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Best wishes to YOU. Heart Failure Basics to Recent Advances. Dr. R.V.S.N. Sarma., M.D., M.Sc.(Canada), FIMSA Consultant Physician and Cardiometabolic Specialist. Definition, Etiology Epidemiology and Pathophysiology. Floor Plan of This Talk. - PowerPoint PPT Presentation

Transcript of Best wishes to YOU

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Best wishes to YOUBest wishes to YOU

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Heart Failure Basics to Recent Advances

Heart Failure Basics to Recent Advances

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Definition, Etiology

Epidemiology and

Pathophysiology

Definition, Etiology

Epidemiology and

Pathophysiology

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Floor Plan of This TalkFloor Plan of This Talk

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“The very essence of

cardiovascular practice is early

detection of Heart Failure”

“The very essence of

cardiovascular practice is early

detection of Heart Failure”

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HF is a ‘BIG’ SubjectHF is a ‘BIG’ Subject

• It afflicts millions of people worldwide

• Has many diverse causes and risk factors

• Large number of Mega trials and literature

• High mortality; Several drugs and devices

• A paradigm shift in understanding & Rx.

• Extremely costly – huge no. of bed days

• Complicated by many co morbidities

• Truly multidisciplinary in its management

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Detection of Heart FailureDetection of Heart Failure

About half of the patients with left

ventricular dysfunction had no symptoms

and therefore would be difficult to identify at

this early stage by clinical examination

alone – underscoring the need for

echocardiography.

Framingham Heart Study has been the most

important longitudinal source of data on the

epidemiology of heart failure.

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Why HF is increasing ?Why HF is increasing ?

• Almost any disease of heart can cause it

• More of HT, DM, MS, Obesity - ASCVD

• CAD - which is its commonest cause

• Better tools for diagnosis and availability

• Better detection and treatment of causes

• Better Rx. of RF, CAD, MI - PTCA, CABG

• Increasing longevity of the population

• HF is an aging process – longer life span

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Important PointsImportant Points

• Chronic Heart Failure (CHF) can be caused by any type of cardiac dysfunction

• Most commonly attributable to LV Dysfunction

• Rarely HF is due to isolated RV dysfunction

• Most common and best studied cause of CHF is LV Systolic Dysfunction (LVSD)

• Normal Ejection Fraction Heart Failure (NEFHF) is due to LV Diastolic Dysfunction – (HFPSF)

• It is difficult to diagnose and quantify.

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Floor Plan of This TalkFloor Plan of This Talk

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Definitions of Heart FailureDefinitions of Heart Failure

Heart failure is a clinical syndrome characterized

by decreased systemic perfusion, inadequate to

meet the body's metabolic demands as a result of

impaired cardiac pump function - Cleveland Clinic

A pathophysiologic state in which an abnormality

of cardiac function is responsible for failure of the

heart to pump blood at a rate commensurate with

metabolic requirements of the tissues -E Braunwald

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Definition of HFDefinition of HF

Physiological:

Inability of the heart to pump sufficient oxygenated blood to the metabolizing tissues despite an adequate filling pressure.

Working Clinical Definition:

Clinical syndrome consisting of symptoms such as breathlessness, fatigue, and swelling of ankle caused by cardiac dysfunction.

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Types of Heart FailureTypes of Heart Failure

• Chronic Heart Failure (CHF)• Acute Heart Failure (Cardiogenic

Shock)• Systolic Failure (LVSD) – Reduced EFHF• Diastolic Heart Failure (LVDD) – NEFHF• Left Heart Failure (LVF)• Right Heart Failure (Congestive CCF)• Forward Failure and Backward Failure• High output failure -Thyrotoxic,

Paget's, Anemia, Pregnancy, A-V fistula

• Low output failure – 95% of HF is this

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Floor Plan of This TalkFloor Plan of This Talk

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Heart Failure – Some Statistics

Heart Failure – Some Statistics

• Affects 10% of people over 65 years• Affects over 50% of people with 85+ years• Approx 10% of patients with HF die each yr. • It is the most common condition for which

patients 65 + require admission to hospital• It is NOT a single disease – A syndrome

• Results from any cardiac disorder that impairs the ability of the ventricles to fill with or eject blood

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Epidemiology of Heart Failure

