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Outline Pathophysiology:Heart FailureMat Maurer, MDIrving Assistant Professor of MedicineDefinitions and ClassificationsEpidemiologyMuscle and Chamber FunctionPathophysiologyHeart Failure: DefinitionsHeart Failure An inability of the heart to pump blood at a sufficient rateto meet the metabolic demands of the body (e.g. oxygenand cell nutrients) at rest and during effort or to do soonly if the cardiac filling pressures are abnormally high. A complex clinical syndrome characterized byabnormalities in cardiac function and neurohormonalregulation, which are accompanied by effort intolerance,fluid retention and a reduced longevity A complex clinical syndrome that can result from anystructural or functional cardiac disorder that impairs theability of the ventricle to fill with or eject blood. Not a disease A syndrome– From "syn“ meaning "together“ and "dromos"meaning "a running“.– A group of signs and symptoms that occur togetherand characterize a particular abnormality. Diverse etiologies Several ologiesValvular DiseaseInfiltrativeDiseasePericardialDisease Ischemic cardiomyopathyValvular cardiomyopathyHypertensive cardiomyopathy.Inflammatory cardiomyopathyMetabolic cardiomyopathyGeneral system diseaseMuscular dystrophies.Neuromuscular disorders.Sensitivity and toxic reactions.Peripartal cardiomyopathyCirculation. 1996;93:841-8421

Heart Failure: ClassificationsForward vs.BackwardHigh vs. LowOutput 3.5 million in 1991, 4.7 millionin 2000, estimated 10 millionin 20371210 Incidence: 550,000 newcases/year86 Prevalence: 1% ages 50--59, 10% over age 804 More deaths from HF thanfrom all forms of cancercombined20199120002037 Most common cause forhospitalization in age 65From Muscle to ChamberCardiac Muscle FunctionAfterloadPreloadContractility norepinephrineTension (g)Heart Failure Patients in the US(Millions)Epidemiology Heart Failure:The Problemdba Lce LacTension (g)Acute vs. ChronicCompensated vs.DecompensatedTension (g)Heart Failurefbga cMuscle Length (mm)Muscle Length (mm) The length of a cardiacmuscle fiber prior to theonset of contraction. Frank Starling The against which acardiac muscle fibermust shorten. Isotonic ContractioneaMuscle Length (mm) The force of contractionindependent of preloadand afterload. Inotropic StateThe Pressure Volume LoopSystoleDilated vs.Hypertrophic vs.RestrcitiveSystolic vs. DiastolicDiastoleCardiac vs.Non-cardiacRight vs. LeftSidedHeart Failure Paradigms2

The Pressure Volume LoopCompliance/Stiffness vs CapacitancePesdoaelPr1510Capacitance volume at specified pressure5Slope stiffness 1/compliance0-5406080100 120 140LV Volume (ml)Volume“Remodeling”302010050100150200250LV Volume (ml)AfterloadFrank Starling CurvesContractilityHypotension EDV EDP Wall stress at end diastoleNormal400Cardiac Chamber FunctionPreload“Diastolic Dysfunciton”5020EDPVRESPVREDPVR20LV Pressure (mmHg) LV Pressure (mmHg)Pressure25 Aortic Pressure Total peripheral resistance Arterial impedance Wall stressPulmonaryCongestion Pressure generated atgiven volume. Inotropic StatePathophysiology - PV LoopPathophyisiology of myocardial remodeling:Transition from compensated hypertrophy to heart failureInsult / RemodelingStimuli Wall Stress Cytokines Neurohormones Oxidative stressIncreased Wall StressMyocyte HypertrophyAltered interstitial matrixFetal Gene ExpressionAltered calcium handlingproteinsMyocyte tolicDysfunction3

