Heart Failure - uniba.sk...Chronic heart failure (CHF) Gradual progressive loss of cardiac function...

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12/06/2017 1 Heart Failure Heart Failure (General Medicine) (General Medicine) Cardiovascular continuum Cardiovascular continuum Function of the heart Function of the heart Supply the organs by Supply the organs by O 2 and nutrients sufficient and nutrients sufficient for the metabolic status for the metabolic status Accept blood from organs and push it through Accept blood from organs and push it through pulmonary circulation to the left heart pulmonary circulation to the left heart Requirement equirements Normal structure and function of the heart Normal structure and function of the heart Appropriate blood return from the periphery Appropriate blood return from the periphery Normal structure and function of the tissues Normal structure and function of the tissues surrounding the heart surrounding the heart BLOOD PRESSURE (heart work) Cardiac Output (CO) Peripheral Resistance (PR) Stroke Volume (SV) Heart Rate (HR) Preload Contractility Afterload Vessel length Vessel diameter Viscosity of blood Blood volume Venous compliance Vasoconstriction Vasodilation Compliance of large arteries Vessel wall remodelling Heart failure Heart failure Inability of the heart to supply adequate blood Inability of the heart to supply adequate blood flow and oxygen delivery to peripheral tissues flow and oxygen delivery to peripheral tissues and organs in spite of and organs in spite of normal normal or or increased increased filling pressure ( filling pressure (venous return venous return) Epidemiol Epidemiology of HF ogy of HF Prevalenc Prevalency: 2 : 2 - 3 % 3 % after after 75 75 years years: 10 10 -20 % 20 % In younger individuals is more frequent in men In younger individuals is more frequent in men 50 % 50 % of patients dies within of patients dies within 4 4 years years 40 % 40 % of patients hospitalized with HF dies or is re of patients hospitalized with HF dies or is re- admitted within 1 year admitted within 1 year

Transcript of Heart Failure - uniba.sk...Chronic heart failure (CHF) Gradual progressive loss of cardiac function...

Page 1: Heart Failure - uniba.sk...Chronic heart failure (CHF) Gradual progressive loss of cardiac function Partly compensated by regulatory mechanisms that become maladaptive Peripheral edemas

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Heart FailureHeart Failure

(General Medicine)(General Medicine)

Cardiovascular continuumCardiovascular continuum

Function of the heartFunction of the heart�� Supply the organs by Supply the organs by OO22 and nutrients sufficient and nutrients sufficient

for the metabolic status for the metabolic status

�� Accept blood from organs and push it through Accept blood from organs and push it through

pulmonary circulation to the left heartpulmonary circulation to the left heart

RRequirementequirementss�� Normal structure and function of the heartNormal structure and function of the heart

�� Appropriate blood return from the peripheryAppropriate blood return from the periphery

�� Normal structure and function of the tissues Normal structure and function of the tissues surrounding the heartsurrounding the heart

BLOOD PRESSURE

(heart work)

Cardiac Output (CO) Peripheral Resistance (PR)

Stroke Volume (SV) Heart Rate (HR)

Preload

Contractility

Afterload

Vessel length

Vessel diameter

Viscosity of blood

Blood volume

Venous compliance

Vasoconstriction

Vasodilation

Compliance of large arteries

Vessel wall

remodelling

Heart failureHeart failure

�� Inability of the heart to supply adequate blood Inability of the heart to supply adequate blood

flow and oxygen delivery to peripheral tissues flow and oxygen delivery to peripheral tissues

and organs in spite of and organs in spite of normalnormal or or increasedincreased

filling pressure (filling pressure (venous returnvenous return))

EpidemiolEpidemiology of HFogy of HF

�� PrevalencPrevalencyy: 2 : 2 -- 3 %3 %

�� ���� after after 75 75 yearsyears:: 10 10 --20 %20 %

�� In younger individuals is more frequent in men In younger individuals is more frequent in men

�� 50 % 50 % of patients dies within of patients dies within 4 4 yearsyears

�� 40 % 40 % of patients hospitalized with HF dies or is reof patients hospitalized with HF dies or is re--

admitted within 1 yearadmitted within 1 year

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Causes of HFCauses of HF

1.1. Chronic hemodynamic overloadChronic hemodynamic overload

2.2. Restricted filling of ventriclesRestricted filling of ventricles

3.3. Myocardial impairmentMyocardial impairment

4.4. ArrythmiasArrythmias

Causes of HFCauses of HF

1.1. Chronic hemodynamic overloadChronic hemodynamic overload

�� Pressure:Pressure:

�� Left: Left: hypertensionhypertension, stenosis and coarctation of aorta, stenosis and coarctation of aorta

�� Right: pulmonary hypertension, a. pulmonalis stenosisRight: pulmonary hypertension, a. pulmonalis stenosis

�� Volume:Volume:

�� Mitral, aortic insufficiency, arterioMitral, aortic insufficiency, arterio--venous shunts, hyperkinetic venous shunts, hyperkinetic circulationcirculation

2.2. Restricted filling of ventriclesRestricted filling of ventricles

�� Impaired ventricular dilationImpaired ventricular dilation

�� Disorder of the ventricular fillingDisorder of the ventricular filling

Causes of HFCauses of HF

3.3. Myocardial impairmentMyocardial impairment

�� Ischemic heart diseaseIschemic heart disease

�� CardiomyopathiesCardiomyopathies

�� Toxic substances: ethanol, diphtheria, drugsToxic substances: ethanol, diphtheria, drugs

�� Endocrinopathies: DM, hyperEndocrinopathies: DM, hyper--/hypo/hypo--thyreoidismthyreoidism

4.4. ArrythmiasArrythmias

�� Extreme tachyarrhythmia: supraventricular tachycardia, Extreme tachyarrhythmia: supraventricular tachycardia,

fibrillation, flutterfibrillation, flutter

�� Extreme bradycardia: sinus, AV blockExtreme bradycardia: sinus, AV block

Consequences of myocardial Consequences of myocardial

hypoxia/ischemiahypoxia/ischemia�� Energy production: aerobicEnergy production: aerobic → → anearobicanearobic

�� glycogenolysisglycogenolysis

�� �� ATP ATP in heartin heart

�� Lactate accumulation, intracellular acidosisLactate accumulation, intracellular acidosis::�� �� cell membrane permeabilitycell membrane permeability→ → enzyme and electrolyte enzyme and electrolyte escape into ECLescape into ECL