Epidemiology of Heart Failure

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Epidemiology of Heart Failure

Epidemiology of Heart Failure

Data from Framingham Heart Study per 1000 population

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Incidence of Heart FailureIncidence of Heart Failure

McKee PA et al. Framingham study; N Eng J Med 1971; 285: 1441-6

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Ethnic Differences in HFEthnic Differences in HF

Sosin MD, et al. Eur J Heart Fail 2004;6:669-72

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Age, MI and Heart FailureAge, MI and Heart Failure

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Prevalence of Chronic AF in HFPrevalence of Chronic AF in HF

Cleland JG, et al. Heart Fail Rev 2002;7:229-42

181 92 9970 11062 11016 No in study

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Systolic Heart FailureSystolic Heart Failure• LVSD – Left Ventricular Systolic Dysfunction

• Most common type of Heart Failure; 60-70%

• LV is usually dilated & enlarged.

• Fails to contract normally due to WMA, Ischemia

• Cannot pump sufficient blood to meet needs

• Normal ejection fraction (EF) is at least 50-55%

• In LVSD heart failure the EF is <40 -45%

• This carries a 10% mortality per annum

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Diastolic Heart FailureDiastolic Heart Failure• Accounts for 20-40% of patients

• Ventricles are normal-sized with normal emptying

• But there is an impairment in the ability of the ventricles to fill with blood during diastole.

• Because of stiff myocardium due to hypertrophy

• The heart fails to relax normally (relaxation poor)

• Generally older women

• Hypertension is the commonest cause

• This carries a 5-8% mortality per annum

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Population Differences in DHF

Population Differences in DHF

McMurray JJ, et al. Lancet 2005;365:1877

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Floor Plan of This TalkFloor Plan of This Talk

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Causes of Heart FailureCauses of Heart Failure1. Coronary Artery Disease (MI, IHD) (2/3 of cases)

2. Hypertension (common fore runner of LVSD, LVDD)

3. Diabetes Mellitus (via IHD, direct cardiomyopathy)

• Cardiomyopathy (DCM, HOCM, OCM, RCM)

• Valvular Heart Disease (MS, MR, AS, AR)

• Congenital Heart Disease (ASD, VSD)

• Arrhythmias (AF, Brady, Tachy, Heart Block, SSS)

• ‘High output’ failures (Anemia, hyperthyroidism, AV-F)

• Pericardial Disease (Constrictive, Effusion)

• Right Heart Failure (PHT, PE, Cor Pulmonale)

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Drugs and Heart FailureDrugs and Heart FailureMany drugs may precipitate HF or cause its deteriorate

Sodium and water retention agents

• Glucocorticoids, androgens, estrogens, NSAIDs (dose

dependent), Aspirins, Alginates

Negative Inotropic agents

• Anti arrhythmics, NDHP CCBS-Diltiazem & Verapamil

• Non selective beta blockers especially in NYHA class IV

particularly when used in large doses

Cardio toxins: Anthracyclines – Anti tumour- doxorubicin

Decongestants, High sodium containing drugs

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Precipitating Causes of HFPrecipitating Causes of HF• Arrhythmias, especially atrial fibrillation

• Infections (especially pneumonia)

• AMI, Angina pectoris or recurrent MI

• Anemia, Alcohol excess, Pregnancy

• Iatrogenic - postoperative fluid replacement or

• Poor drug compliance in pts on treatment for HT

• Thyroid disorders—Thyrotoxicosis

• Use of steroids or NSAIDs

• Pulmonary embolism

BMJ Vol . 320, 22 Jan 2000

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Changing Pattern of Etiology

Changing Pattern of Etiology

McMurray J J, Stewart S Heart 2000;83:596-602

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Major Risk FactorsMajor Risk Factors

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Ethnicity – Etiological factors

Ethnicity – Etiological factors

Sosin MD, et al. Eur J Heart Fail 2004;6:831-43

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CardiomyopathiesCardiomyopathies

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Floor Plan of This TalkFloor Plan of This Talk

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Pathophysiology of Heart Failure

Pathophysiology of Heart Failure

Developments in our understanding of the

Pathophysiology of heart failure have been

essential for recent therapeutic advances

After MI, plasma concentration of

norepinephrine is of prognostic value in the

early phase after MI

Natriuretic peptides are also shown to predict

outcome after MI – “The Leukocyte Count of HF”

