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ACC Heart Failure Guidelines Slide Deck Based on the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult January 2006 Supported by Medtronic, Inc. Medtronic, Inc. was not involved in the development of this slide deck and in no way influenced its contents. ACC/AHA 2005 Guideline Update for the Management of Patients With Chronic Heart Failure in the Adult Writing Committee Members Sharon Ann Hunt, MD, FACC, FAHA, Chair William T. Abraham, MD, FACC, FAHA Donna M. Mancini, MD Marshall H. Chin, MD, MPH, FACP Keith Michl, MD, FACP Arthur M. Feldman, MD, PhD, FACC, FAHA John A. Oates, MD, FAHA Gary S. Francis, MD, FACC, FAHA Theodore G. Ganiats, MD Peter S. Rahko, MD, FACC, FAHA Marc A. Silver, MD, FACC, FAHA Mariell Jessup, MD, FACC, FAHA Lynne Warner Stevenson, MD, FACC, FAHA Marvin A. Konstam, MD, FACC Clyde W. Yancy, MD, FACC, FAHA Applying Classification of Recommendations and Level of Evidence Class I Class IIa Class IIb Class III Benefit >>> Risk Benefit >> Risk Additional studies with focused objectives needed Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Risk ≥ Benefit No additional studies needed Procedure/ Treatment SHOULD be performed/ administered IT IS REASONABLE to perform procedure/administer treatment should is recommended is indicated is useful/effective/ beneficial is reasonable can be useful/effective/ beneficial is probably recommended or indicated Procedure/Treatment MAY BE CONSIDERED may/might be considered may/might be reasonable usefulness/effectiveness is unknown /unclear/uncertain or not well established Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL is not recommended is not indicated should not is not useful/effective/beneficial may be harmful Applying Classification of Recommendations and Level of Evidence Level A Multiple (3-5) population risk strata evaluated General consistency of direction and magnitude of effect Class I Class IIa • Recommendation that procedure or treatment is useful/ effective • Sufficient evidence from multiple randomized trials or metaanalyses • Recommendation in favor of treatment or procedure being useful/ effective • Some conflicting evidence from multiple randomized trials or metaanalyses Class IIb Class III • Recommen• Recommendation’s dation that usefulness/ procedure or efficacy less treatment not well useful/effectiv established e and may be • Greater harmful conflicting • Sufficient evidence from evidence from multiple multiple randomized randomized trials or metatrials or metaanalyses analyses Applying Classification of Recommendations and Level of Evidence Level B Limited (2-3) population risk strata evaluated Class I • Recommendation that procedure or treatment is useful/effecti ve • Limited evidence from single randomized trial or nonrandomized studies Class IIa Class IIb • Recommen• Recommendation’s dation in favor of treatment or usefulness/ efficacy less procedure well being useful/ established effective • Greater • Some conflicting conflicting evidence from evidence from single single randomized randomized trial or nontrial or nonrandomized randomized studies studies Class III • Recommendation that procedure or treatment not useful/effectiv e and may be harmful • Limited evidence from single randomized trial or nonrandomized studies Applying Classification of Recommendations and Level of Evidence Level C Very limited (12) population risk strata evaluated Class I • Recommendation that procedure or treatment is useful/ effective • Only expert opinion, case studies, or standard-ofcare Class IIa Class IIb Class III • Recommen• Recommen• Recommenddation in favor dation’s ation that of treatment or usefulness/ procedure or procedure efficacy less treatment not being well useful/effectiv established useful/effectiv e and may be e harmful • Only diverging • Only diverging expert opinion, • Only expert expert opinion, case studies, opinion, case case studies, or standard-ofstudies, or or standard-ofcare standard-ofcare care Heart Failure is a Major and Growing Public Health Problem in the U.S. Approximately 5 million patients in this country have HF Over 550,000 patients are diagnosed with HF for the first time each