Congestive heart failure with preserved EF pharmacotherapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]
Overview
Treatment of HFpEF is focused on treating underlying disease, such as hypertension, coronary artery disease and atrial fibrillation. Diuretics are the mainstay of pharmacotherapy. Other effective measures to control HFpEF include exercise, weight control and lipid control.
Heart failure mildly reduced ejection fraction (HPmrEF), EF (41-49%)
The diagnosis of heart failure with mildly reduced ejection fraction
- The diagnosis of HFmrEF requires the presence of symptoms and/or signs of HF, and a mildly reduced EF (41-49%) The presence of elevated NPs (BNP >_35 pg/mL or NT-proBNP >_125 pg/mL) and other evidence of structural heart disease including increased left atrial (LA) size, LVH or echocardiographic measures of LV filling.
Clinical characteristics
- Clinical characteristics, risk factors, patterns of cardiac remodelling are similar to other subgroups of HF.
- HFmrEF is more common in men, younger, and are more likely to have CAD (50-60%) and less likely to have AF and non-cardiac comorbidities. ambulatory
- HFmrEF have lower mortality rate than those with HFrEF.
Treatment
Angiotensin-converting enzyme inhibitors
- ACE-I may be considered in patients with HFmrEF and underlying CAD, hypertension, or post-MI LV systolic dysfunction.
Angiotensin receptor II type 1 receptor blockers
- Candesartan reduced the number of patients hospitalized for HF among those with HFmrEF.
- Treatment with ARBs may be considered in patients with HFmrEF patients with other cardiovascular indications.
Beta-blockers
- Treatment with beta-blockers may be considered in patients with HFmrEF and another cardiovascular indication, such as AF or angina.
Mineralocorticoid receptor antagonists
- In a retrospective analysis of the TOPCAT trial in patients with LVEF >_45%, spironolactone reduced hospitalizations for HF in patients with an LVEF <55%.
- Treatment with an MRA may be considered in patients with HFmrEF.
Angiotensin receptor-neprilysin inhibitor
- Analysis of the PARADIGM-HF and PARAGON-HF trials showed that sacubitril/valsartan, compared to other forms of RAAS blockade reduced hospitalizations in patients with HFmrEF.
Other drugs
- In the DIG trial, use of digoxin for patients with HFmrEF in sinus rhythm was associated with fewer hospitalizations but no reduction in mortality and a trend to increase of cardiovascular deaths.
- Therefore, there are insufficient data to recommend its use.
- There are insufficient data on ivabradine in HFmrEF.
Devices
Medications indicated in patients with New York Heart Association (NYHA class II–IV) HFmrEF (heart failure with mildly reduced ejection fraction) (LVEF41-49%)
| Recommedation for patients with NYHA class 2-4 heart failure with mildly reduced ejection fraction |
| Diuretics (Class I, Level of Evidence C): |
|
❑ Diuretics are recommended in patients with congestion and HFmrEF in order reduce symptoms and signs |
| ACEI (Class IIb, Level of Evidence C): |
|
❑ ACE-I may be considered for patients with HFmrEF to reduce the risk of HF hospitalization and death |
| The above table adopted from 2021 ESC Guideline |
|---|
| Recommedation for treatment of patients with HFpEF (heart failure preserved ejection fraction) |
| (Class I, Level of Evidence C): |
|
❑ Screening, treatment, investigation about underlying etiologies, and
cardiovascular and non-cardiovascular comorbidities is recommended in patients with HFpEF |
| The above table adopted from 2021 ESC Guideline |
|---|
Treatment for HFpEF is based on underlying associated conditions. These measure are mainly focused on:
- Hypertension Control[2]
- It is recommended to maintain BP less than 150/90 mm Hg in persons who are 60 years of age or older in the general population and of less than 140/90 mm Hg in persons with kidney disease (estimated GFR<60 ml per minute per 1.73 m2 of body-surface area or >30 mg of albumin per gram of creatinine,regardless of diabetic status) and for persons with diabetes, regardless of age.[3]
- Diuretics must be used to relief symptoms of volume overload according to patients' weight, symptoms and electrolyte status. Also, sodium restriction may be helpful in patients who are prone to volume overload.[6]
- Atrial fibrillation treatment[7]
- Patients with Atrial fibrillation (AF) must be treated according to last guideline for rate control and anti coagulation but if the symptoms remained consider rhythm control.[8]
- Appropriate diet and exercise[9][10]
- Weight control[9]
- Control of co-morbid conditions, such as diabetes, anemia, hyperlipidemia, sleep apnea and COPD.[11]
- Patients with coronary artery diseases (CAD) should be treated based on the guidelines recommendations.