�� �� i.c. i.c. calciumcalcium

�� �� electrical stabilityelectrical stability → → dysrrhythmiasdysrrhythmias

�� �� myocardial contractilitymyocardial contractility

�� Cardiomyocyte damageCardiomyocyte damage::�� calcium overloadcalcium overload

�� deficit ofdeficit of ATPATP

Pathomechanism of cardiomyocyte Pathomechanism of cardiomyocyte

damage in HFdamage in HF

�� Calcium overloadCalcium overload

�� Primary ATP deficit in cardiomyocytesPrimary ATP deficit in cardiomyocytes

Pathomechanism of HFPathomechanism of HF

Calcium overloadCalcium overloadDamaged sarcoplasmatic Damaged sarcoplasmatic

reticulumreticulumHyperpermeable sarcolemmaHyperpermeable sarcolemma

↑ i.c. Ca↑ i.c. Ca2+2+

Transport capacity of Transport capacity of CaCa2+2+ in in mitochondriamitochondria

((longlastinglonglasting stimulstimulusus))

CaCa2+2+ accumulation in accumulation in mitochondriamitochondria

Impaired ATP productionImpaired ATP production

ATPATP escapeescape

Irreversible diastolic Irreversible diastolic contracturescontractures

Necrosis of Necrosis of

cardiomyocytescardiomyocytes

↓ ATP

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Pathomechanism of HFPathomechanism of HF

ATP dATP deficit eficit

HHypoxia, substrate and energy deficit, ypoxia, substrate and energy deficit, inhibinhibited glycolysis:ited glycolysis:•• CADCAD

•• ccardiomyopatardiomyopathy, hy, myomyoccarditarditisis

Energy deficitEnergy deficit

Sarcolemmal NaSarcolemmal Na++--KK++ ATPATP--ase failurease failure

i.c. i.c. NaNa+ + accumulationaccumulation

cell edemacell edema NaNa++--CaCa2+2+ exchangerexchanger

↑ i.c. Ca↑ i.c. Ca2+2+Necrosis of cardiomyocytesNecrosis of cardiomyocytes

Forms of Forms of HFHF�� AcuteAcute

�� ChronicChronic

�� RightRight

�� LeftLeft

�� SystolicSystolic

�� DiastolicDiastolic

�� HighHigh--output HFoutput HF

�� LowLow--output HFoutput HF

�� ForwardForward

�� BackwardBackward

ManifestationManifestation of HFof HF

LowLow--output vs. highoutput vs. high--output HFoutput HF

�� LowLow--output HFoutput HF

�� cardiac output lower than before HF, under effort doesn`t cardiac output lower than before HF, under effort doesn`t increase sufficientlyincrease sufficiently

�� CADCAD, , hypertension, dilatative cardiomyopathy, valvular, hypertension, dilatative cardiomyopathy, valvular, pericardial diseasespericardial diseases

�� HHighigh--output HFoutput HF

�� cardiac output during HF is HIGHER than before HF, cardiac output during HF is HIGHER than before HF, cannot supply inadequately high requestscannot supply inadequately high requests

�� Thyreotoxicosis, Paget’s disease, beriThyreotoxicosis, Paget’s disease, beri--beri, anemia, beri, anemia, septicaemia, arteriovenous fistulaesepticaemia, arteriovenous fistulae

�� Warm extremities, normal or widened pulse pressureWarm extremities, normal or widened pulse pressure

Acute heart failure (AHF)Acute heart failure (AHF)

�� Sudden deterioration of cardiac functionSudden deterioration of cardiac function

�� Acute compensatory mechanisms set onAcute compensatory mechanisms set on

�� HypotensionHypotension without edemas, acute onset of without edemas, acute onset of dyspneadyspnea, pulmonary edema, pulmonary edema

�� LV HF:LV HF: myocardial infarction, arrythmia, acute myocardial infarction, arrythmia, acute valve dysfunctionvalve dysfunction

�� RV HF:RV HF: mitral insufficiency, mitral insufficiency, massive pulmonary

embolism

Chronic heart failure (CHF)Chronic heart failure (CHF)

�� Gradual progressive loss of cardiac function Gradual progressive loss of cardiac function

�� Partly compensated by regulatory mechanisms that Partly compensated by regulatory mechanisms that

become maladaptive become maladaptive

�� Peripheral Peripheral edemasedemas, BP does not change, BP does not change

�� LV HF:LV HF: volume (volume (valvular insufficiencyvalvular insufficiency) or pressure ) or pressure

((hypertension, valvular stenosishypertension, valvular stenosis) overload or heart muscle ) overload or heart muscle

disease (disease (MI, cardiomyopathy, myocarditisMI, cardiomyopathy, myocarditis))

�� RV HF:RV HF: precapillary, capillary or postcapillary precapillary, capillary or postcapillary

pulmonary hypertension pulmonary hypertension --> cor pulmonale or > cor pulmonale or

tricuspidal valvular disease. tricuspidal valvular disease.

Systolic dysfunctionSystolic dysfunction

�� �� myocardial contractilitymyocardial contractility�� myocardial damagemyocardial damage: isch: ischeemia, mia, inflammationinflammation, intoxi, intoxicationcation(et(ethhanol, anol, ccooccaaiin, amn, amphphetametamiinnss), ), ionic changesionic changes

�� volume overloadvolume overload

�� �� afterloadafterload�� preddure overloadpreddure overload�� stenosis ofstenosis of aortaortic valveic valve, , arterial hypertensionarterial hypertension

�� Failure of left ventricle to eject bloodFailure of left ventricle to eject blood in systolein systole→ → ��ventricular volumeventricular volume → → �� ventricular pressureventricular pressure → → ��systolic volumesystolic volume → → ventricular hypertrophyventricular hypertrophy

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Diastolic dysfunctionDiastolic dysfunction

�� Impaired ventricular dilationImpaired ventricular dilation

�� hypertrophyhypertrophy, , fibrosisfibrosis

�� increased resistance during ventricular fillingincreased resistance during ventricular filling: : �� filling filling pressurepressure → → pulmonarypulmonary//venous congestionvenous congestion

�� exertional dyspnoeaexertional dyspnoea

�� aortic stenosis, hypertension, hypertrophic cardiomyopathyaortic stenosis, hypertension, hypertrophic cardiomyopathy

�� Disorder of ventricular fillingDisorder of ventricular filling

�� mitral stenosis, tamponade, constrictive pericarditis, mitral stenosis, tamponade, constrictive pericarditis, tachyarrhythmiastachyarrhythmias

Systolic dysfunction Diastolic dysfunction

↑ end-diastolic volume

atrium

Left side

Pulmonary edema

Right side

Peripheral edema

Inadequate filling of ventricle

↑ end-diastolic pressure

Inadequate empting of ventricle

Forward HFForward HF

�� ↓↓ stroke volume, stroke volume, ↓ ↓ ejection fraction (EF) ejection fraction (EF) → → �� peripheral, peripheral, renal perfusion renal perfusion → → reninrenin--angiotensisangiotensis--aldosterone system aldosterone system

activation activation → Na→ Na++ aandnd HH22OO retentionretention

�� LV HF: LV HF:

