Effects of early initiation of comprehensive heart failure therapy on echocardiographic parameters of young patients with newly diagnosed idiopathic dilated cardiomyopathy

Abstract

Introduction: Heart failure with reduced ejection fraction (HFrEF) is a growing problem worldwide and is associated with significant morbidity and mortality. Angiotensin receptor neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are now seen as disease modifying agents with growing evidence to support their early initiation in order to prolong lives of patients with HFrEF. However, most of these trials were conducted in the developed world involving older patients with ischaemic cardiomyopathies, in contrast to younger patients with idiopathic dilated cardiomyopathies (DCMO) typically seen in Africa. Further, these drugs are expensive and remain out of reach for most patients in the developing world. Purpose: To determine the effects of early initiation of comprehensive heart failure (HF) therapy consisting of ARNI, SGLT2-i, β-blocker and mineralocorticoid receptor antagonist on the clinical, laboratory, and transthoracic echocardiography (TTE) parameters of patients with newly diagnosed idiopathic DCMO. Methods: This is a retrospective cross-sectional study. All patients presenting to a single tertiary centre in South Africa between January and July 2021 with newly diagnosed idiopathic DCMO that were initiated on a regimen of comprehensive heart failure therapy as first line therapy were included. 6 minute walk test (6MWT), NT-proBNP and TTE were performed at initiation and at monthly follow up visits. Results: Eight patients (mean age 35.4±7 yrs, 25% females) were included. At baseline, the mean 6MWT distance was 396.9±74.9m, median NT-proBNP 1311.5 ng/L (IQR 292-2448), mean left ventricular ejection fraction (LVEF) was 17.1±3.2%, mean left ventricular end diastolic diameter (LVEDD) was 68.0±7.6mm, mean E' 4.0±1.9m/s, mean LV global longitudinal strain (GLS) -4.5±1.9%, mean LVOT VTI 10.9±3.2cm and mean TAPSE 14.3±4.1mm. After an average follow up period of 4 months (range 1-5 months), the mean 6MWT distance increased significantly to 478.1±80.7m (p = 0.01) and the median NT-proBNP decreased significantly to 57ng/L (IQR 20-512; p = 0.03). TTE performed at the latest follow up visit showed a significant increase in LVEF (21.3%; 95% CI 13.5-29.0; p = 0.01), average E' (2.5m/s; 95% 0.3-4.7; p = 0.05), GLS (-6.7%; 95% CI -1.0 - -8.9; p = 0.01), LVOT VTI (5.0cm; 95% CI 1.4-8.5; p = 0.03) and TAPSE (7mm; 95% CI 2.6-11.4; p = 0.02), and a significant reduction in LVEDD (6.5mm; 95% CI 1.1-11.9; p = 0.03). Conclusion: Early initiation of comprehensive HF therapy including ARNI and SGLT2-i is associated with significant improvements in clinical, laboratory and TTE parameters in a small cohort of young South African patients with newly diagnosed idiopathic DCMO. This supports the widespread adoption of this therapeutic strategy, even in a resource limited setting, in a population of patients with limited access to other therapeutic options such as mechanical circulatory support and cardiac transplantation.