Hearth failureHearth failure

Doc.Dr Emir Fazlibegović,ESC,FESCDoc.Dr Emir Fazlibegović,ESC,FESCProf.Dr Mustafa Hadžiomerović, Prof.Dr Mustafa Hadžiomerović, ESC,FESCESC,FESC

5th International Congress of 5th International Congress of cardiologysts and angyologysts of cardiologysts and angyologysts of Bosnia and Herzegovina,Sarajevo Bosnia and Herzegovina,Sarajevo 2010.2010.

WHAT IS HEART WHAT IS HEART FAILURE?FAILURE?

““HF is a complex clinical syndrome that can result from any HF is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. The cardinal manifestations the ventricle to fill with or eject blood. The cardinal manifestations of HF are dyspnea and fatigue, which may limit exercise tolerance, of HF are dyspnea and fatigue, which may limit exercise tolerance, and fluid retention, which may lead to pulmonary and peripheral and fluid retention, which may lead to pulmonary and peripheral edema.edema.Both abnormalities can impair the functional capacity and quality of Both abnormalities can impair the functional capacity and quality of life of affected individuals, but they may not necessarily dominate life of affected individuals, but they may not necessarily dominate the clinical picture at the same time.”the clinical picture at the same time.”

Evaluation and Management of Chronic Heart Failure in the AdultEvaluation and Management of Chronic Heart Failure in the AdultA Report of the A Report of the ACC/AHAACC/AHA Task Force on Practice Guidelines Task Force on Practice Guidelines

February 2002February 2002

Supply is less then demandSupply is less then demand Failure of the heart as a pumpFailure of the heart as a pump

Systolic/Diastolic – does it matter?Systolic/Diastolic – does it matter?

Systolic:Systolic: heart heart cannot contract normallycannot contract normally and cannot pump enough blood into and cannot pump enough blood into the arteries (EF<40%)the arteries (EF<40%)

DiastolicDiastolic: : heart heart cannot relaxcannot relax and fill normallyand fill normally and cannot pump enough blood into and cannot pump enough blood into the arteries (EF>40%)the arteries (EF>40%)

Left, right, or both?Left, right, or both?

Right Heart FailureRight Heart Failure Results in increased, systemic Results in increased, systemic

venous congestion and peripheral venous congestion and peripheral oedemaoedema

Left Heart FailureLeft Heart Failure Results in pulmonary congestionResults in pulmonary congestion

Different etiology – so what?Different etiology – so what?

Many causesMany causes but clinical but clinical manifestations similarmanifestations similar– Coronary artery diseaseCoronary artery disease is the underlying cause of HF in is the underlying cause of HF in

approximately two thirds of patients with approximately two thirds of patients with ischemicischemic left left ventricular systolic dysfunction. ventricular systolic dysfunction.

– The remainder have The remainder have nonischemicnonischemic causes, e.g. causes, e.g. hypertension, valvular disease, myocardial toxins, or hypertension, valvular disease, myocardial toxins, or myocarditismyocarditis

– or may have no discernible cause (e.g., or may have no discernible cause (e.g., idiopathicidiopathic dilateddilated cardiomyopathycardiomyopathy).).

Compensated phaseCompensated phase– Supply temporarily meets the altered Supply temporarily meets the altered

demand, no or very mild symtoms demand, no or very mild symtoms and signsand signs

Decompensated heart failure:Decompensated heart failure:– new or worsening symptoms/signs of new or worsening symptoms/signs of

dyspnoea, fatigue or oedema leading dyspnoea, fatigue or oedema leading to hospitalisation or unscheduled to hospitalisation or unscheduled medical caremedical care

PHASE

Terminology or just Terminology or just semantics?semantics?