Ventricular RemodelingLaplace’s LawWhere P ventricular pressure, r ventricular chamberradius and h ventricular wall thicknessNeurohormonal Activation inHeart FailureNeurohormones in Heart FailureMyocardial injury to the heart (CAD, HTN, CMP, valvular disease)Fall in LV PerformanceMyocardial InjuryInitial fall in LV performance, wall stressActivation of RAAS and SNS(endothelin, AVP, cytokines)Activation of RAS and SNSRemodeling and progressiveworsening of LV functionFibrosis, s,myotoxicityPeripheral vasoconstrictionSodium retentionHemodynamic alterationsHeart failure symptomsFatigueActivity alteredChest congestionEdemaShortness of breathMorbidity and mortalityArrhythmiasPump failureRAS, renin-angiotensin system; SNS, sympathetic nervous system.Morbidity and MortalityPeripheral VasoconstrictionSodium/Water RetentionRemodeling andProgressiveWorsening ofLV FunctionHF SymptomsShah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2Adrenergic Pathway in HeartFailure ProgressionNeurohormonal Activation inHeart FailureAngiotensin IIANPBNPMyocardial ToxicityChange in Gene Expression CNS sympathetic outflowNorepinephrine Vascular sympathetic activity Cardiac sympathetic activityβ1Hypertrophy, apoptosis, ischemia,arrhythmias, remodeling, fibrosisMorbidity and Mortalityβ2α1Myocyte hypertrophyMyocyte injuryIncreased arrhythmias Renal sympathetic activityα1Vasoconstrictionβ1Activationof RASα1Sodium retentionDisease progression4

Increased Blood VolumePathophysiology of Heart FailureAorticRegurgitationAI RemodelingAI HFFour Basic MechanismsVentricularRemodeling1. Increased Blood Volume (Excessive Preload)2. Increased Resistant to Blood Flow (ExcessiveAfterload)3. Decreased contractility4. Decreased FillingEtiologies Mitral Regurgitation Aortic Regurgitation Volume Overload Left to Right Shunts Chronic Kidney DiseaseIncreased AfterloadHypertensionHTN DDDiastolicDysfunctionEtiologies Aortic Stenosis Aortic Coarctation HypertensionNormalBP (mm Hg)HTNHTN DDHTN Heart failure159/122170/129206/15961515465Cardiac Output (L/min)3.73.13.23.9PCWP (mm Hg)10101221Decreased FillingAI RemodelingAI Heart failureBP (mm Hg)104/45/68140/75/99128/507885/35/54SV (ml)64805463Cardiac Output (L/min)3.83.02.12.6PCWP (mm Hg)10101020MI RemodelingNa RetentionVasoconstrictionEtiologies Ischemic Cardiomyopathy Parameter– Myocardial Infarction– Myocardial Ischemia MyocarditisToxins– Anthracycline– Alcohol– CocaineMI Heart FailureNormalMIMI RemodelingMI HF80/50BP (mm Hg)124/8168/4668/45SV (ml)61353438Cardiac Output (L/min)3.72.12.02.3PCWP (mm Hg)10161833Heart Failure: ClassificationsHCMEtiologies Mitral Stenosis Constriction Restrictive Cardiomypoathy Cardiac Tamponade HypertrophicCardiomyopathy Infiltrative ularRemodelingNormalDecreased ContractilitySV (ml)NormalParameterMIHTN DD HFNa RetentionVasoconstrictionParameterNa RetentionVasoconstrictionHCM HFRight vs. LeftSidedNa RetentionVasoconstrictionParameterNormalHCMHCM HFBP (mm Hg)131/87124/81112/74SV (ml)615766Cardiac Output (L/min)3.73.44.0PCWP (mm Hg)101027Dilated vs.Hypertrophic vs.RestrcitiveAcute vs. ChronicCardiac vs.Non-cardiacHeart FailureForward vs.BackwardSystolic vs. DiastolicCompensated vs.DecompensatedHigh vs. LowOutput5

Systolic Versus Diastolic FailureTypes of Heart functionNormalDemographics1 CauseImpaired fillingAll ages 60 yearsCoronary Artery DiseaseHypertensionSystolic Versus Diastolic FailureVolumeVolume CapacitanceVolumeHeart Failure: ClassificationsRight vs. LeftSidedDilated vs.Hypertrophic vs.RestrcitiveAcute vs. ChronicDecompensated Heart FailurePressureImpaired ContractionPressurePathophysiologyPressure ContractilityCardiac vs.Non-cardiacHeart FailureForward vs.BackwardSystolic vs. DiastolicCompensated vs.DecompensatedHigh vs. LowOutputHeart Failure: ClassificationsRight vs. LeftSidedDilated vs.Hypertrophic vs.RestrictiveAcute vs. ChronicCardiac vs.Non-cardiacHeart FailureForward vs.BackwardSystolic vs. DiastolicCompensated vs.DecompensatedHigh vs. LowOutput6

