MSR, May4 2010 Kenali, Ceagh dan Obati Gagal Jantung ! M. Saifur Rohman, MD, PhD Cardiologist Medical Faculty, Brawijaya University.

MSR, May4 2010

Kenali, Ceagh dan Obati Gagal Jantung !

M. Saifur Rohman, MD, PhDCardiologist

Medical Faculty, Brawijaya University

Definition of HF A syndrome associated with inadequate

performance of the heart.

Leading to neurohormonal and circulatory abnormalities

Adam KF et al. HFSA 2006 comprehensive heart failure guideline J Card Fail 2006; 12: e1-e122

Epidemiology

Heart failure is a major and growing cause of cardiovascular morbidity and mortality throughout the world

Approximately 5 million patients in USA have HF, and over 550 000 patients are diagnosed with HF for the first time each year.

HF is the primary reason for 12 to 15 million office visits and 6.5 million hospital days each year.

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

Causes of HF

• CAD• Hypertension• Valve disease (RHD, endocarditis)• Arrhythmias• Cardiomyopathy• Congenital heart disease• Pericardial Effusion

Systolic vs. Diastolic HF

Heart failure is a major and growing cause of cardiovascular morbidity and mortality throughout the world

Previously, it had often been assumed that most heart failure patients have underlying systolic dysfunction, which is responsible for their clinical presentation

It has become increasingly apparent over the last decade that many heart failure patients have a normal or nearly normal ejection fraction described as heart failure with preserved systolic function or preserved ejection fraction

HF-PEF affects primarily older patients, especially women; hypertension is the primary underlying condition, with CAD and prior MI being relatively infrequent

Hogg K, Swedberg K, McMurray J. J Am Coll Cardiol 2004; 43:317-327.

Systolic vs. Diastolic HF

Heart failure is 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

Diastolic Heart Failure/HF-PEF

Systolic Heart Failure

ACC-AHA guidelines 2001

Normal

Systolic heart failure

Heart failure with preserved systolic

function

Pathological/Echocardiographic Differences in LV Thickness with Different Forms of HF

Aurigemma GP et al. Circulation. 2006;113:296-304.

ParametersParameters SystolicSystolic HF-PSFHF-PSF

HistoryHistory• Coronary artery diseaseCoronary artery disease• HypertensionHypertension• DiabetesDiabetes• Valvular heart diseaseValvular heart disease• Paroxysmal dyspneaParoxysmal dyspnea

+ + ++ + ++ ++ ++ ++ +

+ + + ++ + + ++ ++ +

+ ++ ++ + + ++ + + +

+ ++ +——

+ + ++ + +

Physical ExaminationPhysical Examination• CardiomegalyCardiomegaly• Soft heart soundsSoft heart sounds• S3 gallopS3 gallop• S4 gallopS4 gallop• HypertensionHypertension• Mitral regurgitationMitral regurgitation• RalesRales• EdemaEdema• Jugular venous distentionJugular venous distention

+ + ++ + ++ + + ++ + + ++ + ++ + +

+++ ++ +

+ + ++ + ++ ++ +

+ + ++ + ++ + ++ + +

++++++

+ + ++ + ++ + + ++ + + +

+++ ++ +++++

Chest Roentgenogram (X-ray)Chest Roentgenogram (X-ray)• CardiomegalyCardiomegaly• Pulmonary congestionPulmonary congestion

+ + ++ + ++ + ++ + +

+++ + ++ + +

+ + + ++ + + +

+ + ++ + ++ + + ++ + + +

Systolic HF vs HF-PEF: Signs and Symptoms

Givertz MM et al. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease, A Textbook of Cardiovascular Medicine. 7th edition. Philadelphia, WB Saunders. 2001;534-561.

CHF vs. AHF

Current management of acute coronary syndrome has resulted in an improved survival after acute myocardial infarction.

This fact has created a rapid growth in the number of patients currently living with chronic heart failure.

Decompensation of preexisting chronic heart failure may cause acute heart failure (AHF).

Eur Heart J 2005;26:384-416

• AHF is defined as the rapid onset of symptoms and signs, secondary to abnormal cardiac function

• Cardiac dysfunction can be related to systolic or diastolic, to abnormalities in cardiac rhythm or to preload and afterload mismatch

• It is often life threatening and requires urgent treatment

Definition of Acute Heart Failure

ESC guideline for Acute Heart Failure, 2005

Cause of Acute Heart Failure

Acute coronary syndrome, hypertensive crisis and other cardiac or non cardiac also precipitate an AHF.

