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Heart Failure With Reduced Ejection FractionA Review

Educational Objective
To review the clinical management of patients who have heart failure with reduced ejection fraction (HFrEF).
1 Credit CME
Abstract

Importance  Worldwide, the burden of heart failure has increased to an estimated 23 million people, and approximately 50% of cases are HF with reduced ejection fraction (HFrEF).

Observations  Heart failure is a clinical syndrome characterized by dyspnea or exertional limitation due to impairment of ventricular filling or ejection of blood or both. HFrEF occurs when the left ventricular ejection fraction (LVEF) is 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling. Assessment for heart failure begins with obtaining a medical history and physical examination. Also central to diagnosis are elevated natriuretic peptides above age- and context-specific thresholds and identification of left ventricular systolic dysfunction with LVEF of 40% or less as measured by echocardiography. Treatment strategies include the use of diuretics to relieve symptoms and application of an expanding armamentarium of disease-modifying drug and device therapies. Unless there are specific contraindications, patients with HFrEF should be treated with a β-blocker and one of an angiotensin receptor–neprilysin inhibitor, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker as foundational therapy, with addition of a mineralocorticoid receptor antagonist in patients with persistent symptoms. Ivabradine and hydralazine/isosorbide dinitrate also have a role in the care of certain patients with HFrEF. More recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors have further improved disease outcomes, significantly reducing cardiovascular and all-cause mortality irrespective of diabetes status, and vericiguat, a soluble guanylate cyclase stimulator, reduces heart failure hospitalization in high-risk patients with HFrEF. Device therapies may be beneficial in specific subpopulations, such as cardiac resynchronization therapy in patients with interventricular dyssynchrony, transcatheter mitral valve repair in patients with severe secondary mitral regurgitation, and implantable cardiac defibrillators in patients with more severe left ventricular dysfunction particularly of ischemic etiology.

Conclusions and Relevance  HFrEF is a major public health concern with substantial morbidity and mortality. The management of HFrEF has seen significant scientific breakthrough in recent decades, and the ability to alter the natural history of the disease has never been better. Recent developments include SGLT2 inhibitors, vericiguat, and transcatheter mitral valve repair, all of which incrementally improve prognosis beyond foundational neurohormonal therapies. Disease morbidity and mortality remain high, with a 5-year survival rate of 25% after hospitalization for HFrEF.

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Article Information

Corresponding Author: James L. Januzzi Jr, MD, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114-2696 (jjanuzzi@partners.org).

Correction: This article was corrected on November 24, 2020, to fix dosages in Table 3.

Accepted for Publication: May 27, 2020.

Author Contributions: Dr Januzzi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of Interest Disclosures: Dr Ibrahim reports having received honoraria from Novartis Pharmaceuticals and Roche Diagnostics. Dr Januzzi reports being a trustee of the American College of Cardiology, receipt of grant support from Novartis Pharmaceuticals and Abbott Diagnostics and honoraria from Abbott, Janssen, Novartis, and Roche Diagnostics, and participation in clinical end point committees and data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, and Takeda. Dr Murphy reports no disclosures.

Funding/Support: Dr Ibrahim is supported in part by the Dennis and Marilyn Barry fund for cardiology research. Dr Januzzi is supported in part by the Hutter Family Professorship.

Role of the Funder/Sponsor: Funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Maggioni  AP , Dahlström  U , Filippatos  G ,  et al; Heart Failure Association of the European Society of Cardiology (HFA).  EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot).   Eur J Heart Fail. 2013;15(7):808-817. doi:10.1093/eurjhf/hft050PubMedGoogle ScholarCrossref
2.
Yancy  CW , Jessup  M , Bozkurt  B ,  et al.  2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.   Circulation. 2017;136(6):e137-e161. doi:10.1161/CIR.0000000000000509PubMedGoogle ScholarCrossref
3.
Shah  KS , Xu  H , Matsouaka  RA ,  et al.  Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes.   J Am Coll Cardiol. 2017;70(20):2476-2486. doi:10.1016/j.jacc.2017.08.074PubMedGoogle ScholarCrossref
4.
Virani  SS , Alonso  A , Benjamin  EJ ,  et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.  Heart disease and stroke statistics-2020 update: a report from the American Heart Association.   Circulation. 2020;141(9):e139-e596. doi:10.1161/CIR.0000000000000757PubMedGoogle ScholarCrossref
5.
