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Heart Failure --- HFSA 2010 Practice Guideline --- 清泉醫院 柯國銓 2012.03.06 錢非萬能,沒錢萬萬不能。 Guideline非萬能, 沒Guideline萬萬不能。 HFSA 2010 Comprehensive Heart Failure Practice Guideline Strength of Recommendation “Is recommended” “Should be considered” Part of routine care » Exceptions should be minimized Majority of patients should receive intervention » Some discretion allowed “May be considered” “Is not recommended” Individualization of therapy is indicated Therapy should not be used Number 1 Killer >65years Leading cause of hospitalization 1-2% of Health Care cost $ 39.2 Billion 5 years from diagnosis only 50% alive In 1950 first edition of Harrison’s Principles of Internal Medicine Decubitus Dietary sodium restriction Digitalis Diuretics (mercurial) Venesection and Morphine The Management of Heart Failure: The Past, the Present, and the Future Eugene Braunwald,MD Circulation: Heart Failure. 2008;1:58-62 In 1970 Sixth edition of Harrison’s Principles of Internal Medicine Diuretics (Thiazide, Loop, Potassium sparing) β-adrenergic agonist Precipitating cause The Management of Heart Failure: The Past, the Present, and the Future Eugene Braunwald,MD Circulation: Heart Failure. 2008;1:58-62 OPT: Optimal Pharmacologic Therapy SPIRONOLACTONE DIGOXIN DIURETICS BETA BLOCKERS ACE INHIBITORS or ARB ADJUNCT: HYDRALAZINE and NITRATES ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult. 2001; 1-56. Management of heart failure over the past 40 years Katz, A. M. Circ Heart Fail 2008;1:63-71 Copyright ©2008 American Heart Association What Causes Heart Failure? Factors contributing to CHF ♥ Coronary Artery Disease : most prevalent ♥ Ischemic Heart Disease ♥ CAD: Myocardial Infarct ♥ Untreated High Blood Pressure ♥ Faulty Heart Valves ♥ Cardiomyopathy ♥ Cardiac Arrhythmia ♥ Lung Disease ♥ Diabetes ♥ Infections ♥ Alcoholism ♥ Toxic Drugs ♥ Severe Anemia ♥ Hyperthyroidism ACC/AHA Heart Failure Stages Stage Description A Patients without structural heart disease but at increased risk to develop heart failure. B Patients with structural heart disease but no heart failure symptoms. C Patients with structural heart disease with past or current heart failure symptoms . Correlates with NYHA Heart Failure Class I, II, and III. D Patients with refractory end-stage heart failure (heart failure symptoms at rest despite maximal medical therapy). Correlates with NYHA Heart Failure Class IV. HFSA 2010 Practice Guideline (3.2) HF Risk Factor Treatment Goals Risk Factor Goal Hypertension Generally < 130/80 Diabetes See ADA guidelines1 Hyperlipidemia See NCEP guidelines2 Inactivity 20-30 min. aerobic 3-5 x wk. Obesity Weight reduction < 30 BMI Alcohol Men ≤ 2 drinks/day, women ≤ 1 Smoking Cessation Dietary Sodium Maximum 2-3 g/day 1Diabetes 2JAMA Adapted from: Care 2006; 29: S4-S42 2001; 285:2486-97 Treating Hypertension to Prevent HF Aggressive blood pressure control: Decreases risk of new HF by ~ 50% 56% in DM2 Lancet 1991;338:1281-5 (STOP-Hypertension JAMA 1997;278:212-6 (SHEP) UKPDS Group. UKPDS 38. BMJ 1998;317:703-713 Aggressive BP control in patients with prior MI: Decreases risk of new HF by ~ 80% Heart Failure Inability of heart to pump blood out as rapidly as it enters Often referred to as congestive heart failure (CHF) Congestive Heart Failure Congestion of pulmonary or systemic circulation (backward failure) Reduced output to body tissues (forward failure) 2 Types of Heart Failure Systolic Dysfunction Diastolic Dysfunction (Contraction) 2/3 of Patients (Relaxation) ♥ The heart ♥ Chambers don’t fill up so less blood goes to the lungs and body ♥ Stiff heart muscle can’t relax ♥ Not enough blood fills the chambers becomes weak and enlarged ♥ The weakened heart muscle can’t contract ♥ Not enough blood is pumped from the chambers Figure 11.1. Diagnostic Criteria: HF with Reduced vs. HF with Preserved EF Clinical evidence of HF: Clear clinical presentation of HF LVEF ≥ 50% LVEF < 50% Supportive evidence: Supportive evidence: Eccentric LVH or remodeling Concentric LVH or remodeling Exclusions: Non-myocardial disease Left atrial enlargement in absence of AF Echo Doppler or catheter evidence of diastolic dysfunction Exclusions: Non-myocardial disease Adapted from Yturralde FR. Prog Cardiovasc Dis 2005;47:314-19 Figure 11.2. Etiology of HF with Reduced vs. HF with Preserved LVEF HF with Reduced EF NonMyocardiala Myocardialb Hypertension CAD Valvular disease AS, AR, MR, MS High output Anemia, AV fistula Diabetes HF with Preserved EF NonMyocardiala Valvular disease AS, AR, MR, MS Cardiomyopathy genetic, postpartum, viral, drug/radiation Infiltrative myopathyc Myocardialb Hypertension CAD Diabetes Cardiomyopathy Pericardial constraint constriction, tamponade High output Anemia, AV fistula genetic, postpartum, viral, drug/radiation Infiltrative myopathyc CHF May develop acutely or may be a chronic disease Chronic CHF may worsen