Clinical and histopathological effects of heart failure drug therapy in advanced heart failure patients on chronic mechanical circulatory support

Abstract

Aims Adjuvant heart failure (HF) drug therapy in patients undergoing chronic mechanical circulatory support (MCS) is often used in conjunction with a continuous‐flow left ventricular assist device (LVAD), but its potential impact is not well defined. The objective of the present study was to examine the effects of conventional HF drug therapy on myocardial structure and function, peripheral organ function and the incidence of adverse events in the setting of MCS. Methods and results Patients with chronic HF requiring LVAD support were prospectively enrolled. Paired myocardial tissue samples were obtained prior to LVAD implantation and at transplantation for histopathology. The Meds group comprised patients treated with neurohormonal blocking therapy (concurrent beta‐blocker, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and aldosterone antagonist), and the No Meds group comprised patients on none of these. Both the Meds (n = 37) and No Meds (n = 44) groups experienced significant improvements in cardiac structure and function over the 6 months following LVAD implantation. The degree of improvement was greater in the Meds group, including after adjustment for baseline differences. There were no differences between the two groups in arrhythmias, end‐organ injury, or neurological events. In patients with high baseline pre‐LVAD myocardial fibrosis, treatment with HF drug therapy was associated with a reduction in fibrosis. Conclusions Clinical and histopathological evidence showed that adjuvant HF drug therapy was associated with additional favourable effects on the structure and function of the unloaded myocardium that extended beyond the beneficial effects attributed to LVAD‐induced unloading alone. Adjuvant HF drug therapy did not influence the incidence of major post‐LVAD adverse events during the follow‐up period.

Medical and mechanical unloading in advanced heart failure: hope for cardiac recovery?

“…In this issue of the Journal, Catino et al . present further evidence of the beneficial effects of neurohormonal blockade on cardiac structure and function during mechanical unloading with an LVAD . In their observational follow‐up study, the authors enrolled patients with chronic heart failure requiring LVAD support and compared patients who were treated with neurohormonal blocking therapy (concurrent beta‐blocker, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker or aldosterone antagonist) ( n = 37) with patients who were not treated with any of these agents ( n = 44).…”

“…Paired cardiac tissue samples from pre‐ and post‐LVAD unloading were available for a small subset of patients and were used to evaluate changes in cardiac fibrosis . The tissue was collected from the LV apical core at LVAD implantation and at heart explantation at the time of heart transplantation or during LVAD explantation.…”

Highlights in heart failure

“…Up to 26% of the patients with low LVEF and NYHA Class II-IV had a potential indication to LVAD and only half of them accepted the procedure once offered. 115 Infections and thromboembolic and haemorrhagic complications remain major causes of morbidity and mortality. 4, 113 In a retrospective study conducted in Spain on 291 patients listed for urgent heart transplantation, bridging with temporary LVAD was associated with more favourable outcomes than bridging with temporary biventricular assist Highlights in heart failure devices or venoarterial extracorporeal membrane oxygenation.…”

“…Treatment with neurohormonal antagonists was associated with a reduction in fibrosis. 115 Infections and thromboembolic and haemorrhagic complications remain major causes of morbidity and mortality. 113 Predictors of such adverse events, such as abnormalities in platelet activity, 116 are sought.…”

January 2018 at a glance: biomarkers, co‐morbidities and mechanical circulatory support

“…Catino et al . show that concomitant administration of HF treatment with neurohormonal antagonists is associated with a larger improvement in cardiac function and less fibrosis in HF patients on MCS.…”