Heart Failure Pathophysiology.ppt [Read-Only]

1 1 pathophysiology : Heart FailureMat Maurer, MDIrving Assistant Professor of MedicineOutline Definitions and Classifications Epidemiology Muscle and Chamber Function PathophysiologyHeart Failure : Definitions An inability of the Heart to pump blood at a sufficient rate to meet the metabolic demands of the body ( oxygen and cell nutrients) at rest and during effort or to do so only if the cardiac filling pressures are abnormally high. A complex clinical syndrome characterized by abnormalities in cardiac function and neurohormonal regulation, which are accompanied by effort intolerance, fluid retention and a reduced longevity 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.

2 Heart Failure Not a disease A syndrome From "syn meaning "together and "dromos" meaning "a running . A group of signs and symptoms that occur together and characterize a particular abnormality. Diverse etiologies Several mechanismsEtiologiesHypertensionCADI schemiaHypertrophyValvular DiseaseAtrial FibrillationPericardial DiseaseInfiltrative DiseaseDiabetesArterial StiffnessEtiologies Ischemic cardiomyopathy Valvular cardiomyopathy Hypertensive cardiomyopathy. Inflammatory cardiomyopathy Metabolic cardiomyopathy General system disease Muscular dystrophies. Neuromuscular disorders. Sensitivity and toxic reactions. Peripartal ;93:841-8422 Heart Failure : ClassificationsHeart FailureSystolic vs.

3 Diastolic High vs. Low OutputRight vs. LeftSided Acute vs. ChronicCardiac vs. BackwardDilated Failure ParadigmsEpidemiology Heart Failure : The Problem024681012199120002037 Heart Failure Patients in the US (Millions) million in 1991, million in 2000, estimated 10 million in 2037 Incidence: 550,000 new cases/year Prevalence: 1% ages 50--59, >10% over age 80 More deaths from HF than from all forms of cancer combined Most common cause for hospitalization in age >65 Cardiac Muscle FunctionPreload The length of a cardiacmuscle fiber prior to theonset of contraction. Frank StarlingMuscle Length (mm)Tension (g)abcdAfterloadMuscle Length (mm)Tension (g)aec La Lc The against which a cardiac muscle fiber must shorten.

4 Isotonic ContractionContractilityMuscle Length (mm)Tension (g)agfbe+norepinephrine The force of contractionindependent of preloadand afterload. Inotropic StateFrom Muscle to ChamberThe Pressure Volume LoopSystoleDiastole3 The Pressure Volume LoopVolumePressureESPVResPEDPVR Preload Compliance/Stiffness vs Capacitance20406080100 120 140-50510152025LV Volume (ml)LV Pressure (mmHg)Slope = stiffness= 1/complianceCapacitance = volume at specified pressureEDPVR05010015020025001020304050L V Volume (ml)LV Pressure (mmHg)Normal Diastolic Dysfunciton Remodeling Cardiac Chamber FunctionPreloadAfterloadContractility EDV EDP Wall stress at end diastole Aortic Pressure Total peripheral resistance Arterial impedance Wall stress Pressure generated at given volume.

5 Inotropic StateFrank Starling CurvesPulmonaryCongestionHypotensionPath ophysiology - PV LoopPathophyisiology of myocardial remodeling: Transition from compensated hypertrophy to Heart failureInsult / Remodeling Stimuli Wall Stress Cytokines Neurohormones Oxidative stressMyocyte Hypertrophy Altered interstitial matrixFetal Gene ExpressionAltered calcium handling proteinsMyocyte DeathSystolic DysfunctionDiastolicDysfunctionVentricul ar EnlargementIncreased Wall Stress4 Ventricular RemodelingLaplace s LawWhere P = ventricular pressure, r = ventricular chamber radius and h = ventricular wall thicknessRAS, renin-angiotensin system; SNS, sympathetic nervous injury to the Heart (CAD, HTN, CMP, valvular disease) Morbidity and mortalityArrhythmiasPump failurePeripheral vasoconstrictionSodium retentionHemodynamic alterationsHeart Failure symptomsRemodeling and progressiveworsening of LV functionInitial fall in LV performance, wall stressActivation of RAS and SNSF atigueActivity altered Chest congestionEdemaShortness of breathNeurohormonal Activation in Heart FailureFibrosis, apoptosis,hypertrophy, cellular/molecular alterations,myotoxicity ANPBNPM yocardial InjuryFall in LV PerformanceActivation of RAAS and SNS(endothelin, AVP, cytokines)

6 Myocardial ToxicityChange in Gene Expression Peripheral Vasoconstriction Sodium/Water RetentionHF SymptomsMorbidity and MortalityRemodeling andProgressiveWorsening ofLV FunctionShah M et al. Rev Cardiovasc ;2(suppl 2):S2 Neurohormones in Heart FailureNeurohormonal Activation in Heart FailureHypertrophy, apoptosis, ischemia,arrhythmias, remodeling, fibrosisAngiotensin IINorepinephrineMorbidity and mortality CNS sympathetic outflow Cardiac sympathetic activity Renal sympathetic activitySodium retentionMyocyte hypertrophyMyocyte injuryIncreased arrhythmiasDisease progression 1 1 1 2 1 Vascular sympathetic activityVasoconstriction 1 Activationof RASA drenergic Pathway in Heart Failure Progression5 pathophysiology of Heart FailureFour Basic Mechanisms1.