CAD contributes to 60-70 % in elderly Cardiomyopathy, CHD, arrhythmia, myocarditis and

valve diseases found in young

AHF therefore has significantly become the single most costly medical syndrome in emergency.

Eur Heart J 2005;26:384-416

Cause of Acute Heart Failure

Ischemic heart Disease Circulatory failureAcute Coronary Syndromes SepticemiaMechanical complication of acute MI ThyrotoxicosisRV infarction ShuntsValvular TamponadeValve stenosis Pulmonary embolismValve regurgitation DecompensationEndocarditis of preexisting CHFAortic disection Lack of adherenceMyopathies Volume overloadPostpartum cardiomyopathy Infection; pneumoniaAcute myocarditis Cerebrovascular insultHypertension/arrhythmia SurgeryHypertension Renal dysfunctionArrhythmia Asthma, COPD  Drug abuse  Alcohol abuse

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

Classification of AHF

• Patient with AHF present with six distinct

clinical conditions :

Worsening decompensated of chronic HF

Pulmonary edema

Cardiogenic shock

Hypertensive HF

Isolated right HF

ACS and HF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

In Hospital mortality ( 60 days) : 9.6% Rehospitalization and mortality : 32,5% 1 year mortality : 30%.

Mortality of AHF

Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.

Diagnosis of Heart Failure

Symptoms typical of HF Sign typical of HF Objective evidence of a structural or functional

abnormality of the heart at rest

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

Framingham Heart Failure Study Criteria

Major Acute pulmonary edema PND or orthopnea Crackles S3 gallop HJR/Increased JVP Cardiomegaly Wt loss >4.5 kg 5d into

Rx

Minor Night cough Tachycardia >120 Pleural effusion Hepatomegaly Ankle edema Vital capacity decrease

>1/3 from max

*Two major or one major and two minor*

NYHA I: no symptoms on ordinary activity

NYHA II: symptoms on ordinary exertion

NYHA III: symptoms on less-than ordinary

exertion

NYHA IV: symptoms at rest

NYHA Functional Heart Class

At Risk for CHF (ACC/AHA)

Stage A

At high risk of HF but without structural heart disease or HF symptoms:

Pts. with HTN, CHD, diabetes,obesity, metabolic syndrome OR Pts. using cardiotoxins or

family hx. cardiomyopathy

Stage B

Structural Heart Disease but without signs or symptoms of HF:

Pts. with previous MI, LV remodeling including LVH, and low LVEF OR asymptomatic valvular disease

Heart Failure (ACC/AHA)

Stage C

Structural heart disease with prior or current HF:

Pts. with known structural heart disease ANDSOB, fatigue, reduced exercise tolerance

Stage D

Refractory HF requiring specialized intervention:

Pts. with marked symptoms atrest despite maximalmedical therapyRecurrent hospitalizationUnsafe hospital discharge

Common Clinical Manifestation of HF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

Common ECG abnormalities in HF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

Common X-ray abnormalities in HF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

Common lab. abnormalities in HF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

Common echo. abnormalities in HF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

Diagnosis of HFClinical examination, ECG, Xray, Echocardiography

Natriuretic peptides

BNP 100-400 pg/mlNT-proBNP 400-2000 pg/ml

BNP<100 pg/mlNT-proBN P<400 pg/mL

BNP>400 pg/mlNT-proBNP>2000 pg/ml

Uncertain diagnosis

Chronic HF likelyChronic HF unlikely

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

A

L C

B

Congestion at rest

Yes

Yes

No

NoWarm & dry

Cold & WetCold & dry

Warm & wet

Low

perf

usi

on

at

rest

Sign of low perfusion:

Narrow pulse pressure,cool extremities,sleepy, suspect from ACEI hypotension, low Na, renal worsening

Sign of congestion:

Orthopnea,elevated JVP,edema,pulsatile hepatomegaly, ascites, rales,louder S3,P2 radiation left ward, abdomino-jugular reflex, valsava square wave

European Heart Journal of Heart Failure,2005; 7:323-331

Assessment of Haemodynamic Profile

Treatment HF

Bed rest Fluid management Drug Device Stem cell

ERAS OF HEART FAILURE MANAGEMENT

pre -1980’s 1980’s 1990’s 2000’s 2020’s ⇒

Pharmacological

• Digitalis

• Diuretics

• Vasodilators

• Inotropes

Device

• CRT

• ICDs

• LVADs

• Others?

