, bisoprolol, carvedilol, and sustained-release metoprolol succi- nate) is recommended for all patients with current or prior symptomsofHFrEF,unlesscontraindicated,toreducemorbidity and mortality (137,172 175,187). (Level of Evidence: A) 6.3.2.5. ALDOSTERONE RECEPTOR ANTAGONISTS See Table 12 for aldosterone receptor antagonists drug dosing. CLASS I 1. Aldosterone receptor antagonists (or mineralocorticoid receptor antagonists) are recommended in patients with NYHA class II IV HF and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity and mortality. Patients with NYHA class II HF should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be consid- ered for aldosterone receptor antagonists. Creatinine should be 2.5 mg/dL or less in men or 2.0 mg/dL or less in women (or estimated glomerular ltration rate >30 ), and potassium should be less than 5.0 mEq/L. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insuf ciency (181,182,197). (Level of Evidence: A) 2. Aldosterone receptor antagonists are recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of 40% or less who develop symp- toms of HF or have a history of diabetes mellitus, unless contraindicated (184). (Level of Evidence: B) CLASS III: HARM 1. Inappropriate use of aldosterone receptor antagonists is potentially harmful because of life-threatening hyperkalemia or renal insuf ciency when serum creatinine is greater than HFrEF Stage C NYHA Class I IV Treatment: For NYHA class II-IV patients. Provided estimated creatinine >30 mL/min and K+ <5.0 mEq/dL For persistently symptomatic African Americans, NYHA class III-IV Class I, LOE A ACEI or ARB AND Beta Blocker Class I, LOE C Loop Diuretics Class I, LOE A Hydral-Nitrates Class I, LOE A Aldosterone Antagonist Add Add Add For all volume overload, NYHA class II-IV patients Figure 1. Stage C HFrEF: evidence-based, guideline-directed medical therapy. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; HFrEF, heart failure with reduced ejection fraction; Hydral-Nitrates, hydralazine and isosorbide dinitrate; LOE, Level of Evidence; and NYHA, New York Heart Association. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary 2.5 mg/dL in men or greater than 2.0 mg/dL in women (or ), and/or potassium greater than 5.0 mEq/L (198,199). (Level of Evidence: B) 6.3.2.6. HYDRALAZINE AND ISOSORBIDE DINITRATE CLASS I 1. The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated (179,180). (Level of Evidence: A) CLASS IIa 1. A combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypoten- sion, or renal insuf ciency, unless contraindicated (188). (Level of Evidence: B) See Table 13 for a summary of the treatment bene t of GDMT in HFrEF. CLASS IIa 1. Digoxin can be bene cial in patients with HFrEF, unless contraindicated, to decrease hospitalizations for HF (202 209). (Level of Evidence: B) 6.3.2.8. OTHER DRUG TREATMENT CLASS I 1. Patients with chronic HF with permanent/persistent/ paroxysmal atrial brillation (AF) and an additional risk factor for cardioembolic stroke (history of hyper- tension, diabetes mellitus, previous stroke or transient ischemic attack, or 75 years of age) should receive chronic anticoagulant therapy* (210 216). (Level of Evidence: A) 2. The selection of an anticoagulant agent (warfarin, dabiga- tran, apixaban, or rivaroxaban) for permanent/persistent/ paroxysmal AF should be individualized on the basis of risk factors, cost, tolerability, patient preference, potential for drug interactions, and other clinical characteristics, including time in the international normalized ratio thera- peutic range if the patient has been taking warfarin. (Level of Evidence: C) CLASS IIa 1. Chronic anticoagulation is reasonable for patients with chronic HF who have permanent/persistent/paroxysmal AF but are without an additional risk factor for cardioembolic stroke* (211 213,217 219). (Level of Evidence: B) CLASS III: NO BENEFIT 1. Anticoagulation is not recommended in patients with chronic HFrEF without AF, a prior thromboembolic event, or a cardioembolic source (220 222). (Level of Evidence: B) CLASS III: NO BENEFIT 1. Statins are not bene cial as adjunctive therapy when prescribed solely for the diagnosis of HF in the absence of other indications for their use (223 228). (Level of Evidence: A) CLASS IIa 1. Omega-3 polyunsaturated fatty acid supplementation is reasonable to use as adjunctive therapy in patients with NYHA class II IV symptoms and HFrEF or HFpEF, unless contraindicated, to reduce mortality and cardiovascular hospitalizations (229,230). (Level of Evidence: B) Table 10. Oral Diuretics Recommended for Use in the Treatment of Chronic HF Drug Initial Daily Dose(s) Maximum Total Daily Dose Duration of Action Loop diuretics Bumetanide 0.5 to 1.0 mg once or twice Furosemide 20 to 40 mg once or twice Thiazide diuretics Chlorothiazide 250 to 500 mg once or twice Hydrochlorothiazide 25 mg once or twice Indapamide 2.5 mg once 5 mg 36 h Metolazone 2.5 mg once 20 mg 12 to 24 h Potassium-sparing diuretics* Amiloride 5 mg once 20 mg 24 h Sequential nephron blockade Metolazonez 2.5 to 10.0 mg once plus loop diuretic N/A N/A Hydrochlorothiazide 25 to 100 mg once or twice plus loop diuretic N/A N/A Chlorothiazide (IV) 500 to 1,000 mg once plus loop diuretic N/A N/A *Eplerenone, although also a diuretic, is primarily used in chronic HF. yHigher doses may occasionally be used with close monitoring. zSee Section 7.3. HF indicates heart failure; IV, intravenous; and N/A, not applicable. * In the absence of contraindications to anticoagulation. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 6.3.2.9. DRUGS OF UNPROVEN VALUE OR THAT MAY WORSEN HF CLASS III: NO BENEFIT 1. Nutritional supplements as treatment for HF are not rec- ommended in patients with current or prior symptoms of HFrEF (231,232). (Level of Evidence: B) 2. Hormonal therapies other than to correct de ciencies are not recommended for patients with current or prior symp- toms of HFrEF. (Level of Evidence: C) CLASS III: HARM 1. Drugs known to adversely affect the clinical status of patients with current or prior symptoms of HFrEF are potentially harmful and should be avoided or withdrawn Table 11. Drugs Commonly Used for Stage C HFrEF Drug Initial Daily Dose(s) Maximum Dose(s) Mean Doses Achieved in Clinical Trials ACE inhibitors Fosinopril 5 to 10 mg once 40 mg once N/A Perindopril 2 mg once 8 to 16 mg once N/A Quinapril 5 mg twice 20 mg twice N/A Ramipril 1.25 to 2.5 mg once 10 mg once N/A Trandolapril 1 mg once 4 mg once N/A ARBs Aldosterone antagonists Spironolactone 12.5 to 25.0 mg once 25 mg once or twice 26 mg/d (181) Eplerenone 25 mg once 50 mg once 42.6 mg/d (184) Beta blockers Bisoprolol 1.25 mg once 10 mg once 8.6 mg/d (185) Carvedilol 3.125 mg twice 50 mg twice 37 mg/d (186) Carvedilol CR 10 mg once 80 mg once N/A Metoprolol succinate extended release (metoprolol CR/XL) Hydralazine and isosorbide dinitrate Fixed-dose combination (180) 37.5 mg hydralazine/20 mg isosorbide dinitrate 3 times daily 75 mg hydralazine/40 mg isosorbide dinitrate 3 times daily isosorbide dinitrate daily Hydralazine and isosorbide daily and isosorbide dinitrate: 20 to Hydralazine: 300 mg daily in divided doses and isosorbide dinitrate: 120 mg daily in divided doses N/A ACE indicates angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CR, controlled release; CR/XL, controlled release/extended release; HFrEF, heart failure with reduced ejection fraction; and N/A, not applicable. Table 12. Drug Dosing for Aldosterone Receptor Antagonists Eplerenone Spironolactone Initial dose (only if K 5 mEq/L) 25 mg once daily 25 mg once every other day 12.5 to 25.0 mg once daily 12.5 mg once daily or every other day Maintenance dose (after 4 wk for K 50 mg once daily 25 mg once daily 25 mg once or twice daily 12.5 to 25.0 