�� Peripheral hypoperfusionPeripheral hypoperfusion

�� muscle weakness, fatigue, dyspepsia, oliguria, dizziness, confusion, cool muscle weakness, fatigue, dyspepsia, oliguria, dizziness, confusion, cool extremities at restextremities at rest

�� RV HF: RV HF:

�� Hypoperfusion of lungs: Hypoperfusion of lungs:

�� disorders of gas exchange disorders of gas exchange –– cyanosiscyanosis

�� ↓ blood supply to the left heart↓ blood supply to the left heart

Backward HFBackward HF

�� ↓↓ EF … blood congests EF … blood congests in front of ventriclesin front of ventricles in atria in atria and veinsand veins

�� LV HFLV HF::

�� ↑ pulmonary capillary pressure↑ pulmonary capillary pressure

�� dyspnea, tachypnea, pulmonary edema (cardiac asthma) … arterial dyspnea, tachypnea, pulmonary edema (cardiac asthma) … arterial hypoxemia and hypercapniahypoxemia and hypercapnia

�� RV HF:RV HF:

�� ↑ pressure in systemic venous system↑ pressure in systemic venous system

�� peripheral edemas, abdominal discomfort, hepatomegaly, ascites, peripheral edemas, abdominal discomfort, hepatomegaly, ascites,

increased jugular venous pressure … increased jugular venous pressure … ↑ nocturnal diuresis↑ nocturnal diuresis

Compensatory mechanismsCompensatory mechanisms

Pathologic processPathologic process

Compensated HFCompensated HF Decompensated HFDecompensated HF

Without clinical signs of HF With clinical signs of HF

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Compensatory mechanismsCompensatory mechanisms

�� Cardiac:Cardiac:

�� AcuteAcute

��FrankFrank--Starling mechanismStarling mechanism

��CatecholaminesCatecholamines

�� ChronicChronic

��Myocardial hypertrophyMyocardial hypertrophy

�� PeripheralPeripheral

Acute compensatory mechanismsAcute compensatory mechanismsFrankFrank--Starling mechanismStarling mechanism

�� ↓↓ ejection fractionejection fraction ... ↑ end... ↑ end--diastolic diastolic volume in ventricles volume in ventricles ... ...

myocytemyocyte stretchingstretching ... ↑ ... ↑ sarcomere lengthsarcomere length ... ↑ tropon... ↑ troponiin C n C

sensitivity tosensitivity to Ca2+ ... ↑ Ca2+ ... ↑ crosscross--link actin and myosin filamentslink actin and myosin filaments

... ... ↑ ↑ contractioncontraction ... ... ↑↑ stroke volumestroke volume

�� Maximal force of contraction: sarcomere length nearMaximal force of contraction: sarcomere length near 2,2 um2,2 um

�� >> 2,2 um ... ↓ 2,2 um ... ↓ myofilament overlappingmyofilament overlapping ((HFHF))

�� << 2,2 um ... ↓ tropon2,2 um ... ↓ troponiin C n C sensitivity tosensitivity to Ca2+ Ca2+

↓ ejection fraction ↓ ejection fraction ↑ contraction ↑ contraction

Acute compensatory mechanismsAcute compensatory mechanismsCatecholaminesCatecholamines

↓↓ aortic pressure (BP)aortic pressure (BP) ↑↑ LV, LA, pulmonary bed pressureLV, LA, pulmonary bed pressure

Stim. of baroreceptors, chemoreceptors in Stim. of baroreceptors, chemoreceptors in aorta, ventricles, atrii, aorta, ventricles, atrii, pulmonary bedpulmonary bed

CNSCNS

↓↓ PSpPSp ↑↑ SpSp

↑↑ contractilitycontractility

↑↑ cardiac outputcardiac output

↑↑ peripheral perfusionperipheral perfusion

↑↑ frequencyfrequency

vasoconstrictionvasoconstriction

ββ11

ββ11

αα11

↑↑ BPBP

Antidiuretic Antidiuretic hormone (ADH)hormone (ADH)

↑↑ fluid retentionfluid retention

↑ blood volume↑ blood volume

↑ BP↑ BP

↑ ↑ RAASRAAS

myocyte, myocyte,

vascular vascular

hypertrophyhypertrophy

Chronic HF:Chronic HF:

�� norepinephrine 2norepinephrine 2--3x 3x ↑ at rest than in healthy subjects↑ at rest than in healthy subjects

�� ↓ number of ↓ number of ββ11--adrenergic receptors adrenergic receptors

… …

↓ sensitivity of cardiomyocytes to catecholamines ↓ sensitivity of cardiomyocytes to catecholamines

… …

↓ contractility↓ contractility

Acute compensatory mechanismsAcute compensatory mechanismsCatecholaminesCatecholamines

SNS in chronic HFSNS in chronic HF

G Jackson, C R Gibbs, M K Davies and G Y H Lip: ABC of heart failure: Pathophysiology, BMJ 2000;320;167-170

�� Structural adaptation of the heart to a longStructural adaptation of the heart to a long--term term hemodynamic overload hemodynamic overload

�� Stimulated by inadequate Stimulated by inadequate ↑↑ in ventricular wall stress in ventricular wall stress -- pressure pressure load and neurohumoral agents (angiotensin II, aldosterone)load and neurohumoral agents (angiotensin II, aldosterone)

�� Leads to remodeling of the myocardial architectureLeads to remodeling of the myocardial architecture

�� Laplace’s lawLaplace’s law

Chronic compensatory mechanismsChronic compensatory mechanismsMyocardial hypertrophyMyocardial hypertrophy

TT = = ventricular wall stressventricular wall stress

PP = = intraventricular pressureintraventricular pressure

r r = = ventricular radiusventricular radius

h h = = ventricular wall widthventricular wall widthh

rPT

2

×=

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�� Physiologic hypertrophyPhysiologic hypertrophy

�� Pathologic hypertrophyPathologic hypertrophy

Chronic compensatory mechanismsChronic compensatory mechanismsMyocardial hypertrophyMyocardial hypertrophy

Physiologic hypertrophyPhysiologic hypertrophy�� ontogenetic developmentontogenetic development

�� adaptation to increased physical activityadaptation to increased physical activity

�� the intensity and duration of overload do not exceed particular the intensity and duration of overload do not exceed particular measuremeasure

�� overload develops graduallyoverload develops gradually

�� function of each mass unit is normal or even increased: function of each mass unit is normal or even increased: �� enlargement of the muscle massenlargement of the muscle mass�� improvement of contractility of each mass unit … improvement of contractility of each mass unit … ↑ systolic ↑ systolic

functionfunction

�� the content of connective tissue does not increase … elasticity … the content of connective tissue does not increase … elasticity … diastolic functiondiastolic function

Chronic compensatory mechanismsChronic compensatory mechanismsMyocardial hypertrophyMyocardial hypertrophy