acutely Congestive Heart Failure Left sided Right sided Biventricular Left-Sided Heart Failure Increase pressure in pulmonary capillaries forces blood serum out of capillaries into interstitial spaces and alveoli Increase respiratory work and decrease gas exchange occur Left Heart Failure Symptoms Dyspnea on exertion(FcI, II,III) Paroxysmal nocturnal dyspnea (FcIV) Orthopnea(FcIV) Fatigue, generalized weakness New York Heart Association (NYHA) Functional Classification Class I Ordinary physical activity does not cause undue fatigue, Fc I palpitation or dyspnea (shortness of breath). Class II Comfortable at rest, but ordinary physical activity Fc II results in fatigue, palpitation, or dyspnea. ClassIII Fc III Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. ClassIV Fc IV Symptoms at rest. Left Heart Failure Signs Anxiety, confusion, restlessness Persistent cough » Pink, frothy sputum Tachycardia Tachypnea Noisy, labored breathing » Rales, wheezing (“cardiac asthma”) Cyanosis (late) Third heart sound (S3) Management Primary assessment & Focused Hx Identify source of problem » Acute pulmonary edema » Volume problem » Pump problem » Rate problem Acute Pulmonary Edema Management Sit patient up, » Do not lay flat Oxygen by non-rebreather mask Consider positive pressure ventilation Acute Pulmonary Edema Management Consider intubation if: » O2 saturation cannot be kept >90% on 100% O2 » PaO2 cannot be kept >60 torr on 100 % O2 » Patient displays signs of worsening cerebral hypoxia » PaCO2 progressively increases » Patient becoming exhausted Acute Pulmonary Edema Management First line interventions » IV / O2 / ECG Monitor » If BP > 90-100 mm Hg: Nitroglycerin 0.4 mg SL Morphine 2 – 10 mg slow IV furosemide 0.5 – 1.0 mg/kg slow IV (or twice patient’s single daily dose up to 120 mg) » If BP < 90 mm Hg: Vasopressors based on SBP CHF First Line Drug Therapy Nitroglycerin » » » » » » 0.4mg SL q 5 min prn Systolic BP should be > 90 - 100 mm Hg Nitrate therapy before IV is started Reduces preload/afterload Improves coronary artery perfusion Caution in RVF NTG, Lasix or MS may worsen hypotension Use inotropes if fluid does not improve BP following NTG administration CHF First Line Drug Therapy Morphine Sulfate » 2 mg IV push slowly q 10-15 min » Peripheral vasodilation leads to Decreased preload Decreased afterload » Decreased venous return leads to Decreased cardiac work Decreased O2 demand » Decreased anxiety Decreased release of catecholamines » Monitor Ventilations and BP Systolic BP should be > 90 - 100 mm Hg CHF First Line Drug Therapy Furosemide (Lasix®) - » 40 mg (0.5 - 1 mg/kg) slow IV Patients already on furosemide may have tolerance Increase dose to 2X daily oral dose » Direct vasodilation leads to decreased venous return » Diuresis leads to decreased intravascular volume » May cause hypokalemia, dysrhythmias especially dangerous if patient on digitalis » May worsen hypotension in RVF Volume Management If rate/rhythm adequate, treat BP » Consider fluid challenge of 250cc LR over 10-15 minutes if relative or absolute hypovolemia possible, including RVF and No pulmonary edema » Avoid use of vasopressors until volume deficits corrected or pulmonary edema presents Pump Problem IV / O2 / ECG Monitor SBP <70 mmHg: » norepinephrine 0.5 – 30 mcg/min IV inf SBP 70 – 100 mm Hg & shock » dopamine 5 – 15 mcg/kg/min IV inf SBP > 100 mm Hg w/o shock » dobutamine 2 – 20 mcg/kg/min IV inf Dopamine 2 - 20 mcg/kg/min » Place 200 mg/250cc of D5W » Begin at 5 mcg/kg/min » In 2 - 10 mcg/kg/min range, effects dominate » > 20 mcg/kg/min effects dominate » Use lowest dose that produces good perfusion May cause tachycardia, ectopy, nausea DO NOT use until hypovolemia is corrected Norepinephrine 0.5 - 30 mcg/min Inotropic and vasoconstrictive properties Can be used if systolic BP < 70 If systolic BP > 70, use dopamine instead DO NOT use until hypovolemia corrected CHF Second Line Therapy Dobutamine » 2 - 20 mcg/kg/min » Potent 1 stimulation Increases contractility Increases level of cardiac output » Drug of choice if systolic BP >100 CHF Second Line Therapy Nitroglycerin » 10 mcg/min increased by 5-10 mcg/min q 5 min » Vasodilation Decreased venous return leads to » Decreased cardiac work » Decreased O2 demand Decreased afterload leads to increased cardiac output CHF Third Line Drug Therapy Bronchodilators (beta agonists) » May be useful if wheezing is present » Mild peripheral vasodilator » Myocardial and respiratory stimulant » May cause arrhythmias in hypoxic patients or those with coronary artery disease HFSA 2010 Practice Guideline Recommendation Acute HF—Diagnosis 12.1 The diagnosis of ADHF should be based primarily on signs and symptoms. Strength of Evidence = C When the diagnosis is uncertain, determination of BNP or NT-proBNP concentration is recommended in patients being evaluated for dyspnea who have signs and symptoms compatible with HF. Strength