mg once daily *After dose initiation for K , increase6.0 mEq/L, or worsening renal function, hold until K <5.0 mEq/L. Consider restarting reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 h. eGFR indicates estimated glomerular filtration rate; and K , potassium. Adapted from Butler et al. (200). JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary whenever possible (e.g., most antiarrhythmic drugs, most calcium channel blocking drugs [except amlodipine], nonsteroidal anti-in ammatory drugs, or thiazolidinediones) (233 244). (Level of Evidence: B) 2. Long-term use of infused positive inotropic drugs is poten- tially harmful for patients with HFrEF, except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment (see recommendations for stage D). (Level of Evidence: C) 6.3.2.9.1. Calcium Channel Blockers CLASS III: NO BENEFIT 1. Calcium channel blocking drugs are not recommended as routine treatment for patients with HFrEF (238,245,246). (Level of Evidence: A) See Table 14 for a summary of recommendations from this section and Table 15 for strategies for achieving optimal GDMT. 6.3.3. Pharmacological Treatment for Stage C HFpEF See Table 16 for a summary of recommendations from this section. CLASS I 1. Systolic and diastolic blood pressure should be controlled in patients with HFpEF in accordance with published clinical practice guidelines to prevent morbidity (28,247). (Level of Evidence: B) 2. Diuretics should be used for relief of symptoms due to volume overload in patients with HFpEF. (Level of Evidence: C) CLASS IIa 1. Coronary revascularization is reasonable in patients with CAD in whom symptoms (angina) or demonstrable myo- cardial ischemia is judged to be having an adverse effect on symptomatic HFpEF despite GDMT. (Level of Evidence: C) 2. Management of AF according to published clinical practice guidelines in patients with HFpEF is reasonable to improve symptomatic HF. (Level of Evidence: C) 3. The use of beta-blocking agents, ACE inhibitors, and ARBs in patients with hypertension is reasonable to control blood pressure in patients with HFpEF. (Level of Evidence: C) CLASS IIb 1. The use of ARBs might be considered to decrease hospitalizations for patients with HFpEF (248). (Level of Evidence: B) CLASS III: NO BENEFIT 1. Routine use of nutritional supplements is not recommended for patients with HFpEF. (Level of Evidence: C) 6.3.4. Device Therapy for Stage C HFrEF See Table 17 for a summary of recommendations from this section. CLASS I 1. ICD therapy is recommended for primary prevention of sudden cardiac death to reduce total mortality in selected patients with nonischemic dilated cardiomyopathy or ischemic heart disease at least 40 days post-MI with LVEF of 35% or less and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of mean- ingful survival for more than 1 yeary (148,249). (Level of Evidence: A) 2. Cardiac resynchronization therapy (CRT) is indicated for patients who have LVEF of 35% or less, sinus rhythm, left bundle-branch block (LBBB) with a QRS duration of 150 ms or greater, and NYHA class II, III, or ambulatory IV symptoms on GDMT. (Level of Evidence: A for NYHA class III/IV (37,250 252); Level of Evidence: B for NYHA class II (253,254). 3. ICD therapy is recommended for primary prevention of sudden cardiac death to reduce total mortality in selected patients at least 40 days post-MI with LVEF of 30% or less and NYHA class I symptoms while receiving GDMT, who have reasonable expectation of meaningful survival for more than 1 yeary (255 257). (Level of Evidence: B) CLASS IIa 1. CRT can be useful for patients who have LVEF of 35% or less, sinus rhythm, a non-LBBB pattern with a QRS duration of 150 ms or greater, and NYHA class III/ambulatory class IV symptoms on GDMT (250 252,254). (Level of Evidence: A) 2. CRT can be useful for patients who have LVEF of 35% or less, sinus rhythm, LBBB with a QRS duration of 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT (250 254,258). (Level of Evidence: B) 3. CRT can be useful in patients with AF and LVEF of 35% or less on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) atrioventricular nodal ablation or pharmacological rate control will allow near 100% ventricular pacing with CRT (259 264). (Level of Evidence: B) 4. CRT can be useful for patients on GDMT who have LVEF of 35% or less and are undergoing placement of a new or re- placement device implantation with anticipated requirement for signi cant (>40%) ventricular pacing (261,265 267). (Level of Evidence: C) Table 13. Medical Therapy for Stage C HFrEF: Magnitude of Benefit Demonstrated in RCTs GDMT RR Reduction in Mortality (%) NNT for Mortality Reduction (Standardized to 36 mo) RR Reduction in HF Hospitalizations (%) ACE inhibitor or ARB Aldosterone antagonist ACE indicates angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; GDMT, guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; NNT, number needed to treat; RCTs, randomized controlled trials; and RR, relative risk. Adapted with permission from Fonarow et al. (201). yCounseling should be speci c to each individual patient and should include documentation of a discussion about the potential for sudden death and nonsudden death from HF or noncardiac conditions. Information should be provided about the ef cacy, safety, and potential complications of an ICD and the potential for de - brillation to be inactivated if desired in the future, notably when a patient is approaching end of life. This will facilitate shared decision making between patients, families, and the medical care team about ICDs (31). Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Table 14. Recommendations for Pharmacological Therapy for Management of Stage C HFrEF Recommendations COR LOE References Diuretics Diuretics are recommended in patients with HFrEF with fluid retention I C N/A ACE inhibitors ACE inhibitors are recommended for all patients with HFrEF I A 134,167 169 ARBs ARBs are recommended in patients with HFrEF who are ACE inhibitor intolerant I A 136,170,171,189 ARBs are reasonable as alternatives to ACE inhibitors as first-line therapy in HFrEF IIa A 190 195 Addition of an ARB may be considered in persistently symptomatic patients with HFrEF on GDMT IIb A 176,196 Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful III: Harm C N/A Beta blockers Use of 1 of the 3 beta blockers proven to reduce mortality is recommended for all stable patients I A 137,172 175,187 Aldosterone receptor antagonists Aldosterone receptor antagonists are recommended in patients with NYHA class II IV who have LVEF 35% I A 181,182,197 Aldosterone receptor antagonists are recommended in patients following an acute MI who have LVEF 40% with symptoms of HF or DM I B 184 Inappropriate use of aldosterone receptor antagonists may be harmful III: Harm B 198,199 Hydralazine and isosorbide dinitrate The combination of hydralazine and isosorbide dinitrate is recommended for African Americans with NYHA class III IV HFrEF on GDMT I A 179,180 A combination of hydralazine and isosorbide dinitrate can be useful in patients with HFrEF who cannot be given ACE inhibitors or ARBs IIa B 188 Digoxin Digoxin can be beneficial in patients with HFrEF IIa B 202 209 Anticoagulation Patients with chronic HF with permanent/persistent/paroxysmal AF and an additional risk factor for cardioembolic stroke should receive chronic anticoagulant therapy* I A 210 216 The selection of an anticoagulant agent should be individualized I C N/A Chronic anticoagulation is reasonable for patients with chronic HF who have permanent/ persistent/paroxysmal AF but are without an additional risk factor for cardioembolic stroke* IIa B 211 213,217 219 Anticoagulation is not recommended in patients with chronic HFrEF without AF, a prior thromboembolic