Best wishes to YOU

1. Best wishes to YOU

2. Heart Failure Basics to Recent Advances Dr. R.V.S.N. Sarma., M.D., M.Sc.(Canada), FIMSA Consultant Physician and Cardiometabolic Specialist

3. Definition, Etiology Epidemiology and Pathophysiology

4. Floor Plan of This Talk

5. “The very essence of cardiovascular practice is early detection of Heart Failure” Sir Thomas Lewis, 1933

6. HF is a ‘BIG’ Subject • It afflicts millions of people worldwide • Has many diverse causes and risk factors • Large number of Mega trials and literature • High mortality; Several drugs and devices • A paradigm shift in understanding & Rx. • Extremely costly – huge no. of bed days • Complicated by many co morbidities • Truly multidisciplinary in its management

7. Detection of Heart Failure About half of the patients with left ventricular dysfunction had no symptoms and therefore would be difficult to identify at this early stage by clinical examination alone – underscoring the need for echocardiography. Framingham Heart Study has been the most important longitudinal source of data on the epidemiology of heart failure.

8. Why HF is increasing ? • Almost any disease of heart can cause it • More of HT, DM, MS, Obesity - ASCVD • CAD - which is its commonest cause • Better tools for diagnosis and availability • Better detection and treatment of causes • Better Rx. of RF, CAD, MI - PTCA, CABG • Increasing longevity of the population • HF is an aging process – longer life span

9. Important Points • Chronic Heart Failure (CHF) can be caused by any type of cardiac dysfunction • Most commonly attributable to LV Dysfunction • Rarely HF is due to isolated RV dysfunction • Most common and best studied cause of CHF is LV Systolic Dysfunction (LVSD) • Normal Ejection Fraction Heart Failure (NEFHF) is due to LV Diastolic Dysfunction – (HFPSF) • It is difficult to diagnose and quantify.

10. Floor Plan of This Talk

11. Definitions of Heart Failure Heart failure is a clinical syndrome characterized by decreased systemic perfusion, inadequate to meet the body's metabolic demands as a result of impaired cardiac pump function - Cleveland Clinic A pathophysiologic state in which an abnormality of cardiac function is responsible for failure of the heart to pump blood at a rate commensurate with metabolic requirements of the tissues -E Braunwald

12. Definition of HF Physiological: Inability of the heart to pump sufficient oxygenated blood to the metabolizing tissues despite an adequate filling pressure. Working Clinical Definition: Clinical syndrome consisting of symptoms such as breathlessness, fatigue, and swelling of ankle caused by cardiac dysfunction.

13. Types of Heart Failure • Chronic Heart Failure (CHF) • Acute Heart Failure (Cardiogenic Shock) • Systolic Failure (LVSD) – Reduced EFHF • Diastolic Heart Failure (LVDD) – NEFHF • Left Heart Failure (LVF) • Right Heart Failure (Congestive CCF) • Forward Failure and Backward Failure • High output failure -Thyrotoxic, Paget's, Anemia, Pregnancy, A-V fistula • Low output failure – 95% of HF is this

14. Floor Plan of This Talk

15. Heart Failure – Some Statistics • Affects 10% of people over 65 years • Affects over 50% of people with 85+ years • Approx 10% of patients with HF die each yr. • It is the most common condition for which patients 65 + require admission to hospital • It is NOT a single disease – A syndrome • Results from any cardiac disorder that impairs the ability of the ventricles to fill with or eject blood

16. Epidemiology of Heart Failure

17. Epidemiology of Heart Failure Data from Framingham Heart Study per 1000 population

18. Incidence of Heart Failure McKee PA et al. Framingham study; N Eng J Med 1971; 285: 1441-6

19. Ethnic Differences in HF Sosin MD, et al. Eur J Heart Fail 2004;6:669-72

20. Age, MI and Heart Failure

21. Prevalence of Chronic AF in HF 181 92 9970 11062 11016 No in study Cleland JG, et al. Heart Fail Rev 2002;7:229-42

22. Systolic Heart Failure • LVSD – Left Ventricular Systolic Dysfunction • Most common type of Heart Failure; 60-70% • LV is usually dilated & enlarged. • Fails to contract normally due to WMA, Ischemia • Cannot pump sufficient blood to meet needs • Normal ejection fraction (EF) is at least 50-55% • In LVSD heart failure the EF is <40 -45% • This carries a 10% mortality per annum

23. Diastolic Heart Failure • Accounts for 20-40% of patients • Ventricles are normal-sized with normal emptying • But there is an impairment in the ability of the ventricles to fill with blood during diastole. • Because of stiff myocardium due to hypertrophy • The heart fails to relax normally (relaxation poor) • Generally older women • Hypertension is the commonest cause • This carries a 5-8% mortality per annum

24. Population Differences in DHF McMurray JJ, et al. Lancet 2005;365:1877

25. Floor Plan of This Talk

26. Causes of Heart Failure • Coronary Artery Disease (MI, IHD) (2/3 of cases) • Hypertension(common fore runner of LVSD, LVDD) • Diabetes Mellitus (via IHD, direct cardiomyopathy) • Cardiomyopathy (DCM, HOCM, OCM, RCM) • Valvular Heart Disease (MS, MR, AS, AR) • Congenital Heart Disease (ASD, VSD) • Arrhythmias (AF, Brady, Tachy, Heart Block, SSS) • ‘High output’ failures (Anemia, hyperthyroidism, AV-F) • Pericardial Disease (Constrictive, Effusion) • Right Heart Failure (PHT, PE, Cor Pulmonale)