Congestive Heart Failure (CHF)Congestive Heart Failure (CHF) Heart failure withHeart failure with extra fluid in vessels and tissues extra fluid in vessels and tissues

Acute heart failure (AHF)Acute heart failure (AHF) sudden initial episode of HF, severe symptoms; frequent sudden initial episode of HF, severe symptoms; frequent pulmonary edemapulmonary edema Chronic heart failure (CHF) – (chronic HF)Chronic heart failure (CHF) – (chronic HF) Slow process of myocardium destruction, often Slow process of myocardium destruction, often unnoticed, mild to moderate symptoms; frequent unnoticed, mild to moderate symptoms; frequent peripheral edema, may follow acute insult peripheral edema, may follow acute insult

Acute exacerbation of chronic heart failureAcute exacerbation of chronic heart failure Immediate and massive decompensation of the Immediate and massive decompensation of the previously existing chronic heart previously existing chronic heart

Current indicationCurrent indication

Acutely Decompensated Severe Low-output Chronic

-24 hours?-Abruptly-Suddenly

SymptomaticNYHA III-IV

Cardiac –-EF<40%-CI<2.0 l/min/m2

-Cold

Pre-existing

Congestive Heart Failure (CHF)

Acute heart failure:Acute heart failure:

– sudden onset of symptoms or signs sudden onset of symptoms or signs of heart failure in a patient with no of heart failure in a patient with no history of heart failure and history of heart failure and previously normal cardiac functionpreviously normal cardiac function

ONSET

ONSETONSET

Exacerbation of chronic heart Exacerbation of chronic heart failure:failure:

– patient with established diagnosis of patient with established diagnosis of heart failure who develops heart failure who develops increasing signs or symptoms of the increasing signs or symptoms of the disease after a period of relative disease after a period of relative stabilitystability

Conceptual differences between Conceptual differences between acute and chronic heart failureacute and chronic heart failure

Chronic heart failure:Chronic heart failure:– neurohumoral disease that responds neurohumoral disease that responds

to neurohumoral interventionto neurohumoral intervention– Remodeling, RAAS, cateholamines, Remodeling, RAAS, cateholamines,

PDEPDE Acute heart failure:Acute heart failure:

– haemodynamic disease that responds haemodynamic disease that responds to haemodynamic interventionsto haemodynamic interventions

Classification and causes Classification and causes of heart failureof heart failure

Acute Acute de novode novo heart failureheart failure– Myocardial Myocardial

infarctioninfarction– ArrhythmiasArrhythmias– Valve destructionValve destruction– MyocarditisMyocarditis– Hypertensive crisisHypertensive crisis– Cardiac surgeryCardiac surgery

Decompensated Decompensated chronic heart chronic heart failurefailure– Myocardial Myocardial

ischaemiaischaemia– ArrhythmiasArrhythmias– MalcomplianceMalcompliance– InfectionsInfections– Salt overloadSalt overload– HypertensionHypertensionPulmonary oedema

Low output heart failure (congestion)Cardiogenic shock

Differences between acute heart Differences between acute heart failure and decompensated Chronic failure and decompensated Chronic HFHF

HaemodynamicsHaemodynamics::

AHFAHF: RV +/- LV, : RV +/- LV, normovolaemicnormovolaemic

Decompensation of Chronic HFDecompensation of Chronic HF: both RV and : both RV and LV, increased EDV, LV, increased EDV, hypervolaemichypervolaemic

PrognosisPrognosis::

AHFAHF: potentially reversible, stunning, sepsis: potentially reversible, stunning, sepsis

Decompensation of Chronic HFDecompensation of Chronic HF: chronic disease: chronic disease

DIAGNOSISDIAGNOSISFramingham CriteriaFramingham Criteria

Major CriteriaMajor Criteria

Parox. Nocturnal Parox. Nocturnal dyspneadyspnea

OrthopneaOrthopnea JVPJVP Pulmonary ralesPulmonary rales Third heart soundThird heart sound CardiomegalyCardiomegaly Pulmonary edemaPulmonary edema

Minor CriteriaMinor Criteria

Peripheral edemaPeripheral edema Night coughNight cough Dyspnea on exertionDyspnea on exertion HepatomegalyHepatomegaly Pleural effusionPleural effusion Heart rate>120/minHeart rate>120/min Wight loss Wight loss >> 4.5 kg 4.5 kg

in 5 daysin 5 days

ClassificationClassification

ONSETONSET ETIOLOGYETIOLOGY PATOPHYSIPATOPHYSIOLOGYOLOGY LOCATIONLOCATION NYHANYHA DIAGNOSISDIAGNOSIS

ACUTEACUTE

CHRONICHRONICC

ISCHEMICISCHEMIC

TOXICTOXIC

INFALMATORYINFALMATORY

REUMATOIDREUMATOID

IDIOPATICIDIOPATIC

SYSTOLICSYSTOLIC

DIASTOLICDIASTOLIC

LEFTLEFT

RIGHTRIGHT

II

IIII

IIIIII

IVIV

HEART HEART FAILUREFAILURE

Cardiac Cardiac insufficieninsufficiencycy

CARDIOMICARDIOMIOPATHYOPATHY

Cardiac Cardiac dysfunctiodysfunctionn

Treatment of Decompensated CHFTreatment of Decompensated CHF

DecompensatedHF PatientEdema (+)

