Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Advances in the Management of Heart Failure with Reduced Ejection Fraction; The Role of SGLT2is, ARNI, Myotropes, Vericiguat, and Anti-inflammatory Agents: A Mini-review

Author(s): Dimitrios A. Vrachatis*, Konstantinos A. Papathanasiou, Sotiria G. Giotaki, Konstantinos Raisakis, Andreas Kaoukis, Charalampos Kossyvakis, Andreas Theodorakis, Stauros Pediotidis, Dimitrios Avramides, Gerasimos Siasos and Spyridon Deftereos

Volume 29, Issue 7, 2023

Published on: 17 March, 2023

Page: [509 - 518] Pages: 10

DOI: 10.2174/1381612829666230316142450

Price: $65


Heart failure with reduced ejection fraction (HFrEF) has been associated with poor prognosis, reduced quality of life, and increased healthcare expenditure. Despite tremendous advances in HFrEF management, reduced survival and a high rate of hospitalization remain unsolved issues. Furthermore, HFrEF morbidity and economic burden are estimated to increase in the following years; hence, new therapies are constantly emerging. In the last few years, a series of landmark clinical trials have expanded our therapeutic armamentarium with a ground-breaking change in HFrEF-related outcomes. Sodium-glucose co-transporter 2 inhibitors (mainly dapagliflozin and empagliflozin) have already revolutionized the management of HFrEF patients via a significant reduction in cardiovascular mortality and heart failure hospitalizations. Furthermore, vericiguat and omecamtiv mecarbil have emerged as promising and novel disease-modifying therapies. The former restores the impaired cyclic guanosine monophosphate pathway, and the latter stimulates cardiac myosin without marked arrhythmogenesis. Both vericiguat and omecamtiv mecarbil have been shown to reduce heart failure admissions. Sacubitril/valsartan is an established and effective therapy in HFrEF patients and should be considered as a replacement for angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). Lastly, inflammasome activity is implicated in HFrEF pathophysiology, and the role of anti-inflammatory agents in HFrEF trajectories is readily scrutinized, yet available therapies are ineffective. This mini-review summarizes the major and most recent studies in this field, thus covering the current advances in HFrEF therapeutics.

Keywords: HFrEF, HF, ARNIs, sacubitril/valsartan, SGLT2 inhibitors, vericiguat, omecamtiv mecarbil, anti-inflammatory agents, inflammation.

Roger VL. Epidemiology of heart failure. Circ Res 2013; 113(6): 646-59.
[] [PMID: 23989710]
Roger VL. Epidemiology of Heart Failure. Circ Res 2021; 128(10): 1421-34.
[] [PMID: 33983838]
Cowie MR, Anker SD, Cleland JGF, et al. Improving care for patients with acute heart failure: Before, during and after hospitalization. ESC Heart Fail 2014; 1(2): 110-45.
[] [PMID: 28834628]
Van Nuys KE, Xie Z, Tysinger B, Hlatky MA, Goldman DP. Innovation in heart failure treatment. JACC Heart Fail 2018; 6(5): 401-9.
[] [PMID: 29525333]
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): 678-85.
[] [PMID: 30007560]
Mamas MA, Sperrin M, Watson MC, et al. Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. Eur J Heart Fail 2017; 19(9): 1095-104.
[] [PMID: 28470962]
Conrad N, Judge A, Canoy D, et al. Temporal trends and patterns in mortality after incident heart failure. JAMA Cardiol 2019; 4(11): 1102-11.
[] [PMID: 31479100]
Mozaffarian D, Benjamin EJ, Go AS, et al. Executive summary: Heart disease and stroke statistics-2016 update. Circulation 2016; 133(4): 447-54.
[] [PMID: 26811276]
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42(36): 3599-726.
[] [PMID: 34447992]
Vaduganathan M, Claggett BL, Jhund PS, et al. 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; 396(10244): 121-8.