7 Increased Blood Volume (Excessive Preload)2. Increased Resistant to Blood Flow (Excessive Afterload)3. decreased contractility4. decreased FillingIncreased Blood VolumeAorticRegurgitationEtiologies Mitral Regurgitation Aortic Regurgitation Volume Overload Left to Right Shunts Chronic Kidney + + Heart (mm Hg) Output (L/min)64SV (ml)140/75/99BP (mm Hg)NormalParameterVentricularRemodelingN a RetentionVasoconstrictionAI + RemodelingAI + HFIncreased AfterloadEtiologies Aortic Stenosis Aortic Coarctation + + Heart (mm Hg) Output (L/min)61SV (ml)124/81BP (mm Hg)NormalParameterDiastolic DysfunctionNa RetentionVasoconstrictionHTN + DDHTN + DD + HFDecreased ContractilityEtiologies Ischemic Cardiomyopathy Myocardial Infarction Myocardial Ischemia Myocarditis Toxins Anthracycline Alcohol + + (mm Hg) Output (L/min)61SV (ml)124/81BP (mm Hg)NormalParameterMIMI + RemodelingMI + Heart FailureVentricularRemodelingNa RetentionVasoconstrictionDecreased FillingEtiologies Mitral Stenosis Constriction Restrictive Cardiomypoathy Cardiac Tamponade Hypertrophic Cardiomyopathy Infiltrative + (mm Hg) Output (L/min)61SV (ml)124/81BP (mm Hg)

8 NormalParameterNormalHCMHCM + HFVentricularRemodelingNa RetentionVasoconstrictionHeart Failure : ClassificationsHeart FailureSystolic vs. Diastolic High vs. Low OutputRight vs. LeftSided Acute vs. ChronicCardiac vs. BackwardDilated of Heart FailureHypertensionCoronary Artery Disease1 Cause> 60 yearsAll agesDemographicsImpaired fillingImpaired ContractionPathophysiologyDiastolicSHFS ystolic Versus Diastolic FailureVolumePressureVolumePressureVolum ePressureNormalSystolicDysfunction Contractility CapacitanceDiastolicDysfunctionSystolic Versus Diastolic FailureHeart Failure : ClassificationsHeart FailureSystolic vs. Diastolic High vs. Low OutputRight vs. LeftSided Acute vs. ChronicCardiac vs. BackwardDilated Heart FailureHeart Failure : ClassificationsHeart FailureSystolic vs.

9 Diastolic High vs. Low OutputRight vs. LeftSided Acute vs. ChronicCardiac vs. BackwardDilated vs. Low Output Failure Causes: Anemia Systemic arteriovenous fistulas Hyperthyroidism Beriberi Heart disease Paget disease of bone Glomerulonephritis Polycythemia vera Carcinoid syndrome ObesityHeart Failure : ClassificationsHeart FailureSystolic vs. Diastolic High vs. Low OutputRight vs. LeftSided Acute vs. ChronicCardiac vs. BackwardDilated vs. Hypertrophic vs. RestrictiveFamilial with autosomaldominant inheritanceLeft and/or right ventricular hypertrophyHypertrophicIdiopathic, amyloidosis,endomyocardialfibrosisRestri ctive filling and reduced diastolic filling of one/both ventricles, Normal/near normal systolic functionRestrictiveIschemic, idiopathic, familial, viral, alcoholic, toxic, valvularDilated left/both ventricle(s) with impaired contractionDilatedSample EtiologiesDefinitionTypeDilated vs.

10 Hypertrophic vs. RestrictiveClinical ManifestationsSymptoms Reduced exercise tolerance Shortness of breath Congestion Fluid retention Difficulty in sleeping Weight lossDiagnosis of Heart Failure Physical examination Chest X ray EKG Echocardiogram Blood tests: Na, BUN, Creatinine, BNP Exercise test MRI Cardiac catheterization8 IIIIIIIVNYHA Classification Unable to carry out any physical activity without discomfort Symptoms of cardiac insufficiency at rest Physical activity causes increased discomfortSevere Marked limitation of physical activity Comfortable at rest Less than ordinary activity results in fatigue, palpitation, or dyspneaModerate Slight limitation of physical activity Comfortable at rest Less than ordinary activity results in fatigue, palpitation, or dyspneaMild No limitation of physical activity No undue fatigue.