Cardiac Reverse Remodeling in Ischemic Heart Disease with Novel Therapies for Heart Failure with Reduced Ejection Fraction

Abstract

Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients.

Keywords: heart failure; ischemic heart disease; left ventricular remodeling; myocardial infarction.

Figure 1

Mechanisms involved in the appearance and progression of cardiac remodeling in IHD. ROS, reactive oxygen species.

Figure 2

Novel HFrEF strategies with a potential role in IHD reverse remodeling. ARNI, angiotensin receptor neprilysin inhibitor; CRT, cardiac resynchronization therapy; EF, ejection fraction; LBBB, left bundle branch block; HF, heart failure; OM, omecamtiv mecarbil; SGLT2i, sodium-glucose co-transporter 2 inhibitors.

Figure 3

Major trials of novel HFrEF strategies and trials that evaluate these therapies in IHD. ARNI, angiotensin receptor neprilysin inhibitor; SGLT2i, sodium-glucose co-transporter 2 inhibitor; OM, omecamtiv mecarbil; CRT, cardiac resynchronization therapy; BAT, baroreflex activation therapy; CCM, cardiac contractility modulation.