[] [PMID: 32446323]
Packer M. Critical reanalysis of the mechanisms underlying the cardiorenal benefits of SGLT2 inhibitors and reaffirmation of the nutrient deprivation signaling/autophagy hypothesis. Circulation 2022; 146(18): 1383-405.
[] [PMID: 36315602]
Kaplan A, Abidi E, El-Yazbi A, Eid A, Booz GW, Zouein FA. Direct cardiovascular impact of SGLT2 inhibitors: Mechanisms and effects. Heart Fail Rev 2018; 23(3): 419-37.
[] [PMID: 29322280]
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381(21): 1995-2008.
[] [PMID: 31535829]
Jackson AM, Dewan P, Anand IS, et al. Dapagliflozin and diuretic use in patients with heart failure and reduced ejection fraction in DAPA-HF. Circulation 2020; 142(11): 1040-54.
[] [PMID: 32673497]
Martinez FA, Serenelli M, Nicolau JC, et al. Efficacy and safety of dapagliflozin in heart failure with reduced ejection fraction according to age. Circulation 2020; 141(2): 100-11.
[] [PMID: 31736328]
Solomon SD, Jhund PS, Claggett BL, et al. Effect of dapagliflozin in patients with HFrEF treated with sacubitril/valsartan. JACC Heart Fail 2020; 8(10): 811-8.
[] [PMID: 32653447]
Shen L, Kristensen SL, Bengtsson O, et al. Dapagliflozin in HFrEF patients treated with mineralocorticoid receptor antagonists. JACC Heart Fail 2021; 9(4): 254-64.
[] [PMID: 33549554]
Curtain JP, Docherty KF, Jhund PS, et al. Effect of dapagliflozin on ventricular arrhythmias, resuscitated cardiac arrest, or sudden death in DAPA-HF. Eur Heart J 2021; 42(36): 3727-38.
[] [PMID: 34448003]
Vrachatis DA, Papathanasiou KA, Iliodromitis KE, et al. Could sodium/glucose co-transporter-2 inhibitors have antiarrhythmic potential in atrial fibrillation? literature review and future considerations. Drugs 2021; 81(12): 1381-95.
[] [PMID: 34297330]
Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020; 383(15): 1413-24.
[] [PMID: 32865377]
Ferreira JP, Zannad F, Pocock SJ, et al. Interplay of mineralocorticoid receptor antagonists and empagliflozin in heart failure. J Am Coll Cardiol 2021; 77(11): 1397-407.
[] [PMID: 33736821]
Nassif ME, Windsor SL, Tang F, et al. Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction. Circulation 2019; 140(18): 1463-76.
[] [PMID: 31524498]
Jensen J, Omar M, Kistorp C, et al. Twelve weeks of treatment with empagliflozin in patients with heart failure and reduced ejection fraction: A double-blinded, randomized, and placebo-controlled trial. Am Heart J 2020; 228: 47-56.
[] [PMID: 32798787]
Abraham WT, Lindenfeld J, Ponikowski P, et al. Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes. Eur Heart J 2021; 42(6): 700-10.
[] [PMID: 33351892]
Lee MMY, Brooksbank KJM, Wetherall K, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation 2021; 143(6): 516-25.
[] [PMID: 33186500]
Omar M, Jensen J, Ali M, et al. Associations of empagliflozin with left ventricular volumes, mass, and function in patients with heart failure and reduced ejection fraction. JAMA Cardiol 2021; 6(7): 836-40.
[] [PMID: 33404637]
Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 2021; 77(3): 243-55.
[] [PMID: 33197559]
Nassif ME, Qintar M, Windsor SL, et al. Empagliflozin effects on pulmonary artery pressure in patients with heart failure. Circulation 2021; 143(17): 1673-86.
[] [PMID: 33550815]
Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 2022; 28(3): 568-74.
