Kenali, Ceagh dan Obati Gagal Jantung !

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

2. Definition of HF • A syndrome associated with inadequate performance of the heart. • Leading to neurohormonaland circulatory abnormalities Adam KF et al. HFSA 2006 comprehensive heart failure guideline J Card Fail 2006; 12: e1-e122

3. 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

4. Causes of HF • CAD • Hypertension • Valve disease (RHD, endocarditis) • Arrhythmias • Cardiomyopathy • Congenital heart disease • Pericardial Effusion

5. 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.

6. 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

7. Pathological/Echocardiographic Differences in LV Thickness with Different Forms of HF Systolic heart failure Normal Heart failure with preserved systolic function Aurigemma GP et al. Circulation. 2006;113:296-304.

8. 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.

9. 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

10. Definition of Acute Heart Failure • 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 ESC guideline for Acute Heart Failure, 2005

11. 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

12. Cause of Acute Heart Failure ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

13. 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

14. Mortality of AHF • In Hospital mortality ( 60 days) : 9.6% • Rehospitalization and mortality : 32,5% • 1 year mortality : 30%. Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.

15. 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

16. 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 Framingham Heart Failure Study Criteria *Two major or one major and two minor*

17. NYHA Functional Heart Class 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

18. 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 At Risk for CHF (ACC/AHA)

19. Stage C Structural heart disease with prior or current HF: Pts. with known structural heart disease AND SOB, fatigue, reduced exercise tolerance Stage D Refractory HF requiring specialized intervention: Pts. with marked symptoms at rest despite maximal medical therapy Recurrent hospitalization Unsafe hospital discharge Heart Failure (ACC/AHA)

20. Common Clinical Manifestation of HF ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

21. Common ECG abnormalities in HF ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

22. Common X-ray abnormalities in HF ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

23. Common lab. abnormalities in HF ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

24. Common echo. abnormalities in HF ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

25. Diagnosis of HF Clinical examination, ECG, Xray, Echocardiography Natriuretic peptides BNP 100-400 pg/ml NT-proBNP 400-2000 pg/ml BNP<100 pg/ml NT-proBN P<400 pg/mL BNP>400 pg/ml NT-proBNP>2000 pg/ml Uncertain diagnosis Chronic HF unlikely Chronic HF likely ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

26. Assessment of Haemodynamic Profile Sign of congestion: Orthopnea,elevated JVP,edema,pulsatile hepatomegaly, ascites, rales,louder S3,P2 radiation left ward, abdomino-jugular reflex, valsava square wave Congestion at rest Low perfusion at rest No Yes B A No Warm & dry Warm & wet Cold & dry Cold & Wet L C Yes Sign of low perfusion: Narrow pulse pressure,cool extremities,sleepy, suspect from ACEI hypotension, low Na, renal worsening European Heart Journal of Heart Failure,2005; 7:323-331

27. Treatment HF • Bed rest • Fluid management • Drug • Device • Stem cell

28. ERAS OF HEART FAILURE MANAGEMENT • Non-pharmacological • Bed rest • Inactivity • Fluid restriction • (Digitalis, diuretics) • Cellular/genetic • Gene therapies • Cell implantation/ regeneration • Xenotransplantation • Pharmacological • Digitalis • Diuretics • Neurohormonal interventions pre -1980’s 1980’s 1990’s 2000’s 2020’s ⇒ • Pharmacological • Digitalis • Diuretics • Vasodilators • Inotropes • Device • CRT • ICDs • LVADs • Others? Heart Failure Updates, 2003

29. THE DONKEY ANALOGY Ventricular dysfunction limits a patient's ability to perform the routine activities of daily living… HEART FAILURE

30. TREATMENT OPTION FOR HF INOTROPIC Like the carrot placed in front of the donkey

31. Reduce the number of sacks on the wagon ACEI AND DIURETICS

32. ß-BLOKERS Limit the donkey’s speed, thus saving energy

33. Patient Treatment Selection Dry Wet Diuretic Vasodilator B A Warm Inotropic drugs : Dobutamine Milrinone Levosimendan Cold L C Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.