year Primary reason for 12 to 15 million office visits and 6.5 million hospital days each year In 2001, nearly 53,000 patients died of HF as a primary cause Heart Failure is Primarily a Condition of the Elderly The incidence of HF approaches 10 per 1000 population after age 65 HF is the most common Medicare diagnosisrelated group More dollars are spent for the diagnosis and treatment of HF than any other diagnosis by Medicare Guideline Scope Document focuses on : Prevention of HF Diagnosis and management of chronic HF in the adult Definition of Heart Failure HF 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. “Heart Failure” vs. “Congestive Heart Failure” Because not all patients have volume overload at the time of initial or subsequent evaluation, the term “heart failure” is preferred over the older term “congestive heart failure.” Causes of HF in Western World For a substantial proportion of patients, causes are: 1. Coronary artery disease 2. Hypertension 3. Dilated cardiomyopathy Stages of Heart Failure At Risk for Heart Failure: STAGE A High risk for developing HF STAGE B Asymptomatic LV dysfunction Heart Failure: STAGE C Past or current symptoms of HF STAGE D End-stage HF Stages of Heart Failure • Designed to emphasize preventability of HF • Designed to recognize the progressive nature of LV dysfunction Stages of Heart Failure COMPLEMENT, DO NOT REPLACE NYHA CLASSES • NYHA Classes - shift back/forth in individual patient (in response to Rx and/or progression of disease) • Stages - progress in one direction due to cardiac remodeling Stage A Patients at High Risk for Developing Heart Failure Stage A Therapy Recommended Therapies to Reduce Risk Include: • Treating known risk factors (hypertension, diabetes, etc.) with therapy consistent with contemporary guidelines • Avoiding behaviors increasing risk (i.e., smoking excessive consumption of alcohol, illicit drug use) • Periodic evaluation for signs and symptoms of HF • Ventricular rate control or sinus rhythm restoration • Noninvasive evaluation of LV function • Drug therapy – •Angiotensin Converting Enzyme Inhibitors (ACEI) •Angiotensin Receptor Blockers (ARBs) Stage A Therapy Using Therapy Consistent with Contemporary Guidelines I IIa IIb III In patients at high risk for developing HF, systolic and diastolic hypertension should be controlled in accordance with contemporary guidelines. I IIa IIb III In patients at high risk for developing HF, lipid disorders should be treated in accordance with contemporary guidelines. Stage A Therapy Using Therapy Consistent with Contemporary Guidelines I IIa IIb III In patients at high risk for developing HF who have known atherosclerotic vascular disease, healthcare providers should follow current guidelines for secondary prevention. I IIa IIb III For patients with diabetes mellitus (who are all at high risk for developing HF), blood sugar should be controlled in accordance with contemporary guidelines. Stage A Therapy Using Therapy Consistent with Contemporary Guidelines I IIa IIb III Thyroid disorders should be treated in accordance with contemporary guidelines in patients at high risk for developing HF. Stage A Therapy Avoiding Behaviors That Increase Risk I IIa IIb III Patients at high risk for developing HF should be counseled to avoid behaviors that may increase the risk of HF (e.g., smoking, excessive alcohol consumption, and illicit drug use). Stage A Therapy Periodic Evaluation for Signs and Symptoms I IIa IIb III Healthcare providers should perform periodic evaluation for signs and symptoms of HF in patients at high risk for developing HF. Stage A Therapy Ventricular Rate Control or Sinus Rhythm Restoration I IIa IIb III Ventricular rate should be controlled or sinus rhythm restored in patients with supraventricular tachyarrhythmias who are at high risk for developing HF. Stage A Therapy Noninvasive Evaluation of LV Function I IIa IIb III Healthcare providers should perform a noninvasive evaluation of LV function (i.e., LVEF) in patients with a strong family history of cardiomyopathy or in those receiving cardiotoxic interventions. Stage A Therapy Angiotensin Converting Enzyme Inhibitors (ACEI) I IIa IIb III ACEI can be useful to prevent HF