Pathologic hypertrophyPathologic hypertrophy

�� hypertrophy of myocytes (↑ length / width)hypertrophy of myocytes (↑ length / width)

�� volume / pressure overloadvolume / pressure overload

�� hormonal stimulation: NE, Ang IIhormonal stimulation: NE, Ang II

�� ↑ non↑ non--myocytic cells in myocardiummyocytic cells in myocardium

�� Endothelial cellsEndothelial cells … endothelins:… endothelins:

�� Mitogenic ability … stimulation of growth of smooth muscle Mitogenic ability … stimulation of growth of smooth muscle

cells of vessels and of fibroblastscells of vessels and of fibroblasts

�� Fibroblasts Fibroblasts … ↑ production of collagens … … ↑ production of collagens … fibrosisfibrosis

Chronic compensatory mechanismsChronic compensatory mechanismsMyocardial hypertrophyMyocardial hypertrophy

� Concentric hypertrophy

� Pressure overload (↑ LV end-diastolic wall stress)

� ↑ wall thickness / ventricular volume

� ↑ afterload

� stenosis, coarctation of aorta, arterial hypertension,

obstructive hypertrophic cardiomyopathy, stenosis of a.

pulmonalis, pulmonary hypertension

� hypoperfusion of the subendocardium … worsening of

LV function

� expression of stretch-activated genes: Ang II,

endothelin, TNF

Chronic compensatory mechanismsChronic compensatory mechanismsMyocardial hypertrophyMyocardial hypertrophy

� Eccentric hypertrophy

� Volume overload (↑ LV end-diastolic volume)

� ↓ wall thickness / ventricular volume

� LV wall thinning, dilating

� ↑ preload

� aortic, mitral valve insufficiency, pulmonal, tricuspidal

valve insufficiency, atrial septum defect

Chronic compensatory mechanismsChronic compensatory mechanismsMyocardial hypertrophyMyocardial hypertrophy

�� Heart enlargement, ventricular wall is absolutely or Heart enlargement, ventricular wall is absolutely or relatively thinnerrelatively thinner

�� Primary dilationPrimary dilation�� Acute hemodynamic overloadAcute hemodynamic overload

�� ventricular wall is absolutely thinner vs. normalventricular wall is absolutely thinner vs. normal

�� Secundary dilationSecundary dilation�� Chronic hemodynamic overloadChronic hemodynamic overload ... ... hypertrofic, but failing hypertrofic, but failing heart, exhausted compensatory mechanismsheart, exhausted compensatory mechanisms

�� hypertrophied ventricular wall is getting thinnerhypertrophied ventricular wall is getting thinner

Myocardial dilationMyocardial dilation

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Peripheral compensatory mechanismsPeripheral compensatory mechanisms

�� NeurohumoralNeurohumoral: : �� Sp., PSp. activitySp., PSp. activity, , RAASRAAS, , ADH, ANPADH, ANP

�� Blood redistributionBlood redistribution → → centralization of blood centralization of blood

flowflow

�� HormonalHormonal: tyrox: tyroxiin, n, growth hormonegrowth hormone, dopam, dopamiinnee

�� �������� oxygen extractionoxygen extraction from capillary bloodfrom capillary blood → → peripheral cyanosisperipheral cyanosis

�� �������� red blood cells countred blood cells count

AngiotenAngiotenssinoginogeenn

AngiotenAngiotensisin In I

AngiotenAngiotensisin IIn II

AldosterAldosteroonn

fluid, Na+

retention

↑ ↑ blood volumeblood volume

↑ preload↑ preload

adrenalsadrenalshypophysishypophysis

ADHADH thirstthirst

systemic systemic

vasoconstrictionvasoconstriction

↑ afterload↑ afterload

Myocardial, Myocardial,

vascular vascular

hypertrophyhypertrophy

RenReniinn

AngiotenAngiotensinsin convertingconverting

enzenzyymmee (ACE)(ACE)

RenReniinn--angiotenangiotensinsin--aldosteraldosteroon systn systeem (RAAS)m (RAAS)

↑ ↑ BPBP

FibroblastsFibroblasts CardiomyocytesCardiomyocytes EndotheliumEndothelium

Tissue Ang IITissue Ang II

cardiomyocyte cardiomyocyte hypertrophyhypertrophy

proliferationproliferation vascular wall vascular wall hypertrophyhypertrophy

Myocardial remodelingMyocardial remodeling

Myocardial hypertrophy (volume/pressure overload)Myocardial hypertrophy (volume/pressure overload)

↑ preload↑ preload ↑ afterload↑ afterload ↑ Sp↑ Sp

Systemic (plasma) Ang IISystemic (plasma) Ang II

↑ blood osmolarity↑ blood osmolarity ↓ ↓ blood volumeblood volume ↓ ↓ BPBP

ADHADH from hypothalamusfrom hypothalamus

↑↑ amount ofamount of aaquaporinesquaporines in in collecting tubulescollecting tubules

↑↑ water rearpsorptionwater rearpsorption

↓ blood osmolarity↓ blood osmolarity ↑ blood volume↑ blood volume

Systemic Systemic vasoconstrictionvasoconstriction

↑ BP↑ BP

Antidiuretic hormone (ADH) = VasopressinAntidiuretic hormone (ADH) = Vasopressin

Acute atrial Acute atrial

stretchingstretching

ANPANP secretion from atrial cardiomyocytessecretion from atrial cardiomyocytes

↑ glomerular filtration↑ glomerular filtration

↑ Na↑ Na++ excretionexcretion

↓↓ aldosteraldosteroneone, ADH, , ADH,

renreniinn

↓ preload↓ preload

↓ peripheral ↓ peripheral

resistanceresistance

↓ BP↓ BP

↑↑ extracellular fluid volumeextracellular fluid volume

↑ Na↑ Na++ incomeincome

Chron. Chron. Heart failureHeart failure

VolumexpanVolumexpansionsion

Natriuresis and diuresisNatriuresis and diuresis

Atrial natriuretic peptide (ANP)Atrial natriuretic peptide (ANP)

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Adrenalin, noradrenalin, ang. II, aldosterone,

ADH

preservation of the perfusion of vital organs on

the expense of increased afterload

deterioration of heart failure

Centralization of the circulationCentralization of the circulation Decompensated HFDecompensated HF

�� Exhausted compensatory mechanismsExhausted compensatory mechanisms

�� Stress reactionStress reaction::

�� CatecholaminesCatecholamines

�� RAASRAAS

�� Adequate perfusion through vital organs (heart, Adequate perfusion through vital organs (heart, brain, kidneys)brain, kidneys)

�� Relative ischemia of peripheral organs (skin, Relative ischemia of peripheral organs (skin, digestive tract, muscles, …)digestive tract, muscles, …)

Stress reactionStress reaction↓↓ aortic pressureaortic pressure ↑↑ BPBP in LV, RA, pulmonary circulationin LV, RA, pulmonary circulation

Stim. baroreceptors, chemoreceptors inStim. baroreceptors, chemoreceptors in aortaortaa, , ventriclesventricles, , atriaatria, , pulmonary circulationpulmonary circulation

Peripheral vasoconstriction

↑ BP

↓ renal perfusion

RAAS activation

Angiotensin II Aldosterone

↑ blood volumeAntidiuretic hormAntidiuretic hormoonne e

(ADH)(ADH)

NANA

↑ Sp.↑ Sp.