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Cardiac OutputCardiac Output

CO = SV x HRCO is cardiac output expressed in L/min

Normal Cardiac Output is 5 L/min

SV ( Stroke Volume) is volume of blood put out/beat

Pre load, After load and Contractility determine the SV

HR (Heart rate) - number of beats/minute (Chronotrop)

Normally SV = 70 ml/beat. HR = 70/mt; so

CO = 70 x 70 = 4,900 ml/mt or 5 L approximately

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Important ConceptsImportant Concepts• Contractility:  Contractility is the intrinsic ability of

cardiac muscle to develop force for a given muscle length.  It is also referred to as inotropism.

• Pre load:  Preload is the muscle (stretch) length prior to contractility, and it is dependent of ventricular filling (or LV end diastolic volume). This is in turn dependent on LV end diastolic pressure and LA pressure. The most important determining factor for pre load is venous return.

• After load:  It is the tension (or the arterial pressure) against which the ventricle must contract.  After load for the left ventricle is determined by aortic pressure which in turn is dependent on peripheral arterial resistance.  

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LV Ejection Fraction (EF%)LV Ejection Fraction (EF%)

LV EF% =

LV Diastolic Volume – LV Systolic Volume

LV Diastolic Volume X 100

LV EF% =

(140 ml – 70 ml) = 70 ml

140 ml

LV-EF% = 50% (Normal 50 to 70%)

May go up to 90% with exercise

LV-EF% = 50% (Normal 50 to 70%)

May go up to 90% with exercise

X 100

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Mechanisms of Heart failure

Mechanisms of Heart failure

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Frank-Starling CurvesFrank-Starling Curves

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Sustained LVDF Leads toSustained LVDF Leads to

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Complex Mechanisms in HFComplex Mechanisms in HF• Heart Failure is multi system syndrome

– Abnormalities of cardiac and skeletal muscle– Abnormal renal function– Stimulation of sympathetic nervous system– Complex pattern of neuro humoral changes

• Ventricular Remodeling– Damage to the myocytes & extracellular

matrix– Changes in size, shape and function of LV

• Electrical instability – causing arrhythmias• Systemic processes with sequelae in

organs

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Pathophysiology of HFPathophysiology of HF

• Decreased cardiac output results in End Diastolic Pressure (LVEDP), LVH, LVD Pulmonary Capillary Wedge Pressure (PCWP)– The development of pulmonary edema

• Activation of Neurohormonal Mechanism– Renin-Angiotensin-Aldosterone- System

(RAAS)– Sympathetic Nervous System (SNS)– Other circulating and paracrine effects

• Counter-regulatory systems– Natriuretic Peptide System (BNP, pro BNP)

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Understanding RAASUnderstanding RAAS

Globular

protein

Deca (10 AA)

peptide

Octa (8 AA)peptide

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Angiotensin II ReceptorsAngiotensin II Receptors

ARBs ALDO

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AT II – Major Effector HormoneAT II – Major Effector Hormone

AT-I (1- 7,9)

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Pathological Effects of RAAS

Pathological Effects of RAAS

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AT II and Aldosterone Havoc

AT II and Aldosterone Havoc

AT II is the key hormone

• Increased AT II

• Vasoconstriction

• Myocyte hypertrophy

• Myofibril fibrosis Aldosterone release

• Activation of NA

• Activation of ETH

• ED – NO, Inflam.

Aldosterone Excess imp.

• Na and H2O retention

• Hypokalemia

• Volume over load

• Pulmonary edema

• Peripheral edema

• Myocardial apoptosis

• Myocardial fibrosis

• Increased after load

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Harmful Effects of Angiotensin II

Harmful Effects of Angiotensin II

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Adverse Effects of AldosteroneAdverse Effects of Aldosterone

Glomerulosclerosis

Interstitial Fibrosis

Proteinuria

Renal Failure

LVH

Cardiac Fibrosis

LV Dysfunction

Heart Failure

Endothelial

Dysfunction

Inflammation

Oxidative Stress

Aldosterone

MRA – EplerenoneBrand name: Eplirestat

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RAAS Axis and its BlockadeRAAS Axis and its Blockade