Pharmacological

• Digitalis

• Diuretics

• Neurohormonal interventions

Non-pharmacological

• Bed rest

• Inactivity

• Fluid restriction

• (Digitalis, diuretics)

Cellular/genetic

• Gene therapies

• Cell implantation/ regeneration

• Xenotransplantation

Heart Failure Updates, 2003

THE DONKEY ANALOGY

Ventricular dysfunction limits a patient's ability to perform the routine activities of daily living…

HEART FAILURE

TREATMENT OPTION FOR HF

Like the carrot placed in front of the donkeyLike the carrot placed in front of the donkeyINOTROPIC

Reduce the number of sacks on the wagon

ACEI AND DIURETICS

ß-BLOKERS

Limit the donkey’s speed, thus saving energy

C

A

L

BWarm

Dry

Cold

Wet DiureticVasodilator

Inotropic drugs :DobutamineMilrinoneLevosimendan

Patient Treatment Selection

Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.

Treatment Algorithm in AHF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

Acute Heart Failure

Immediate symtomatic treatment

Patient distress or in pain

Pulmonary congestion

Arterial Oxygen saturation < 95%

Normal heart rate and rhythm

Yes

Yes

Yes

No

Analgesia, sedation

Medical therapyDiuretic/vasodilator

Increase FiO2,consider CPAP, NIVMechanical ventilation

Pacing, antiarrhythmias,electroversion

Treatment Algorithm in AHF

ESC Guideline for Acute Heart Failure, 2005

Treatment Algorithm in AHF

ESC Guideline for Acute Heart Failure, 2005

AHF with Systolic DysfunctionOxygen/CPAP

Furosemide + vasodilatorClinical evaluation (leading to mechanistic therapy)

SBP > 100 mmHg SBP 85-100 mmHg SBP <85 mmHg

Vasodilator(NTG, nitroprusside, BNP)

Vasodilator and/orInotropic (dobutamin

PDEI or Levosimendan)

Volume loading ?Inotrope and/or

Dopamin > 5mcg/kg/mntAnd/or norepinephrine

Good responseOral therapy

Furosemide, ACE-I

No respon :Reconsider mechanistic

therapyInotropic agent

Eur Heart J 2005;26:384-416

Treatment of HF

ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart

Failure , 2008

HF Prevention

Early diagnosis and prompt treatment of MI = ACS treatment

Treat Hypertension Treat and prevent DM to prevent

Cardiomyopathy DM Early diagnosis of Myocarditis to prevent

cardiomyoptahy

From MI to HF

Early diagnosis and vascularization prevent HF

Delay and inadequate treatment iireversible cardiomyocyte loss

Myocardial infarction leads to heart failure

Obstruction of coronary arteries leads to myocardial infarction (heart attack) with the associated death of cardiomyocytes

Regenerative capacity ? Not adequately compensate

Overloads the surviving myocardium and eventually leads to heart failure

Segers VF, Lee RT. Nature 2008; 451: 937-942.

Terminal differentiation of cardiomyocytes

Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle soon after birth in mammals1

The vast majority of adult cardiac myocytes the predominant form of growth postnatally is an increase in cell size (hypertrophy)2

This limits the ability to restore function after any significant injury2

1. Ahuja P, et al. Physiol Rev 2007; 87: 521–544. 2. Segers VF, Lee RT. Nature 2008; 451: 937-942.

Problem with Infarcted Heart

Current medical therapies of heart failure only delay progression of the disease

The only standard therapy for cardiomyocyte loss is cardiac transplantation

New discoveries on the regenerative potential of stem cells have transformed experimental research and led to an explosion in clinical investigation

Results ?

Segers VF, Lee RT. Nature 2008; 451: 937-942.