Stress reactionStress reactionMaximMaximalal utilization of all compensatory mechanismsutilization of all compensatory mechanisms

Peripheral vasoconstrictionPeripheral vasoconstriction

↑ afterload↑ afterload

↓ ↓ pumping capacity of the heartpumping capacity of the heart

↓ ↓ cardiac outputcardiac output

↑ preload↑ preload

Impairment of pulmonary stasisImpairment of pulmonary stasis

↓ ATP ↓ ATP in myocardiumin myocardium

Impaired cardiac functionImpaired cardiac function

VenoconstrictionVenoconstriction

Definitive heart failureDefinitive heart failure

Fluid overloadFluid overloadEdemaEdema

↑↑ water reabsorptionwater reabsorption

↑↑ ADHADH

↑↑ osmotic pressureosmotic pressure

↑↑ Na+ retentionNa+ retention

↓ renal perfusion↓ renal perfusion

↓ cardiac output↓ cardiac output

TachycardiaTachycardiaVentricular dilationVentricular dilation

Myocardial hypertrophyMyocardial hypertrophy

Heart damageHeart damage

Ventricular overloadVentricular overload

↓ ventricular contraction↓ ventricular contraction

Symptoms of HFSymptoms of HF

�� DyspnoeaDyspnoea

�� OrthopnoeaOrthopnoea

�� Paroxysmal nocturnal Paroxysmal nocturnal dyspnoeadyspnoea

�� ↓ exercise tolerance↓ exercise tolerance

�� Lethargy, fatigueLethargy, fatigue

�� Nocturnal coughNocturnal cough

�� WheezeWheeze

�� Ankle swellingAnkle swelling

�� AnorexiaAnorexia

�� Cachexia, muscle wastingCachexia, muscle wasting

�� TachycardiaTachycardia

�� Pulsus alternansPulsus alternans

�� ↑ jugular venous pressure↑ jugular venous pressure

�� Displaced apex beatDisplaced apex beat

�� Right ventricular heaveRight ventricular heave

�� Crepitations or wheezeCrepitations or wheeze

�� 33rdrd heart soundheart sound

�� EdemaEdema

�� HepatomegalyHepatomegaly

�� AscitesAscites

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Forward HFForward HF

�� ↓↓ stroke volume, stroke volume, ↓ ↓ ejection fraction (EF)ejection fraction (EF)

�� LV HF: LV HF:

�� Peripheral hypoperfusionPeripheral hypoperfusion

�� muscle weakness, fatigue, dyspepsia, oliguria, dizziness, confusion, muscle weakness, fatigue, dyspepsia, oliguria, dizziness, confusion,

cool extremities at restcool extremities at rest

�� RV HF: RV HF:

�� Hypoperfusion of lungsHypoperfusion of lungs

�� disorders of gas exchange disorders of gas exchange –– cyanosiscyanosis

�� ↓ blood supply to the left heart↓ blood supply to the left heart

Backward HFBackward HF

�� ↓↓ EF … blood congests EF … blood congests in front of ventriclesin front of ventricles

�� LV HFLV HF: :

�� ↑ pulmonary capillary pressure ↑ pulmonary capillary pressure … dyspnea, tachypnea, … dyspnea, tachypnea,

pulmonary edema (cardiac asthma) … arterial hypoxemia pulmonary edema (cardiac asthma) … arterial hypoxemia

and hypercapniaand hypercapnia

�� RV HF:RV HF:

�� ↑ pressure in systemic venous system ↑ pressure in systemic venous system … peripheral … peripheral edemas, abdominal discomfort, hepatomegaly, ascites, edemas, abdominal discomfort, hepatomegaly, ascites,

increased jugular venous pressure … increased jugular venous pressure … ↑ nocturnal diuresis↑ nocturnal diuresis

DyspnoeaDyspnoea

�� Subjectively perceived sensation of breathlessnessSubjectively perceived sensation of breathlessness

�� Exertional dyspneaExertional dyspnea�� Symptomless during restSymptomless during rest�� �� physical activityphysical activity → → �� Sp. → Sp. → vasoconstrictionvasoconstriction→ → �� venous returnvenous return → → �� pulmonary pressurepulmonary pressure → → �� pulmonary pulmonary compliancecompliance

�� OrthopneaOrthopnea�� Dyspnea in horizontal positionDyspnea in horizontal position�� blood redistribution from distal parts into the heartblood redistribution from distal parts into the heart

�� Paroxysmal nocturnal dyspneaParoxysmal nocturnal dyspnea�� horisontal positionhorisontal position ++�� PSp. PSp. during sleepingduring sleeping→ → �� contractility andcontractility and�� activityactivity of centre of breathingof centre of breathing

EdemaEdema

�� RV HF!RV HF!

�� Swelling of ankles, feetSwelling of ankles, feet

�� Right hypochondrial pain: liver distensionRight hypochondrial pain: liver distension

�� Abdominal swelling (ascites)Abdominal swelling (ascites)

�� Loss of appetiteLoss of appetite

�� Malabsorption: bowel edemaMalabsorption: bowel edema

�� ↑ in weight: fluid retention↑ in weight: fluid retention

Pulmonary edemaPulmonary edema

�� Accumulation of excessive amount of fluid in pulmonary Accumulation of excessive amount of fluid in pulmonary

interstice or in alveoliinterstice or in alveoli

�� ↑ hydrostatic pressure in pulmonary capillaries↑ hydrostatic pressure in pulmonary capillaries

�� ↑ permeability of capillary wall↑ permeability of capillary wall

�� ↓ colloid osmotic pressure in blood (↓ colloid osmotic pressure in blood (hypoproteinemiahypoproteinemia))

�� hypoxemia of the liver … ↓ albumin synthesishypoxemia of the liver … ↓ albumin synthesis

�� renal hypoperfusion … proteinuriarenal hypoperfusion … proteinuria

�� Breathlessness, cyanosis, Breathlessness, cyanosis, bbreath soundsreath sounds: : ccrackles, rackles,

wheezes, decreased breath sounds at bases (effusions)wheezes, decreased breath sounds at bases (effusions);;

expectoration of pink foamy sputum, horror mortiexpectoration of pink foamy sputum, horror mortiss