Warm ExtremitiesSBP > 90 mm Hg

DecompensatedHF PatientEdema (+)

Cold ExtremitiesSBP > 90 mm Hg

DecompensatedHF PatientEdema (-)

Cold ExtremitiesSBP > 90 mm Hg

Optimization of therapy:•Increase ACEI doses•IV diuretics•Other PO or IV vasodilators (nitroprusside)

Levosimendan

DecompensatedHF Patient

Edema (+) or (-)Cold Extremities

SBP < 90 mm Hg

Dobutamine/Dopamine/Norepinephrine

Add Levo?

67% 20% 5%8%

Inadequate response:• Increasing BUN• Persisting edema• Persisting dyspnea

Low-output HF Cardio shockHigh output

Calcium-Induced Conformational Calcium-Induced Conformational Changes in Troponin ComplexChanges in Troponin Complex

Actin

Actin

TnT

TnT

cTnC

TnI

Tm

Tm

TnI

cTnC

cTnC

TnI

cTnC

TnI

Tm

TnTTm

Actin

Actin

Tm

Tm

TnT Myosin head

Myosin head

Ca2+

Ca2+

Ca2+

Ca2+

Myosin head

Myosin head

Myofilament length Myofilament length

LLevosimendanevosimendan

Calcium sensitisation through bindingCalcium sensitisation through bindingto troponin Cto troponin C

– increases cardiac contractility and increases cardiac contractility and efficiencyefficiency

Opening of ATP-sensitive potassium Opening of ATP-sensitive potassium channels in vascular smooth muscleschannels in vascular smooth muscles

– pulmonary, coronary, systemic pulmonary, coronary, systemic vasodilationvasodilation

Calcium Sensitization by Calcium Sensitization by LevosimendanLevosimendan

No increase in cAMPNo increase in i/c calcium

•No increase in energy consumption

•No arrhythmogenicity

•No impairment in relaxation

•Anti-stunning effect

•No antagonism by -blockers

Heart FailureHeart Failure

LIDO studyLIDO study– 203 patients with severe HF, levo vs. dobut203 patients with severe HF, levo vs. dobut

CASINO studyCASINO study– 299 patients low-output HF, levo vs. dobut vs. 299 patients low-output HF, levo vs. dobut vs.

placebo.placebo.

REVIVE-2 studyREVIVE-2 study– 600 patients. Levo vs placebo. Higher early 600 patients. Levo vs placebo. Higher early

mortality, but no difference at 90 days.mortality, but no difference at 90 days.

SURVIVE trialSURVIVE trial1327 patients, levo vs. dobutamine: No 1327 patients, levo vs. dobutamine: No mortality difference at 180 days.mortality difference at 180 days.

IHD and Cardiac IHD and Cardiac surgerysurgery RUSSLAN studyRUSSLAN study

– 504 patients with recent MI, levo vs. 504 patients with recent MI, levo vs. placebo. Trend to lower mortality at placebo. Trend to lower mortality at 180 days.180 days.

Small studies in cardiac surgery Small studies in cardiac surgery show levosimendan increases show levosimendan increases cardiac output and lowers SVRcardiac output and lowers SVR

Mostar study in 20 Mostar study in 20 patients NYHA III-IVpatients NYHA III-IV aged 43-84, average 69aged 43-84, average 69 All patients treated with ACE inhibitors, All patients treated with ACE inhibitors,

diuretic, beta blockers, aldosterone diuretic, beta blockers, aldosterone blockers, statins, and cardiotonics blockers, statins, and cardiotonics (digoxin chronically and dobutamin, (digoxin chronically and dobutamin, dopamine in the shortly crisis period). dopamine in the shortly crisis period).

on follow-upon follow-up 1-3 day after infusion and 1-3 day after infusion and 3 and 6 month, and 1-2-3 year after.3 and 6 month, and 1-2-3 year after.