Mozaffarian  D , Benjamin  EJ , Go  AS ,  et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee.  Heart disease and stroke statistics—2015 update: a report from the American Heart Association.   Circulation. 2015;131(4):e29-e322. doi:10.1161/CIR.0000000000000152PubMedGoogle Scholar
6.
Conrad  N , Judge  A , Tran  J ,  et al.  Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.   Lancet. 2018;391(10120):572-580. doi:10.1016/S0140-6736(17)32520-5PubMedGoogle ScholarCrossref
7.
Ho  JE , Lyass  A , Lee  DS ,  et al.  Predictors of new-onset heart failure: differences in preserved versus reduced ejection fraction.   Circ Heart Fail. 2013;6(2):279-286. doi:10.1161/CIRCHEARTFAILURE.112.972828PubMedGoogle ScholarCrossref
8.
Thibodeau  JT , Turer  AT , Gualano  SK ,  et al.  Characterization of a novel symptom of advanced heart failure: bendopnea.   JACC Heart Fail. 2014;2(1):24-31. doi:10.1016/j.jchf.2013.07.009PubMedGoogle ScholarCrossref
9.
Stevenson  LW , Perloff  JK .  The limited reliability of physical signs for estimating hemodynamics in chronic heart failure.   JAMA. 1989;261(6):884-888. doi:10.1001/jama.1989.03420060100040PubMedGoogle ScholarCrossref
10.
Januzzi  JL  Jr , Chen-Tournoux  AA , Christenson  RH ,  et al; ICON-RELOADED Investigators.  N-terminal pro-B-type natriuretic peptide in the emergency department: the ICON-RELOADED study.   J Am Coll Cardiol. 2018;71(11):1191-1200. doi:10.1016/j.jacc.2018.01.021PubMedGoogle ScholarCrossref
11.
Maisel  AS , Krishnaswamy  P , Nowak  RM ,  et al; Breathing Not Properly Multinational Study Investigators.  Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.   N Engl J Med. 2002;347(3):161-167. doi:10.1056/NEJMoa020233PubMedGoogle ScholarCrossref
12.
Ponikowski  P , Voors  AA , Anker  SD ,  et al; ESC Scientific Document Group.  2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.   Eur Heart J. 2016;37(27):2129-2200. doi:10.1093/eurheartj/ehw128PubMedGoogle ScholarCrossref
13.
Bayés-Genís  A , Lopez  L , Zapico  E ,  et al.  NT-ProBNP reduction percentage during admission for acutely decompensated heart failure predicts long-term cardiovascular mortality.   J Card Fail. 2005;11(5)(suppl):S3-S8. doi:10.1016/j.cardfail.2005.04.006PubMedGoogle ScholarCrossref
14.
Januzzi  JL  Jr , Ahmad  T , Mulder  H ,  et al.  Natriuretic peptide response and outcomes in chronic heart failure with reduced ejection fraction.   J Am Coll Cardiol. 2019;74(9):1205-1217. doi:10.1016/j.jacc.2019.06.055PubMedGoogle ScholarCrossref
15.
Selvaraj  S , Claggett  B , Pozzi  A ,  et al.  Prognostic implications of congestion on physical examination among contemporary patients with heart failure and reduced ejection fraction: PARADIGM-HF.   Circulation. 2019;140(17):1369-1379. doi:10.1161/CIRCULATIONAHA.119.039920PubMedGoogle ScholarCrossref
16.
Collins  SP , Lindsell  CJ , Storrow  AB , Abraham  WT ; ADHERE Scientific Advisory Committee, Investigators and Study Group.  Prevalence of negative chest radiography results in the emergency department patient with decompensated heart failure.   Ann Emerg Med. 2006;47(1):13-18. doi:10.1016/j.annemergmed.2005.04.003PubMedGoogle ScholarCrossref
17.
Mueller-Lenke  N , Rudez  J , Staub  D ,  et al.  Use of chest radiography in the emergency diagnosis of acute congestive heart failure.   Heart. 2006;92(5):695-696. doi:10.1136/hrt.2005.074583PubMedGoogle ScholarCrossref
18.
Mahdyoon  H , Klein  R , Eyler  W , Lakier  JB , Chakko  SC , Gheorghiade  M .  Radiographic pulmonary congestion in end-stage congestive heart failure.   Am J Cardiol. 1989;63(9):625-627. doi:10.1016/0002-9149(89)90912-0PubMedGoogle ScholarCrossref
19.
Halliday  BP , Wassall  R , Lota  AS ,  et al.  Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial.   Lancet. 2019;393(10166):61-73. doi:10.1016/S0140-6736(18)32484-XPubMedGoogle ScholarCrossref
20.