Fatigue and lethargyFatigue and lethargy

�� Impaired muscle blood flowImpaired muscle blood flow

�� Accumulation of lactateAccumulation of lactate

�� ↓ cerebral blood flow↓ cerebral blood flow

�� Somnolence, sleep disorders, confusionSomnolence, sleep disorders, confusion

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Dyspeptic syndromeDyspeptic syndrome

�� Insufficient perfusion of digenstive organsInsufficient perfusion of digenstive organs

�� Impairment of digestion, absorption of nutrients Impairment of digestion, absorption of nutrients

�� ↓ detoxication function of liver↓ detoxication function of liver

�� ↓ proteosynthesis in liver↓ proteosynthesis in liver

�� ↓ pancreas functions↓ pancreas functions

�� Generalized ↓ of muscular massGeneralized ↓ of muscular mass

�� Cardiac cachexiaCardiac cachexia

CyanosisCyanosis�� Blue color of the skin and mucose membranesBlue color of the skin and mucose membranes

�� ↑ reduced hemoglobin (>50 mg/L)↑ reduced hemoglobin (>50 mg/L)

�� Peripheral cyanosisPeripheral cyanosis

�� Normal saturationNormal saturation

�� Vasoconstriction: blood stagnating in tissues: cold, shock, HFVasoconstriction: blood stagnating in tissues: cold, shock, HF

�� Cold, pale auricles, nose, cheeks, external lips, tips of fingers and Cold, pale auricles, nose, cheeks, external lips, tips of fingers and toestoes

�� Central cyanosisCentral cyanosis

�� ↓ saturation↓ saturation

�� ↑ physical exercise, (inborn) heart defects with right↑ physical exercise, (inborn) heart defects with right--left shunts, left shunts, pulmonary diseases, HFpulmonary diseases, HF

�� Peripheral vasodilation: warm skin, dilated veinsPeripheral vasodilation: warm skin, dilated veins

�� Cyanotic tongue, palate, internal mucose of lipsCyanotic tongue, palate, internal mucose of lips

�� Polyglobulia, clubbed fingersPolyglobulia, clubbed fingers

ArrhythmiasArrhythmias

�� Atrial fibrillationAtrial fibrillation�� Cause / consequence of HFCause / consequence of HF

�� Mitral valve disease, thyreotoxicosisMitral valve disease, thyreotoxicosis

�� High risk of of stroke, thromboembolic complicationsHigh risk of of stroke, thromboembolic complications

�� Ventricular arrhythmiasVentricular arrhythmias�� Coronary ischemia, recurrent MI, hypoCoronary ischemia, recurrent MI, hypo--/hyper/hyper--kalaemia, kalaemia, hypomagnesaemia, digoxinhypomagnesaemia, digoxin

�� TachycardiaTachycardia�� Distension of atrial / ventricular wallsDistension of atrial / ventricular walls

�� ↑ Sp. ↑ Sp. sstimulationtimulation

Changes of heart rhythmChanges of heart rhythm Third heart sound (S3)Third heart sound (S3)

�� S1:S1: closing of mitral and tricuspid valves during systoleclosing of mitral and tricuspid valves during systole

�� S2:S2: closing of aortic and pulmonary valves during closing of aortic and pulmonary valves during diastolediastole

�� S3: S3: �� at the end of diastole, the ventricle is forced to dilate beyond at the end of diastole, the ventricle is forced to dilate beyond its normal range because the atrium has overloaded volumeits normal range because the atrium has overloaded volume

�� normal in children, young adults and pregnant women in 3rd normal in children, young adults and pregnant women in 3rd trimestertrimester

�� pathologic in dilated heart overloaded with blood (HF, mitral pathologic in dilated heart overloaded with blood (HF, mitral regurgitation)regurgitation)

�� heard best with the bell of the stethoscope placed at the apex heard best with the bell of the stethoscope placed at the apex while the patient is in the left lateral decubitus positionwhile the patient is in the left lateral decubitus position

S1S1 S2 S3S2 S3

Cardiovascular continuumCardiovascular continuumFramingham criteria for diagnosis of HFFramingham criteria for diagnosis of HF**

�� Major criteriaMajor criteria

•• Paroxysmal nocturnal dyspnoeaParoxysmal nocturnal dyspnoea

•• Raised JVP; distended neck Raised JVP; distended neck

veinsveins

•• Crepitations in lung fieldsCrepitations in lung fields

•• Cardiomegaly on CXRCardiomegaly on CXR

•• Acute pulmonary oedemaAcute pulmonary oedema

•• S3 gallop rhythmS3 gallop rhythm

•• Hepatojugular refluxHepatojugular reflux

•• Weight loss > 4.5kg in 5 days in Weight loss > 4.5kg in 5 days in

response to treatment of heart response to treatment of heart

failure.failure.

�� Minor criteriaMinor criteria

•• Bilateral ankle oedemaBilateral ankle oedema

•• Nocturnal coughNocturnal cough

•• Dyspnoea on ordinary exertionDyspnoea on ordinary exertion

•• HepatomegalyHepatomegaly

•• Pleural effusionPleural effusion

•• Tachycardia rate > 120/minTachycardia rate > 120/min

•• Decrease in vital capacity by Decrease in vital capacity by

one third.one third.

The diagnosis of heart failure required 2 major or one major and 2 minor criteria. Minor criteria The diagnosis of heart failure required 2 major or one major and 2 minor criteria. Minor criteria

were only acceptable if they could not be attributed to another medical disorder. were only acceptable if they could not be attributed to another medical disorder.

* From Ho, KL * From Ho, KL et alet al The epidemiology of heart failure: The Framingham Study. The epidemiology of heart failure: The Framingham Study. J Am Coll Cardiol 22J Am Coll Cardiol 22(Suppl A): 6A, (1993). (Suppl A): 6A, (1993).

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NYHA classification of heart failureNYHA classification of heart failure

�� Class IClass I No limitation of physical activity.No limitation of physical activity.

�� Class IIClass II Slight limitation of physical activitySlight limitation of physical activity——

symptoms with ordinary levels of exertion (e.g. symptoms with ordinary levels of exertion (e.g.

walking up stairs).walking up stairs).

�� Class IIIClass III Marked limitation of physical activityMarked limitation of physical activity——

symptoms with minimal levels of exertion (e.g. symptoms with minimal levels of exertion (e.g.

dressing).dressing).

�� Class IVClass IV Symptoms at rest.Symptoms at rest.

Pathophysiological principles of HF Pathophysiological principles of HF

therapytherapy

�� ↓↓ requirements on the work of the heartrequirements on the work of the heart

�� Improvement of the output of the heartImprovement of the output of the heart

�� Improvement of the function of peripheral Improvement of the function of peripheral

organs: kidneys!organs: kidneys!