[] [PMID: 35228754]
Spertus JA, Birmingham MC, Nassif M, et al. The SGLT2 inhibitor canagliflozin in heart failure: The CHIEF-HF remote, patient- centered randomized trial. Nat Med 2022; 28(4): 809-13.
[] [PMID: 35228753]
Kang DH, Park SJ, Shin SH, et al. Angiotensin receptor neprilysin inhibitor for functional mitral regurgitation. Circulation 2019; 139(11): 1354-65.
[] [PMID: 30586756]
Mann DL, Givertz MM, Vader JM, et al. Effect of treatment with sacubitril/valsartan in patients with advanced heart failure and reduced ejection fraction. JAMA Cardiol 2022; 7(1): 17-25.
[] [PMID: 34730769]
Pfeffer MA, Claggett B, Lewis EF, et al. Angiotensin receptor–neprilysin inhibition in acute myocardial infarction. N Engl J Med 2021; 385(20): 1845-55.
[] [PMID: 34758252]
Powers JD, Malingen SA, Regnier M, Daniel TL. The sliding filament theory since andrew huxley: Multiscale and multidisciplinary muscle research. Annu Rev Biophys 2021; 50(1): 373-400.
[] [PMID: 33637009]
Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail 2010; 3(4): 522-7.
[] [PMID: 20498236]
Teerlink JR, Clarke CP, Saikali KG, et al. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: A first-in-man study. Lancet 2011; 378(9792): 667-75.
[] [PMID: 21856480]
Cleland JGF, Teerlink JR, Senior R, et al. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: A double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet 2011; 378(9792): 676-83.
[] [PMID: 21856481]
Teerlink JR, Felker GM, McMurray JJV, et al. Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): A phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet 2016; 388(10062): 2895-903.
[] [PMID: 27914656]
Teerlink JR, Felker GM, McMurray JJV, et al. Acute treatment with omecamtiv mecarbil to increase contractility in acute heart failure. J Am Coll Cardiol 2016; 67(12): 1444-55.
[] [PMID: 27012405]
Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med 2021; 384(2): 105-16.
[] [PMID: 33185990]
Teerlink JR, Diaz R, Felker GM, et al. Effect of ejection fraction on clinical outcomes in patients treated with omecamtiv mecarbil in GALACTIC-HF. J Am Coll Cardiol 2021; 78(2): 97-108.
[] [PMID: 34015475]
Felker GM, Solomon SD, Claggett B, et al. Assessment of omecamtiv mecarbil for the treatment of patients with severe heart failure. JAMA Cardiol 2022; 7(1): 26-34.
[] [PMID: 34643642]
Mefford MT, Koyama SY, De Jesus J, et al. Representativeness of the GALACTIC-HF clinical trial in patients having heart failure with reduced ejection fraction. J Am Heart Assoc 2022; 11(7): e023766.
[] [PMID: 35322672]
Lewis GD, Docherty KF, Voors AA, Cohen-Solal A, Metra M, Whellan DJ, et al. Developments in exercise capacity assessment in heart failure clinical trials and the rationale for the design of METEORIC-HF. Circ Hear Fail 2022; 15(5): e008970.
Gregory DL, Lewis GD, Alain CS, et al. Effect of omecamtiv mecarbil on exercise capacity in chronic heart failure with reduced ejection fraction. JAMA 2022; 328(3): 259-69.
Voors AA, Tamby JF, Cleland JG, et al. Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial. Eur J Heart Fail 2020; 22(9): 1649-58.
[] [PMID: 32558989]
He H, Baka T, Balschi J, et al. Novel small-molecule troponin activator increases cardiac contractile function without negative impact on energetics. Circ Heart Fail 2022; 15(3): e009195.
[] [PMID: 34743528]
Gheorghiade M, Marti CN, Sabbah HN, et al. Soluble guanylate cyclase: A potential therapeutic target for heart failure. Heart Fail Rev 2013; 18(2): 123-34.
[] [PMID: 22622468]
Gheorghiade M, Greene SJ, Butler J, et al. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction. JAMA 2015; 314(21): 2251-62.