Yancy  CW , Jessup  M , Bozkurt  B ,  et al.  2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.   Circulation. 2013;128(16):1810-1852. doi:10.1016/j.jacc.2013.05.020PubMedGoogle ScholarCrossref
21.
Yancy  CW , Januzzi  JL  Jr , Allen  LA ,  et al.  2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways.   J Am Coll Cardiol. 2018;71(2):201-230. doi:10.1016/j.jacc.2017.11.025PubMedGoogle ScholarCrossref
22.
Fitzgerald  AA , Powers  JD , Ho  PM ,  et al.  Impact of medication nonadherence on hospitalizations and mortality in heart failure.   J Card Fail. 2011;17(8):664-669. doi:10.1016/j.cardfail.2011.04.011PubMedGoogle ScholarCrossref
23.
McMurray  JJV , Solomon  SD , Inzucchi  SE ,  et al; DAPA-HF Trial Committees and Investigators.  Dapagliflozin in patients with heart failure and reduced ejection fraction.   N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303PubMedGoogle ScholarCrossref
24.
Armstrong  PW , Pieske  B , Anstrom  KJ ,  et al; VICTORIA Study Group.  Vericiguat in patients with heart failure and reduced ejection fraction.   N Engl J Med. 2020;382(20):1883-1893. doi:10.1056/NEJMoa1915928PubMedGoogle ScholarCrossref
25.
Greene  SJ , Butler  J , Albert  NM ,  et al.  Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry.   J Am Coll Cardiol. 2018;72(4):351-366. doi:10.1016/j.jacc.2018.04.070PubMedGoogle ScholarCrossref
26.
Fiuzat  M , Wojdyla  D , Kitzman  D ,  et al.  Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial.   J Am Coll Cardiol. 2012;60(3):208-215. doi:10.1016/j.jacc.2012.03.023PubMedGoogle ScholarCrossref
27.
Bristow  MR , Gilbert  EM , Abraham  WT ,  et al; MOCHA Investigators.  Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure.   Circulation. 1996;94(11):2807-2816. doi:10.1161/01.CIR.94.11.2807PubMedGoogle ScholarCrossref
28.
Packer  M , Poole-Wilson  PA , Armstrong  PW ,  et al; ATLAS Study Group.  Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure.   Circulation. 1999;100(23):2312-2318. doi:10.1161/01.CIR.100.23.2312PubMedGoogle ScholarCrossref
29.
Konstam  MA , Neaton  JD , Dickstein  K ,  et al; HEAAL Investigators.  Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial.   Lancet. 2009;374(9704):1840-1848. doi:10.1016/S0140-6736(09)61913-9PubMedGoogle ScholarCrossref
30.
Hartupee  J , Mann  DL .  Neurohormonal activation in heart failure with reduced ejection fraction.   Nat Rev Cardiol. 2017;14(1):30-38. doi:10.1038/nrcardio.2016.163PubMedGoogle ScholarCrossref
31.
 The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial.   Lancet. 1999;353(9146):9-13. doi:10.1016/S0140-6736(98)11181-9PubMedGoogle ScholarCrossref
32.
Hjalmarson  A , Goldstein  S , Fagerberg  B ,  et al; MERIT-HF Study Group.  Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF).   JAMA. 2000;283(10):1295-1302. doi:10.1001/jama.283.10.1295PubMedGoogle ScholarCrossref
33.
Packer  M , Bristow  MR , Cohn  JN ,  et al; U.S. Carvedilol Heart Failure Study Group.  The effect of carvedilol on morbidity and mortality in patients with chronic heart failure.   N Engl J Med. 1996;334(21):1349-1355. doi:10.1056/NEJM199605233342101PubMedGoogle ScholarCrossref
34.
Pfeffer  MA , Braunwald  E , Moyé  LA ,  et al; The SAVE Investigators.  Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial.   N Engl J Med. 1992;327(10):669-677. doi:10.1056/NEJM199209033271001PubMedGoogle ScholarCrossref
35.
The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.  Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure.   Lancet. 1993;342(8875):821-828.PubMedGoogle Scholar
36.
Yusuf  S , Pitt  B , Davis  CE , Hood  WB , Cohn  JN ; SOLVD Investigators.  Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.   N Engl J Med. 1991;325(5):293-302. doi:10.1056/NEJM199108013250501PubMedGoogle ScholarCrossref
37.
McMurray  JJ , Ostergren  J , Swedberg  K ,  et al; CHARM Investigators and Committees.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial.   Lancet. 2003;362(9386):767-771. doi:10.1016/S0140-6736(03)14283-3PubMedGoogle ScholarCrossref
38.
Dickstein  K , Kjekshus  J ; OPTIMAAL Steering Committee of the OPTIMAAL Study Group.  Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial: Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan.   Lancet. 2002;360(9335):752-760. doi:10.1016/S0140-6736(02)09895-1PubMedGoogle ScholarCrossref
39.
Cohn  JN , Tognoni  G ; Valsartan Heart Failure Trial Investigators.  A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.   N Engl J Med. 2001;345(23):1667-1675. doi:10.1056/NEJMoa010713PubMedGoogle ScholarCrossref
40.
McMurray  JJV , Packer  M , Desai  AS ,  et al; PARADIGM-HF Investigators and Committees.  Angiotensin-neprilysin inhibition versus enalapril in heart failure.   N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077PubMedGoogle ScholarCrossref
41.
Morrow  DA , Velazquez  EJ , DeVore  AD ,  et al.  Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF Trial.   Circulation. 2019;139(19):2285-2288. doi:10.1161/CIRCULATIONAHA.118.039331PubMedGoogle ScholarCrossref
42.
Pitt  B , Zannad  F , Remme  WJ ,  et al; Randomized Aldactone Evaluation Study Investigators.  The effect of spironolactone on morbidity and mortality in patients with severe heart failure.   N Engl J Med. 1999;341(10):709-717. doi:10.1056/NEJM199909023411001PubMedGoogle ScholarCrossref
43.
Taylor  AL , Ziesche  S , Yancy  C ,  et al; African-American Heart Failure Trial Investigators.  Combination of isosorbide dinitrate and hydralazine in blacks with heart failure.   N Engl J Med. 2004;351(20):2049-2057. doi:10.1056/NEJMoa042934PubMedGoogle ScholarCrossref
44.
Swedberg  K , Komajda  M , Böhm  M ,  et al; SHIFT Investigators.  Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study.   Lancet. 2010;376(9744):875-885. doi:10.1016/S0140-6736(10)61198-1PubMedGoogle ScholarCrossref
45.
CONSENSUS Trial Study Group.  Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).   N Engl J Med. 1987;316(23):1429-1435. doi:10.1056/NEJM198706043162301PubMedGoogle ScholarCrossref
46.
Yusuf  S , Pitt  B , Davis  CE , Hood  WB  Jr , Cohn  JN ; SOLVD Investigators.  Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.   N Engl J Med. 1992;327(10):685-691. doi:10.1056/NEJM199209033271003PubMedGoogle ScholarCrossref
47.
Garg  R , Yusuf  S ; Collaborative Group on ACE Inhibitor Trials.  Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure.   JAMA. 1995;273(18):1450-1456. doi:10.1001/jama.1995.03520420066040PubMedGoogle ScholarCrossref
48.
Granger  CB , McMurray  JJ , Yusuf  S ,  et al; CHARM Investigators and Committees.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial.   Lancet. 2003;362(9386):772-776. doi:10.1016/S0140-6736(03)14284-5PubMedGoogle ScholarCrossref
49.
Velazquez  EJ , Morrow  DA , DeVore  AD ,  et al; PIONEER-HF Investigators.  Angiotensin-neprilysin inhibition in acute decompensated heart failure.   N Engl J Med. 2019;380(6):539-548. doi:10.1056/NEJMoa1812851PubMedGoogle ScholarCrossref
50.
Wachter  R , Senni  M , Belohlavek  J ,  et al; TRANSITION Investigators.  Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.   Eur J Heart Fail. 2019;21(8):998-1007. doi:10.1002/ejhf.1498PubMedGoogle ScholarCrossref
51.
Januzzi  JL  Jr , Prescott  MF , Butler  J ,  et al; PROVE-HF Investigators.  Association of change in N-terminal pro-B-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction.   JAMA. 2019;322(11):1-11. doi:10.1001/jama.2019.12821PubMedGoogle ScholarCrossref
52.
Solomon  SD , McMurray  JJV , Anand  IS ,  et al; PARAGON-HF Investigators and Committees.  Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction.   N Engl J Med. 2019;381(17):1609-1620. doi:10.1056/NEJMoa1908655PubMedGoogle ScholarCrossref
53.
Solomon  SD , Vaduganathan  M , L Claggett  B ,  et al.  Sacubitril/valsartan across the spectrum of ejection fraction in heart failure.   Circulation. 2020;141(5):352-361. doi:10.1161/CIRCULATIONAHA.119.044586PubMedGoogle ScholarCrossref
54.
Packer  M , Coats  AJ , Fowler  MB ,  et al; Carvedilol Prospective Randomized Cumulative Survival Study Group.  Effect of carvedilol on survival in severe chronic heart failure.   N Engl J Med. 2001;344(22):1651-1658. doi:10.1056/NEJM200105313442201PubMedGoogle ScholarCrossref
55.
Kotecha  D , Holmes  J , Krum  H ,  et al; Beta-Blockers in Heart Failure Collaborative Group.  Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis.   Lancet. 2014;384(9961):2235-2243. doi:10.1016/S0140-6736(14)61373-8PubMedGoogle ScholarCrossref
56.
Talajic  M , Khairy  P , Levesque  S ,  et al; AF-CHF Investigators.  Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation.   J Am Coll Cardiol. 2010;55(17):1796-1802. doi:10.1016/j.jacc.2010.01.023PubMedGoogle ScholarCrossref
57.
Morales  DR , Lipworth  BJ , Donnan  PT , Jackson  C , Guthrie  B .  Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study.   BMC Med. 2017;15(1):18. doi:10.1186/s12916-017-0781-0PubMedGoogle ScholarCrossref
58.
Zannad  F , McMurray  JJ , Krum  H ,  et al; EMPHASIS-HF Study Group.  Eplerenone in patients with systolic heart failure and mild symptoms.   N Engl J Med. 2011;364(1):11-21. doi:10.1056/NEJMoa1009492PubMedGoogle ScholarCrossref
59.
Pitt  B , Remme  W , Zannad  F ,  et al; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators.  Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.   N Engl J Med. 2003;348(14):1309-1321. doi:10.1056/NEJMoa030207PubMedGoogle ScholarCrossref
60.
Savelieva  I , Camm  AJ .  I f inhibition with ivabradine : electrophysiological effects and safety.   Drug Saf. 2008;31(2):95-107. doi:10.2165/00002018-200831020-00001PubMedGoogle ScholarCrossref
61.
Kotecha  D , Flather  MD , Altman  DG ,  et al; Beta-Blockers in Heart Failure Collaborative Group.  Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure.   J Am Coll Cardiol. 2017;69(24):2885-2896. doi:10.1016/j.jacc.2017.04.001PubMedGoogle ScholarCrossref
62.
Anker  SD , Comin Colet  J , Filippatos  G ,  et al; FAIR-HF Trial Investigators.  Ferric carboxymaltose in patients with heart failure and iron deficiency.   N Engl J Med. 2009;361(25):2436-2448. doi:10.1056/NEJMoa0908355PubMedGoogle ScholarCrossref
63.
Ponikowski  P , van Veldhuisen  DJ , Comin-Colet  J ,  et al; CONFIRM-HF Investigators.  Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency.   Eur Heart J. 2015;36(11):657-668. doi:10.1093/eurheartj/ehu385PubMedGoogle ScholarCrossref
64.
Lewis  GD , Malhotra  R , Hernandez  AF ,  et al; NHLBI Heart Failure Clinical Research Network.  Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: the IRONOUT HF randomized clinical trial.   JAMA. 2017;317(19):1958-1966. doi:10.1001/jama.2017.5427PubMedGoogle ScholarCrossref
65.
Serenelli  M , Jackson  A , Dewan  P ,  et al.  Mineralocorticoid receptor antagonists, blood pressure, and outcomes in heart failure with reduced ejection fraction.   JACC Heart Fail. 2020;8(3):188-198. doi:10.1016/j.jchf.2019.09.011PubMedGoogle ScholarCrossref
66.
Jefferies  JL , Ibrahim  NE .  Are guidelines merely suggestions?   J Am Coll Cardiol. 2018;72(4):367-369. doi:10.1016/j.jacc.2018.05.023PubMedGoogle ScholarCrossref
67.
Petrie  MC , Verma  S , Docherty  KF ,  et al.  Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes.   JAMA. 2020;323(14):1353-1368. doi:10.1001/jama.2020.1906PubMedGoogle ScholarCrossref
68.
Packer  M , Anker  SD , Butler  J , Filippatos  G , Zannad  F .  Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action.   JAMA Cardiol. 2017;2(9):1025-1029. doi:10.1001/jamacardio.2017.2275PubMedGoogle ScholarCrossref
69.
Verma  S , McMurray  JJV .  SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review.   Diabetologia. 2018;61(10):2108-2117. doi:10.1007/s00125-018-4670-7PubMedGoogle ScholarCrossref
70.
Lytvyn  Y , Bjornstad  P , Udell  JA , Lovshin  JA , Cherney  DZI .  Sodium glucose cotransporter-2 inhibition in heart failure: potential mechanisms, clinical applications, and summary of clinical trials.   Circulation. 2017;136(17):1643-1658. doi:10.1161/CIRCULATIONAHA.117.030012PubMedGoogle ScholarCrossref
71.
Butler  J , Anstrom Kevin  J , Armstrong Paul  W .  Comparing the benefit of novel therapies across clinical trials: insights from the VICTORIA trial.   Circulation. Published online March 28, 2020. doi:10.1161/CIRCULATIONAHA.120.047086Google Scholar
72.
Cleland  JGF , Daubert  J-C , Erdmann  E ,  et al; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators.  The effect of cardiac resynchronization on morbidity and mortality in heart failure.   N Engl J Med. 2005;352(15):1539-1549. doi:10.1056/NEJMoa050496PubMedGoogle ScholarCrossref
73.
Moss  AJ , Hall  WJ , Cannom  DS ,  et al; MADIT-CRT Trial Investigators.  Cardiac-resynchronization therapy for the prevention of heart-failure events.   N Engl J Med. 2009;361(14):1329-1338. doi:10.1056/NEJMoa0906431PubMedGoogle ScholarCrossref
74.
Moss  AJ , Zareba  W , Hall  WJ ,  et al; Multicenter Automatic Defibrillator Implantation Trial II Investigators.  Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.   N Engl J Med. 2002;346(12):877-883. doi:10.1056/NEJMoa013474PubMedGoogle ScholarCrossref
75.
Bardy  GH , Lee  KL , Mark  DB ,  et al; Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators.  Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.   N Engl J Med. 2005;352(3):225-237. doi:10.1056/NEJMoa043399PubMedGoogle ScholarCrossref
76.
Kadish  A , Dyer  A , Daubert  JP ,  et al; Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators.  Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy.   N Engl J Med. 2004;350(21):2151-2158. doi:10.1056/NEJMoa033088PubMedGoogle ScholarCrossref
77.
Stone  GW , Lindenfeld  J , Abraham  WT ,  et al; COAPT Investigators.  Transcatheter Mitral-valve repair in patients with heart failure.   N Engl J Med. 2018;379(24):2307-2318. doi:10.1056/NEJMoa1806640PubMedGoogle ScholarCrossref
78.
Obadia  J-F , Messika-Zeitoun  D , Leurent  G ,  et al; MITRA-FR Investigators.  Percutaneous repair or medical treatment for secondary mitral regurgitation.   N Engl J Med. 2018;379(24):2297-2306. doi:10.1056/NEJMoa1805374PubMedGoogle ScholarCrossref
79.
Givertz  MM , Stevenson  LW , Costanzo  MR ,  et al; CHAMPION Trial Investigators.  Pulmonary artery pressure-guided management of patients with heart failure and reduced ejection fraction.   J Am Coll Cardiol. 2017;70(15):1875-1886. doi:10.1016/j.jacc.2017.08.010PubMedGoogle ScholarCrossref
80.
Zareba  W , Klein  H , Cygankiewicz  I ,  et al; MADIT-CRT Investigators.  Effectiveness of cardiac resynchronization therapy by qrs morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT).   Circulation. 2011;123(10):1061-1072. doi:10.1161/CIRCULATIONAHA.110.960898PubMedGoogle ScholarCrossref
81.
Ruschitzka  F , Abraham  WT , Singh  JP ,  et al; EchoCRT Study Group.  Cardiac-resynchronization therapy in heart failure with a narrow QRS complex.   N Engl J Med. 2013;369(15):1395-1405. doi:10.1056/NEJMoa1306687PubMedGoogle ScholarCrossref
82.
Køber  L , Thune  JJ , Nielsen  JC ,  et al; DANISH Investigators.  Defibrillator implantation in patients with nonischemic systolic heart failure.   N Engl J Med. 2016;375(13):1221-1230. doi:10.1056/NEJMoa1608029PubMedGoogle ScholarCrossref
83.
Packer  M , Grayburn  PA .  New evidence supporting a novel conceptual framework for distinguishing proportionate and disproportionate functional mitral regurgitation.   JAMA Cardiol. 2020;5(4):469-475. doi:10.1001/jamacardio.2019.5971PubMedGoogle ScholarCrossref
84.
Gaasch  WH , Aurigemma  GP , Meyer  TE .  An appraisal of the association of clinical outcomes with the severity of regurgitant volume relative to end-diastolic volume in patients with secondary mitral regurgitation.   JAMA Cardiol. 2020;5(4):476-481. doi:10.1001/jamacardio.2019.5980PubMedGoogle ScholarCrossref
85.
Braunstein  JB , Anderson  GF , Gerstenblith  G ,  et al.  Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure.   J Am Coll Cardiol. 2003;42(7):1226-1233. doi:10.1016/S0735-1097(03)00947-1PubMedGoogle ScholarCrossref
86.
Das  SR , Everett  BM , Birtcher  KK ,  et al.  2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways.   J Am Coll Cardiol. 2018;72(24):3200-3223. doi:10.1016/j.jacc.2018.09.020PubMedGoogle ScholarCrossref
87.
Dunlay  SM , Givertz  MM , Aguilar  D ,  et al; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and the Heart Failure Society of America.  Type 2 diabetes mellitus and heart failure: a scientific statement from the American Heart Association and the Heart Failure Society of America: this statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update.   Circulation. 2019;140(7):e294-e324.PubMedGoogle ScholarCrossref
88.
Cosentino  F , Grant  PJ , Aboyans  V ,  et al; ESC Scientific Document Group.  2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD.   Eur Heart J. 2020;41(2):255-323. doi:10.1093/eurheartj/ehz486PubMedGoogle ScholarCrossref
89.
Scirica  BM , Bhatt  DL , Braunwald  E ,  et al; SAVOR-TIMI 53 Steering Committee and Investigators.  Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.   N Engl J Med. 2013;369(14):1317-1326. doi:10.1056/NEJMoa1307684PubMedGoogle ScholarCrossref
90.
Margulies  KB , Hernandez  AF , Redfield  MM ,  et al; NHLBI Heart Failure Clinical Research Network.  Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial.   JAMA. 2016;316(5):500-508. doi:10.1001/jama.2016.10260PubMedGoogle ScholarCrossref
91.
Mamas  MA , Caldwell  JC , Chacko  S , Garratt  CJ , Fath-Ordoubadi  F , Neyses  L .  A meta-analysis of the prognostic significance of atrial fibrillation in chronic heart failure.   Eur J Heart Fail. 2009;11(7):676-683. doi:10.1093/eurjhf/hfp085PubMedGoogle ScholarCrossref
92.
Marrouche  NF , Brachmann  J , Andresen  D ,  et al; CASTLE-AF Investigators.  Catheter ablation for atrial fibrillation with heart failure.   N Engl J Med. 2018;378(5):417-427. doi:10.1056/NEJMoa1707855PubMedGoogle ScholarCrossref
93.
Löfman  I , Szummer  K , Dahlström  U , Jernberg  T , Lund  LH .  Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction.   Eur J Heart Fail. 2017;19(12):1606-1614. doi:10.1002/ejhf.821PubMedGoogle ScholarCrossref
94.
Rangaswami  J , Bhalla  V , Blair  JEA ,  et al; American Heart Association Council on the Kidney in Cardiovascular Disease and Council on Clinical Cardiology.  Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the American Heart Association.   Circulation. 2019;139(16):e840-e878. doi:10.1161/CIR.0000000000000664PubMedGoogle ScholarCrossref
95.
Felker  GM , Ellison  DH , Mullens  W , Cox  ZL , Testani  JM .  Diuretic therapy for patients with heart failure: JACC state-of-the-art review.   J Am Coll Cardiol. 2020;75(10):1178-1195. doi:10.1016/j.jacc.2019.12.059PubMedGoogle ScholarCrossref
96.
Wu  W , Bush  KT , Nigam  SK .  Key Role for the organic anion transporters, OAT1 and OAT3, in the in vivo handling of uremic toxins and solutes.   Sci Rep. 2017;7(1):4939. doi:10.1038/s41598-017-04949-2PubMedGoogle ScholarCrossref
97.
Brater  DC .  Disposition and response to bumetanide and furosemide.   Am J Cardiol. 1986;57(2):20A-25A. doi:10.1016/0002-9149(86)91002-7PubMedGoogle ScholarCrossref
98.
Dormans  TP , van Meyel  JJ , Gerlag  PG , Tan  Y , Russel  FG , Smits  P .  Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion.   J Am Coll Cardiol. 1996;28(2):376-382. doi:10.1016/0735-1097(96)00161-1PubMedGoogle ScholarCrossref
99.
Perera  D , Clayton  T , Petrie  MC ,  et al; REVIVED investigators.  Percutaneous revascularization for ischemic ventricular dysfunction: rationale and design of the REVIVED-BCIS2 trial: percutaneous coronary intervention for ischemic cardiomyopathy.   JACC Heart Fail. 2018;6(6):517-526. doi:10.1016/j.jchf.2018.01.024PubMedGoogle ScholarCrossref
100.
Velazquez  EJ , Lee  KL , Deja  MA ,  et al; STICH Investigators.  Coronary-artery bypass surgery in patients with left ventricular dysfunction.   N Engl J Med. 2011;364(17):1607-1616. doi:10.1056/NEJMoa1100356PubMedGoogle ScholarCrossref
101.
Velazquez  EJ , Lee  KL , Jones  RH ,  et al; STICHES Investigators.  Coronary-artery bypass surgery in patients with ischemic cardiomyopathy.   N Engl J Med. 2016;374(16):1511-1520. doi:10.1056/NEJMoa1602001PubMedGoogle ScholarCrossref
102.
Yancy  CW .  Heart failure in African Americans.   Am J Cardiol. 2005;96(7B):3i-12i. doi:10.1016/j.amjcard.2005.07.028PubMedGoogle ScholarCrossref
103.
Shi  V , Senni  M , Streefkerk  H , Modgill  V , Zhou  W , Kaplan  A .  Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study.   Int J Cardiol. 2018;264:118-123. doi:10.1016/j.ijcard.2018.03.121PubMedGoogle ScholarCrossref
104.
Colvin  M , Sweitzer  NK , Albert  NM ,  et al.  Heart failure in non-caucasians, women, and older adults: a white paper on special populations from the Heart Failure Society of America Guideline Committee.   J Card Fail. 2015;21(8):674-693. doi:10.1016/j.cardfail.2015.05.013PubMedGoogle ScholarCrossref
105.
Austin  J , Williams  R , Ross  L , Moseley  L , Hutchison  S .  Randomised controlled trial of cardiac rehabilitation in elderly patients with heart failure.   Eur J Heart Fail. 2005;7(3):411-417. doi:10.1016/j.ejheart.2004.10.004PubMedGoogle ScholarCrossref
106.
Piña  IL , Apstein  CS , Balady  GJ ,  et al; American Heart Association Committee on exercise, rehabilitation, and prevention.  Exercise and heart failure: A statement from the American Heart Association Committee on exercise, rehabilitation, and prevention.   Circulation. 2003;107(8):1210-1225. doi:10.1161/01.CIR.0000055013.92097.40PubMedGoogle ScholarCrossref
107.
O’Connor  CM , Whellan  DJ , Lee  KL ,  et al; HF-ACTION Investigators.  Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial.   JAMA. 2009;301(14):1439-1450. doi:10.1001/jama.2009.454PubMedGoogle ScholarCrossref
108.
Barker  WH , Mullooly  JP , Getchell  W .  Changing incidence and survival for heart failure in a well-defined older population, 1970-1974 and 1990-1994.   Circulation. 2006;113(6):799-805. doi:10.1161/CIRCULATIONAHA.104.492033PubMedGoogle ScholarCrossref
109.
Tsao  CW , Lyass  A , Enserro  D ,  et al.  Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction.   JACC Heart Fail. 2018;6(8):678-685. doi:10.1016/j.jchf.2018.03.006PubMedGoogle ScholarCrossref
110.
Ouwerkerk  W , Voors  AA , Zwinderman  AH .  Factors influencing the predictive power of models for predicting mortality and/or heart failure hospitalization in patients with heart failure.   JACC Heart Fail. 2014;2(5):429-436. doi:10.1016/j.jchf.2014.04.006PubMedGoogle ScholarCrossref
111.
Rahimi  K , Bennett  D , Conrad  N ,  et al.  Risk prediction in patients with heart failure: a systematic review and analysis.   JACC Heart Fail. 2014;2(5):440-446. doi:10.1016/j.jchf.2014.04.008PubMedGoogle ScholarCrossref
112.
Simpson  J , Jhund  PS , Lund  LH ,  et al.  Prognostic Models derived in PARADIGM-HF and validated in ATMOSPHERE and the Swedish Heart Failure Registry to predict mortality and morbidity in chronic heart failure.   JAMA Cardiol. 2020;5(4):432-441. doi:10.1001/jamacardio.2019.5850PubMedGoogle ScholarCrossref
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