34. Treatment Algorithm in AHF Acute Heart Failure Immediate symtomatic treatment Patient distress or in pain Yes Analgesia, sedation Medical therapy Diuretic/vasodilator Pulmonary congestion Yes Increase FiO2, consider CPAP, NIV Mechanical ventilation Arterial Oxygen saturation < 95% Yes Normal heart rate and rhythm No Pacing, antiarrhythmias, electroversion ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

35. Treatment Algorithm in AHF ESC Guideline for Acute Heart Failure, 2005

36. Treatment Algorithm in AHF ESC Guideline for Acute Heart Failure, 2005

37. AHF with Systolic Dysfunction Oxygen/CPAP Furosemide + vasodilator Clinical evaluation (leading to mechanistic therapy) SBP > 100 mmHg SBP 85-100 mmHg SBP <85 mmHg Vasodilator (NTG, nitroprusside, BNP) Vasodilator and/or Inotropic (dobutamin PDEI or Levosimendan) Volume loading ? Inotrope and/or Dopamin > 5mcg/kg/mnt And/or norepinephrine Good response Oral therapy Furosemide, ACE-I No respon : Reconsider mechanistic therapy Inotropic agent Eur Heart J 2005;26:384-416

38. Treatment of HF ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008

39. 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

40. From MI to HF • Early diagnosis and vascularization prevent HF • Delay and inadequate treatment  iireversible cardiomyocyte loss

41. 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.

42. 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.

43. 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.

44. 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

45. Prevention II X Myocardialinfarction The Cardiovascular Continuum Sudden Death Coronarythrombosis Arrhythmia &loss of muscle Myocardialischaemia Remodelling Ventriculardilatation CAD Congestiveheart failure AtherosclerosisLVH Prevention I X Risk factorsHypertension,smoking, cholesterol, diabetes Death Dzau V. Braunwald E, Am Heart J. 1991

46. Classification of Blood Pressure ESC-ESH 2007 JNC-VII Optimal : <120 and < 80 Normal : 120-129 and/or 80 - 84 High Normal : 130-139 and/or 85-89 Normal Pre-hypertension HYPERT ENS ION Stage 1 Grade 1 : 140-159 and/or 90-99 Grade 2 : 160-179 and/or 100-109 Grade 3 : > 180 and/or > 110 Stage 2 JNC VII committee, JAMA 2003: 289;2560-2572

47. Epidemiology of 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

48. Prevalence of Hypertension Prevalence of hypertension in different regions of the world: Actual figures for 2000 - predicted for 2025 Rate of hypertension % 50 Men 2000 40 Women 30 20 10 number of 116.2 123.3 40.8 52.5 60.4 57.8 60.0 54.3 35.9 37.9 98.5 83.1 38.4 33.0 38.2 41.6 people with 0 HT (millions) ± 2x 50 ± 2x 2025 40 30 20 number of 10 147.9 161.8 44.0 59.7 107.3 106.2 102.1 98.5 72.2 80.4 151.7 147.5 67.3 62.1 73.6 77.1 people with 0 HT (millions) Other India China Saharan Africa Asia & Market Established Crescent Middle Eastern Latin America & Economies Former Socialist Islands - the Caribbean Economies Sub Kearney et al Lancet 2005

49. 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

50. Prevalence of Hypertension US 55 Canada 100 Italy 50 Sweden 90 45 England 80 Spain 40 70 Finland 35 % % Germany 60 30 50 25 40 20 30 15 20 10 10 5 0 0 Country Country Hypertension Prevalence and Treatment Patients on Therapy US Canada Italy Sweden England Spain Finland Germany Wolf-Maier K et al. JAMA. 2003;289:2363-2369.