HF Prevention

Treat Hypertension Early diagnosis and prompt treatment of

MI Treat and prevent DM to prevent

Cardiomyopathy DM Early diagnosis of Myocarditis to prevent

cardiomyoptahy

MyocardialMyocardialinfarctioninfarction

Arrhythmia &Arrhythmia &loss of muscleloss of muscle

RemodellingRemodelling

VentricularVentriculardilatationdilatation

CongestiveCongestiveheart failureheart failure

DeathDeath

CoronaryCoronarythrombosisthrombosis

Myocardialischaemia

CADCAD

AtherosclerosisAtherosclerosisLVHLVH

Sudden DeathSudden Death

Risk factorsRisk factors HHypertensionypertension,, smoking, cholesterol, diabetessmoking, cholesterol, diabetes

Dzau V. Braunwald E, Am Heart J. 1991

The Cardiovascular Continuum

XPrevention I

XPrevention II

Optimal : <120 and < 80

Normal : 120-129 and/or 80 - 84

High Normal : 130-139 and/or 85-89 Pre-hypertension

Normal

Grade 1 : 140-159 and/or 90-99

Grade 2 : 160-179 and/or 100-109

Grade 3 : > 180 and/or > 110

Stage 1

Stage 2

ESC-ESH 2007 JNC-VII

Classification of Blood Pressure

JNC VII committee, JAMA 2003: 289;2560-2572

HYPERTENSION

90% lifetime risk of developing hypertension in people normotensive at age 55

People with lower educational and income levels tend to higher levels of blood pressure

American Heart Association Heart Disease and Stroke statistic 2006 Update, Texas, AHA2006

Epidemiology of Hypertension

Prevalence of Hypertension

± 2x

Kearney et al Lancet 2005Est

ablis

hed

Mar

ket

Econom

ies

Latin

Am

eric

a &

the

Carib

bean

Mid

dle E

aste

rn

Cresc

ent

Other

Asia

&

Isla

nds

Sub -Sah

aran

Africa

Former

Soci

alis

t

Econom

ies

Rate of hypertension%

Prevalence of hypertension in different regions of the world: Actual figures for 2000 - predicted for 2025

India

China

0

10

20

30

40

50

2025

0

10

20

30

40

50Men 2000Women

number of people with HT (millions)

number of people with HT (millions)

116.2 40.8 60.4 60.0 35.9 98.5 38.4 38.2123.3 52.5 57.8 54.3 37.9 83.1 33.0 41.6

147.9 44.0 107.3 102.1 72.2 151.7 67.3 73.6161.8 59.7 106.2 98.5 80.4 147.5 62.1 77.1

± 2x

Hypertension is Not Adequately Treated

Off all the USA people with high blood pressure:

11% are not on treatment regimen 25% are not on adequate treatment 34% are on adequate treatment

American Heart Association Heart Disease and Stroke statistic 2006 Update, Texas, AHA2006

Hypertension Prevalence and Treatment

Prevalence of Hypertension

0

5

10

15

20

25

30

35

40

45

50

55

Country

%

USCanada

Germany

ItalySwedenEnglandSpainFinland

0

10

20

30

40

50

60

70

80

90

100

Country

%

Wolf-Maier K et al. JAMA. 2003;289:2363-2369.

Patients on Therapy USCanada

Germany

ItalySwedenEnglandSpainFinland

Adapted from G. Mancia / L. Ruilope

USA: JNC VI. Arch Intern Med 1997Canada: Joffres et al. Am J Hypertens 1997 England: Colhoun et al. J Hypertens 1998France: Chamontin et al. Am J Hypertens 1998

< 140/90 mmHg< 140/90 mmHg

Canada

16

USA

27

England6

France

24

Marques-Vidal P et al. J Hum Hypertens 1997

< 160/95 mmHg< 160/95 mmHg

Finland

20.5

Spain

20

Australia

19

Germany

22.5

> 65 years

Scotland

17.5

India

9

Controlled Hypertension

Uncontrolled BP in Outpatient Clinic

HTN65.8%

Non HTN34.2%

Controlled39.3%

Uncontrolled60.7%

Three hundred third teen patients were randomly chosen among patients with or without known hypertension visited to Harapan Kita out patient

Hypertensinwas diagnosed in 65.8 % patients visiting to outpatient clinic Harapan Kita Cardiovascular Center

Among hypertensive patients only 39.3% reached blood pressure target of SBP<140 and DBP<90 mmHg Saifur Rohman et al. unpublished data, 2008

Blood Pressure Target Achievement in dr. Saiful Anwar Hospital

Optimized antihypertensive drug and Education for Compliance

Mifetika Lukitasari et al. ASMIHA abstract book, 2012Saifur Rohman et al. Asean Heart Journal 2011;19:20-23Mifetika Lukitasari et al. INASH abstract book, 2013