[] [PMID: 26547357]
Pieske B, Maggioni AP, Lam CSP, et al. Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: Results of the soluble guanylate cyclase stimulator in heart failure patients with PRESERVED EF (SOCRATES-PRESERVED) study. Eur Heart J 2017; 38(15): 1119-27.
[] [PMID: 28369340]
Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med 2020; 382(20): 1883-93.
[] [PMID: 32222134]
Deftereos SG, Beerkens FJ, Shah B, et al. Colchicine in cardiovascular disease: In-depth review. Circulation 2022; 145(1): 61-78.
[PMID: 34965168]
Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377(12): 1119-31.
[] [PMID: 28845751]
Pascual-Figal DA, Bayes-Genis A, Asensio-Lopez MC, et al. The interleukin-1 axis and risk of death in patients with acutely decompensated heart failure. J Am Coll Cardiol 2019; 73(9): 1016-25.
[] [PMID: 30846095]
Van Tassell BW, Canada J, Carbone S, et al. Interleukin-1 blockade in recently decompensated systolic heart failure. Circ Heart Fail 2017; 10(11): e004373.
[] [PMID: 29141858]
Abbate A, Trankle CR, Buckley LF, et al. Interleukin-1 blockade inhibits the acute inflammatory response in patients with st-segment–elevation myocardial infarction. J Am Heart Assoc 2020; 9(5): e014941.
[] [PMID: 32122219]
Everett BM, Cornel JH, Lainscak M, et al. Anti-inflammatory therapy with canakinumab for the prevention of hospitalization for heart failure. Circulation 2019; 139(10): 1289-99.
[] [PMID: 30586730]
Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: Further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J 2020; 41(23): 2153-63.
[] [PMID: 31504417]
Markousis-Mavrogenis G, Tromp J, Ouwerkerk W, et al. The clinical significance of interleukin-6 in heart failure: Results from the BIOSTAT-CHF study. Eur J Heart Fail 2019; 21(8): 965-73.
[] [PMID: 31087601]
Sano S, Oshima K, Wang Y, et al. Tet2-mediated clonal hematopoiesis accelerates heart failure through a mechanism involving the il-1β/nlrp3 inflammasome. J Am Coll Cardiol 2018; 71(8): 875-86.
[] [PMID: 29471939]
Pascual-Figal DA, Bayes-Genis A, Díez-Díez M, et al. Clonal hematopoiesis and risk of progression of heart failure with reduced left ventricular ejection fraction. J Am Coll Cardiol 2021; 77(14): 1747-59.
[] [PMID: 33832602]
Svensson EC, Madar A, Campbell CD, et al. TET2 -Driven clonal hematopoiesis and response to canakinumab. JAMA Cardiol 2022; 7(5): 521-8.
[] [PMID: 35385050]
Vrachatis DA, Papathanasiou KA, Giotaki SG, et al. Repurposing colchicine’s journey in view of drug-to-drug interactions. A review. Toxicol Rep 2021; 8: 1389-93.
[] [PMID: 34285885]
Deftereos S, Giannopoulos G, Panagopoulou V, et al. Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. JACC Heart Fail 2014; 2(2): 131-7.
[] [PMID: 24720919]
Roth ME, Chinn ME, Dunn SP, Bilchick KC, Mazimba S. Association of colchicine use for acute gout with clinical outcomes in acute decompensated heart failure. Clin Cardiol 2022; 45(7): 733-41.
[] [PMID: 35481608]
Bresson D, Roubille F, Prieur C, et al. Colchicine for left ventricular infarct size reduction in acute myocardial infarction: A phase II, Multicenter, randomized, double-blinded, placebo-controlled study protocol - the COVERT-MI study. Cardiology 2021; 146(2): 151-60.