�� ↑ i.c. Ca2+↑ i.c. Ca2+

�� Inh. of Na+Inh. of Na+--K+ ATPase:K+ ATPase:

�� Accumulation of i.c. Na+ … stim. of Na+Accumulation of i.c. Na+ … stim. of Na+--Ca2+ exchanger … ↑ Ca2+ exchanger … ↑

Ca2+Ca2+

�� Cardiac glycosids: Cardiac glycosids: digoxindigoxin

�� Stim. of Stim. of ββ11--rec. of cardiomyocytes … rec. of cardiomyocytes … ↑ Ca2+↑ Ca2+

�� CatecholaminesCatecholamines

�� Inh. of cardiac phosphodiesteraseInh. of cardiac phosphodiesterase

�� ↑ cAMP … ↑ Ca2+↑ cAMP … ↑ Ca2+

�� Amrinon, milrinonAmrinon, milrinon

�� LongLong--term ↑ i.c. Ca2+ … toxicity on cellsterm ↑ i.c. Ca2+ … toxicity on cells

�� Except of digoxin could ↑ mortalityExcept of digoxin could ↑ mortality

Stimulation of contractilityStimulation of contractility Inotropic agentsInotropic agents

�� ↑↑ coronary and cerebral blood flow coronary and cerebral blood flow

�� severe acute HF with low cardiac outputsevere acute HF with low cardiac output

�� DigoxinDigoxin

�� Cardiac glycosideCardiac glycoside

�� direct inotropic effects: directly on cardiac muscle … direct inotropic effects: directly on cardiac muscle … ↑↑ systolic systolic contractionscontractions

�� Indirect actions: Indirect actions: ↑↑ carotid sinus nerve activitycarotid sinus nerve activity

�� DobutamineDobutamine

�� Vasodilation, Vasodilation, ↑↑ inotropyinotropy

�� At higher dosages may cause At higher dosages may cause ↑↑ heart rate, exacerbating myocardial heart rate, exacerbating myocardial ischemia.ischemia.

�� DopamineDopamine

�� Catecholamine, precursor to NECatecholamine, precursor to NE

�� Stimulates adrenergic and dopaminergic receptorsStimulates adrenergic and dopaminergic receptors

�� LowLow--dose: dilation within renal and splanchnic vasculature … dose: dilation within renal and splanchnic vasculature … ↑↑ diuresisdiuresis

�� Moderate doses: Moderate doses: ↑↑ cardiac contractility and heart ratecardiac contractility and heart rate

�� Higher doses: Higher doses: ↑↑ afterload through peripheral vasoconstriction.afterload through peripheral vasoconstriction.

�� in severe heart failurein severe heart failure

�� NorepinephrineNorepinephrine

�� catecholamine catecholamine

�� Stimulates beta1Stimulates beta1-- and alphaand alpha--adrenergic receptorsadrenergic receptors

�� ↑↑ cardiac muscle contractility, heart rate, and vasoconstrictioncardiac muscle contractility, heart rate, and vasoconstriction

�� ↑↑ blood pressure and afterloadblood pressure and afterload

�� ↑↑ afterload may result in afterload may result in ↓↓ cardiac output, cardiac output, ↑↑ myocardial oxygen demand, and myocardial oxygen demand, and cardiac ischemiacardiac ischemia

Inotropic agentsInotropic agents

�� Optimal ventricular filling for ideal utilization of Optimal ventricular filling for ideal utilization of

FrankFrank--Starling mechanismStarling mechanism

�� ↓ venous return to optimal level↓ venous return to optimal level

�� restriction of physical activityrestriction of physical activity

�� ↓ salt intake↓ salt intake

�� venodilatorsvenodilators

�� �� dyspnoedyspnoe

Modification of preloadModification of preload

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DiureticsDiuretics

�� Symptomatic relief, in the presence of edemaSymptomatic relief, in the presence of edema�� elimination of retained fluid and preload reductionelimination of retained fluid and preload reduction

�� hhelp counteract the sodium and water retention caused by activation elp counteract the sodium and water retention caused by activation of the RAASof the RAAS

�� Loop diuretics:Loop diuretics: furosemidefurosemide

�� Thiazides:Thiazides: hydrochlorothiazidehydrochlorothiazide

plasma K+ levels! (K+ supplementation)plasma K+ levels! (K+ supplementation)

�� Potassium sparing diuretics:Potassium sparing diuretics: amiloride, spironolactoneamiloride, spironolactone

in combination with loop diureticsin combination with loop diuretics

�� In combination with iACEIn combination with iACE

VasodilatorsVasodilators�� Acute decompensationAcute decompensation

�� Intolerance of ACEIntolerance of ACE--I and ARBsI and ARBs

�� Nitrates:Nitrates: coronary vasodilation!coronary vasodilation!

�� Isosorbide dinitrate (nitroglycerin)Isosorbide dinitrate (nitroglycerin)�� firstfirst--line therapy for not hypotensive patients. line therapy for not hypotensive patients.

�� ↓↓ preload preload

�� mild mild ↓↓ afterloadafterload

�� rapid onset and offsetrapid onset and offset

�� Combine with Combine with hydralazinehydralazine�� ↓↓ systemic resistance (direct vasodilation of arterioles)systemic resistance (direct vasodilation of arterioles)

�� Nitroprusside (Nitropress)Nitroprusside (Nitropress)�� vasodilation and vasodilation and ↑↑ inotropic activity of the heart. At higher dosages, may inotropic activity of the heart. At higher dosages, may

exacerbate myocardial ischemia by increasing heart rate.exacerbate myocardial ischemia by increasing heart rate.

�� Nesiritide:Nesiritide: human BNPhuman BNP

Modification of afterloadModification of afterload

�� �� peripheral resistanceperipheral resistance, , �� peripheral vasoconstrictionperipheral vasoconstriction

�� �� resistance for cardiac workresistance for cardiac work

�� �� systolic volume and peripheral perfusionsystolic volume and peripheral perfusion

�� �� cardiac performance with lower energy consumptioncardiac performance with lower energy consumption

�� VasodilatorsVasodilators

�� Hydralasine, Hydralasine, αααααααα--sympatholyticssympatholytics

InodilatorsInodilators

�� Inotropic + vasodilatory effectInotropic + vasodilatory effect

�� Stim. heart contractility: Stim. heart contractility: ββ11--rec.: rec.: dobutaminedobutamine

�� Vasodilation: Vasodilation: ββ22--rec. rec.

�� Renal vasodilation: DA1Renal vasodilation: DA1--rec.: rec.: dopaminedopamine

�� Inh. of NE release from Sp. nerve endings: DA2Inh. of NE release from Sp. nerve endings: DA2--rec.rec.