event, or a cardioembolic source III: No Benefit B 220 222 Statins Statins are not beneficial as adjunctive therapy when prescribed solely for HF III: No Benefit A 223 228 Omega-3 fatty acids Omega-3 PUFA supplementation is reasonable to use as adjunctive therapy in HFrEF or HFpEF patients IIa B 229,230 Other drugs Nutritional supplements as treatment for HF are not recommended in HFrEF III: No Benefit B 231,232 Hormonal therapies other than to correct deficiencies are not recommended in HFrEF III: No Benefit C N/A Drugs known to adversely affect the clinical status of patients with HFrEF are potentially harmful and should be avoided or withdrawn III: Harm B 233 244 Long-term use of an infusion of a positive inotropic drug is not recommended and may be harmful except as palliation III: Harm C N/A Calcium channel blockers Calcium channel blocking drugs are not recommended as routine treatment in HFrEF III: No Benefit A 238,245,246 *In the absence of contraindications to anticoagulation. ACE indicates angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin-receptor blocker; COR, Class of Recommendation; DM, diabetes mellitus; GDMT, guideline-directed medical therapy; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LOE, Level of Evidence; LVEF, left ventricular ejection fraction; MI, myocardial infarction; N/A, not available; NYHA, New York Heart Association; and PUFA, poly- unsaturated fatty acids. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary CLASS IIb 1. The usefulness of implantation of an ICD is of uncertain bene t to prolong meaningful survival in patients with a high risk of nonsudden death as predicted by frequent hospitali- zations, advanced frailty, or comorbidities such as systemic malignancy or severe renal dysfunctiony (268 271). (Level of Evidence: B) 2. CRT may be considered for patients who have LVEF of 35% or less, sinus rhythm, a non-LBBB pattern with a QRS duration of 120 to 149 ms, and NYHA class III/ambulatory class IV on GDMT (254,272). (Level of Evidence: B) 3. CRT may be considered for patients who have LVEF of 35% or less, sinus rhythm, a non-LBBB pattern with a QRS duration of 150 ms or greater, and NYHA class II symptoms on GDMT (253,254). (Level of Evidence: B) 4. CRT may be considered for patients who have LVEF of 30% or less, ischemic etiology of HF, sinus rhythm, LBBB with a QRS duration of 150 ms or greater, and NYHA class I symptoms on GDMT (253,254). (Level of Evidence: C) CLASS III: NO BENEFIT 1. CRT is not recommended for patients with NYHA class I or II symptoms and non-LBBB pattern with a QRS dura- tion of less than 150 ms (253,254,272). (Level of Evidence: B) 2. CRT is not indicated for patients whose comorbidities and/ or frailty limit survival with good functional capacity to less than 1 year (37). (Level of Evidence: C) See Figure 2, indications for CRT therapy algorithm. Table 15. Strategies for Achieving Optimal GDMT 1. Uptitrate in small increments to the recommended target dose or the highest tolerated dose for those medications listed in Table 11 with an appreciation that some patients cannot tolerate the full recommended doses of all medications, particularly patients with low baseline heart rate or blood pressure or with a tendency to postural symptoms. 2. Certain patients (e.g., the elderly, patients with chronic kidney disease) may require more frequent visits and laboratory monitoring during dose titration and more gradual dose changes. However, such vulnerable patients may accrue considerable benefits from GDMT. Inability to tolerate optimal doses of GDMT may change after disease-modifying interventions such as CRT. 3. Monitor vital signs closely before and during uptitration, including postural changes in blood pressure or heart rate, particularly in patients with orthostatic symptoms, bradycardia, and/or low systolic blood pressure (e.g., 80 to 100 mm Hg). 4. Alternate adjustments of different medication classes (especially ACE inhibitors/ARBs and beta blockers) listed in Table 11. Patients with elevated or normal blood pressure and heart rate may tolerate faster incremental increases in dosages. 5. Monitor renal function and electrolytes for rising creatinine and hyperkalemia, recognizing that an initial rise in creatinine may be expected and does not necessarily require discontinuation of therapy; discuss tolerable levels of creatinine above baseline with a nephrologist if necessary. 6. Patients may complain of symptoms of fatigue and weakness with dosage increases; in the absence of instability in vital signs, reassure them that these symptoms are often transient and usually resolve within a few days of changes in therapy. 7. Discourage sudden spontaneous discontinuation of GDMT medications by the patient and/or other clinicians without discussion with managing clinicians. 8. Carefully review doses of other medications for HF symptom control (e.g., diuretics, nitrates) during uptitration. 9. Consider temporary adjustments in dosages of GDMT during acute episodes of noncardiac illnesses (e.g., respiratory infections, risk of dehydration, etc). 10. Educate patients, family members, and other clinicians about the expected benefits of achieving GDMT, including an understanding of the potential benefits of myocardial reverse remodeling, increased survival, and improved functional status and HRQOL. ACE indicates angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CRT, cardiac resynchronization therapy; GDMT, guideline-directed medical therapy; HF, heart failure; and HRQOL, health-related quality of life. Table 16. Recommendations for Treatment of HFpEF Recommendations COR LOE Systolic and diastolic blood pressure should be controlled according to published clinical practice guidelines I B (28,247) Diuretics should be used for relief of symptoms due to volume overload I C Coronary revascularization for patients with CAD in whom angina or demonstrable myocardial ischemia is present despite GDMT IIa C Management of AF according to published clinical practice guidelines for HFpEF to improve symptomatic HF IIa C Use of beta-blocking agents, ACE inhibitors, and ARBs for hypertension in HFpEF IIa C ARBs might be considered to decrease hospitalizations in HFpEF IIb B (248) Nutritional supplementation is not recommended in HFpEF III: No Benefit C ACE indicates angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin-receptor blocker; CAD, coronary artery disease; COR, Class of Recommendation; GDMT, guideline-directed medical therapy; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; and LOE, Level of Evidence. yCounseling should be speci c to each individual patient and should include documentation of a discussion about the potential for sudden death and nonsudden death from HF or noncardiac conditions. Information should be provided about the ef cacy, safety, and potential complications of an ICD and the potential for de - brillation to be inactivated if desired in the future, notably when a patient is approaching end of life. This will facilitate shared decision making between patients, families, and the medical care team about ICDs (31). Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 6.4. Stage D See Table 18 for the European Society of Cardiology de nition of advanced HF and Table 19 for clinical events and ndings useful for identifying patients with advanced HF. 6.4.1. Water Restriction CLASS IIa 1. Fluid restriction (1.5 to 2 L/d) is reasonable in stage D, especially in patients with hyponatremia, to reduce congestive symptoms. (Level of Evidence: C) 6.4.2. Inotropic Support See Table 20 for inotropic agents used in HF management and Table 21 for a summary of recommendations from this section. CLASS I 1. Until de nitive therapy (e.g., coronary revascularization, MCS, heart transplantation) or resolution of the acute precipitating problem, patients with cardiogenic shock should receive tempo- rary intravenous inotropic support to maintain systemic perfusion and preserve end-organ performance. (Level of Evidence: C) CLASS IIa 1. Continuous intravenous inotropic support is reasonable as bridge therapy in patients with stage D HF refractory to GDMT and device therapy who are eligible for and awaiting MCS or cardiac transplantation (275,276). (Level of Evidence: B) CLASS IIb 1. Short-term, continuous intravenous inotropic support may be reasonable in those hospitalized patients presenting with documented severe systolic dysfunction who present with low blood pressure and signi cantly depressed cardiac output to maintain systemic perfusion and preserve end-organ performance (277 279). (Level of Evidence: B) 2. Long-term, continuous intravenous inotropic support may be considered as palliative therapy for symptom control in select patients with stage D HF despite optimal GDMT and device therapy who are not eligible for either MCS or cardiac transplantation (280 282). (Level of Evidence: B) Table 17. Recommendations for Device Therapy for Management of Stage C HF Recommendations COR LOE References ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 d post-MI with LVEF 35% and NYHA class II or III symptoms on chronic GDMT, who are expected to live >1 y* I A 148,249 CRT is indicated for patients who have LVEF 35%, sinus rhythm, and LBBB with a QRS 150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT I A (NYHA class III/IV) B (NYHA class II) ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 d post-MI with LVEF 30% and NYHA class I symptoms while receiving GDMT, who are expected to live >1 y* I B 255 257 CRT can be useful for patients who have LVEF 35%, sinus rhythm, a non-LBBB pattern with a QRS 150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT IIa A 250 252,254 CRT can be useful for patients who have LVEF 35%, sinus rhythm, LBBB with a QRS 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT IIa B 250 254,258 CRT can be useful in patients with AF and LVEF 35% on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) AV nodal ablation or rate control allows near 100% ventricular pacing with CRT IIa B 259 264 CRT can be useful for patients on GDMT who have LVEF 35% and are undergoing new or replacement device implantation with anticipated ventricular pacing (>40%) IIa C 261,265 267 An ICD is of uncertain benefit to prolong meaningful survival in patients with a high risk of nonsudden death such as frequent hospitalizations, frailty, or severe comorbidities* IIb B 268 271 CRT may be considered for patients who have LVEF 35%, sinus rhythm, a non-LBBB pattern with QRS 120 to 149 ms, and NYHA class III/ambulatory class IV on GDMT IIb B 254,272 CRT may be considered for patients who have LVEF 35%, sinus rhythm, a non-LBBB pattern with a QRS 150 ms, and NYHA class II symptoms on GDMT IIb B 253,254 CRT may be considered for patients who have LVEF 30%, ischemic etiology of HF, sinus rhythm, LBBB with QRS 150 ms, and NYHA class I symptoms on GDMT IIb C 253,254 CRT is not recommended for patients with NYHA class I or II symptoms and a non-LBBB pattern with QRS <150 ms III: No Benefit B 253,254,272 CRT is not indicated for patients whose comorbidities and/or frailty limit survival to <1 y III: No Benefit C 37 *Counseling should be specific to each individual patient and should include documentation of a discussion about the potential for sudden death and nonsudden death from HF or noncardiac conditions. Information should be provided about the efficacy, safety, and potential complications of an ICD and the potential for defibrillation to be inactivated if desired in the future, notably when a patient is approaching end of life. This will facilitate shared decision making between patients, families, and the medical care team about ICDs (31). AF indicates atrial fibrillation; AV, atrioventricular; COR, Class of Recommendation; CRT, cardiac resynchronization therapy; GDMT, guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter-defibrillator; LBBB, left bundle-branch block; LOE, Level of Evidence; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association; and SCD, sudden cardiac death. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Figure 2. Indications for CRT therapy algorithm. CRT indicates cardiac resynchronization therapy; CRT-D, cardiac resynchronization therapy-de brillator; GDMT, guideline-directed medical therapy; HF, heart failure; ICD, implantable cardioverter-de brillator; LBBB, left bundle-branch block; LVEF, left ventricular ejection fraction; MI, myocardial infarction; and NYHA, New York Heart Association. Table 18. ESC Definition of Advanced HF 1. Severe symptoms of HF with dyspnea and/or fatigue at rest or with minimal exertion (NYHA class III or IV) 2. Episodes of fluid retention (pulmonary and/or systemic congestion, peripheral edema) and/or reduced cardiac output at rest (peripheral hypoperfusion) 3. Objective evidence of severe cardiac dysfunction shown by at least 1 of the following: a. LVEF <30% b. Pseudonormal or restrictive mitral inflow pattern c. Mean PCWP >16 mm Hg and/or RAP >12 mm Hg by PA catheterization d. High BNP or NT-proBNP plasma levels in the absence of noncardiac causes 4. Severe impairment of functional capacity shown by 1 of the following: a. Inability to exercise b. 6-Minute walk distance 300 m c. Peak _ 5. History of 1 HF hospitalization in past 6 mo 6. Presence of all the previous features despite attempts to optimize therapy, including diuretics and GDMT, unless these are poorly tolerated or contraindicated, and CRT when indicated BNP indicates B-type natriuretic peptide; CRT, cardiac resynchronization therapy; ESC, European Society of Cardiology; GDMT, guideline-directed medical therapy; HF, heart failure; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; and RAP, right atrial pressure. Adapted from Metra et al. (33). Table 19. Clinical Events and Findings Useful for Identifying Patients With Advanced HF Repeated (2) hospitalizations or ED visits for HF in the past year Progressive deterioration in renal function (e.g., rise in BUN and creatinine) Weight loss without other cause (e.g., cardiac cachexia) Intolerance to ACE inhibitors due to hypotension and/or worsening renal function Intolerance to beta blockers due to worsening HF or hypotension Frequent systolic blood pressure <90 mm Hg Persistent dyspnea with dressing or bathing requiring rest Inability to walk 1 block on the level ground due to dyspnea or fatigue Recent need to escalate diuretics to maintain volume status, often reaching daily furosemide equivalent dose over 160 mg/d and/or use of supplemental metolazone therapy Progressive decline in serum sodium, usually to <133 mEq/L Frequent ICD shocks ACE indicates angiotensin-converting enzyme; BUN, blood urea nitrogen; ED, emergency department; HF, heart failure; and ICD, implantable cardioverter- defibrillator. Adapted from Russell et al. (274). Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 CLASS III: HARM 1. Long-term use of either continuous or intermittent, intrave- nous parenteral positive inotropic agents, in the absence of speci c indications or for reasons other than palliative care, is potentially harmful in the patient with HF (172,283 288). (Level of Evidence: B) 2. Use of parenteral inotropic agents in hospitalized patients without documented severe systolic dysfunction, low blood pressure, or impaired perfusion and evidence of signi cantly depressed cardiac output, with or without congestion, is potentially harmful (277 279). (Level of Evidence: B) Table 20. Intravenous Inotropic Agents Used in Management of HF Inotropic Agent Dose (mcg/kg) Drug Kinetics and Metabolism Effects Adverse Effects Special Considerations Bolus Infusion (/min) CO HR SVR PVR Adrenergic agonists R,H,P [ [ 4 4 T, HA, N, tissue necrosis Caution: MAO-I N/A 10 to 15 [ [ [ 4 H [ [ Y 4 [/YBP, HA, T, N, F, hypersensitivity Caution: MAO-I; CI: sulfite allergy PDE inhibitor Milrinone N/R 0.125 to 0.75 t1/2: 2.5 h H [ [ Y Y T, YBP Renal dosing, monitor LFTs BP indicates blood pressure; CI, contraindication; CO, cardiac output; F, fever; H, hepatic; HA, headache; HF, heart failure; HR, heart rate; LFT, liver function test; MAO-I, monoamine oxidase inhibitor; N, nausea; N/A, not applicable; N/R, not recommended; P, plasma; PDE, phosphodiesterase; PVR, pulmonary vascular resistance; R, renal; SVR, systemic vascular resistance; T, tachyarrhythmias; and t1/2, elimination half-life. Table 21. Recommendations for Inotropic Support, MCS, and Cardiac Transplantation Recommendations COR LOE References Inotropic support Cardiogenic shock pending definitive therapy or resolution I C N/A BTT or MCS in stage D refractory to GDMT IIa B 275,276 Short-term support for threatened end-organ dysfunction in hospitalized patients with stage D and severe HFrEF IIb B 277 279 Long-term support with continuous infusion palliative therapy in select stage D HF IIb B 280 282 Routine intravenous use, either continuous or intermittent, is potentially harmful in stage D HF III: Harm B 172,283 288 Short-term intravenous use in hospitalized patients without evidence of shock or threatened end-organ performance is potentially harmful III: Harm B 277 279 MCS MCS is beneficial in carefully selected* patients with stage D HF in whom definitive management (e.g., cardiac transplantation) is anticipated or planned IIa B 289 296 Nondurable MCS is reasonable as a bridge to recovery or a bridge to decision for carefully selected* patients with HF and acute profound disease IIa B 297 300 Durable MCS is reasonable to prolong survival for carefully selected* patients with stage D HFrEF IIa B 301 304 Cardiac transplantation Evaluation for cardiac transplantation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management I C 305 *Although optimal patient selection for MCS remains an active area of investigation, general indications for referral for MCS therapy include patients with LVEF <25% and NYHA class III IV functional status despite GDMT, including, when indicated, CRT, with either high predicted 1- to 2- year mortality (e.g., as suggested by markedly reduced peak oxygen consumption and clinical prognostic scores) or dependence on continuous parenteral inotropic support. Patient selection requires a multidisciplinary team of experienced advanced HF and transplantation cardiologists, cardiothoracic surgeons, nurses, and ideally, social workers and palliative care clinicians. BTT indicates bridge to transplant; COR, Class of Recommendation; CRT, cardiac resynchronization therapy; GDMT, guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; LOE, Level of Evidence; LVEF, left ventricular ejection fraction; MCS, mechanical circulatory support; N/A, not applicable; and NYHA, New York Heart Association. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary 6.4.3. Mechanical Circulatory Support CLASS IIa 1. MCS is bene cial in carefully selectedz patients with stage D HFrEF in whom de nitive management (e.g., cardiac transplantation) or cardiac recovery is anticipated or planned (289 296). (Level of Evidence: B) 2. Nondurable MCS, including the use of percutaneous and extracorporeal ventricular assist devices, is reasonable as a bridge to recovery or a bridge to decision for carefully selectedz patients with HFrEF with acute, profound hemody- namic compromise (297 300). (Level of Evidence: B) 3. Durable MCS is reasonable to prolong survival for carefully selectedz patients with stage D HFrEF (301 304). (Level of Evidence: B) 6.4.4. Cardiac Transplantation CLASS I 1. Evaluation for cardiac transplantation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management (305). (Level of Evidence: C) See Figure 3 for the stages in the development of HF. 7. The Hospitalized Patient: Recommendations See Table 22 for a summary of recommendations from this section and Figure 4 for the classi cation of patients presenting with acutely decompensated HF. Figure 3. Stages in the development of HF and recommended therapy by stage. ACEI indicates angiotensin-converting enzyme inhibitor; AF, atrial brillation; ARB, angiotensin-receptor blocker; CAD, coronary artery disease; CRT, cardiac resynchronization therapy; DM, diabetes mellitus; EF, ejection fraction; GDMT, guideline-directed medical therapy; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HRQOL, health-related quality of life; HTN, hypertension; ICD, implantable cardioverter-de brillator; LV, left ventricular; LVH, left ventricular hypertrophy; MCS, mechanical circulatory support; and MI, myocardial infarction. Adapted from Hunt et al (37). zAlthough optimal patient selection for MCS remains an active area of investiga- tion, general indications for referral for MCS therapy include patients with LVEF <25% and NYHA class III IV functional status despite GDMT, including, when indicated, CRT, with either high predicted 1- to 2-year mortality (e.g., as suggested by markedly reduced peak oxygen consumption and clinical prognostic scores) or dependence on continuous parenteral inotropic support. Patient selection requires a multidisciplinary team of experienced advanced HF and transplantation cardiologists, cardiothoracic surgeons, nurses, and ideally, social workers and palliative care clinicians. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 7.1. Precipitating Causes of Decompensated HF CLASS I 1. ACS precipitating acute HF decompensation should be promptly identi ed by electrocardiogram and serum biomarkers, including cardiac troponin testing, and treated optimally as appropriate to the overall condition and prog- nosis of the patient. (Level of Evidence: C) 2. Common precipitating factors for acute HF should be considered during initial evaluation, as recognition of these conditions is critical to guide appropriate therapy. (Level of Evidence: C) 7.2. Maintenance of GDMT During Hospitalization CLASS I 1. In patients with HFrEF experiencing a symptomatic exac- erbation of HF requiring hospitalization during chronic maintenance treatment with GDMT, it is recommended that GDMT be continued in the absence of hemodynamic insta- bility or contraindications (307 309). (Level of Evidence: B) 2. Initiation of beta-blocker therapy is recommended after optimization of volume status and successful discontinua- tion of intravenous diuretics, vasodilators, and inotropic agents. Beta-blocker therapy should be initiated at a low dose and only in stable patients. Caution should be used when initiating beta blockers in patients who have required inotropes during their hospital course (307 309). (Level of Evidence: B) 7.3. Diuretics in Hospitalized Patients CLASS I 1. Patients with HF admitted with evidence of signi cant uid overload should be promptly treated with intravenous loop diuretics to reduce morbidity (310,311). (Level of Evidence: B) 2. If patients are already receiving loop diuretic therapy, the initial intravenous dose should equal or exceed their chronic oral daily dose and should be given as either intermittent boluses or continuous infusion. Urine output and signs and symptoms of congestion should be serially assessed, and the diuretic dose should be adjusted accordingly to relieve symptoms, reduce volume excess, and avoid hypotension (312). (Level of Evidence: B) Table 22. Recommendations for Therapies in the Hospitalized HF Patient Recommendations COR LOE References HF patients hospitalized with fluid overload should be treated