in patients at high risk for developing HF who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. Stage A Therapy Angiotension Receptor Blockers (ARBs) I IIa IIb III ARBs can be useful to prevent HF in patients at high risk for developing HF who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. Stage A Therapy Therapies NOT Recommended I IIa IIb III Routine use of nutritional supplements solely to prevent the development of structural heart disease should not be recommended for patients at high risk for developing HF. Stage B Patients with Asymptomatic LV Dysfunction Stage B Therapy Recommended Therapies: General Measures as advised for Stage A •Drug therapy for all patients •ACEI or ARBs •Beta-Blockers •ICDs in appropriate patients •Coronary revascularization in appropriate patients •Valve replacement or repair in appropriate patients Stage B Therapy General Measures I IIa IIb III All Class I recommendations for Stage A should apply to patients with cardiac structural abnormalities who have not developed HF. (Levels of Evidence: A, B, and C as appropriate) I IIa IIb III Patients who have not developed HF symptoms should be treated according to contemporary guidelines after an acute MI. Stage B Therapy Angiotensin Converting Enzyme Inhibitors (ACEI) I IIa IIb III Beta-blockers and ACEIs should be used in all patients with a recent or remote history of MI regardless of EF or presence of HF. I IIa IIb III ACEI should be used in patients with a reduced EF and no symptoms of HF, even if they have not experienced MI. I IIa IIb III ACEI or ARBs can be beneficial in patients with hypertension and LVH and no symptoms of HF. Stage B Therapy Angiotensin Receptor Blockers (ARBs) I IIa IIb III An ARB should be administered to post-MI patients without HF who are intolerant of ACEIs and have a low LVEF. I IIa IIb III I IIa IIb III ACEIs or ARBs can be beneficial in patients with hypertension and LVH and no symptoms of HF. ARBs can be beneficial in patients with low EF and no symptoms of HF who are intolerant of ACEIs. Stage B Therapy Beta-Blockers I IIa IIb III Beta-blockers and ACEIs should be used in all patients with a recent or remote history of MI regardless of EF or presence of HF. I IIa IIb III Beta-blockers are indicated in all patients without a history of MI who have a reduced LVEF with no HF symptoms. Stage B Therapy Internal Cardioverter Defibrillator (ICD) I IIa IIb III Placement of an ICD is reasonable in patients with ischemic cardiomyopathy who are at least 40 days post-MI, have an LVEF of 30% or less, are NYHA functional class I on chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. I IIa IIb III Placement of an ICD might be considered in patients without HF who have nonischemic cardiomyopathy and an LVEF less than or equal to 30% who are in NYHA functional class I with chronic optimal medical therapy and have a reasonable expectation of survival with good functional status for more than 1 year. Stage B Therapy Coronary Revascularization I IIa IIb III Coronary revascularization should be recommended in appropriate patients without symptoms of HF in accordance with contemporary guidelines (see ACC/AHA Guidelines for the Management of Patients With Chronic Stable Angina). Stage B Therapy Valve Replacement/Repair I IIa IIb III Valve replacement or repair should be recommended for patients with hemodynamically significant valvular stenosis or regurgitation and no symptoms of HF in accordance with contemporary guidelines. Stage B Therapy Therapies NOT Recommended I IIa IIb III I IIa IIb III I IIa IIb III Digoxin should not be used in patients with low EF, sinus rhythm, and no history of HF symptoms, because in this population, the risk of harm is not balanced by any known benefit. Use of nutritional supplements to treat structural heart disease or to prevent the development of symptoms of HF is not recommended. Calcium channel blockers with negative inotropic effects may be harmful in asymptomatic patients with low LVEF and no symptoms of HF after MI. Stage C Patients with Past or Current Symptoms of Heart Failure Stage C Therapy (Reduced LVEF with Symptoms) Recommended Therapies: •General measures as advised for Stages A and B •Drug