of Evidence = A The natriuretic peptide concentration should not be interpreted in isolation, BNP Levels with Different Heart Failure Classes (NYHA = New York Heart Association) CHF Class/Stage BNP Levels (pg/mL) Mild (NYHA Class I) 83-152 Mild to moderate (NYHA Class II) 235-322 Moderate to severe (NYHA ClassIII) 459-590 Severe (NYHA Class IV) 960-1119 BNP<100(not HF) BNP>400(HF) NT-proBNP<400(not HF) NT-proBNP>2000(HF) HFSA 2010 Practice Guideline Acute HF—IV Vasodilators Recommendation 12.17 In the absence of symptomatic hypotension, intravenous nitroglycerin, nitroprusside or nesiritide may be considered as an addition to diuretic therapy for rapid improvement of congestive symptoms Strength of Evidence = B HFSA 2010 Practice Guideline Acute HF—IV Vasodilators Recommendation 12.18 Intravenous vasodilators (intravenous nitroglycerin or nitroprusside) and diuretics are recommended for rapid symptom relief in patients with acute pulmonary edema or severe hypertension. Strength of Evidence = C HFSA 2010 Practice Guideline Acute HF—Hemodynamic Monitoring Recommendation 12.22 Invasive hemodynamic monitoring should be considered in a patient: Rrefractory to initial therapy » Volume status and cardiac filling pressures are unclear » Significant hypotension (typically SBP < 80 mm Hg) » Documentation of an adequate hemodynamic response to the inotropic agent is necessary. >> Strength of Evidence = C Right-sided Heart Failure Right ventricle fails as effective pump Right ventricle cannot eject blood returning through vena cavae Blood backs up into systemic circulation Right Heart Failure Causes Most Common Cause: Left sided Heart Failure Right Heart Failure Causes Others » Chronic hypertension » COPD (cor pulmonale) » Pulmonary embolism » Right ventricular infarction Right Heart Failure Signs/Symptoms Tachycardia Jugular vein distension Pedal, pre-tibial, sacral edema Hepatomegaly Splenomegaly Classic Triad of Right Ventricular Failure: JVD, Hypotension, Clear Lungs Right Heart Failure Signs/Symptoms Anasarca (generalized edema) Fluid accumulation in body cavities » Ascites » Pleural effusion » Pericardial effusion Heart Failure in Patients with Reduced Ejection Fraction HFSA 2010 Recommendations Evidence-Based Treatment Across the Continuum of Systolic LVD and HF Control Volume Diuretics Renal Replacement Therapy* Improve Clinical Outcomes Aldosterone ACEI -Blocker Antagonist or ARB or ARB CRT an ICD* HDZN/ISDN* *In selected patients Treat Residual Symptoms Digoxin Compensatory Mechanisms HFSA 2010 Practice Guideline ACE Inhibitors Recommendation 7.1 ACE inhibitors are recommended for routine administration to symptomatic and asymptomatic patients with LVEF ≤ 40%. Strength of Evidence = A ACE inhibitors should be titrated to doses used in clinical trials, as tolerated during concomitant uptitration of beta blockers. Strength of Evidence = C ACE Inhibitors in Heart Failure: From Asymptomatic LVD to Severe HF (Asymptomatic LVD) 20% 29% death or HF hosp. death or new HF (Chronic Heart Failure) 16% (Severe Heart Failure) 40% mortality at 6 mos. 31% mortality at 1 year 27% mortality at end of study mortality SOLVD Investigators. N Engl J Med 1992;327:685-91 SOLVD Investigators. N Engl J Med 1991;325:293-302 CONSENSUS Study Trial Group. N Engl J Med 1987;316:1429-35 HFSA 2010 Practice Guideline ACE Inhibitors Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose in Clinical Trials Captopril Capoten 6.25 mg tid 50 mg tid 122.7 mg/day Enalapril Vasotec 2.5 mg bid 10 mg bid 16.6 mg/day Fosinopril Monopril 5-10 mg qd 80 mg qd N/A Lisinopril 2.5-5 mg qd 20 mg qd Quinapril Zestril, Prinivil Accupril 5 mg bid 80 mg qd 4.5 mg/day, 33.2 mg/day* N/A Ramipril Altace 1.25-2.5 mg qd 10 mg qd N/A Imidapril Tanatril 2.5 mg qd 10 mg qd N/A *No mortality difference between high and low dose groups, but 12% lower risk of death or hospitalization in high dose group vs. low dose group. HFSA 2010 Practice Guideline ARBs Recommendation 7.3 ARBs are recommended for routine administration to symptomatic and asymptomatic patients with an LVEF ≤ 40% who are intolerant to ACE inhibitors for reasons other than hyperkalemia or renal insufficiency. A Strength of Evidence = HFSA 2010 Practice Guideline ARBs Recommendation 7.5 Individual ARBs may be considered as initial therapy rather than ACE inhibitors for patients with the following conditions: » HF Post-MI Strength of Evidence = A » Chronic HF and reduced LVEF Strength of Evidence = B ARBS in Patients Not Taking ACE Inhibitors: Val-HeFT & CHARM-Alternative Survival % ValHeFT Valsartan 90 CHARM-Alternative 50 CV Death or HF Hosp % 100 80 Placebo 70 60 Placebo 40 30 Candesartan 20 10 p = 0.017 HR 0.77, p = 0.0004 50 0 0 3 6 9 12 15 18 21 24 27 0 9 Months 18 27 Months Maggioni AP et al. JACC 2002;40:1422-4 Granger CB et al. Lancet 2003;362:772-6 36 HFSA 2010 Practice Guideline ARBs Recommendation 7.13 (NEW in 2010) The