with intravenous diuretics I B 310,311 HF patients receiving loop diuretic therapy should receive an initial parenteral dose greater than or equal to their chronic oral daily dose; then dose should be serially adjusted I B 312 HFrEF patients requiring HF hospitalization on GDMT should continue GDMT except in cases of hemodynamic instability or where contraindicated I B 307 309 Initiation of beta-blocker therapy at a low dose is recommended after optimization of volume status and discontinuation of intravenous agents I B 307 309 Thrombosis/thromboembolism prophylaxis is recommended for patients hospitalized with HF I B 22,324 328 Serum electrolytes, urea nitrogen, and creatinine should be measured during titration of HF medications, including diuretics I C N/A When diuresis is inadequate, it is reasonable to IIa a. give higher doses of intravenous loop diuretics; or b. add a second diuretic (e.g., thiazide) B 313 316 Low-dose dopamine infusion may be considered with loop diuretics to improve diuresis IIb B 317,318 Ultrafiltration may be considered for patients with obvious volume overload IIb B 319 Ultrafiltration may be considered for patients with refractory congestion IIb C N/A Intravenous nitroglycerin, nitroprusside, or nesiritide may be considered an adjuvant to diuretic therapy for stable patients with HF IIb A 320 323 In patients hospitalized with volume overload and severe hyponatremia, vasopressin antagonists may be considered IIb B 330,331 COR indicates Class of Recommendation; GDMT, guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; LOE, Level of Evidence; and N/A, not available. No No Warm and Dry Cold and Dry Yes Yes Warm and Wet Cold and Wet Congestion at rest? (e.g. orthopnea, elevated jugular venous pressure, pulmonary rales, S3 gallop, edema) (e.g. narrow pulse pressure, cool extremities, hypotension) Low perfusion at rest? Figure 4. Classi cation of patients presenting with acutely decompensated heart failure. Adapted with permission from Nohria et al. (306). JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary 3. The effect of HF treatment should be monitored with careful measurement of uid intake and output, vital signs, body weight that is determined at the same time each day, and clinical signs and symptoms of systemic perfusion and congestion. Daily serum electrolytes, urea nitrogen, and creatinine concentrations should be measured during the use of intravenous diuretics or active titration of HF medi- cations. (Level of Evidence: C) CLASS IIa 1. When diuresis is inadequate to relieve symptoms, it is reasonable to intensify the diuretic regimen using either: a. higher doses of intravenous loop diuretics (37,312) (Level of Evidence: B); b. addition of a second (e.g., thiazide) diuretic (313 316). (Level of Evidence: B) CLASS IIb 1. Low-dose dopamine infusion may be considered in addition to loop diuretic therapy to improve diuresis and better preserve renal function and renal blood ow (317,318). (Level of Evidence: B) 7.4. Renal Replacement Therapyd Ultra ltration CLASS IIb 1. Ultra ltration may be considered for patients with obvious volume overload to alleviate congestive symptoms and uid weight (319). (Level of Evidence: B) 2. Ultra ltration may be considered for patients with refractory congestion not responding to medical therapy. (Level of Evidence: C) 7.5. Parenteral Therapy in Hospitalized HF CLASS IIb 1. If symptomatic hypotension is absent, intravenous nitro- glycerin, nitroprusside, or nesiritide may be considered an adjuvant to diuretic therapy for relief of dyspnea in patients admitted with acutely decompensated HF (320 323). (Level of Evidence: A) 7.6. Venous Thromboembolism Prophylaxis in Hospitalized Patients CLASS I 1. A patient admitted to the hospital with decompensated HF should receive venous thromboembolism prophylaxis with an anticoagulant medication if the riskLbene t ratio is favorable (22,324 328). (Level of Evidence: B) 7.7. Arginine Vasopressin Antagonists CLASS IIb 1. In patients hospitalized with volume overload, including HF, who have persistent severe hyponatremia and are at risk for or having active cognitive symptoms despite water restriction and maximization of GDMT, vasopressin antagonists may be considered in the short term to improve serum sodium concentration in hypervolemic, hypona- tremic states with either a V2 receptor selective or a nonselective vasopressin antagonist (330,331). (Level of Evidence: B) 7.8. Inpatient and Transitions of Care See Table 23 for a summary of recommendations from this section. CLASS I 1. The use of performance improvement systems and/or evidence-based systems of care is recommended in the hospital and early postdischarge outpatient setting to identify appropriate HF patients for GDMT, provide clinicians with useful reminders to advance GDMT, and assess the clinical response (151,332 338). (Level of Evidence: B) 2. Throughout the hospitalization as appropriate, before hospital discharge, at the rst postdischarge visit, and in Table 23. Recommendations for Hospital Discharge Recommendations or Indications COR LOE References Performance improvement systems in the hospital and early postdischarge outpatient setting to identify HF for GDMT I B 151,332 338 Before hospital discharge, at the first postdischarge visit, and in subsequent follow-up visits, the following should be addressed: a. initiation of GDMT if not done or contraindicated; b. causes of HF, barriers to care, and limitations in support; c. assessment of volume status and blood pressure with adjustment of HF therapy; d. optimization of chronic oral HF therapy; e. renal function and electrolytes; f. management of comorbid conditions; g. HF education, self-care, emergency plans, and adherence; and h. palliative or hospice care I B 57,337,339 341 Multidisciplinary HF disease management for patients at high risk for hospital readmission I B 336,342 344 A follow-up visit within 7 to 14 d and a telephone follow-up within 3 d of hospital discharge are reasonable IIa B 345,346 Use of clinical risk-prediction tools and/or biomarkers to identify higher-risk patients are reasonable IIa B 62 OR indicates Class of Recommendation; GDMT, guideline-directed medical therapy; HF, heart failure; and LOE, Level of Evidence. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 subsequent follow-up visits, the following should be addressed (57,337,339 341). (Level of Evidence: B): a. initiation of GDMT if not previously established and not contraindicated; b. precipitant causes of HF, barriers to optimal care tran- sitions, and limitations in postdischarge support; c. assessment of volume status and supine/upright hypo- tension with adjustment of HF therapy as appropriate; d. titration and optimization of chronic oral HF therapy; e. assessment of renal function and electrolytes where appropriate; f. assessment and management of comorbid conditions; g. reinforcement of HF education, self-care, emergency plans, and need for adherence; and h. consideration for palliative care or hospice care in selected patients. 