Heart Failure

1. Heart Failure J.B. Handler, M.D. Physician Assistant Program University of New England

2. CO- cardiac output PCW- pulmonary capillary wedge SVR- systemic vascular resistance SVR  PVR (peripheral vascular resistance) HR- heart rate JVD- jugular venous distension A+V- arterial and venous C- cardiac EF- ejection fraction ED- emergency department LHF- left heart failure BVF- biventricular failure P- Pulmonary ACEI- angiotensin converting enzyme inhibitor ARB- angiotensin receptor blocker NYHA- New York Heart Association criterion BNP- beta natiuretic peptide MVO2- myocardial oxygen consumption ICD- implantable cardioverter defibrillator RHF- right heart failure CRT- cardiac resynchronization therapy Abbreviations

3. Heart Failure: Definition • 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 the requirements of the metabolizing tissues and/or can do so only from an abnormally elevated diastolic volume/pressure.

4. Heart Failure Basics • Over 5 million patients in U.S. with HF • 550,000 patients newly diagnosed each year • > 1 million hospitalizations/yr- HF as 1st Dx; >2.5 hospitalizations- HF among Dx. •  number of HF deaths in spite of advances in Rx: • Increased salvage of patients with acute MI • Numbers are rising as “baby boomers” age • Management must be individualized

5. Etiologies of Heart Failure (HF) • Coronary Heart Disease: MI(s) or ischemia superimposed on prior infarction(s) 75% of all cases. • Primary pump failure - Cardiomyopathy, viral myocarditis • Valvular heart disease • Congenital heart disease • Long standing, uncontrolled hypertension

6. Precipating Causes • Progressive weakening of the myocardium and consequences heart failure • Infection • Anemia • Thyrotoxicosis • Arrhythmias • Aggravation of hypertension • Myocardial ischemia or infarction • Physical, dietary (Na/fluid) or emotional excesses

7. HF: Systolic or Diastolic? • Systolic Failure (or dysfunction): Primary contraction abnormality; inadequate delivery of O2 to tissues and associated symptoms; e.g: large or multiple MI(s), dilated cardiomyopathy, chronic AR, MR. • Diastolic Failure (or dysfunction) - Impaired ventricular relaxation- elevation of ventricular filling pressures and associated symptoms; e.g: long standing hypertension (with LVH), hypertrophic cardiomyopathy, acute ischemia, prior infarcts, restrictive cardiomyopathy. • Systolic and diastolic failure often occur together.

8. HF: Acute or Chronic? • Acute - Large MI sudden onset of symptoms, systolic failure, hypotension, pulmonary edema. • Chronic - pathophysiology and symptoms develop slowly, BP usually maintained until late in course; peripheral edema common; e.g: dilated cardiomyopathy, chronic valvular insufficiency, large or multiple infarcts. • Acute episodes may be superimposed on chronic HF development of pulmonary edema in patient with previously compensated (treated) HF.

9. HF: Rt Sided or Lt Sided? • Lt sided failure e.g: post MI, aortic/mitral valve disease. Inadequate CO with pulmonary congestion and related symptoms. • Rt. sided failure e.g: COPD/pulmonary hypertension, pulmonic stenosis; associated with peripheral edema, hepatic congestion, etc. • Most common cause of right sided failure is left sided failure/dysfunction!

10. Cardiac Pressures 4-12 4-12 4-12 4-12 8-15 4-12 4-12 Images.google.com

11. HF: Backward or Forward? • Backward failure: Inadequate ventricular emptying; pressures in the atrium and venous system behind the failing ventricle rise resulting in transudation of fluid into interstitial spaces. • Forward failure: Inadequate forward CO; Na and water retention result from diminished renal perfusion and activation of renin-angiotensin-aldosterone system.

12. Compensatory Mechanisms • Redistribution of CO: Blood flow redistributed to vital organs- brain and myocardium with reduced blood flow to skin and muscle mediated via activation of the adrenergic nervous system and vasoconstriction to less vital tissues. • Na and water retention: Complex sequence of adjustments occurs resulting in accumulation of fluid and increasing SVR: • Helps maintain CO via Starling mechanism • Cost is volume overload and afterload.

13. Adrenergic Nervous System • Activated in CHF-beneficial and harmful. • Increase levels of norepinephrine result in increase HR, contractility and SVR- helps maintain arterial perfusion pressure (BP) in presence of decreased CO. • Elevation of SVR results in increased hemodynamic burden (afterload) and O2 requirement of the failing ventricle. Long term elevation of catecholamines lead to progressive myocardial damage and fibrosis. BP = CO x SVR CO = BP/SVR

14. Renin-Angiotensin System • Renin: enzyme released by kidneys if perfusion or BP. • Angiotensinogen (renin substrate) converted to Angiotensin I by renin. • Angiotensin I converted to Angiotensin II in lungs by angiotensin converting enzyme. • Angiotensin II – extremely potent vasoconstrictor- leads to arteriolar constriction and increase in SVR, raising BP.

15. Renin-Angiotensin System • Angiotensin II stimulates adrenal gland to secrete Aldosterone. • Aldosterone a mineralocorticoid hormoneincreases renal Na and H2O reabsorption. • Renin-angiotensin-aldosterone activation (by decreased cardiac output) in heart failure is a major factor in edema formation and increased SVR. • Long term activation of angiotensin II and aldosterone lead to myocardial thinning and fibrosis (remodeling).

16. Functional Classification of Heart Disease: NYHA Criterion • I: No limitation of physical activity. No symptoms of SOB, CP dizzyness, etc. • II: Slight limitation of physical activity. Some (ordinary) activities (exercise, exertion, etc) cause symptoms. • III: Marked limitation of physical activity. Less than ordinary activities (walking, dressing, etc.) cause symptoms. • IV: Symptomatic at rest or minimal activity; unable to engage in any physical activity.

17. Clinical Manifestation of HF • Dyspnea: Initially with activity, then at rest; due to elevation of pulmonary venous pressure. • Orthopnea: Dyspnea in recumbent position; redistribution of fluid from abdomen and lower extremities into chest. • Paroxysmal Nocturnal Dyspnea: Attacks of severe SOB, coughing and wheezing awakening patient from sleep. • Unexplained weight gain: Sodium and water retention. Patients may note swelling of the legs. • Nocturia commonly occurs

18. Fatigue, weakness, abdominal symptoms, decreased exercise capacity; reflects CO to muscles, GI tract and other organs. • Cerebral symptoms (esp. in patients with co-existing cerebrovascular disease): Decreased perfusion to brain. • Acute Pulmonary Edema : Severe dyspnea at rest as pulmonary congestion progresses; accompanied by marked elevation of pulmonary capillary pressure leading to alveolar edema; *PCW >20  interstitial edema; PCW > 25  alveolar edema. A medical emergency usually addressed in ED. *PCW: Pulmonary Capillary Wedge pressure

19. Physical Exam (L+R sided HF) • Symptoms vary depending on severity. • Patient may be uncomfortable lying flat; BP normal or low; tachycardia common. Cyanosis of lips & nailbeds reflects hypoxemia. • Crackles (Rales- older term)- moist inspiratory crackles; wheezes. Begin at bases and progress upwards through the lungs. • S3 gallop- low pitched sound in early diastole.

20. Physical Exam (L+R sided HF) • Increased systemic venous pressure; JVD reflects JVP. • + Hepato-Jugular Reflux. • Congestive hepatomegaly- enlarged, tender, pulsatile liver.

21. Physical Exam • Peripheral edema develops with progressive HF. • Hydrothorax and ascites- pleural effusions. • Cardiac cachexia- “Wasted appearance” occurs with severe chronic heart failureweight loss, anorexia, nausea; correlates with increased levels of cytokines like circulating tumor necrosis factor.

22. Additional Findings • CxR: Cardiomegaly; distension of pulmonary veins; venous redistribution to apices; interstitialalveolar edema; pleural effusions. • Echo-Doppler- findings unique to pathology responsible for HF; best non-invasive tool. Identifies ventricular dysfunction and EF. • ECG- may reflect underlying pathology i.e. infarct, LVH, arrhythmia, etc.

23. CxR: CHF

24. -type Natriuretic Peptide • NP- hormone produced by heart (ventricle) in response to wall stress- marker of decompensated heart failure in blood. • Blood test for acute ventricular dysfunction  symptomatic heart failure • Useful in diagnosis of HF in patients presenting with SOB of uncertain (C vs P) etiology and confirming HF when suspected clinically. • Has vasodilator (a&v) and diuretic properties- new Rx for treating refractory heart failure (below). • Normal is < 100 pg/ml

25. Pathophysiologic Basis of Therapy • Taylor treatment to the manifestations of heart failure in each individual patient. • Excessive increase in preload: diuretics, venodilators (nitrates). • Excess Na retention with edema: diuretics. • Increased afterload: Vasodilator therapy • ACE inhibitors, Angiotensin Receptor blockers and others.

26. Pathophysiologic Basis of Therapy • Myocardial systolic failure -Rx. to improve contractility- Digoxin; sympathomimetics. • Slow progression of cardiac deterioration- ACE inhibitorsBeta blockers Spironolactone • Improve diastolic dysfunction if possible: regression of LVH with treatment of co-existing HTN • Treat arrhythmias as needed Prevent Remodeling

27. Mortality in Heart Failure • Overall poor prognosis once symptomatic • Severe failure (class IV)- 40-50% mortality in 12 months • Moderate failure (class III)- 40-50% mortality in 3-4 yrs • Ejection Fraction (EF) is predictive • 30-40% die suddenly- arrhythmia.