�� ↑ contractility↑ contractility

�� VasodilationVasodilation

�� ↓ blood volume↓ blood volume

Modification of neurohumoral activation

�� positive inotropic, vasocontrictive and positive inotropic, vasocontrictive and proliferative effects:proliferative effects:�� Sp., angiotenSp., angiotensinsin II, aldosterII, aldosteroneone, endotel, endoteliin an andndvavassopresopresiinn

�� Activated during acute HF, acute hemodynamic Activated during acute HF, acute hemodynamic stressstress

�� Lasting activation in chronic HF damages heartLasting activation in chronic HF damages heart

�� EnergyEnergy--consuming, exhausted supplies, consuming, exhausted supplies, myocardial, vascular hypertrophymyocardial, vascular hypertrophy

�� Endothelial dysfunctionEndothelial dysfunction

Modification of neurohumoral activation

�� RAASRAAS inhibitioninhibition: :

�� ACEACE ((angiotensin converting enzyme) inhibitors angiotensin converting enzyme) inhibitors : :

ccaptopril, enalapril, perindoprilaptopril, enalapril, perindopril

�� angiotensin receptor blockersangiotensin receptor blockers:: valsartan, losartan, valsartan, losartan,

candesartancandesartan

�� aldosterone receptor blockersaldosterone receptor blockers:: spironolaspironolactonectone

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ACE inhibitors (ACEACE inhibitors (ACE--I)I)

�� Inhibit production of Ang II (vasoconstrictor, growth factor) Inhibit production of Ang II (vasoconstrictor, growth factor) … … vasodilationvasodilation

�� Increase production of bradykinin (Increase production of bradykinin (vasodilationvasodilation, release of , release of NO, PGI2, cough, hypotension, angioedema)NO, PGI2, cough, hypotension, angioedema)

�� Reduce activity of Sp. Reduce activity of Sp.

�� UpUp--regulate regulate ββ--receptorsreceptors

�� Improve variation in heart rateImprove variation in heart rate

�� Improve baroreceptor functionImprove baroreceptor function

�� Improve autonomic functionImprove autonomic function

�� ↓↓myocardial oxygen demandmyocardial oxygen demand

�� Captopril, enalapril, perindopril, ramiprilCaptopril, enalapril, perindopril, ramipril

Angiotensin receptor antagonists (ARBs)Angiotensin receptor antagonists (ARBs)

�� Effect on reducing mortality and morbidity comparable with Effect on reducing mortality and morbidity comparable with ACEACE--II

�� If intolarable side effects from ACEIf intolarable side effects from ACE--II

�� Valsartan, losartan, candesartanValsartan, losartan, candesartan

Aldosterone receptor antagonistsAldosterone receptor antagonists�� Management of edema from excessive aldosterone excretionManagement of edema from excessive aldosterone excretion

�� Competes with aldosterone for receptor sites in distal renal Competes with aldosterone for receptor sites in distal renal

tubules, tubules, ↑↑ water excretion while retaining potassium and water excretion while retaining potassium and

hydrogen ions hydrogen ions

�� spironolactonespironolactone

BetaBeta--adrenergic blockersadrenergic blockers�� ↓ sympathetic tone↓ sympathetic tone

�� (↓(↓ inotropic effect)inotropic effect)

�� ↓↓ heart rate: heart rate: ↑↑ myocardial perfusionmyocardial perfusion

�� vasodilationvasodilation

�� regression of LVH: regression of LVH: ↓↓ of the deleterious effects of excess of the deleterious effects of excess catecholaminescatecholamines

�� ↓ arrhythmias, ischemia, further infarction, myocardial ↓ arrhythmias, ischemia, further infarction, myocardial fibrosis, apoptosisfibrosis, apoptosis

�� ↓↓ in sudden death: in sudden death: ↓↓ in ventricular fibrillationin ventricular fibrillation

�� Chronic stable HF with LV systolic dysfunctionChronic stable HF with LV systolic dysfunction

�� Combination with diuretics, ACECombination with diuretics, ACE--II

�� Carvedilol, metoprolol, bisoprololCarvedilol, metoprolol, bisoprolol

Modification of neurohumoral activation

�� vasodilationvasodilation

�� �� Sp.Sp. activityactivity

�� �� pathological myocardial and vascular pathological myocardial and vascular remodelingremodeling, , �� fibrosisfibrosis

�� improvement of myocardial metabolism and improvement of myocardial metabolism and endothelial functionendothelial function

�� �� heart failure heart failure

�� �� sudden deathsudden death

Antithrombotic treatmentAntithrombotic treatment

�� Mobile ventricular thrombusMobile ventricular thrombus

�� Atrial fibrillationAtrial fibrillation

�� Severe cardiac impairmentSevere cardiac impairment

�� Ischemic heart diseaseIschemic heart disease

�� AspirinAspirin

�� WarfarinWarfarin

Non­pharmacological managementNon­pharmacological management�� ComplianceCompliance

�� DietDiet -- adequate general nutrition and, in obese patients, weight adequate general nutrition and, in obese patients, weight

reductionreduction

�� SaltSalt -- avoid high salt content foods (in severe cases of congestive heart avoid high salt content foods (in severe cases of congestive heart

failurefailure!)!)

�� FluidFluid -- urge overloaded patients and those with severe congestive heart urge overloaded patients and those with severe congestive heart

failure to restrict fluid intakefailure to restrict fluid intake

�� AlcoholAlcohol -- advise moderate alcohol consumption (abstinence in alcohol advise moderate alcohol consumption (abstinence in alcohol

related cardiomyopathy)related cardiomyopathy)

�� SmokingSmoking -- avoid smoking (adverse effects on coronary disease, adverse avoid smoking (adverse effects on coronary disease, adverse

haemodynamic effects)haemodynamic effects)

�� ExerciseExercise -- regular exercise should be encouragedregular exercise should be encouraged

�� VaccinationVaccination -- patients should consider influenza and pneumococcal patients should consider influenza and pneumococcal vaccinationsvaccinations

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Pharmacological managementPharmacological management

Clyde et al: ACCF/AHA Heart Failure Guidelines 2013

�� Diuretics: furosemide, hydrochlorotiazideDiuretics: furosemide, hydrochlorotiazide

�� ACE inhibitors: captopril, enalapril, perindoprilACE inhibitors: captopril, enalapril, perindopril

�� ββ--blockers: carvedilol, bisoprololblockers: carvedilol, bisoprolol

�� Ang II receptor blockers: candesartanAng II receptor blockers: candesartan

�� Aldosterone receptor antagonists: spironolactoneAldosterone receptor antagonists: spironolactone

�� Cardiac glycosides: digoxinCardiac glycosides: digoxin

�� Vasodilators: nitrates, hydralazineVasodilators: nitrates, hydralazine

�� Positive inotropics: dobutaminePositive inotropics: dobutamine

�� Antiplatelet agents, anticoagulants: (aspirin), warfarinAntiplatelet agents, anticoagulants: (aspirin), warfarin