Medications
Aldosterone Antagonists
May lead to improvement in diastolic function and hypertrophy but not in clinical outcomes.[12][13] However, a subgroup analysis of patients in the TOPCAT trial with brain natriuretic peptide levels showed benefit[13].
Diuretics
Diuretics are useful to control volume overload and decrease the preload.[14]
Angiotensin receptor neprilysin inhibitors
They may improve symptoms and quality of life in HFpEF patients but clinical trials to evaluate their effectiveness are ongoing.[15][16][17]
ACE inhibitors
ACE inhibitors do not have direct effect on mortality and morbidity in HFpEF but they have great role on hypertension, renal function, CAD and diabetes as underlying disease.[18][19]
Angiotensin II receptor blockers
There is no evidence that they improve morbidity or mortality in HFpEF patients.[19]
β-blockers
β-blockers have not shown benefits in HFpEF.[20][21]
References
- ↑ 1.0 1.1 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland J, Coats A, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam C, Lyon AR, McMurray J, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano G, Ruschitzka F, Kathrine Skibelund A (September 2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ (2008). "Treatment of hypertension in patients 80 years of age or older". N. Engl. J. Med. 358 (18): 1887–98. doi:10.1056/NEJMoa0801369. PMID 18378519.
- ↑ Reisin E, Harris RC, Rahman M (2014). "Commentary on the 2014 BP guidelines from the panel appointed to the Eighth Joint National Committee (JNC 8)". J. Am. Soc. Nephrol. 25 (11): 2419–24. doi:10.1681/ASN.2014040371. PMC 4214539. PMID 25114277.
- ↑ Takei M, Kohsaka S, Shiraishi Y, Goda A, Izumi Y, Yagawa M, Mizuno A, Sawano M, Inohara T, Kohno T, Fukuda K, Yoshikawa T (2015). "Effect of estimated plasma volume reduction on renal function for acute heart failure differs between patients with preserved and reduced ejection fraction". Circ Heart Fail. 8 (3): 527–32. doi:10.1161/CIRCHEARTFAILURE.114.001734. PMID 25737498.
- ↑ Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM (2011). "Diuretic strategies in patients with acute decompensated heart failure". N. Engl. J. Med. 364 (9): 797–805. doi:10.1056/NEJMoa1005419. PMC 3412356. PMID 21366472.
- ↑ Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016). "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. 37 (27): 2129–200. doi:10.1093/eurheartj/ehw128. PMID 27206819.
- ↑ Zakeri R, Chamberlain AM, Roger VL, Redfield MM (2013). "Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study". Circulation. 128 (10): 1085–93. doi:10.1161/CIRCULATIONAHA.113.001475. PMC 3910441. PMID 23908348.
- ↑ January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW (2014). "2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society". Circulation. 130 (23): 2071–104. doi:10.1161/CIR.0000000000000040. PMID 24682348.
- ↑ 9.0 9.1 Haass M, Kitzman DW, Anand IS, Miller A, Zile MR, Massie BM, Carson PE (2011). "Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial". Circ Heart Fail. 4 (3): 324–31. doi:10.1161/CIRCHEARTFAILURE.110.959890. PMC 3100162. PMID 21350053.
