An Overview of Heart Failure Treatments and Updates for the Primary Care Clinician
Heart failure is structural or functional cardiac impairment that leads to an inability of the ventricles to fill and eject blood. Treatment depends on the severity of cardiac dysfunction which is measured as the ejection fraction. Standard treatment guidelines for the primary care clinician are presented here along with the newest updates for treating heart failure with reduced ejection fraction.
Heart Failure with Preserved Ejection Fraction of >50% (previously known as diastolic heart failure)
Evidence shows that treatments used in patients with heart failure with reduced ejection fraction do not provide the same reduction in morbidity and mortality in patients with heart failure with preserved ejection fraction (1). Therefore, the treatment of a patient with heart failure with preserved ejection fraction revolves around managing comorbidities that lead to worsening heart failure. This means treating hypertension, coronary artery disease, atrial fibrillation, obesity, kidney disease, diabetes, and sleep apnea (2). Many of the specific treatments for patients with heart failure with preserved ejection fraction are based on the 2013 American College of Cardiology and American Heart Association guidelines for the management of heart failure (3).
- Hypertension
- People who are treated for hypertension are less likely to have fatal coronary heart disease and myocardial infarction, problems that lead to heart failure.
- The choice of antihypertensive agents for patients with preserved ejection fraction is less clear because specific studies do not show improved mortality with one agent versus another in these patients. Analysis of the ALLHAT study shows that the use of chlorthalidone for hypertension reduces new-onset heart failure hospitalization rates. However, the use of all other agents including beta-blockers, calcium channel blockers, ACE inhibitors, and angiotensin receptor blockers does not show mortality benefit in people with heart failure with preserved ejection fraction (4,5).
- Exercise
- People who undergo exercise training have an improved quality of life, but exercise does not change left ventricular function or disease progression (6).
- Obesity
- Compared with nonobese subjects, obese people with heart failure with preserved ejection fraction develop more significant symptoms as the disease progresses, so it is thought that preventing obesity prevents rapidly worsening heart failure (7).
- Hyperlipidemia
- Randomized trials have not been done to determine whether people with heart failure with preserved ejection fraction benefit from the use of statins, but an observational study shows that people treated with stains have improved overall outcomes (8).
Heart Failure with Reduced Ejection Fraction of <40% (previously known as systolic heart failure)
Similar to people with heart failure with preserved ejection fraction, people with reduced ejection fraction should be monitored and treated for comorbidities that contribute to overall heart disease and heart failure, including hypertension, coronary artery disease, atrial fibrillation, obesity, kidney disease, diabetes, and sleep apnea. Although randomized trials have not been done, observational studies and expert opinion suggest that patients should quit smoking tobacco (9), limit alcohol consumption (10), and avoid excessive salt intake (3). There is little evidence to recommend sodium restriction, but experts recommend avoiding excessive salt intake (>6 g/day) (11).
- General Pharmacologic Management Including Blood Pressure Control
- Appropriate treatment of people with heart failure with reduced ejection fraction leads to the greatest decrease in hospitalization rates and mortality. Standard therapy with a renin-angiotensin system blocker plus a beta-blocker improves mortality (3). People with edema or fluid overload also benefit from the addition of a diuretic.
- Treatment of hypertension is based on the 2016 American College of Cardiology updated decision pathway for people with heart failure with reduced ejection fraction. Patients show mortality benefit when treated with either an ACE inhibitor or an angiotensin receptor-blocker plus a beta blocker. However, new guidelines show improved outcomes by switching patients from these regimens to an angiotensin receptor-neprilysin blocker plus a beta-blocker. Evidence-based beta blockers include metoprolol, carvedilol, and bisoprolol. If a person cannot tolerate an angiotensin system blocker then experts recommend hydralazine plus nitrates instead (12).
- In addition to an angiotensin receptor-neprilysin blocker and a beta-blocker, patients who continue to have a resting heart rate above 70 have improved outcomes with the use of ivabradine. The goal resting heart rate is 50–60 bpm (13).
- Sodium-glucose cotransporter-2 drugs are used in patients with diabetes, but new evidence shows that even people without diabetes have improved clinical outcomes and decreased hospitalization rates (14).