therapy for all patients •Diuretics for fluid retention •ACEI •Beta-blockers •Drug therapy for selected patients •Aldosterone Antagonists •ARBs •Digitalis •Hydralazine/nitrates •ICDs in appropriate patients •Cardiac resynchronization in appropriate patients •Exercise Testing and Training Stage C Therapy (Reduced LVEF with Symptoms) General Measures I IIa IIb III Measures listed as Class I recommendations for patients in stages A and B are also appropriate for patients in Stage C. (Levels of Evidence: A, B, and C as appropriate) I IIa IIb III Drugs known to adversely affect the clinical status of patients with current or prior symptoms of HF and reduced LVEF should be avoided or withdrawn whenever possible (e.g., nonsteroidal anti-inflammatory drugs, most antiarrhythmic drugs, and most calcium channel blocking drugs). Stage C Therapy (Reduced LVEF with Symptoms) Diuretics I IIa IIb III Diuretics and salt restriction are indicated in patients with current or prior symptoms of HF and reduced LVEF who have evidence of fluid retention. Stage C Therapy (Reduced LVEF with Symptoms) Angiotensin Enzyme Converting Inhibitors (ACEIs) I IIa IIb III ACEIs are recommended for all patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. I IIa IIb III Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patients with current or prior symptoms of HF and reduced LVEF. Stage C Therapy (Reduced LVEF with Symptoms) Angiotensin Receptor Blockers (ARBs) I IIa IIb III ARBs approved for the treatment of HF are recommended in patients with current or prior symptoms of HF and reduced LVEF who are ACEIintolerant (see full text guidelines for information regarding patients with angioedema). I IIa IIb III ARBs are reasonable to use as alternatives to ACEIs as first-line therapy for patients with mild to moderate HF and reduced LVEF, especially for patients already taking ARBs for other indications. Stage C Therapy (Reduced LVEF with Symptoms) ARBs (cont’d) I IIa IIb III I IIa IIb III The addition of an ARB may be considered in persistently symptomatic patients with reduced LVEF who are already being treated with conventional therapy. Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patientswith current or prior symptoms of HF and reduced LVEF. Stage C Therapy (Reduced LVEF with Symptoms) Aldosterone Antagonists I IIa IIb III I IIa IIb III Addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be less than or equal to 2.5 mg/dL in men or less than or equal to 2.0 mg/dL in women and potassium should be less than 5.0 mEq/L. Under circumstances where monitoring for hyperkalemia or renal dysfunction is not anticipated to be feasible, the risks may outweigh the benefits of aldosterone antagonists. Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patients with current or prior symptoms of HF and reduced LVEF. Stage C Therapy (Reduced LVEF with Symptoms) Beta-Blockers I IIa IIb III Beta-blockers (using 1 of the 3 proven to reduce mortality, i.e., bisoprolol, carvedilol, and sustained release metoprolol succinate) are recommended for all stable patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. Stage C Therapy (Reduced LVEF with Symptoms) Digitalis I IIa IIb III Digitalis can be beneficial in patients with current or prior symptoms of HF and reduced LVEF to decrease hospitalizations for HF. Stage C Therapy (Reduced LVEF with Symptoms) Hydralazine and Isosorbide Dinitrate I IIa IIb III I IIa IIb III The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already taking an ACEI and betablocker for symptomatic HF and who have persistent symptoms. A combination of hydralazine and a nitrate might be reasonable in patients with current or prior symptoms of HF and reduced LVEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency. Stage C Therapy (Reduced LVEF with Symptoms) Implantable CardioverterDefibrillators (ICDs) I IIa IIb III I IIa IIb III An ICD is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with ischemic heart disease who are at least 40 days post-MI, have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. Stage C Therapy (Reduced LVEF with Symptoms) ICDs (cont’d) I IIa IIb III ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with nonischemic