addition of an ARB should be considered in patients with HF due to reduced LVEF who have persistent symptoms or progressive worsening despite optimized therapy with an ACE inhibitor and beta blocker. Strength of Evidence = A HFSA 2010 Practice Guideline ARBs Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose in Clinical Trials Candesartan Atacand, blopress 4-8 mg qd 32 mg qd 24 mg/day Losartan Cozaar 12.5-25 mg qd 150 mg qd 129 mg/day Olmesartan Olmetec 5mg qd 40mg qd Valsartan Diovan 40 mg bid 160 mg bid 254 mg/day HFSA 2010 Practice Guideline Beta Blockers Recommendation 7.6 Beta-blockers shown to be effective in clinical trials of patients with HF are recommended for patients with an LVEF ≤ 40%. Strength of Evidence = A % of Patients With Event COPERNICUS: Death, Hospitalization, in High Risk Patients 30 HR = 0.67 (CI = 0.47-0.96) 20 Placebo 10 Carvedilol 0 0 2 4 6 Weeks After Randomization 8 Krum H et al. JAMA 2003;289:754-6 Krum et al. JAMA 2003;289 IMPACT-HF Primary End Point: Patients Receiving Beta Blocker at 60 Days Improvement 100% 91% 73% 75% Patients 18% P <.0001 50% 25% 0% Carvedilol Predischarge Initiation (n=185) Physician Discretion Postdischarge Initiation* (n=178) Gattis WA et al. JACC 2004;43:1534-41 HFSA 2010 Practice Guideline (7.8) Pharmacologic Therapy: Beta Blockers RECENT DECOMPENSATION Beta blocker therapy is recommended for patients with a recent decompensation of HF after optimization of volume status and successful discontinuation of IV diuretics and vasoactive agents. Whenever possible, beta blocker therapy should be initiated in the hospital at a low dose prior to discharge of stable patients. Strength of Evidence = B Adapted from: HFSA 2010 Practice Guideline Beta Blockers and ACE Inhibitors Recommendation 7.7 The combination of a beta-blocker and an ACE inhibitor is recommended as routine therapy for asymptomatic patients with an LVEF ≤ 40% » Post MI » Non Post-MI Strength of Evidence = B Strength of Evidence = C HFSA 2010 Practice Guideline Beta Blockers Recommendation 7.10 It is recommended that beta blockade be initiated at low doses and uptitrated gradually, typically: At 2-week intervals in patients with reduced LVEF After 3-10 day intervals in patients with reduced LVEF following newly diagnosed MI. Strength of Evidence = B HFSA 2010 Practice Guideline Beta Blockers A temporary reduction of dose (generally by one-half) in this setting may be considered. Abrupt discontinuation in patients with symptomatic exacerbation should be avoided, unless the situation is life-threatening Strength of Evidence = C » If discontinued or reduced, beta blockers should be reinstated before the patient is discharged. In general, doses should be uptitrated to the previous well-tolerated dose as soon as safely possible. HFSA 2010 Practice Guideline Beta Blockers Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose in Clinical Trials Bisoprolol Zebeta, concor Coreg, dilatrend Coreg CR 1.25 mg qd 10 mg qd 8.6 mg/day 3.125 mg bid 25 mg bid 37 mg/day 10 mg qd 80 mg qd Toprol XL 12.5-25 mg qd 200 mg qd Carvedilol Carvedilol Metoprolol succinate CR/XL 159 mg/day HFSA 2010 Practice Guideline (7.9) Pharmacologic Therapy: Beta Blockers CONCOMITANT DISEASE Beta blocker therapy is recommended in the great majority of patients with HF and reduced LVEF—even if there is concomitant diabetes, chronic obstructive lung disease or peripheral vascular disease. » Use with caution in patients with: Diabetes with recurrent hypoglycemia Asthma or resting limb ischemia. » Use with considerable caution in patients with marked bradycardia (<55 bpm) or marked hypotension (SBP < 80 mmHg). » Not recommended in patients with asthma with active bronchospasm. Strength of Evidence = C Diabetes and the Use of Beta Blockers for HF: Relative Risk for Mortality and Hospitalization for Heart Failure COPERNICUS (carvedilol)1 With diabetes Without diabetes MERIT-HF (ER metoprolol succinate)2 With diabetes Without diabetes 0 0.5 1.0 1.5 2.0 Mohacsi. Circulation. 2001;104(17):abstr 3551. Hjalmarson. JAMA. 2000;283(10):1295. HFSA 2010 Practice Guideline (11.8, 15.2) Pharmacologic Therapy: Beta Blockers PRESERVED LVEF Beta blocker treatment is recommended in patients with HF and preserved LVEF who have: » Prior MI Strength of Evidence = A » Hypertension Strength of Evidence = B » Atrial fib. requiring control of ventricular rate Strength of Evidence = B THE ELDERLY Beta-blocker and ACE inhibitor therapy is recommended as standard therapy in all elderly patients with HF due to LV systolic dysfunction. Strength of Evidence =B In the absence of contraindications, these therapies are also recommended in the very elderly (age > 80 years). Effect of Beta Blockade on Outcome in Patients With HF and Post-MI LVD Study US Carvedilol1 Drug Carvedilol (dilatrend) HF Severity Target Dose (mg) Outcome mild/ moderate 6.2525 BID ↓48% disease progression (p= .007) CIBIS-II2 