Levosimendan and Levosimendan and NYHANYHA

4

3

2 2

4

3 3 3 3 3 3

2

4 4 4

2

4

2

3

2

4

3

4

3 3

2

4

2

4

3 3

4

3

2

4

3

4 4 4

3 3 3

0

0,5

1

1,5

2

2,5

3

3,5

4

1 1 1 1 2 2 2 3 3 3 4 4 5 5 6 6 7 7 7 8 8 9 9 10 10 11 11 12 12 13 13 14 15 16 16 17 17 18 18 19 19 20 20

NYHA kl.

Levosimendan and NYHALevosimendan and NYHA

MeanMean==-1.0000-1.0000 Std DevStd Dev==0.61240.6124 P< 0.0001 P< 0.0001

EFLV in patients with EFLV in patients with levosimendanlevosimendan

17%

48%

72%

64%

27%

35%33%

55%58%

53%

38%

69%

45%

37%

20%

57%

32%

45%

41%

82%

20%

43%

17%

27%

57%

71%

26%

45%

21%

37%

27%

32%35%

59%

36%

44%

36%

26%

32%

39%37%

52%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

1 1 1 1 2 2 2 3 3 3 4 4 5 5 6 6 7 7 7 8 8 9 9 10 10 11 11 12 12 13 13 14 15 16 16 17 17 18 18 19 19 20 20

EF

Levosimendan and EFLVLevosimendan and EFLV

MeanMean==15.705915.7059 Std DevStd Dev==14.395214.3952 P= P= 0.00040.0004

Levosimendan and Levosimendan and ENDLVENDLV

7,37,7

5,66,1

6,8 6,9 6,9

5,45,9

5,65

5,6

9,2

7,9

5,55,2

5,9 5,7 5,8 5,9

9,89,2

7,9

76,6

7,3

6,6 6,4 6,35,7 5,9

6,55,9

5,44,8

6,1

8,7 8,89

8,7 8,8

8,1

0

1

2

3

4

5

6

7

8

9

10

1 1 1 1 2 2 2 3 3 3 4 4 5 5 6 6 7 7 7 8 8 9 9 10 10 11 11 12 12 13 13 14 15 16 16 17 17 18 18 19 19 20 20

EndLV

Levosimendan and FSLevosimendan and FS

7%

25%

42%40%

13%

17%16%

29%31%

28%

18%

39%

23%20%

0

30%32%

35%

21%

51%

11%

22%

13%13%

31%

41%

12%

23%

15%18%

24%

17%17%

32%

17%

22%

18%

12%

16%

20%19%20%

0%

10%

20%

30%

40%

50%

60%

1 1 1 1 2 2 2 3 3 3 4 4 5 5 6 6 7 7 7 8 8 9 9 10 10 11 11 12 12 13 13 14 15 16 16 17 17 18 18 19 19 20 20

FS

Distrubtion of FS with Distrubtion of FS with levosimendanlevosimendan

Med=0.Med=0.08180818 SD=0.0915 P= SD=0.0915 P= 0.0020.002

Conclusion 1Conclusion 1

Experience from our practice Experience from our practice shows that single dose of shows that single dose of Levosimendan in patients with Levosimendan in patients with decompensated advanced heart decompensated advanced heart failure produces significant failure produces significant improvement, which reflects in improvement, which reflects in extension of life. extension of life.

Conclusion 2 Conclusion 2

Use of Levosimendan seams to be Use of Levosimendan seams to be beneficial demonstrated by great beneficial demonstrated by great benefit in the quality of life with benefit in the quality of life with better systolic function without better systolic function without any arrythmogenic effectany arrythmogenic effect..

Conclusion 3Conclusion 3

There are probably other benefits There are probably other benefits masked by uknown lusitropic and masked by uknown lusitropic and pleotropic influences of pleotropic influences of Levosimendan in the physiology Levosimendan in the physiology and pathophysiology of heart and and pathophysiology of heart and others systems of body. others systems of body.

Conclusion 4Conclusion 4

Almost all cases of death are Almost all cases of death are results of co-morbidity disease, results of co-morbidity disease, and are not related to and are not related to levosimendan effectlevosimendan effect

In the futureIn the future ICD deviceICD device Cardiac surgeryCardiac surgery TransplantationTransplantation