cardiomyopathy who have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. I IIa IIb III Placement of an ICD is reasonable in patients with LVEF of 30% to 35% of any origin with NYHA functional class II or III symptoms who are taking chronic optimal medical therapy and who have reasonable expectation of survival with good functional status of more than 1 year. Stage C Therapy (Reduced LVEF with Symptoms) Cardiac Resynchronization I IIa IIb III Patients with LVEF less than or equal to 35%, sinus rhythm, and NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony, which is currently defined as a QRS duration greater than 120 ms, should receive cardiac resynchronization therapy unless contraindicated. Stage C Therapy (Reduced LVEF with Symptoms) Exercise Testing and Training I IIa IIb III Maximal exercise testing with or without measurement of respiratory gas exchange is recommended to facilitate prescription of an appropriate exercise program for patients presenting with HF. I IIa IIb III Exercise training is beneficial as an adjunctive approach to improve clinical status in ambulatory patients with current or prior symptoms of HF and reduced LVEF. Stage C Therapy (Reduced LVEF with Symptoms) Unproven/Not Recommended Drugs and Interventions for HF • Nutritional Supplements • Hormonal Therapies • Intermittent Intravenous Positive Inotropic Therapy Stage C Therapy (Reduced LVEF with Symptoms) Unproven/Not Recommended Drugs and Interventions I IIa IIb III Long-term use of an infusion of a positive inotropic drug may be harmful and is not recommended for patients with current or prior symptoms of HF and reduced LVEF, except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment (see recommendations for Stage D). I IIa IIb III Use of nutritional supplements as treatment for HF is not indicated in patients with current or prior symptoms of HF and reduced LVEF. Stage C Therapy (Reduced LVEF with Symptoms) Unproven/Not Recommended Drugs and Interventions I IIa IIb III Calcium channel blocking drugs are not indicated as routine treatment for HF in patients with current or prior symptoms of HF and reduced LVEF. I IIa IIb III Hormonal therapies other than to replete deficiencies are not recommended and may be harmful to patients with current or prior symptoms of HF and reduced LVEF. I IIa IIb III Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patientswith current or prior symptoms of HF and reduced LVEF. Stage C Therapy (Normal LVEF with Symptoms) Recommended Therapies for Routine Use: •Treating known risk factor (hypertension) with therapy consistent with contemporary guidelines •Ventricular rate control for all patients •Drugs for all patients •Diuretics •Drugs for appropriate patients – •ACEI •ARBs •Beta-Blockers •Digitalis •Coronary revascularization in selected patients •Restoration/maintenance of sinus rhythm in appropriate patients Differential Diagnosis in Patient with HF and Normal LVEF with Symptoms • Incorrect diagnosis of HF • Inaccurate measurement of LVEF • Primary valvular disease • Restrictive (infiltrative) cardiomyopathies • Amyloidosis, sarcoidosis, hemochromatosis • Pericardial constriction • Episodic or reversible LV systolic dysfunction • Severe hypertension, myocardial ischemia • HF associated with high metabolic demand (highoutput states) • Anemia, thyrotoxicosis, arteriovenous fistulae • Chronic pulmonary disease with right HF • Pulmonary hypertension associated with pulmonary vascular disorders • Atrial myxoma • Diastolic dysfunction of uncertain origin • Obesity Stage C Therapy (Normal LVEF with Symptoms) Treating known risk factors Hypertension I IIa IIb III Physicians should control systolic and diastolic hypertension in patients with HF and normal LVEF, in accordance with published guidelines. Stage C Therapy (Normal LVEF with Symptoms) Ventricular Rate Control I IIa IIb III Physicians should control ventricular rate in patients with HF and normal LVEF and atrial fibrillation. Stage C Therapy (Normal LVEF with Symptoms) Diuretics I IIa IIb III Physicians should use diuretics to control pulmonary congestion and peripheral edema in patients with HF and normal LVEF. Stage C Therapy (Normal LVEF with Symptoms) Coronary Revascularization I IIa IIb III Coronary revascularization is reasonable in patients with HF and normal LVEF and coronary artery disease in whom symptomatic or demonstrable myocardial ischemia is judged to be having an adverse effect on cardiac function. Stage C Therapy (Normal LVEF with Symptoms) Restoration/Maintenance of Sinus Rhythm I IIa IIb III Restoration and maintenance of sinus rhythm in patients with atrial fibrillation and HF and normal LVEF might be useful to improve symptoms. Stage C Therapy (Normal LVEF with Symptoms) Angiotensin Enzyme Converting Inhibitors (ACEIs) I IIa IIb III The use of beta-adrenergic blocking agents, ACEIs, ARBs, or calcium antagonists in patients with HF and normal LVEF and controlled hypertension might be effective to minimize symptoms of HF. Stage C Therapy (Normal LVEF with Symptoms) Angiotensin Receptor Blockers (ARBs) I IIa IIb III The use of beta-adrenergic blocking agents, ACEIs, ARBs, or calcium antagonists in patients with HF and normal LVEF and controlled hypertension might be effective to minimize symptoms of HF. Stage C Therapy (Normal LVEF with Symptoms) Beta-Blockers I IIa IIb III The use of beta-adrenergic blocking agents, ACEIs, ARBs, or calcium antagonists in patients with HF and normal LVEF and controlled hypertension might be effective to minimize symptoms of HF. Stage C Therapy (Normal LVEF with Symptoms) Digitalis I IIa IIb III The usefulness of digitalis to minimize symptoms of HF in patients with HF and normal LVEF is not well established. Stage D Patients with Refractory End-Stage HF Stage D Therapy Recommended Therapies Include: •Control of fluid retention •Referral to a HF program for appropriate pts •Discussion of options for end-of-life care •Informing re: option to inactivate defibrillator •Device use in appropriate patients •Surgical therapy – •Cardiac transplantation •Mitral valve repair or replacement •Other •Drug Therapy – •Positive inotrope infusion as palliation in appropriate patients Stage D Therapy Control of Fluid Retention I IIa IIb III Meticulous identification and control of fluid retention is recommended in patients with refractory end-stage HF. Stage D Therapy Referral to an HF Program I IIa IIb III Referral of patients with refractory end-stage HF to an HF program with expertise in the management of refractory HF is useful. Stage D Therapy Discussion of Options for End-of-Life Care I IIa IIb III Options for end-of-life care should be discussed with the patient and family when severe symptoms in patients with refractory end-stage HF persist despite application of all recommended therapies. Stage D Therapy Inform on option to inactivate defibrillation I IIa IIb III Patients with refractory end-stage HF and implantable defibrillators should receive information about the option to inactivate defibrillation. Stage D Therapy Surgical Therapy I IIa IIb III Referral for cardiac transplantation in potentially eligible patients is recommended for patients with refractory end-stage HF. I IIa IIb III The effectiveness of mitral valve repair or replacement is not established for severe secondary mitral regurgitation in refractory end-stage HF. Stage D Therapy Device Use I IIa IIb III I IIa IIb III Consideration of an LV assist device as permanentor “destination” therapy is reasonable in highly selected patients with refractory end-stage HF and an estimated 1-year mortality over 50% with medical therapy. Pulmonary artery catheter placement may be reasonable to guide therapy in patients with refractory end-stage HF and persistently severe symptoms. Stage D Therapy Medical Therapy I IIa IIb III Continuous intravenous infusion of a positive inotropic agent may be considered for palliation of symptoms in patients with refractory end-stage HF. I IIa IIb III Routine intermittent infusions of positive inotropic agents are not recommended for patients with refractory end-stage HF. Stage D Therapy Therapies NOT Recommended I IIa IIb III I IIa IIb III Partial left ventriculectomy is not recommended inpatients with nonischemic cardiomyopathy and refractory end-stage HF. Routine intermittent infusions of positive inotropic agents are not recommended for patients with refractory end-stage HF.