28. HF: Goals of Therapy • Removal of precipitating factors. • Treatment of underlying cause active ischemia, valvular disease, cardiomyopathy, etc. • Control of the HF state:Reduction of cardiac workloadControl of excessive Na/water retentionEnhancement of cardiac contractility • Early initiation of ACEI therapy for most patients • Hydralazine and nitrates in black populations; added to ACEI if needed.

29. Treatment of HF • Reduction of cardiac workload – decreased/limited activity; elastic stockings, anxiolytic therapy; anticoagulation for prolonged bed rest. • Control excessive dietary sodium (4 gram Na diet or less). • No added salt; no salt in preparation of foods; avoid foods with high sodium content.

30. Diuretics • Early addition of diuretics beneficial in relieving symptoms (shortness of breath) and reducing preload- does not mortality. • Loop diuretics: Most potent diuretics and cornerstone of diuretic Rx in CHF- Furosemide, Bumetanide, Torsemide • Metolazone - similar to thiazide diuretics; added to and potentiate loop diuretics in severe, refractory heart failure; caution K

31. Diuretics • Loop diuretics remain effective in renal failure. • Must monitor renal function (BUN, Cr.) serum electrolytes (esp. K), uric acid and glucose; loop diuretics can cause hypokalemia, and hyperuricemia as well as metabolic alkalosis. • Over aggressive diuresis can lead to pre-renal azotemia impaired renal fx from hypovolemia and perfusion. • Triamterene and Amiloride are weak diuretics that are K sparing - elevate K levels; may be used in combination with loop diuretics to offset K losses

32. Vasodilator Therapy in HF • LV afterload always elevated in HF due to neural and humoral influences that act to constrict the peripheral vascular bed and elevate SVR; preload also increased from Na/H20 retention. • In presence of impaired cardiac function, increasing afterload will reduce cardiac output further and lead to elevation of pulmonary pressures and pulmonary congestion. • In patients with acute and chronic HF, treatment with vasodilators results in: decreasing SVR, increasing CO, decreasing PCW, and relief of symptoms; also decreases mortality.

33. Angiotensin Converting Enzyme Inhibitors • Activation of the Renin-Angiotensin-Aldosterone system in heart failure results in marked vasoconstriction via Angiotensin II and Na and H2O retention via Aldosterone. • ACE Inhibitors dramatically reduce afterload, and to a lesser degree, preload in patients with HF by ing the production of Angiotensin II and aldosterone. • CO= BP/SVR

34. ACE Inhibitors • Superior to all other treatment of HF in terms of long-term symptomatic improvement and outcome - Reduce mortality by >25+%. • Long term ACEI has significant natriuretic effects resulting in improved diuresis. • Captopril, enalapril, lisinopril, ramipril, fosinopril, perindopril et al; all equally beneficial.

35. ACE Inhibitors • ACEI decrease remodeling of the LV post MI and in HF by reducing wall thinning, fibrosis and interfering with programmed cell death (apoptosis) result is  mortality. • Elevation of kinins from ACE inhibition may also have beneficial effects on hemodynamics (vasodilation) and remodeling – increased levels of prostaglandins and nitric oxide – vasodilation.

36. LV Remodeling NYerRN

37. Limitations of ACEI • Fall in systemic BP. ACEI usually well tolerated if initiate with low dose and gradually increase. • Cough- Drug related persistent cough resulting from elevated bradykinin levels; occurs in up to 15-20% of patients, but only 5% need to DC the drug. • Less effective in black populations. Hydralazine + long acting nitrates are added to ACEI prn. • BiDil: Hydralazine + isosorbidedinitrate • Must monitor renal function; Cr and BUN often increase mildly (and expectedly) with ACEI.

38. Angiotensin II Receptor Blockers • Released and FDA approved for hypertension. • Inhibit angiotensin II receptor - reduce SVR, BP and afterload. • Similar hemodynamic effects to ACEI. • Do not increase bradykinen- no cough but less protection against remodeling. • Useful as an alternative to ACEI (if pt intolerant); sometimes added to ACEI for severe HF. • Comparison studies: ARB vs ACEI have demonstrated ACEI superiority in most large clinical trials.

39. Beta-Blocker Therapy • Previously contraindicated in treating HF. • Now proven that -blockers are not only useful in treating HF, but reduce mortality as well as improve cardiac function and symptoms. • Multiple clinical trials using carvedilol, metoprolol and bisoprolol (MERIT et al). • Begin once patient stable and euvolemic; for chronic heart failure.

40. Beta-Blocker Therapy • Likely that chronic elevations of catecholamines and sympathetic nervous system activity cause progressive myocardial damage, fibrosis and dysfunctionabnormal remodeling. • Beneficial for all classes of heart failure with up to 30% decrease in mortality. • Must begin with very low doses and gradually increase e.g carvedilol 3.125 mgs b.i.d. • Unclear if all -blockers are alike for HF. Carvedilol may be drug of choice because of its combined  and  blocking effects.

41. Aldosterone Antagonists • Spironolactone: Competitive inhibitor of aldosterone; has mild diuretic properties and elevates K (often used in combination with loop diuretics which can cause hypokalemia). • In low dose (12.5-25 mgs/daily) spironolactone has been shown to decrease morbidity and mortality in patients with severe heart failure. • Has anti-androgenic properties. • Must monitor serum K to avoid hyperkalemia.

42. Actions of Spironolactone • Aldosterone mediates some of the deleterious effects of renin-angiotensin-aldosterone system activation, such as myocardial remodeling and fibrosis. • By blocking aldosterone, spironolactone should be considered as a neurohormonal antagonist rather than narrowly as a K sparing diuretic. • Clinical trials (RALES et al) show 29% reduction in mortality in NYHA class III and IV patients. • Eplerenone- released in 2003; aldosterone antagonist without anti-androgenic properties.

43. Aldosterone Blockade Post MI • Spironolactone and eplerenone post MI reduce morbidity and mortality in patients with LV dysfunction/heart failure. • Mineralocorticoid blockade prevents remodeling, blocks collagen production, improves EF and decreases LV dilatation. • Adjunct Rx to ACEI. Should be considered early in Rx of patients with large MI/LV dysfunction and heart failure. • Must monitor K closely

44. Enhancement of Contractility • Digitalis Glycosides - Digoxin most commonly used; only oral inotropic agent available; improves cardiac contractility. • Increases automaticity of cardiac electrical tissue - can induce arrhythmias.

45. Digoxin • Prolongs refractory period of AV node (vagal tone increased): slows rate of Atrial fibrillation and flutter. • Modest improvement in cardiac function in patients with LV dilatation and dysfunction. • Falling out of favor for Rx of CHF; improves symptom but not mortality. • Low Therapeutic/Toxic index- toxicity includes N, V, arrhythmias (PVC’s, atrial tachycardia) and 2nd/3rd degree A-V block.

46. Sympathomimmetic Amines • Indication: refractory HF. Must be given (short term) by continuous IV infusion in a hospitalized setting, preferably with invasive hemodynamic monitoring (rt. heart catheter). • Dobutamine: Potent inotrope- stimulates Beta receptors, raises CO. • Dopamine: Low dose-dilates renal and mesenteric blood vessels via Dopaminergic receptors Moderate dose- Stimulates B receptorsHigh dose- Stimulates Alpha receptors.

47. Phosphodiesterase Inhibitors • Indication: refractory HF. Improve cardiac contractility by inhibiting myocardial phosphodiesterase. • Potent inotropes administered IV for short term use. • Amrinone, Milrinone. • Trials using these and other newer inotropes orally for long term use have all demonstrated substantial increase in mortality.

48. Nesiritide • New- recombinant form of beta natriuretic peptide (BNP). Indication: refractory HF. • Potent vasodilator (venous>arteriolar); decreases LV filling pressures (pre-load) and SVR (afterload); improves cardiac output. • Must monitor renal function- renal failure occurs. • Continuous IV infusion following a bolus. • May have diuretic effects in some individuals.

49. Biventricular Pacing and ICD’s • Abnormal IVCD results in dyssynchronous contraction. • If QRS > 120ms and severe refractory CHF, synchronized biventricular pacing (CRT*) improves symptoms and quality of life; may decrease mortality. • ICD decrease mortality in patients with LV dysfunction and symptoms of HF. • Indications for ICD: • Secondary: Rescusitated cardiac arrest/Vfib or hemodynamically unstable Vtach • Primary: EF  .35 + mild to moderate HF symptoms • CRT-D’s address resynchronization pacing + ICD *CRT: cardiac resynchronization therapy

50. End-Stage Heart Failure • HF unresponsive to intensive medical Rx. • LV assist devices: Implantable assist device (pump) connected to external power supply. Decrease workload of native heart and buy time (“bridge”) to heart transplant. • Allow mobility and discharge from hospital to await transplant. Heart may improve over time. • Complications: Bleeding, infections, thromboembolism. • Very expensive: $2-300,000 for up to 3 months.