27. Drugs and Heart Failure Many drugs may precipitate HF or cause its deteriorate Sodium and water retention agents • Glucocorticoids, androgens, estrogens, NSAIDs (dose dependent), Aspirins, Alginates Negative Inotropic agents • Anti arrhythmics, NDHP CCBS-Diltiazem & Verapamil • Non selective beta blockers especially in NYHA class IV particularly when used in large doses Cardio toxins: Anthracyclines – Anti tumour- doxorubicin Decongestants, High sodium containing drugs

28. Precipitating Causes of HF • Arrhythmias, especially atrial fibrillation • Infections (especially pneumonia) • AMI, Angina pectoris or recurrent MI • Anemia, Alcohol excess, Pregnancy • Iatrogenic - postoperative fluid replacement or • Poor drug compliance in pts on treatment for HT • Thyroid disorders—Thyrotoxicosis • Use of steroids or NSAIDs • Pulmonary embolism BMJ Vol . 320, 22 Jan 2000

29. Changing Pattern of Etiology McMurray J J, Stewart S Heart 2000;83:596-602

30. Major Risk Factors

31. Ethnicity – Etiological factors Sosin MD, et al. Eur J Heart Fail 2004;6:831-43

32. Cardiomyopathies

33. Floor Plan of This Talk

34. Pathophysiology of Heart Failure Developments in our understanding of the Pathophysiology of heart failure have been essential for recent therapeutic advances After MI, plasma concentration of norepinephrine is of prognostic value in the early phase after MI Natriuretic peptides are also shown to predict outcome after MI – “The Leukocyte Count of HF”

35. Cardiac Output CO = SV x HR CO is cardiac output expressed in L/min Normal Cardiac Output is 5 L/min SV ( Stroke Volume) is volume of blood put out/beat Pre load, After load and Contractility determine the SV HR (Heart rate) - number of beats/minute (Chronotrop) Normally SV = 70 ml/beat. HR = 70/mt; so CO = 70 x 70 = 4,900 ml/mt or 5 L approximately

36. Important Concepts • Contractility:  Contractility is the intrinsic ability of cardiac muscle to develop force for a given muscle length.  It is also referred to as inotropism. • Pre load:  Preload is the muscle (stretch) length prior to contractility, and it is dependent of ventricular filling (or LVend diastolic volume). This is in turn dependent on LV end diastolic pressureand LA pressure. The most important determining factor for pre load is venous return. • After load:  It is the tension (or the arterial pressure) against which the ventricle must contract.  After load for the left ventricle is determined by aortic pressure which in turn is dependent on peripheral arterial resistance.

37. LV Ejection Fraction (EF%) LV EF% = LV Diastolic Volume – LV Systolic Volume LV Diastolic Volume X 100 LV EF% = (140 ml – 70 ml) = 70 ml 140 ml X 100 LV-EF% = 50% (Normal 50 to 70%) May go up to 90% with exercise

38. Mechanisms of Heart failure

39. Frank-Starling Curves

40. Sustained LVDF Leads to

41. Complex Mechanisms in HF • Heart Failure is multi system syndrome • Abnormalities of cardiac and skeletal muscle • Abnormal renal function • Stimulation of sympathetic nervous system • Complex pattern of neuro humoral changes • Ventricular Remodeling • Damage to the myocytes & extracellular matrix • Changes in size, shape and function of LV • Electrical instability – causing arrhythmias • Systemic processes with sequelae in organs

42. Pathophysiology of HF • Decreased cardiac output results in •  End Diastolic Pressure (LVEDP), LVH, LVD •  Pulmonary Capillary Wedge Pressure (PCWP) • The development of pulmonary edema • Activation of Neurohormonal Mechanism • Renin-Angiotensin-Aldosterone- System (RAAS) • Sympathetic Nervous System (SNS) • Other circulating and paracrine effects • Counter-regulatory systems • Natriuretic Peptide System (BNP, pro BNP)

43. Understanding RAAS Globular protein Deca (10 AA) peptide Octa (8 AA) peptide

44. Angiotensin II Receptors ARBs ALDO

45. ACE ACE2 RENIN ACE2 AT II – Major Effector Hormone AT-I (1- 7,9) Vasoconstriction  Sympathetic  Aldosterone Non ACE pathways

46. Pathological Effects of RAAS

47. AT II and Aldosterone Havoc AT II is the key hormone • Increased AT II • Vasoconstriction • Myocyte hypertrophy • Myofibril fibrosis •  Aldosterone release • Activation of NA • Activation of ETH • ED – NO,  Inflam. Aldosterone Excess imp. • Na and H2O retention • Hypokalemia • Volume over load • Pulmonary edema • Peripheral edema • Myocardial apoptosis • Myocardial fibrosis • Increased after load

48. Harmful Effects of Angiotensin II

49. Adverse Effects of Aldosterone Aldosterone Glomerulosclerosis Interstitial Fibrosis Proteinuria Renal Failure LVH Cardiac Fibrosis LV Dysfunction Heart Failure Endothelial Dysfunction Inflammation Oxidative Stress MRA – Eplerenone Brand name: Eplirestat

50. RAAS Axis and its Blockade