[] [PMID: 33582664]
Wohlford GF, Van Tassell BW, Billingsley HE, et al. Phase 1B, randomized, double-blinded, dose escalation, single-center, repeat dose safety and pharmacodynamics study of the oral NLRP3 inhibitor dapansutrile in subjects with NYHA II-III systolic heart failure. J Cardiovasc Pharmacol 2021; 77(1): 49-60.
[] [PMID: 33235030]
Wehbe N, Nasser S, Pintus G, Badran A, Eid A, Baydoun E. MicroRNAs in cardiac hypertrophy. Int J Mol Sci 2019; 20(19): 4714.
[] [PMID: 31547607]
Alonso-Villa E, Bonet F, Hernandez-Torres F, et al. The role of MicroRNAs in dilated cardiomyopathy: New insights for an old entity. Int J Mol Sci 2022; 23(21): 13573.
[] [PMID: 36362356]
Li DM, Li BX, Yang LJ, Gao P, Ma ZY, Li ZJ. Diagnostic value of circulating microRNA-208a in differentiation of preserved from reduced ejection fraction heart failure. Heart Lung 2021; 50(1): 71-4.
[] [PMID: 32711895]
Watson CJ, Gupta SK, O’Connell E, et al. MicroRNA signatures differentiate preserved from reduced ejection fraction heart failure. Eur J Heart Fail 2015; 17(4): 405-15.
[] [PMID: 25739750]
Parvan R, Hosseinpour M, Moradi Y, Devaux Y, Cataliotti A, da Silva GJJ. Diagnostic performance of microRNAs in the detection of heart failure with reduced or preserved ejection fraction: A systematic review and meta-analysis. Eur J Heart Fail 2022; 24(12): 2212-25.
[] [PMID: 36161443]
Stojkovic S, Koller L, Sulzgruber P, et al. Liver-specific microRNA-122 as prognostic biomarker in patients with chronic systolic heart failure. Int J Cardiol 2020; 303: 80-5.
[] [PMID: 31757654]
Scrutinio D, Conserva F, Guida P, Passantino A. Long-term prognostic potential of microRNA-150-5p in optimally treated heart failure patients with reduced ejection fraction: A pilot study. Minerva Cardiol Angiol 2022; 70(4): 439-46.
[] [PMID: 33059402]
Witvrouwen I, Gevaert AB, Possemiers N, et al. Circulating microRNA as predictors for exercise response in heart failure with reduced ejection fraction. Eur J Prev Cardiol 2021; 28(15): 1673-81.
[] [PMID: 33742210]
Sciatti E, Gori M, D’elia E, Iacovoni A, Senni M. Empagliflozin in heart failure with preserved ejection fraction: First success in mission impossible. Eur Heart J Suppl 2022; 24(S1): I153-9.
[] [PMID: 36380802]
Mone P, Lombardi A, Kansakar U, et al. Empagliflozin improves the MicroRNA signature of endothelial dysfunction in patients with heart failure with preserved ejection fraction and diabetes. J Pharmacol Exp Ther 2023; 384(1): 116-22.
[] [PMID: 36549862]
Gargiulo P, Marzano F, Salvatore M, Basile C, Buonocore D, Parlati ALM, et al. MicroRNAs: Diagnostic, prognostic and therapeutic role in heart failure - a review. ESC Hear Fail 2022.
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018; 19(4): 213-28.
[] [PMID: 29339798]
Fang J, Zhang Y, Chen D, Zheng Y, Jiang J. Exosomes and exosomal cargos: A promising world for ventricular remodeling following myocardial infarction. Int J Nanomedicine 2022; 17: 4699-719.
[] [PMID: 36217495]
Botello-Flores YA, Yocupicio-Monroy M, Balderrábano-Saucedo N, Contreras-Ramos A. A systematic review on the role of MSC-derived exosomal miRNAs in the treatment of heart failure. Mol Biol Rep 2022; 49(9): 8953-73.
