Review of novel therapeutic targets for improving heart failure treatment based on experimental and clinical studies

Abstract

Heart failure (HF) is a major public health priority due to its epidemiological transition and the world’s aging population. HF is typified by continuous loss of contractile function with reduced, normal, or preserved ejection fraction, elevated vascular resistance, fluid and autonomic imbalance, and ventricular dilatation. Despite considerable advances in the treatment of HF over the past few decades, mortality remains substantial. Pharmacological treatments including β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists have been proven to prolong the survival of patients with HF. However, there are still instances where patients remain symptomatic, despite optimal use of existing therapeutic agents. This understanding that patients with chronic HF progress into advanced stages despite receiving optimal treatment has increased the quest for alternatives, exploring the roles of additional pathways that contribute to the development and progression of HF. Several pharmacological targets associated with pathogenesis of HF have been identified and novel therapies have emerged. In this work, we review recent evidence from proposed mechanisms to the outcomes of experimental and clinical studies of the novel pharmacological agents that have emerged for the treatment of HF.

Rapid Development of Targeting circRNAs in Cardiovascular Diseases

“…Use of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists showed prolonged survival of patients with HF and cardiac fibrosis. 55 , 57 Biomaterial-based approaches have preserved or improved cardiac function in MI patients. 57 There are also several ongoing clinical trials for novel biomaterials (hydrogels) and regenerative medicine (autologous stem-cell sheet).…”

<p>Impact of Sacubitril/Valsartan on Patient Outcomes in Heart Failure: Evidence to Date</p>

“…17 Therefore, the neprilysin inhibitors also potentiate vasoconstrictors like angiotensin II as well as vasodilators, thereby neutralizing any beneficial effects. 18 To resolve this dilemma, the OVERTURE (Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events) trial comparing combination omapatrilat (NEPI)enalapril (ACEI) with enalapril showed a modest reduction in heart failure hospitalizations in chronic HF patients with the combination drug; however, the greater frequency of angioedema compared to enalapril alone limited the benefits of the NEPI-ACEI. 19…”

“… 17 Therefore, the neprilysin inhibitors also potentiate vasoconstrictors like angiotensin II as well as vasodilators, thereby neutralizing any beneficial effects. 18 …”

Modern approaches to treatment of patients with decompensated chronic heart failure: the role of inflammation in the pathogenesis of decomposition

“…Выявлено много биологических активных молекул -маркеров, демонстрирующих значение воспаления в прогрессировании синдрома ХСН. Определены наиболее значимые сывороточные маркеры, отражающие активность воспаления (С-реактивный белок, фактор некроза опухоли альфа, интерлейкин-6 и С-концевая часть провазопрессина (копептин)), гемодинамического стресса (хромогранин А, адреномедуллин, ST2, предсердный (ANP), мозговой натрийуретический пептид (BNP) и N-термальный мозговой натрийуретический пропептид (NT-pro-BNP), фиброза миокарда (пропептид проколлинатного типа I (PINP), матриксные металлопротеиназы (MMP-2, MMP-8), тканевый ингибитор MMP-4 и N-концевой пропептид III коллагена III (PIIINP)) [22,23]. Однако, несмотря на достигнутые успехи поиска новых ключевых звеньев патогенеза и потенциальных терапевтических мишеней, влияние на которые позволило бы изменить клиническую ситуацию относительно частоты декомпенсации, следует констатировать факт, что частота госпитализаций по поводу декомпенсации ХСН остается высокой.…”