High vs. Low Output FailureHeart Failure: ClassificationsRight vs. LeftSided Causes:–––––––––AnemiaSystemic arteriovenous fistulasHyperthyroidismBeriberi heart diseasePaget disease of boneGlomerulonephritisPolycythemia veraCarcinoid syndromeObesityDilated vs.Hypertrophic vs.RestrictiveAcute vs. ChronicDilated vs. Hypertrophic vs. itionDilated left/bothventricle(s) with impairedcontractionLeft and/or rightventricular hypertrophySample EtiologiesIschemic, idiopathic,familial, viral, alcoholic,toxic, valvularFamilial with autosomaldominant inheritanceRestrictive filling andreduced diastolic fillingof one/both ventricles,Normal/near normalsystolic functionIdiopathic, amyloidosis,endomyocardialfibrosisSymptomsReduced exercise toleranceShortness of breathCongestionFluid retentionDifficulty in sleepingWeight lossHeart FailureForward vs.BackwardSystolic vs. DiastolicCompensated vs.DecompensatedHigh vs. LowOutputDilated vs. Hypertrophic vs. RestrictiveClinical Manifestations Cardiac vs.Non-cardiacDiagnosis of heart failure Physical examinationChest X rayEKGEchocardiogramBlood tests: Na, BUN, Creatinine, BNPExercise testMRICardiac catheterization7

NYHA ClassificationClassPatient SymptomsIMild No limitation of physical activity No undue fatigue, palpitation or dyspneaIIMildIIIModerateIVSevere Slight limitation of physical activity Comfortable at rest Less than ordinary activity results in fatigue,palpitation, or dyspnea Marked limitation of physical activity Comfortable at rest Less than ordinary activity results in fatigue,palpitation, or dyspnea Unable to carry out any physical activity withoutdiscomfort Symptoms of cardiac insufficiency at rest Physical activity causes increased discomfortACC/AHA Staging SystemStageABCDTreatmentABCDSTAGE A High risk for developing HFSTAGE B Asymptomatic LV dysfunctionSTAGE C Past or current symptoms of HFSTAGE D End-stage HFHunt, et al. J Am Coll Cardiol. 2001; 38:2101-2113.Goals of TreatmentPatient DescriptionHigh risk for Hypertensiondeveloping heart failure Coronary artery disease Diabetes mellitus Family history of cardiomyopathy Previous myocardial infarctionAsymptomatic heart Left ventricular systolic dysfunctionfailure Asymptomatic valvular disease Known structural heart diseaseSymptomatic heart Shortness of breath and fatiguefailure Reduced exercise tolerance Marked symptoms at rest despite maximalRefractorymedical therapy (e.g., those who are recurrentlyend-stage heart failurehospitalized or cannot be safely discharged fromthe hospital without specialized interventions)StageACC/AHA Staging System1. Identification and correction of underlyingcondition causing heart failure.2. Elimination of acute precipitating cause ofsymptoms.3. Modulation of neurohormonal response toprevent progression of disease.4. Improve long term survival.Targets of TreatmentPatient TreatmentHigh risk for Hypertensionpharmacologic therapy (OPT)developing heart failure OptimalCoronary artery disease Aspirin, ACE inhibitors, statins, b-blockers, a-b-blockersDiabetes mellitus(carvedilol) diabetic therapy Family history of cardiomyopathyPrevious myocardial infarctionAsymptomatic heart OPT ICDleft ventricular(LV) dysfunctionLeftif sent Asymptomatic valvular diseaseKnown structural heart diseaseSymptomatic heart OPT ICDif LV dysfunction(systolic)presentShortnessof breath andfatiguefailure CRT(if QRSwide, LVEF 35%)ReducedexercisetoleranceMarked symptoms at rest despite maximal OPTRefractoryIV inotropesmedical therapy(e.g., those who are recurrentlyend-stage heart failure Intermittent ICDas a bridgetransplantationhospitalizedortocannotbe safely discharged from CRTthe hospital without specialized interventions)Standard PharmacologicalTherapy ACE inhibitorsAngiotensin Receptor Blockers Beta Blcokers Diuretics Aldosterone Antagonists Statins Vasodilators Inotropes Other devices (LVAD, pericardial restraint)8

ACC/AHA Staging SystemTreatmentSummary Complex Clinical Syndrome Multiple Etiologies and Classification Systems Physiologic Understanding artsim/9

Myocardial injury to the heart (CAD, HTN, CMP, valvular disease) Morbidity and mortality Arrhythmias Pump failure Peripheral vasoconstriction Sodium retention Hemodynamic alterations Heart failure symptoms Remodeling and progressive worsening of LV function Initial fall in LV performance, wall stress Activation of RAS and SNS Fatigue .