Bisoprolol (concor) moderate/ severe 10 QD ↓34% mortality (p <.0001) MERIT-HF3 metoprolol succinate mild/ moderate 200 QD ↓34% mortality (p = .0062) COPERNICU S4 carvedilol severe 25 BID ↓35% mortality (p = .0014) CAPRICORN5 carvedilol post-MI LVD 25 BID ↓23% mortality (p =.031) HFSA 2010 Practice Guideline Aldosterone Antagonists Recommendation 7.14 Administration of an aldosterone antagonist is recommended for patients already receiving standard therapy, including diuretics, who have: » NYHA class IV HF (or class III, previously class IV) from reduced LVEF (≤ 35%) Strength of Evidence = A Aldosterone Antagonists in HF RALES Probability of Survival HF) (Advanced EPHESUS (Post-MI) 1.00 1 .0 0 0.90 Eplerenone 0 .9 0 Spironolactone 0.80 Placebo 0 .8 0 0.70 0 .7 0 0.60 Placebo 0 .6 0 0 .5 0 0.50 RR = 0.70 P < 0.001 RR = 0.85 P < 0.008 0.40 0 3 6 9 12 15 18 21 24 27 30 33 36 0 .4 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Pitt B. N Engl J Med 1999;341:709-17 Pitt B. N Engl J Med 2003;348:1309-21 Aldosterone Antagonists in HF RALES Probability of Survival HF) (Advanced EPHESUS (Post-MI) 1.00 1 .0 0 0.90 Eplerenone 0 .9 0 Spironolactone 0.80 Placebo 0 .8 0 0.70 0 .7 0 0.60 Placebo 0 .6 0 0 .5 0 0.50 RR = 0.70 P < 0.001 RR = 0.85 P < 0.008 0.40 0 3 6 9 12 15 18 21 24 27 30 33 36 0 .4 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Pitt B. N Engl J Med 1999;341:709-17 Pitt B. N Engl J Med 2003;348:1309-21 HFSA 2010 Practice Guideline Aldosterone Antagonists Recommendation 7.16 Aldosterone antagonists are not recommended when: » creatinine is > 2.5 mg/dL (or creatinine clearance is < 30 ml/min) » or serum potassium is > 5.0 mmol/L » or in conjunction with other potassiumsparing diuretics. Strength of Evidence = A xHFSA 2010 Practice Guideline Aldosterone Antagonists Recommendation 7.17 It is recommended that serum potassium concentration be monitored frequently following initiation or change in an aldosterone antagonist. Strength of Evidence = A Potassium-Sparing Diuretics Agent Initial Daily Dose Max Total Daily Dose Elimination Duration of Action Spironolactone 12.5-25 mg qd 50 mg Metabolic 48-72 hrs Eplerenone 25-50 mg qd 100 mg Renal, Metabolic Amilioride 5 mg qd Triamterene 50-75 mg bid 20 mg 200 mg Renal 24 hrs Metabolic 7-9 hrs HFSA 2010 Practice Guideline Hydralazine and Oral Nitrates Recommendation 7.19 A combination of hydralazine and isosorbide dinitrate is recommended as part of standard therapy in addition to beta-blockers and ACEinhibitors for African Americans with HF and reduced LVEF: » NYHA III or IV HF Strength of Evidence = A » NYHA II HF Strength of Evidence = B HFSA 2010 Practice Guideline Hydralazine and Oral Nitrates Recommendation 7.20 A combination of hydralazine and isosorbide dinitrate may be considered in non-African American patients with HF and reduced LVEF who remain symptomatic despite optimized standard therapy. Strength of Evidence = C HFSA 2010 Practice Guideline Other Vasodilators Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose in Clinical Trials Fixed dose hydralazine / isosorbide dinitrate BiDil 37.5 mg hydralazine/ 20 mg isosorbide dinitrate tid 75 mg hydralazin e/ 40 mg isosorbide dinitrate tid 142.5 mg hydralazine / 76 mg isosorbide dinitrate/da y Hydralazine Apresoline 37.5 mg qid 75 mg qid 270 mg/day Isosorbide dinitrate 20 mg qid 75 mg qid 270 mg/day Isordil A-HeFT All-Cause Mortality 43% Decrease in Mortality 100 Survival % Fixed Dose ISDN/HDZN 95 Placebo 90 P = 0.01 85 Days Baseline Visit 0 Since 100 200 300 400 500 600 Taylor AL et al. N Engl J Med 2004;351:2049-57 1 of 2 HFSA 2010 Practice Guideline Multi-Drug Therapy Recommendation 7.21 (1 of 2) Additional pharmacological therapy should be considered in patients with HF and reduced LVEF who have persistent symptoms or progressive worsening despite optimized therapy with an ACE inhibitor and a beta blocker. » The choice of specific agent will be influenced by clinical considerations, including renal function status, chronic serum potassium concentration, blood pressure, and volume status. » The triple combination of an ACE inhibitor, an ARB, and an aldosterone antagonist is not recommended due to the high risk of hyperkalemia. Strength of Evidence = C 2 of 2 HFSA 2010 Practice Guideline Multi-Drug Therapy cont’d Recommendation 7.21 (2 of 2) Addition of an ARB Strength of Evidence = A Addition of an aldosterone antagonist: » for severe HF » for moderate HF » for post-MI HF Addition Strength of Evidence = A Strength of Evidence = C Strength of Evidence = A of hydralazine/isosorbide dinitrate: » for African-Americans » for others Strength of Evidence = A Strength of Evidence = C HFSA 2010 Practice Guideline (7.23) Pharmacologic Therapy: Diuretics Diuretic therapy is recommended to restore and maintain normal volume status in patients with clinical evidence of fluid overload, generally manifested by: » Congestive symptoms » Signs of elevated filling pressures Strength of Evidence = A Loop diuretics rather than thiazide-type diuretics are typically necessary to restore normal volume status in patients with HF. Strength of Evidence = B Loop Diuretics Agent Initial Daily Dose Max Total Daily Dose Elimination: Renal – Met. Duration of Action Furosemide 20-40mg qd or bid 600 mg 65%R/35%M 4-6 hrs Bumetanide 0.5-1.0 mg qd or bid 10 mg 62%R/38%M 6-8 hrs Torsemide 10-20 mg qd 200 mg 20%R/80%M 12-16 hrs Ethacrynic acid 25-50 mg qd or bid 200 mg 67%R/33%M 6 hrs 1 of 2 HFSA 2010 Practice Guideline Diuretics Recommendation 7.24 (1 of 2) The initial dose of diuretic may be increased as necessary to relieve congestion. Restoration of normal volume status may require multiple adjustments over many days and occasionally weeks in patients with severe fluid overload evidenced by massive edema or ascites. HFSA 2010 Practice Guideline Diuretics Recommendation 7.25 Addition of chlorothiazides or metolazone, once or twice daily, to loop diuretics should be considered in patients with persistent fluid retention despite high dose loop diuretic therapy. » Volume status and electrolytes must be monitored closely when multiple diuretics are utilized. Strength of Evidence = C Thiazide Diuretics Agent Initial Daily Dose Max Total Daily Dose Elimination Duration of Action Chlorothiazide 250-500 mg qd or bid 12.5-25 mg qd 1000 mg Renal 6-12 hrs 24-72 hrs Hydrochlorothiazide 25 mg qd or bid 200 mg 65% Renal, 10% into Bile, 25% Unknown Renal Metolazone 2.5 mg qd 20 mg 12-24 hrs Idapamide 2.5 mg qd 5 mg 80% Renal, 10% Bile, 10% ? Metabolic Chlorthalidone 100 mg 6-12 hrs 36 hrs ?HFSA 2010 Practice Guideline Diuretics Recommendation 7.26 Careful observation for the development of side effects, including electrolyte abnormalities, symptomatic hypotension, renal dysfunction, or worsening renal function is recommended in patients treated with diuretics, especially when used at high doses and in combination. Patients should undergo routine laboratory studies and clinical examination as dictated by their clinical response. Strength of Evidence = B HFSA 2010 Practice Guideline Recommendation 7.28 Diuretics It is recommended that patients and caregivers be given education that will enable them to demonstrate understanding of the early signs of fluid retention and the plan for initial therapy. =C Strength of Evidence Selected patients may be educated to adjust daily dose of diuretic in response to weight gain due to fluid overload (typically short-term weight gain of 2 to 4 pounds). =C Strength of Evidence HFSA 2010 Practice Guideline Digoxin Recommendation 7.29 Digoxin may be considered to improve symptoms for patients with reduced LVEF (≤ 40) who have signs or symptoms of HF while receiving standard therapy, including ACE inhibitors and beta blockers: » NYHA class II-III » NYHA class IV Strength of Evidence = A Strength of Evidence = B HFSA 2010 Practice Guideline Digoxin Recommendation 7.30 It is recommended that: » The dose of digoxin, which should be based on lean body mass, renal function and concomitant medications, should be 0.125 mg daily in the majority of patients. » The serum digoxin level should be < 1.0 ng/mL, generally 0.7-0.9 ng/mL Strength of Evidence = B HFSA 2010 Practice Guideline Digoxin Recommendation 7.31 Digoxin should be considered for achieving adequate control of the ventricular response to atrial fibrillation in patients with HF. Strength of Evidence = B HFSA 2010 Practice Guideline Digoxin Recommendation 7.32 High doses of digoxin (maintenance dose > 0.25 mg daily) for the purpose of rate control are not recommended. Strength of Evidence = C HFSA 2010 Practice Guideline Warfarin Recommendation 7.33 Treatment with warfarin (goal INR 2.0-3.0) is recommended for all patients: » With HF and chronic or documented paroxysmal, persistent, or long-standing atrial fibrillation Strength of Evidence = A » Or a history of systemic or pulmonary emboli, including stroke or transient ischemic attack, unless contraindicated. Strength of Evidence = C HFSA 2010 Practice Guideline Warfarin Recommendation 7.34 It is recommended that patients with anterior MI with documented LV thrombus be treated with warfarin (goal INR 2.0-3.0) for the initial 3 months postMI, unless contraindicated. Strength of Evidence = B Other patients with ischemic or nonischemic cardiomyopathy and LV thrombus should be considered for chronic anticoagulation, Strength of Evidence = C HFSA 2010 Practice Guideline Long-Term Antithrombotic Therapy Recommendation 7.35 Long-term treatment with an antiplatelet agent, generally aspirin in doses of 75-81 mg, is recommended for patients with HF due to ischemic cardiomyopathy, whether or not they are receiving ACE inhibitors. Strength of Evidence = B Warfarin (goal INR 2.0-3.0) and clopidogrel (75 mg) also have prevented vascular events in postMI patients and may be considered as lternatives to aspirin. Strength of Evidence = B HFSA 2010 Practice Guideline Aspirin Recommendation 7.36 Routine use of aspirin is not recommended in patients with HF without atherosclerotic vascular disease. Evidence = C Strength of xHFSA 2010 Practice Guideline Anti-arrhythmics Recommendation 7.37 Anti-arrhythmic agents, including amiodarone, are not recommended for the primary prevention of sudden death in patients with HF. Strength of Evidence = A HFSA 2010 Practice Guideline Amiodarone Recommendation 7.38 In patients with HF and an ICD, amiodarone may be considered to reduce the frequency of recurrent symptomatic arrhythmias causing ICD shocks. Strength of Evidence = C HFSA 2010 Practice Guideline PUFA Recommendation 7.41 n-3 polyunsaturated fatty acids (PUFA) may be considered to reduce mortality in HF patients with NYHA class II-IV symptoms and reduced LVEF. Strength of Evidence = B HFSA 2010 Practice Guideline ICD Placement Recommendation 9.6 ICD implantation is recommended for survivors of cardiac arrest from ventricular fibrillation or hemodynamically unstable sustained VT that is not due to a transient, potentially reversible cause, such as acute MI. Strength of Evidence = A ICD Therapy CLASS I INDICATIONS: Ischemic cardiomyopathy with LVEF < 35%, at least 40 days post MI, NYHA class II OR III. (Strength of Evidence = A) 2. Ischemic cardiomyopathy with LVEF < 30%, at least 40 days post MI, NYHA class I. (Strength of Evidence = A) 3. Non Ischemic cardiomyopathy with LVEF ≤ 35%, NYHA class II OR III. (Strength of Evidence = B) 1. MADIT II: Prophylactic ICD in Ischemic LVD (LVEF 30%) Probability of Survival 1.0 .9 .8 Defibrillator .7 Conventional Therapy .6 0 0 at Risk Defibrillator Conventional 1 2 3 4 Year Number 742 490 503 (.91) 329 (.90) 274 (.84) 170 (.78) 110 (.78) 65 (.69) 9 3 Moss AJ et al. N Engl J Med 2002;346:877-83 Moss AJ, et al. N Engl J Med. 2002;346;877-883. ICD Therapy in the SCD-HeFT Trial: Mortality by Intention-to-Treat HR 97.5% Cl P Value Amiodarone vs Placebo 1.06 .86-1.30 .53 ICD vs Placebo .77 .62-.96 .007 .4 Mortality .3 22% .2 17% .1 Amiodarone ICD Therapy Placebo 0 0 6 12 18 24 30 36 Months of Follow-Up 42 48 54 60 Bardy GH et al. N Engl J Med 2005;352:225-37 HFSA 2010 Practice Guideline Biventricular Pacing Recommendation Biventricular for 9.7 pacing therapy is recommended patients with all of the following: » » » » Sinus rhythm A widened QRS interval (≥120 ms) Severe LV systolic dysfunction (LVEF < 35%) Persistent, moderate to severe HF (NYHA III) despite optimal medical therapy. Strength of Evidence = A HFSA 2010 Practice Guideline Biventricular Pacing Recommendation 9.8 (NEW in 2010) Biventricular pacing therapy may be considered for patients with AF with a widened QRS interval (≥ 120 ms) and severe LV systolic dysfunction (LVEF ≤ 35%) who have persistent, moderate to severe HF (NYHA III) despite optimal medical therapy. Strength of Evidence = A HFSA 2010 Practice Guideline Biventricular Pacing Recommendation 9.9 Selected ambulatory NYHA IV patients in sinus rhythm with QRS ≥ 120 ms and LV systolic dysfunction may be considered for biventricular pacing therapy. Strength of Evidence = B HFSA 2010 Practice Guideline Biventricular Pacing Recommendation 9.10 Biventricular pacing therapy should be considered in patients with reduced LVEF and QRS ≥ 150 ms who have NYHA I-II HF symptoms. Strength of Evidence = B % Event-Free Survival Effect of CRT Without an ICD on All-Cause Mortality: CARE-HF 100 75 50 risk CRT Medical Therapy Medical Therapy 25 HR = 0.64 (95% CI = .48-.85) p = .0019 0 Number CRT at 0 409 404 500 376 365 351 321 Days 213 192 1,000 89 71 1,500 8 5 Cleland JG et al. N Engl J Med 2005;352:1539-49 Percentage of Patients Free of Death from Any Cause or Unplanned Hospitalization for Major Cardiovascular Event Cardiac Resynchronizatio n Therapy Prolongs Survival in Patients With Heart Failure (The CARE-HF Trial) Cleland JG et al. N Engl J Med. 2005:352;1539. Percentage of Patients Free of Death from Any Cause Left Ventricular Assist Devices (LVAD) The Jarvik 2000 The Jarvik-7 The World's First Artificial Heart Transcutaneous Ventricular Assist Device Implantable Ventricular Assist Device Ventricular Assist Device in the market Thoratec CentriMag® Thoratec PVAD™ HeartMate II® Thoratec IVAD™ Arrow LionHeart HeartMate® XVE DeBakey LVAD Surgeries for heart failure Coronary Revascularization Valvular Surgery Left Ventricular Reconstructive Surgery (Dor Procedure) Cardiac Transplant On December 3rd 1967 At Groote Schuur Hospital Mr. Louis Washkansky lived for 18 days 1967 Cape Town / Dr.Barnard Thank you very much !!! Figure 11.3. Diagnostic Algorithm for HF with Preserved LVEF HF with Preserved LVEF Dilated LV Valvular disease AR, MR Non-dilated LV No valvular dis. High output HF Increased thickness Normal or increased QRS Hypertrophic dis. No aortic valve disease No hypertensive history