- ↑ Smart NA, Haluska B, Jeffriess L, Leung D (2012). "Exercise training in heart failure with preserved systolic function: a randomized controlled trial of the effects on cardiac function and functional capacity". Congest Heart Fail. 18 (6): 295–301. doi:10.1111/j.1751-7133.2012.00295.x. PMID 22536983.
- ↑ Alehagen U, Benson L, Edner M, Dahlström U, Lund LH (2015). "Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50". Circ Heart Fail. 8 (5): 862–70. doi:10.1161/CIRCHEARTFAILURE.115.002143. PMID 26243795.
- ↑ Edelmann F, Wachter R, Schmidt AG, Kraigher-Krainer E, Colantonio C, Kamke W, Duvinage A, Stahrenberg R, Durstewitz K, Löffler M, Düngen HD, Tschöpe C, Herrmann-Lingen C, Halle M, Hasenfuss G, Gelbrich G, Pieske B (2013). "Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial". JAMA. 309 (8): 781–91. doi:10.1001/jama.2013.905. PMID 23443441.
- ↑ 13.0 13.1 Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM (2014). "Spironolactone for heart failure with preserved ejection fraction". N. Engl. J. Med. 370 (15): 1383–92. doi:10.1056/NEJMoa1313731. PMID 24716680.
- ↑ Butler J, Fonarow GC, Zile MR, Lam CS, Roessig L, Schelbert EB, Shah SJ, Ahmed A, Bonow RO, Cleland JG, Cody RJ, Chioncel O, Collins SP, Dunnmon P, Filippatos G, Lefkowitz MP, Marti CN, McMurray JJ, Misselwitz F, Nodari S, O'Connor C, Pfeffer MA, Pieske B, Pitt B, Rosano G, Sabbah HN, Senni M, Solomon SD, Stockbridge N, Teerlink JR, Georgiopoulou VV, Gheorghiade M (2014). "Developing therapies for heart failure with preserved ejection fraction: current state and future directions". JACC Heart Fail. 2 (2): 97–112. doi:10.1016/j.jchf.2013.10.006. PMC 4028447. PMID 24720916.
- ↑ Macdonald PS (2015). "Combined angiotensin receptor/neprilysin inhibitors: a review of the new paradigm in the management of chronic heart failure". Clin Ther. 37 (10): 2199–205. doi:10.1016/j.clinthera.2015.08.013. PMID 26386501.
- ↑ Hubers SA, Brown NJ (2016). "Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition". Circulation. 133 (11): 1115–24. doi:10.1161/CIRCULATIONAHA.115.018622. PMID 26976916.
- ↑ Prenner SB, Shah SJ, Yancy CW (2016). "Role of Angiotensin Receptor-Neprilysin Inhibition in Heart Failure". Curr Atheroscler Rep. 18 (8): 48. doi:10.1007/s11883-016-0603-4. PMID 27324636.
- ↑ Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, Yip T, Lau ST, Lau CP, Tang MO, Yu CM, Sanderson JE (2008). "The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction". Heart. 94 (5): 573–80. doi:10.1136/hrt.2007.117978. PMID 18208835.
- ↑ 19.0 19.1 Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J (2003). "Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial". Lancet. 362 (9386): 777–81. doi:10.1016/S0140-6736(03)14285-7. PMID 13678871.
- ↑ Yamamoto K, Origasa H, Hori M (2013). "Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J-DHF)". Eur. J. Heart Fail. 15 (1): 110–8. doi:10.1093/eurjhf/hfs141. PMID 22983988.
- ↑ Conraads VM, Metra M, Kamp O, De Keulenaer GW, Pieske B, Zamorano J, Vardas PE, Böhm M, Dei Cas L (2012). "Effects of the long-term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study". Eur. J. Heart Fail. 14 (2): 219–25. doi:10.1093/eurjhf/hfr161. PMID 22147202.