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RAAS BlockadeRAAS Blockade

Vasoprotection

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Sympathetic Nervous System

Sympathetic Nervous System

CO activates baroreceptors - SNS

Effects of Circulating Epinephrine & NE

– Increased Heart Rate

– Increased Blood Pressure

– Increased myocardial oxygen demand

– Toxic effects on myocardium – cell death

– Down regulation of 1 receptors in heart

– Decrease in parasympathetic activity

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Effect of Norepinephrine in HF

Effect of Norepinephrine in HF

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Circulating Paracrine Effects

Circulating Paracrine Effects

Production of Endothelin (ETH)

– A potent vasoconstrictor through ET1R

in Vasopressin (ADH) from pituitary– Excess water retention and

vasoconstriction

• Excess of Cytokines – TNF, IL-1 & IL-6– Myocyte apoptosis and cardiac cachexia

in circulating Steroids and GH

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Counter Regulatory SystemCounter Regulatory System

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Natriuretic Peptides in HFNatriuretic Peptides in HF

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B-Natriuretic Peptide (BNP)B-Natriuretic Peptide (BNP)

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Endothelium – The Endocrine Organ

Endothelium – The Endocrine Organ

Vasodilators

• NO, Bradykinin, Prostacyclin, EDHF, Serotonin, Histamine CNP, Substance P

Inhibitors of SMCG

• NO, Prostacyclin, Bradykinin, Heparin, CNP, TGF-

Inflammation inhibitors - NO

Thrombolytic factors- t-tPA

Vasoconstrictors

• AT-II, Endothelin, TXA2 AA, PGH2,

Promoters of SMCG

• PDGF, BFGF, ILGF Endothelin, AT-II

Promoters of Inflammation

• Superoxide, TNF- ELCAM, ICAM, VCAM

Thrombotic Factors - PAI-1

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Vaso Activity of Endothelins

Vaso Activity of Endothelins

Harmful

Helpful

Mixed

Endothelium, Heart, Renal Tubule, VSMC

AT-II, Catacholamines, Insulin, LDL, GF, Stress

Endothelin Antagonists:

Darusentan, Sita

xsentan,

Tezosentan & Bosentan

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Other Changes in HFOther Changes in HF

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Ventricular RemodelingVentricular Remodeling

McKay RG, et al. Circulation 1986;74:693-702

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Ventricular RemodelingVentricular Remodeling

McKay RG, et al. Circulation 1986;74:693-702

• After extensive MI - remodeling occurs – Impaired cardiac contractility– Neuro humoral activation leads to regional

eccentric and concentric hypertrophy of the non-infarcted segment

– Regional thinning and dilation of infarct area

• Factors which affect remodeling are– Large infarct, Anterior infarct, HT, Persistent

occlusion of the artery of the infarct area

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Cardiac RemodelingCardiac Remodeling

Na and H2O retention,

Performance

Myocyte hypertrophy, death,

fibrosisDilated and spherical ventricle, thinned

Na and H2O retention,

Performance

Myocyte hypertrophy, death,

fibrosisDilated and spherical ventricle, thinned

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The Cardiovascular Continuum

The Cardiovascular Continuum

Ischemia

HT

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Important Events after MIImportant Events after MI

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“Stunning” and “Hibernation”

“Stunning” and “Hibernation”

• Myocardial “Stunning”– Post ischemic dysfunction– Delayed recovery of the myocardial function

despite restoration of coronary blood flow– In the absence of irreversible damage

• Myocardial “Hibernation”– Persistent myocardial dysfunction at rest– Secondary to reduced myocardial perfusion– Function improves with revascularization– Cardiac myocytes remain viable in

hibernation

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“Stunning” and “Hibernation”

“Stunning” and “Hibernation”

• Myocardial “Stunning” and “Hibernation”

– Viable myocardium retains responsiveness to inotropic stimulation

– Can be identified by resting and stress echo, thallium scintigraphy, PET, MR Imaging with gadolinium

– Revascularization may improve the over all ventricular function with beneficial effects on symptoms and prognosis.

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Thank You AllThank You All

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Clinical Features,

Staging

Investigations, Scoring

Clinical Features,

Staging

Investigations, Scoringwill follow