of PE HCM, Fabry dis. Normal Thickness Low QRS voltage Infiltrative myopathy Aortic valve dis. Aortic stenosis Hypertensive history of PE Hypertensive-HCM Some patients with RV dysfunction have LV dysfunction due to ventricular interaction. Right vent. dysfunction No mitral obstruction Pulmonary hypertension Pericardial dis. Tamponade Constriction Isolated predominant RVMI No pericardial disease Inducible ischemia Intermittent/active ischemia Mitral obstruction MS, atrial myxoma No inducible ischemia, fibrotic, collagenVascular, RCM, cardinoid, diabetes, Radiation or chemotherapy induced heart disease, infiltrative disease, comorbid conditions, reconsider diagnosis of HF HFSA 2010 Practice Guideline (9.1, 9.4) Device Therapy: Prophylactic ICD Placement Prophylactic ICD placement should be considered in patients with an LVEF ≤35% and mild to moderate HF symptoms: » » Ischemic etiology Non-ischemic etiology Strength of Evidence = A Strength of Evidence = B In patients who are undergoing implantation of a biventricular pacing device, use of a device that provides defibrillation should be considered. Strength of Evidence = B Decisions should be made in light of functional status and prognosis based on severity of underlying HF and comorbid conditions, ideally after 3-6 mos. of optimal medical therapy. Strength of Evidence = C Adapted from: Management Monitor ECG » Hypoxia, increased heart wall tension leads to dysrhythmias IV NS TKO via microdrip or lock » Limit Fluids » If RVF only, fluid challenges to preload Volume Problem IV/O2/ECG Monitor Fluid challenge until rales or if evidence of anterior wall AMI Vasopressors based on SBP Management IV TKO with microdrip set or lock » Limit fluids unless suspect RVF Correct rhythm major disorders of rate, » Increase rate in bradycardias » Terminate tachycardias with cardioversion » Suppress frequent ectopic beats BP Treatment Review If rate, rhythm, volume adequate, treat BP with vasopressors: » Norepinephrine, or » Dopamine CHF Management What if the BP is too low for the first and second line drug therapies? » BP < 70 mm Hg norepinephrine, 0.5 - 30 mcg/min IV infusion » BP > 70 but < 100 mm Hg dopamine, After 5 - 15 mcg/kg/min IV infusion BP improves, treat pulmonary edema with first and second line therapies CHF Management Long Term Management usually includes » Fluid minimization Diuretics (+ Potassium if non-potassium sparing) Diet restrictions » Increase contractility Digitalis » Blood pressure control ACE Inhibitors » Coronary artery perfusion Nitroglycerin HFSA 2010 Practice Guideline (12.3, Table 12.3) Acute Decompensated Heart Failure (ADHF)—Treatment Goals for Hospitalized Improve symptoms,Patients especially congestion and low- output symptoms Optimize volume status Identify etiology Identify precipitating factors Optimize chronic oral therapy; minimize side effects Identify who might benefit from revascularization Education patients concerning medication and HF self-assessment Strength of Evidence = C Consider enrollment in a disease management program HFSA 2010 Practice Guideline (12.5-12.20) Overview of Treatment Options for Patients with Acute Decompensated HF » Fluid and sodium restriction » Diuretics, especially loop diuretics » Ultrafiltration/renal replacement therapy (in selected patients only) » Parenteral vasodilators * (nitroglycerin, nitroprusside, nesiritide) » Inotropes * (milrinone or dobutamine) Goals of Management Improve oxygenation, ventilation Decrease venous return to heart Decrease cardiac work, O2 demand Improve cardiac output by » Reducing afterload » Increasing myocardial contractility HFSA 2010 Practice Guideline ACE Inhibitors Recommendation 7.2 In patients who cannot tolerate ACE inhibitors due to cough, ARBs are recommended. Strength of Evidence = A » The combination of hydralazine and an oral nitrate may be considered in such patients not tolerating ARB therapy. Strength of Evidence = C HFSA 2010 Practice Guideline (7.14-7.15) Pharmacologic Therapy: Aldosterone Antagonists An aldosterone antagonist is recommended for patients on standard therapy, including diuretics, who have: » NYHA class IV HF (or class III, previously class IV) HF from reduced LVEF (≤ 35%) One should be considered in patients post-MI with clinical HF or diabetes and an LVEF < 40% who are on standard therapy, including an ACE inhibitor (or ARB) and a beta blocker. Strength of Evidence = A Adapted from: HFSA 2010 Practice Guideline Recommendation Amiodarone 7.39 It is recommended that when amiodarone therapy is initiated, the potential for interactions with other drugs be reviewed. The maintenance doses of digoxin, warfarin, and some statins should be reduced when amiodarone is initiated and then carefully monitored. Adjustment in doses of these drugs and laboratory assessment of drug activity or serum concentration after initiation of amiodarone is recommended. Strength of Evidence = A