favourable long-term compensatory effects.

THANK YOU