[] [PMID: 35359236]
Khan K, Caron C, Mahmoud I, Derish I, Schwertani A, Cecere R. Extracellular vesicles as a cell-free therapy for cardiac repair: A systematic review and meta-analysis of randomized controlled preclinical trials in animal myocardial infarction models. Stem Cell Rev Rep 2022; 18(3): 1143-67.
[] [PMID: 35107768]
Rikhtegar R, Pezeshkian M, Dolati S, et al. Stem cells as therapy for heart disease: iPSCs, ESCs, CSCs, and skeletal myoblasts. Biomed Pharmacother 2019; 109: 304-13.
[] [PMID: 30396088]
Fang J, Li JJ, Zhong X, et al. Engineering stem cell therapeutics for cardiac repair. J Mol Cell Cardiol 2022; 171: 56-68.
[] [PMID: 35863282]
Garbern JC, Lee RT. Heart regeneration: 20 years of progress and renewed optimism. Dev Cell 2022; 57(4): 424-39.
[] [PMID: 35231426]
Abou-Saleh H, Zouein FA, El-Yazbi A, et al. The march of pluripotent stem cells in cardiovascular regenerative medicine. Stem Cell Res Ther 2018; 9(1): 201.
[] [PMID: 30053890]
Kaplan A, Altara R, Eid A, Booz GW, Zouein FA. Update on the protective role of regulatory t cells in myocardial infarction: A promising therapy to repair the heart. J Cardiovasc Pharmacol 2016; 68(6): 401-13.
[] [PMID: 27941502]
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Am Coll Cardiol 2022; 79(17): e263-421.
[] [PMID: 35379503]
McMurray JJV, Packer M. How should we sequence the treatments for heart failure and a reduced ejection fraction? Circulation 2021; 143(9): 875-7.
[] [PMID: 33378214]
Cox ZL, Nandkeolyar S, Johnson AJ, Lindenfeld J, Rali AS. In- hospital initiation and up-titration of guideline-directed medical therapies for heart failure with reduced ejection fraction. Card Fail Rev 2022; 8: e21.
[] [PMID: 35815257]
Dixit NM, Ziaeian B, Fonarow GC. SGLT2 inhibitors in heart failure. Heart Fail Clin 2022; 18(4): 587-96.
[] [PMID: 36216488]
Rao VN, Fudim M, Savarese G, Butler J. Polypharmacy in heart failure with reduced ejection fraction: Progress, not problem. Am J Med 2021; 134(9): 1068-70.
[] [PMID: 33939999]
Mullens W, Martens P, Testani JM, et al. Renal effects of guideline-directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2022; 24(4): 603-19.
[] [PMID: 35239201]
Rastogi T, Girerd N. SGLT2 inhibitors in heart failure with reduced ejection fraction. Heart Fail Clin 2022; 18(4): 561-77.
[] [PMID: 36216486]
Stretti L, Zippo D, Coats AJS, et al. A year in heart failure: An update of recent findings. ESC Heart Fail 2021; 8(6): 4370-93.
[] [PMID: 34918477]
Pölzl G, Allipour Birgani S, Comín-Colet J, et al. Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period. ESC Heart Fail 2019; 6(1): 174-81.
[] [PMID: 30378288]
Bavendiek U, Berliner D, Dávila LA, et al. Rationale and design of the DIGIT-HF trial (DIGitoxin to improve outcomes in patients with advanced chronic heart failure): A randomized, double-blind, placebo-controlled study. Eur J Heart Fail 2019; 21(5): 676-84.
[] [PMID: 30892806]
Bartunek J, Terzic A, Davison BA, et al. Cardiopoietic stem cell therapy in ischaemic heart failure: Long-term clinical outcomes. ESC Heart Fail 2020; 7(6): 3345-54.
[] [PMID: 33094909]
Mathiasen AB, Qayyum AA, Jørgensen E, et al. Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: A randomized placebo-controlled trial (MSC-HF trial). Eur Heart J 2015; 36(27): 1744-53.
[] [PMID: 25926562]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy