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Heart Failure Basics to Recent Advances

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Definition, Etiology Epidemiology and Pathophysiology

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The very essence of cardiovascular practice is early detection of Heart Failure

HF is a BIG SubjectIt afflicts millions of people worldwideHas many diverse causes and risk factorsLarge number of Mega trials and literatureHigh mortality; Several drugs and devicesA paradigm shift in understanding & Rx.Extremely costly huge no. of bed daysComplicated by many co morbiditiesTruly multidisciplinary in its management

Detection 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.

Why HF is increasing ?Almost any disease of heart can cause itMore of HT, DM, MS, Obesity - ASCVDCAD - which is its commonest causeBetter tools for diagnosis and availabilityBetter detection and treatment of causesBetter Rx. of RF, CAD, MI - PTCA, CABGIncreasing longevity of the populationHF is an aging process longer life span

Important PointsChronic Heart Failure (CHF) can be caused by any type of cardiac dysfunctionMost commonly attributable to LV DysfunctionRarely HF is due to isolated RV dysfunctionMost 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.

Floor Plan of This Talk

Definitions 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 ClinicA 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

Definition of HFPhysiological: 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.

Types of Heart FailureChronic Heart Failure (CHF)Acute Heart Failure (Cardiogenic Shock)Systolic Failure (LVSD) Reduced EFHFDiastolic Heart Failure (LVDD) NEFHFLeft Heart Failure (LVF)Right Heart Failure (Congestive CCF)Forward Failure and Backward FailureHigh output failure -Thyrotoxic, Paget's, Anemia, Pregnancy, A-V fistulaLow output failure 95% of HF is this

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Heart Failure Some StatisticsAffects 10% of people over 65 yearsAffects over 50% of people with 85+ yearsApprox 10% of patients with HF die each yr. It is the most common condition for which patients 65 + require admission to hospitalIt is NOT a single disease A syndromeResults from any cardiac disorder that impairs the ability of the ventricles to fill with or eject blood

Epidemiology of Heart Failure

Epidemiology of Heart FailureData from Framingham Heart Study per 1000 population

Incidence of Heart FailureMcKee PA et al. Framingham study; N Eng J Med 1971; 285: 1441-6

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Ethnic Differences in HFSosin MD, et al. Eur J Heart Fail 2004;6:669-72

Age, MI and Heart Failure

Prevalence of Chronic AF in HFCleland JG, et al. Heart Fail Rev 2002;7:229-42

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Diastolic Heart FailureAccounts for 20-40% of patientsVentricles are normal-sized with normal emptyingBut there is an impairment in the ability of the ventricles to fill with blood during diastole.Because of stiff myocardium due to hypertrophyThe heart fails to relax normally (relaxation poor)Generally older womenHypertension is the commonest causeThis carries a 5-8% mortality per annum

Population Differences in DHFMcMurray JJ, et al. Lancet 2005;365:1877

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Causes of Heart FailureCoronary Artery Disease (MI, IHD) (2/3 of cases)Hypertension (common fore runner of LVSD, LVDD)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)

Drugs and Heart FailureMany drugs may precipitate HF or cause its deteriorateSodium and water retention agentsGlucocorticoids, androgens, estrogens, NSAIDs (dose dependent), Aspirins, AlginatesNegative Inotropic agentsAnti arrhythmics, NDHP CCBS-Diltiazem & VerapamilNon selective beta blockers especially in NYHA class IV particularly when used in large doses Cardio toxins: Anthracyclines Anti tumour- doxorubicinDecongestants, High sodium containing drugs

Precipitating Causes of HFArrhythmias, especially atrial fibrillationInfections (especially pneumonia)AMI, Angina pectoris or recurrent MIAnemia, Alcohol excess, PregnancyIatrogenic - postoperative fluid replacement orPoor drug compliance in pts on treatment for HTThyroid disordersThyrotoxicosisUse of steroids or NSAIDsPulmonary embolismBMJ Vol . 320, 22 Jan 2000

Changing Pattern of EtiologyMcMurray J J, Stewart S Heart 2000;83:596-602

Major Risk Factors

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

Cardiomyopathies

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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

Cardiac OutputCO = SV x HRCOis cardiac output expressed in L/min Normal Cardiac Output is 5 L/minSV( Stroke Volume) is volume of blood put out/beat Pre load, After load and Contractility determine the SVHR (Heart rate)- number of beats/minute (Chronotrop)Normally SV = 70 ml/beat. HR = 70/mt; soCO = 70 x 70 = 4,900 ml/mt or 5 L approximately

Important ConceptsContractility: 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.

LV Ejection Fraction (EF%)LV EF% = LV Diastolic Volume LV Systolic VolumeLV Diastolic Volume X 100LV EF% = (140 ml 70 ml) = 70 ml140 mlLV-EF% = 50% (Normal 50 to 70%)May go up to 90% with exercise

X 100

Mechanisms of Heart failure

Frank-Starling Curves

Sustained LVDF Leads to

Complex Mechanisms in HFHeart Failure is multi system syndromeAbnormalities of cardiac and skeletal muscleAbnormal renal functionStimulation of sympathetic nervous systemComplex pattern of neuro humoral changesVentricular RemodelingDamage to the myocytes & extracellular matrixChanges in size, shape and function of LVElectrical instability causing arrhythmiasSystemic processes with sequelae in organs

Pathophysiology of HFDecreased cardiac output results in End Diastolic Pressure (LVEDP), LVH, LVD Pulmonary Capillary Wedge Pressure (PCWP)The development of pulmonary edemaActivation of Neurohormonal Mechanism Renin-Angiotensin-Aldosterone- System (RAAS)Sympathetic Nervous System (SNS)Other circulating and paracrine effectsCounter-regulatory systemsNatriuretic Peptide System (BNP, pro BNP)

Understanding RAASGlobular proteinDeca (10 AA) peptideOcta (8 AA)peptide

Angiotensin II ReceptorsARBsALDO

AT II Major Effector Hormone

Pathological Effects of RAAS

AT II and Aldosterone HavocAT II is the key hormoneIncreased AT IIVasoconstrictionMyocyte hypertrophyMyofibril fibrosis Aldosterone releaseActivation of NAActivation of ETHED NO, Inflam.Aldosterone Excess imp.Na and