Table of content
Volume 1 | Issue 1
Underlying Disease – Specific Heart Failure Treatment
Department of Cardiology, Ubbo Emmius Hospital Norden, Germany
*Corresponding author: Prof. Dr. med. Stefan Peters, Chair Cardiology, UbboEmmius Hospital Norden, Osterstr 110, 26506 Norden, Germany, Tel: +49-94131-181-435, E-mail: H.u.S.Peters@t-online.de
Citation: Peters S (2021) Underlying Disease – Specific Heart Failure Treatment. Cardiol Cases Syst Rev 3:009.
Copyright © Peters S.
Acute or chronic heart failure is one of the most important entites among cardiac diseases. The treatment of heart failure become to be more and more disease - specific as new treatment options develop over time. Heart failure can occur due to ischemic cardiomyopathy, non-ischemic cardiomyopathy like specific forms of cardiomyopathies like dilated, hypertrophic, restrictive and arrhythmogenic one and special cardiomyopathies like acquired takotsubo cardiomyopathy.
Hypertrophic cardiomyopathy is characterized by the risk of sudden cardiac death and developing heart failure. Beneath therapeutic options like beta blocking agents, verapamil, surgical myectomy and septal ablation therapy a new pharmacologic agent is on the horizon: Mavacamten. Approval of mavacamten is supposed in the first period of 2021.
Beneficial effects of mavacamten can be considered for hypertrophic obstructive disease  and also for hypertrophic non-obstructive cardiomyopathy . Especially for hypertrophic non-obstructive cardiomyopathy new options like ranolazin failed.
Arrhythmogenic cardiomyopathy is characterized by fibro fatty replacement of myocytes. Fibrosis is the main feature causing ventricular arrhythmias, the risk of sudden cardiac death and progressive heart failure . In order to prevent fibrosis ramipril is tested in the BRAVE study still waiting for the results . The combination of valsartan and sacubitril had beneficial effects on soluable ST2  and should be tested in a next step.
In phosphohlamban mutations leading to dilated cardomyopathy or arrhythmogenic cardiomyopathy the compound of fibrosis in higher than in plakophilin-2 mutations . Neither mineralocorticoid antagonists nor beta blocking agents are able to prevent fibrosis . A study to assess the effect of eplerenon has been started at the University Hospital of Groningen, The Netherlands, to test the hypothesis, whether eplerenon is more effective than spironon lacton . Newer non-mineralocorticoid agents, called finerenon, should be tested as a next step. To use entresto should be a further attempt.
Cardiac amyloidosis is characterized by fibril deposition in the myocardium which leads to structural and functional abnormalities and heart failure. Amyloid cardiomyopathy can lead to aortic valve dysfunction and pericardial effusion . Cardiac light-chain amyloidosis and here ditary or wild-type transthyretin amyloidos is are the most prevalent forms of amyloid cardiomyopathy . In transthyretin amyloid cardiomyopathy the amyloid stabilizer tafamidis leads to a significant reduction of mortality and cardiovascular morbidity . Neurologic complications can be significantly reduced by patisiran and inotersen [12,13]. The question is whether these two drugs are effective in heart disease, too. Studies are started.
Fabry disease is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of α-galactosidase . Available therapies for fabry disease include enzyme replacement therapy agalsidase alfa and agalsidase beta  and the chaperone migalastat .
Dilated Cardiomyopathy and Ischemic Cardiomyopathy
The by far largest group of heart failure patients are the group of ischemic cardiomyopathy and dilated cardiomyopathy. Therapeutic improvements are obtained by ACE inhibitorsor AT1 recept or blockers , beta blocking agents , mineralocorticoid antagonists , the combination of valsartan and sacubitril (entresto)  and the relatively newly developed sodium-glucose cotransporter (SGLT2) inhibitors [21,22]. In dramatically reduced ejection fraction a rather low, but significant effect can be obtained by omecamtiv mecarbil  and danicamtiv . Vericiguat, an oral soluble guanylate cyclase stimulator, reduced the composite end point of cardiovascular deathor HF hospitalization vs. placebo .
In 2021 a new guideline for the treatment of heart failure is planned from the European Society of Cardiology suggesting the use of SGLT 2 inhibitors, empaglifocin and dapaglifocin, which reduce mortality and morbidity in heart failure.
A major problem is to treat heart failure with preserve dejection fraction, a problem which is revelant for at least 60% of cases. Spironolacton and sacubitril/valsartan just missed significant results. Ejection fractions between 50 to 57% and women, in general, had significant results. The guideline update should include these changes, too.
Both the diagnosis and treatment of heart failure with preserve dejection fraction, as well as management of advanced HF and acute HF, remain challenging.
- Olivotto I, Oreziak A, Barriales-Vitta R, et al. (2020) Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy /EXPLORER-HCM): A randomised, double-blind, placebo-controlle, phase 3 trial. Lancet 396: 759-769.
- Ho CY, Mealiffe ME, Bach RG, et al. (2020) Evaluation of mavacamten in symptomatic patients non obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 75: 2649-2660.
- Maione AS, Pilato CA, Casella M, et al. (2020) Fibrosis in arrhythmogenic cardiomyopathy: The Phantom Thread in the fibro-adipose tissue. Front Physiol 11: 279.
- Mose E, Manati AW, Nony P, et al. (2018) Blockade of the renin-angiotensin-aldosterone system in patients with arrhythmogenic right ventricular dysplasia: A double-blind, multicenter, prospective, randomised, genotype-driven study (BRAVE study). Clin Cardiol 41: 300-306.
- O’Meara E, Prescott MF, Clagett B, et al. (2018) Serum soluable ST2 measurements in patients with heart failure and a reduce dejection fraction in the PARADIGM-HF trial. Circ Heart Fail 11: e004446.
- Sepekhrhouy S, Gho JMIH, van Es R, et al. (2017) Dinstinct fibrosis pattern in dsemosomal and phospholamban mutation carriers in hereditary cardiomyopathies. Heart Rhythm 14: 1024-1032.
- Eijgenraam EM, Boukens BJ, Boogerd CJ, et al. (2020) The phospholambanp.(Arg 14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy. Sci Rep 10: 9819.
- Te Rijdt WP, Hoorntje ET, de Brouwer R, et al. (2021) Rationale and design of the PHO spholamban Related CArdiomyopathy intervention Study (i-PHORECAST). Neth Heart J.
- Eriksson P, Eriksson A, Eriksson S, et al. (1987) Differentiation of cardiac amyloidosis with polyneuropathy and hyper trophic cardiomyopathy by electrocardiography and echocardiography. Acta Med Scand 221: 39-46.
- Chatzantonis G, Bietenbeck M, Elsanhoury A, et al. (2021) Diagnostic value of cardiovascular magnetic resonance in comparison the endomyocardial biopsy in cardiacamyloidosis: A multi-centre study. Clin Res Cardiol 110:555-568.
- Lamb YN (2021) Tafamidis: A review in transthyretin amyloid cardiomyopathy. Am J Cardiovasc Drugs 21: 113-121.
- Fontana M, Martinez-Naharro A, Chacko L, et al. (2021) Reduction in CMR derives extracellular volume with patisiran indicates cardiac amyloid regression. JACC Cardiovasc Imaging 14: 189-199.
- Varga C, Dorbala S, Lousada I, et al. (2020) The diadnostic challenges of cardiac amyloidosis: A practical approach to the two main types. Blood 45: 100720.
- Yang K, Wie MD, Chen XY, et al. (2021) Anderson-Fabry disease: A rare phenocopy of hypertrophic cardiomyopathy. Eur Heart J Cardiovasc Imaging 22: e94.
- Dutra-Clarke M, Tapia D, Curtin E, et al. (2020) Vasiable clinical features of patients with fabry disease and outcome of enzyme replacement therapy. Mol Genet Metab Rep 26: 100700.
- Azevedo O, Gago MF, Miltenberger-Miltenyi G, et al. (2020) Fabry disease therapy: State-of-the-Art and current challenges. Int J Mol Sci 22: 206.
- Cody RJ, Covit AB, Schaer GL, et al. (1983) Evaluation of a long-acting conventing enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure. J Am Coll Cardiol 1: 1154-1159.
- Kelly DT (1993) Carvediol in heart failure. Cardiology 82: 345-349.
- Serenelli M, Jackson A, Dewan P, et al. (2020) Mineralocorticoid receptor antagonists, blood pressure, and outcomes in heart failure with reduced ejection fraction. JACC Heart Fail 8: 188-198.
- Solomon SD, Clagett B, Desai AS, et al. (2016) Influence of ejection fraction on outcomes and efficacy of sacubitril/valsartan (LCZ 696) in heart failure with reduced ejection fracrtion: The prospective comparison of ARNI and ACEI to determine impact on global mortality and morbidity in heart failure (PARADIM-HF) trial. Circ Heart Fail 9: e002744.
- Butler J, Anker SD, Filippatos G, et al. (2021) Empagliflocin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: The EMPEROR-reduced trial. Eur Heart J 42: 1203-1212.
- Yeoh SE, Dewan P, Jhund PS, et al. (2020) Patients characteristics, clinical outcomes, and effect of dapagliflocin in relation of duration of heart failure: Is it ever too late to start a new therapy? Circ Heart Fail 13: e007879.
- Teelink JR, Diaz R, Felker GM, et al. (2020) Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med 384: 105-116.
- Voors AA, Tamby JF, Cleland JG, et al. (2020) Effects of danicamtiv, a novel cardiacmyosin activator, in heart failure with reduced ejection fraction: Experimental data and clinical results from a phase 2a trial. Eur J Heart Fail 22: 1649-1658.
- Lam CSP, Gizewska A, Sliwa K, et al. (2020) Clinical outcomes and response to vericiguat according to index heart failure event: Insights from the VICTORIA trial. JAMA Cardiol 6: 706-712.