- All of these recommendations are highlighted even further in the newest evidence published in The Lancet in July 2020. The study emphasizes comprehensive treatment with a mineralocorticoid receptor antagonist, an angiotensin receptor-neprilysin inhibitor, a beta-blocker, and a sodium-glucose cotransporter-2 inhibitor. This combined comprehensive treatment plan significantly reduces hospitalization rates and mortality compared to previously recommended treatments. For patients age 55, the combined therapy is estimated to add 8 more years of life before hospitalization for heart failure or death (15).
- Hyperlipidemia
- Two large randomized controlled trials show that people have a reduction in cholesterol levels with the use of rosuvastatin, but statin use does not reduce mortality. At this time, experts do not recommend regular statin use in people with heart failure with reduced ejection fraction (16,17).
- Cardiac Resynchronization Therapy and Implantable Cardioverter-Defibrillator (CRT and ICD)
- People with heart failure with a reduced ejection fraction and a wide QRS complex have higher mortality than people with a narrow QRS complex (18). Therefore, experts recommend cardiac resynchronization therapy to pace the left and right ventricles simultaneously and improve cardiac function. People who are medically optimized and who have a reduced ejection should be referred for CRT evaluation, especially if the person has a wide QRS complex and ejection fraction <35% (19).
- Most people who meet the criteria for cardiac resynchronization also meet the criteria for an implantable cardioverter-defibrillator. There are no studies that show a significant benefit to adding a defibrillator over a pacemaker (20). Each patient should be evaluated individually to decide which device is best.
Heart Failure With Mid-Range Ejection Fraction of 41-49%
It is important to know that this category of heart failure exists, but specific studies evaluating treatment of heart failure with mid-range ejection fraction do not exist. Heart failure studies usually include patients with either a preserved ejection fraction or reduced ejection fraction. In general, people with heart failure with mid-range ejection fraction respond to therapy in similar ways as people with heart failure with reduced ejection fraction.
Refractory Heart Failure With Reduced Ejection Fraction
People with heart failure with reduced ejection fraction need to be followed regularly, preferably every 3–6 months, to monitor their clinical stability. Cardiac rehabilitation should also be utilized. Most people respond to optimal medical management, but some continue to decline. People with chronic heart failure complain of symptoms at rest or with minimal exertion. People with chronic heart failure symptoms who have been medically optimized are classified as refractory heart failure patients with reduced ejection fraction. At this point, they benefit from referral to a heart failure specialist (12). Advanced therapies including intravenous vasodilators, inotropic therapies, mechanical circulatory support, cardiac transplantation, and palliative care may be necessary.
If you enjoyed this post, check out Pri-Med’s recent podcast series by Ty Gluckman, MD, on heart failure or explore Pri-Med’s Cardiology online CME/CE courses.
References:
1) Iwano H, Little WC. Heart failure: what does ejection fraction have to do with it? J Cardiol. 2013 Jul;62(1):1-3. doi: 10.1016/j.jjcc.2013.02.017. Epub 2013 May 11. PMID: 23672790.
2) Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, Kjeldsen K, Jankowska EA, Atar D, Butler J, Fiuzat M, Zannad F, Pitt B, O’Connor CM. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol. 2014 Dec 2;64(21):2281-93. doi: 10.1016/j.jacc.2014.08.036. Epub 2014 Nov 24. PMID: 25456761; PMCID: PMC4254505.
3) Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 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 Oct 15;62(16):e147-239. doi: 10.1016/j.jacc.2013.05.019. Epub 2013 Jun 5. PMID: 23747642.
4) ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002 Dec 18;288(23):2981-97. doi: 10.1001/jama.288.23.2981. Erratum in: JAMA 2003 Jan 8;289(2):178. Erratum in: JAMA. 2004 May 12;291(18):2196. PMID: 12479763.
5) Davis BR, Kostis JB, Simpson LM, Black HR, Cushman WC, Einhorn PT, Farber MA, Ford CE, Levy D, Massie BM, Nawaz S; ALLHAT Collaborative Research Group. Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Circulation. 2008 Nov 25;118(22):2259-67. doi: 10.1161/CIRCULATIONAHA.107.762229. Epub 2008 Nov 10. PMID: 19001024; PMCID: PMC2775475.