3. Multidisciplinary HF disease-management programs are recommended for patients at high risk for hospital read- mission, to facilitate the implementation of GDMT, to address different barriers to behavioral change, and to reduce the risk of subsequent rehospitalization for HF (336,342 344). (Level of Evidence: B) CLASS IIa 1. Scheduling an early follow-up visit (within 7 to 14 days) and early telephone follow-up (within 3 days) of hospital discharge are reasonable (345,346). (Level of Evidence: B) 2. Use of clinical risk-prediction tools and/or biomarkers to identify patients at higher risk for postdischarge clinical events are reasonable (62). (Level of Evidence: B) 8. Important Comorbidities in HF Although there are additional and important comorbidities that occur in patients with HF as referenced in Table 24, it remains uncertain how best to generate speci c recommendations, given the status of current evidence. Interventional Treatments of HF: Recommendations See Table 25 for a summary of recommendations from this section. CLASS I 1. Coronary artery revascularization via coronary artery bypass graft surgery (CABG) or percutaneous intervention is indicated for patients (HFpEF and HFrEF) on GDMT with angina and suitable coronary anatomy, especially for a left main stenosis (>50%) or left main equivalent disease (11,13,15,348). (Level of Evidence: C) CLASS IIa 1. CABG to improve survival is reasonable in patients with mild to moderate LV systolic dysfunction (EF 35% to 50%) and signi cant ( 70% diameter stenosis) multivessel CAD or proximal left anterior descending coronary artery stenosis when viable myocardium is present in the region of intended revascularization (348 350). (Level of Evidence: B) 2. CABG or medical therapy is reasonable to improve morbidity and cardiovascular mortality for patients with severe LV dysfunction (EF <35%), HF, and signi cant CAD (351,352). (Level of Evidence: B) 3. Surgical aortic valve replacement is reasonable for patients with critical aortic stenosis and a predicted surgical mortality of no greater than 10% (353). (Level of Evidence: B) 4. Transcatheter aortic valve replacement after careful candi- date consideration is reasonable for patients with critical aortic stenosis who are deemed inoperable (354). (Level of Evidence: B) CLASS IIb 1. CABG may be considered with the intent of improving survival in patients with ischemic heart disease with severe LV systolic dysfunction (EF <35%) and operable coronary anatomy whether or not viable myocardium is present (352,355,356). (Level of Evidence: B) Table 24. Ten Most Common Co-Occurring Chronic Conditions Among Medicare Beneficiaries With Heart Failure (N[4,947,918), 2011 Beneficiaries Age 65 y (N 4,376,150)* Beneficiaries Age <65 y (N 5,71,768)y N % N % Ischemic heart disease 3,145,718 71.9 Ischemic heart disease 365,889 64.0 *Mean No. of conditions is 6.1; median is 6. yMean No. of conditions is 5.5; median is 5. COPD indicates chronic obstructive pulmonary disease. Data source: Centers for Medicare and Medicaid Services administrative claims data, January 2011December 2011, from the Chronic Condition Warehouse (CCW), ccwdata.org (347). JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary 2. Transcatheter mitral valve repair or mitral valve surgery for functional mitral insuf ciency is of uncertain bene t and should only be considered after careful candidate selection and with a background of GDMT (357 360). (Level of Evidence: B) 3. Surgical reverse remodeling or LV aneurysmectomy may be considered in carefully selected patients with HFrEF for speci c indications, including intractable HF and ventricular arrhythmias (361). (Level of Evidence: B) 10. Coordinating Care for Patients With Chronic HF: Recommendations CLASS I 1. Effective systems of care coordination with special atten- tion to care transitions should be deployed for every patient with chronic HF that facilitate and ensure effective care that is designed to achieve GDMT and prevent hospitalization (333,336,362 377). (Level of Evidence: B) 2. Every patient with HF should have a clear, detailed, and evidence-based plan of care that ensures the achievement of GDMT goals, effective management of comorbid condi- tions, timely follow-up with the healthcare team, appropriate dietary and physical activities, and compliance with secondary prevention guidelines for cardiovascular disease. This plan of care should be updated regularly and made readily available to all members of each patient s healthcare team (14). (Level of Evidence: C) 3. Palliative and supportive care is effective for patients with symptomatic advanced HF to improve quality of life (31,378 381). (Level of Evidence: B) 11. Quality Metrics/Performance Measures: Recommendations CLASS I 1. Performance measures based on professionally developed clinical practice guidelines should be used with the goal of improving quality of care for HF (334,343,382). (Level of Evidence: B) CLASS IIa 1. Participation in quality improvement programs and patient registries based on nationally endorsed, clinical practice guidelineLbased quality and performance measures can be bene cial in improving quality of HF care (334,343). (Level of Evidence: B) See Table 26 for a revised ACCF/AHA/PCPI 2011 HF measurement set. 12. Evidence Gaps and Future Research Directions Despite the objective evidence compiled by the writing committee on the basis of hundreds of clinical trials, there are huge gaps in our knowledge base about many fundamental aspects of HF care. Some key examples include an effective management strategy for patients with HFpEF beyond blood pressure control; a convincing method to use biomarkers in the optimizationofmedicaltherapy;therecognitionandtreatmentof cardiorenalsyndrome; andthe critical needfor improving patient adherence to therapeutic regimens. Even the widely embraced dictum of sodium restriction in HF is not well supported by current evidence. Moreover, the majority ofthe clinical trials that inform GDMT were designed around the primary endpoint of mortality, so that there is less certainty about the impact of therapies on the health-related quality of life of patients. It is also ofmajorconcernthatthemajorityofrandomizedcontrolledtrials failed to randomize a suf cient number of the elderly, women, and underrepresented minorities, thus limiting our insight into these important patient cohorts. A growing body of studies on patient-centered outcomes research is likely to address some of these de ciencies, but time will be required. HF is a syndrome with a high prevalence of comorbidities and multiple chronic conditions, but most guidelines are developed for patients with a single disease. Nevertheless, the coexistence of additional diseases such as arthritis, renal Table 25. Recommendations for Surgical/Percutaneous/Transcatheter Interventional Treatments of HF Recommendations COR LOE References CABG or percutaneous intervention is indicated for HF patients on GDMT with angina and suitable coronary anatomy, especially significant left main stenosis or left main equivalent I C 11,13,15,348 CABG to improve survival is reasonable in patients with mild to moderate LV systolic dysfunction and significant multivessel CAD or proximal LAD stenosis when viable myocardium is present IIa B 348 350 CABG or medical therapy is reasonable to improve morbidity and mortality for patients with severe LV dysfunction (EF <35%), HF, and significant CAD IIa B 351,352 Surgical aortic valve replacement is reasonable for patients with critical aortic stenosis and a predicted surgical mortality of no greater than 10% IIa B 353 Transcatheter aortic valve replacement is reasonable for patients with critical aortic stenosis who are deemed inoperable IIa B 354 CABG may be considered in patients with ischemic heart disease, severe LV systolic dysfunction, and operable coronary anatomy whether or not viable myocardium is present IIb B 352,355,356 Transcatheter mitral valve repair or mitral valve surgery for functional mitral insufficiency is of uncertain benefit IIb B 357 360 Surgical reverse remodeling or LV aneurysmectomy may be considered in HFrEF for specific indications, including intractable HF and ventricular arrhythmias IIb B 361 CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COR, Class of Recommendation; EF, ejection fraction; GDMT, guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; LAD, left anterior descending; LOE, Level of Evidence; and LV, left ventricular. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 insuf ciency, diabetes mellitus, or chronic lung disease with the HF syndrome should logically require a modi cation of treatment, outcome assessment, or follow-up care. About 25% of Americans have multiple chronic conditions; this gure rises to 75% in those >65 years of age, including the diseases referred to above, as well as asthma, hypertension, cognitive disorders, or depression (347). Most randomized controlled trials in HF speci cally excluded patients with signi cant Table 26. ACCF/AHA/AMA-PCPI 2011 HF Measurement Set Measure Description* Care Setting Level of Measurement 1. LVEF assessment Percentage of patients aged 18 y with a diagnosis of HF for whom the quantitative or qualitative results of a recent or prior (any time in the past) LVEF assessment is documented within a 12-mo period Outpatient Individual practitioner 2. LVEF assessment Percentage of patients aged 18 y with a principal discharge diagnosis of HF with documentation in the hospital record of the results of an LVEF assessment performed either before arrival or during hospitalization, OR documentation in the hospital record that LVEF assessment is planned for after discharge Inpatient  Individual practitioner  Facility 3. Symptom and activity assessment Percentage of patient visits for patients aged 18 y with a diagnosis of HF with quantitative results of an evaluation of both current level of activity and clinical symptoms documented Outpatient Individual practitioner 4. Symptom managementy Percentage of patient visits for patients aged 18 y with a diagnosis of HF and with quantitative results of an evaluation of both level of activity AND clinical symptoms documented in which patient symptoms have improved or remained consistent with treatment goals since last assessment OR patient symptoms have demonstrated clinically important deterioration since last assessment with a documented plan of care Outpatient Individual practitioner 5. Patient self-care educationyz Percentage of patients aged 18 y with a diagnosis of HF who were provided with self-care education on 3 elements of education during 1 visits within a 12-mo period Outpatient Individual practitioner 6. Beta-blocker therapy for LVSD (outpatient and inpatient setting) Percentage of patients aged 18 y with a diagnosis of HF with a current or prior LVEF <40% who were prescribed beta-blocker therapy with bisoprolol, carvedilol, or sustained-release metoprolol succinate either within a 12-mo period when seen in the outpatient setting or at hospital discharge Inpatient and outpatient  Individual practitioner  Facility 7. ACE inhibitor or ARB therapy for LVSD (outpatient and inpatient setting) Percentage of patients aged 18 y with a diagnosis of HF with a current or prior LVEF <40% who were prescribed ACE inhibitor or ARB therapy either within a 12-mo period when seen in the outpatient setting or at hospital discharge Inpatient and outpatient  Individual practitioner  Facility 8. Counseling about ICD implantation for patients with LVSD on combination medical therapyyz Percentage of patients aged 18 y with a diagnosis of HF with current LVEF 35% despite ACE inhibitor/ARB and beta-blocker therapy for at least 3 mo who were counseled about ICD placement as a treatment option for the prophylaxis of sudden death Outpatient Individual practitioner 9. Postdischarge appointment for HF patients Percentage of patients, regardless of age, discharged from an inpatient facility to ambulatory care or home health care with a principal discharge diagnosis of HF for whom a follow-up appointment was scheduled and documented, including location, date, and time for a follow-up office visit or home health visit (as specified) Inpatient Facility N.B., Regarding test measure no. 8, implantation of an ICD must be consistent with published guidelines. This measure is intended to promote counseling only. *Refer to the complete measures for comprehensive information, including measure exception. yTest measure designated for use in internal quality improvement programs only. These measures are not appropriate for any other purpose (e.g., pay for performance, physician ranking, or public reporting programs). zNew measure. ACCF indicates American College of Cardiology Foundation; ACE, angiotensin-converting enzyme; AHA, American Heart Association; AMA-PCPI, American Medical AssociationPhysician Consortium for Performance Improvement; ARB, angiotensin-receptor blocker; HF, heart failure; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; and LVSD, left ventricular systolic dysfunction. Adapted from Bonow et al. (383). JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary other comorbidities from enrollment, thus limiting our ability to generalize our recommendations to many real-world patients. Therefore, the clinician must, as always, practice the art of using the best of the guideline recommendations as they apply to a speci c patient. Future research will need to focus on novel pharmacolog- ical therapies, especially for patients hospitalized with HF; regenerative cell-based therapies to restore myocardium; and new device platforms that will either improve existing tech- nologies (e.g., CRT, ICD, left ventricular assist device) or introduce simpler, less morbid devices that are capable of changing the natural history of HF. What is critically needed is an evidence base that clearly identi es best processes of care, especially in the transition from hospital to home. Finally, preventing the burden of this disease through more successful risk modi cation, sophisticated screening, perhaps using speci c omics technologies (i.e., systems biology), or effective treatment interventions that reduce the progression from stage A to stage B is an urgent need. Presidents and Staff American College of Cardiology Foundation John Gordon Harold, MD, MACC, President Shalom Jacobovitz, Chief Executive Of cer William J. Oetgen, MD, MBA, FACC, Senior Vice President, Science and Quality Charlene L. May, Senior Director, Science and Clinical Policy American College of Cardiology Foundation/ American Heart Association Lisa Brad eld, CAE, Director, Science and Clinical Policy Debjani Mukherjee, MPH, Associate Director, Evidence- Based Medicine Ezaldeen Ramadhan III, Specialist, Science and Clinical Policy Sarah Jackson, MPH, Specialist, Science and Clinical Policy American Heart Association Donna K. Arnett, PhD, MD, FAHA, President Nancy Brown, Chief Executive Of cer Rose Marie Robertson, MD, FAHA, Chief Science Of cer Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Of ce of Science Operations Judy Bezanson, DSN, RN, CNS-MS, FAHA, Science and Medicine Advisor Jody Hundley, Production Manager, Scienti c Publications, Of ce of Science Operations References 1. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. Available at: http://assets.cardiosource.com/Methodology_Manual_for_ ACC_AHA_Writing_Committees.pdf and http://my.americanheart.org/ idc/groups/ahamah-public/@wcm/sop/documents/downloadable/ ucm_319826.pdf. American College of Cardiology Foundation and American Heart Association. Accessed May 16, 2012. 2. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine: Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press; 2011. 3. Committee on Standards for Systematic Reviews of Comparative Effectiveness Research, Institute of Medicine: Finding What Works in Health Care: Standards for Systematic Reviews. Washington, DC: The National Academies Press; 2011. 4. Yancy C, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:XX-XX. 5. Tracy CM, Epstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Associa- tion Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013;61:e6 75. 6. Warnes CA, Williams RG, Bashore TM, et al. 