2011 2012

BP in AMI pts on EDAdmission : Awareness

Unaware of HT Aware of HT

SBP<140 and DBP<90

SBP≥140 and DBP≥90

Saifur Rohman et al. unpublished data, 2010

Increased blood pressure

Structural changes in compliance arteries

Compliance

Load on heart

Left Ventricular Hypertrophy

Left Ventricular Hypertrophy

Loss of buffering Function

Transmits Systolic pressure

Wave to small arteries

Perpetuation of Hypertension

Perpetuation of Hypertension

Shear stress on Artery wall

Endothelial dysfunction

Predisposes of AtherosclerosisPredisposes of Atherosclerosis

Consequences Structural Changes in Hypertension

Dzau VJ. Hypertension. 2001;37:1047-1052

The Progression from Hypertension to Heart Failure

HypertensionHypertension

M IM I

L V HL V H

DeathDeathC H FC H F

Diastolic dysfunction

Systolic dysfunction

Normal LVStructure & Function

LV remodeling

SubclinicalLV dysfunction

OvertHeart Failure

Time (months)

Time (decades)

Vasan RS, Levy D. 1996. Arch Intern Med 156 : 1759-1796

The Importance of HTN in Development of HF

Hypertension (HTN) is present in 91% of patients who develop CHF, tripling the risk of normotensive

HTN is a common risk factor of HF, treatable, and often under-treated

Hypertension remains the major preventable factor

Vasan RS, Levy D. 1996. Arch Intern Med 156 : 1759-1796

CHFCumulativeIncidence

(%)

Years From Baseline Exam

5 10 15

20

15

10

5

0

Lenfant C, Roccella EJ. J Hypertens Suppl. 1999;17:S3-S7.Data from Levy D et al. JAMA. 1996;275:1557-1562.

Stage 2 hypertension

Stage 1 hypertension

Normal BP

Cumulative Incidence of Heart failure in Normotensive and Hypertensive Patients

1 1.5 3.0 4.5 7.5

Hypertension

MI

Angina pectoris

Diabetes

LVH

Valvular disease

Prevalence (%)

6062

103

119

85

43

58

Attributable risk (%)

3959

3413

56

612

45

78

femaleLevy et al JAMA 1996

Heart failure development:Population-attributable risk

Hazard Ratio

male

Cost model based on 29 million adults in 5 EU countries(13% of population) with BP >160/95 mm Hg and a further

46 million (21%) with BP 140/90-160/95 mm Hg

Hansson et al Blood Press 2002

Annual acute management costs of inadequately treated hypertension

CV event Events (000s)

Costs (billion Euros)

Cost associated with uncontrolled BP

Acute MI

Heart failure

Stroke

All (95% CI)

442

815

964

2220

2.22

2.99

5.09

10.3 (9.8,10.8)

Events (000s)

Costs (billion Euros)

Cost saving if BP target attained

19

122

141

281

0.09

0.45

0.72

1.26 (0.80,1.90)

HF Prevention

Treat Hypertension Early diagnosis and prompt treatment of MI Adequate treatment of RHD Treat and prevent DM to prevent

Cardiomyopathy DM Early diagnosis of Myocarditis to prevent

cardiomyoptahy

Adequate and prevent recurrence of RHD

Recognition of acute rheumatic fever Prompt treatment AB prophylaxis Refer to cardiologist

HF Prevention

Treat Hypertension Early diagnosis and prompt treatment of MI Adequate treatment of RHD Early diagnosis and refer congenital heart

disease Early diagnosis of Myocarditis to prevent

cardiomyoptahy

Prevent development of HF in congenital heart disease

Early diagnosis Sent to cardiologist at proper time AB prophylaxis

HF Prevention

Treat Hypertension Early diagnosis and prompt treatment of MI Adequate treatment of RHD Treat and prevent DM to prevent

Cardiomyopathy DM Early diagnosis of Myocarditis to prevent

cardiomyoptahy

Prevent cardiomyopathy

Carditis : Viral, RHD, etc PPCM, SLE Prevent by early diagnosis and prompt

treatment

Summary

High mortality and morbidity of HF Preventable by HF Risk factor intervention,

Early diagnosis and prompt treatment