6) Pandey A, Parashar A, Kumbhani D, Agarwal S, Garg J, Kitzman D, Levine B, Drazner M, Berry J. Exercise training in patients with heart failure and preserved ejection fraction: meta-analysis of randomized control trials. Circ Heart Fail. 2015 Jan;8(1):33-40. doi: 10.1161/CIRCHEARTFAILURE.114.001615. Epub 2014 Nov 16. PMID: 25399909; PMCID: PMC4792111.
7) Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation. 2017 Jul 4;136(1):6-19. doi: 10.1161/CIRCULATIONAHA.116.026807. Epub 2017 Apr 5. PMID: 28381470; PMCID: PMC5501170.
8) Alehagen U, Benson L, Edner M, Dahlström U, Lund LH. Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50. Circ Heart Fail. 2015 Sep;8(5):862-70. doi: 10.1161/CIRCHEARTFAILURE.115.002143. Epub 2015 Aug 4. PMID: 26243795.
9) Barua RS, Rigotti NA, Benowitz NL, Cummings KM, Jazayeri MA, Morris PB, Ratchford EV, Sarna L, Stecker EC, Wiggins BS. 2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2018 Dec 25;72(25):3332-3365. doi: 10.1016/j.jacc.2018.10.027. Epub 2018 Dec 5. PMID: 30527452.
10) Piano MR, Schwertz DW. Alcoholic heart disease: a review. Heart Lung. 1994 Jan-Feb;23(1):3-17; quiz 18-20. PMID: 8150642.
11) Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; 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 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. Erratum in: Eur Heart J. 2016 Dec 30;: PMID: 27206819.
12) Yancy CW, Januzzi JL Jr, Allen LA, Butler J, Davis LL, Fonarow GC, Ibrahim NE, Jessup M, Lindenfeld J, Maddox TM, Masoudi FA, Motiwala SR, Patterson JH, Walsh MN, Wasserman A. 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 Jan 16;71(2):201-230. doi: 10.1016/j.jacc.2017.11.025. Epub 2017 Dec 22. Erratum in: J Am Coll Cardiol. 2018 Nov 13;72(20):2549. PMID: 29277252.
13) Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1. Erratum in: Lancet. 2010 Dec 11;376(9757):1988. Lajnscak, M [corrected to Lainscak, M]; Rabanedo, I Roldan [corrected to Rabadán, I Roldan]; Leva, M [corrected to Ieva, M]. PMID: 20801500.
14) McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19. PMID: 31535829.
15) Vaduganathan M, Claggett BL, Jhund PS, Cunningham JW, Pedro Ferreira J, Zannad F, Packer M, Fonarow GC, McMurray JJV, Solomon SD. Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Lancet. 2020 Jul 11;396(10244):121-128. doi: 10.1016/S0140-6736(20)30748-0. Epub 2020 May 21. PMID: 32446323.
16) Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Jánosi A, Kamenský G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007 Nov 29;357(22):2248-61. doi: 10.1056/NEJMoa0706201. Epub 2007 Nov 5. PMID: 17984166.
17) Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G; Gissi-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1231-9. doi: 10.1016/S0140-6736(08)61240-4. Epub 2008 Aug 29. PMID: 18757089.
18) Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN; Department of Veterans Affairs Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. QRS duration and mortality in patients with congestive heart failure. Am Heart J. 2002 Jun;143(6):1085-91. doi: 10.1067/mhj.2002.122516. PMID: 12075267.
19) McAlister FA, Ezekowitz J, Hooton N, Vandermeer B, Spooner C, Dryden DM, Page RL, Hlatky MA, Rowe BH. Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA. 2007 Jun 13;297(22):2502-14. doi: 10.1001/jama.297.22.2502. PMID: 17565085.
20) Lam SK, Owen A. Combined resynchronisation and implantable defibrillator therapy in left ventricular dysfunction: Bayesian network meta-analysis of randomised controlled trials. BMJ. 2007 Nov 3;335(7626):925. doi: 10.1136/bmj.39343.511389.BE. Epub 2007 Oct 11. PMID: 17932160; PMCID: PMC2048879.