Long-term hemodynamic responses and reverse remodeling after pharmacotherapy in HFpEF versus HFrEF: a systematic review and meta-analysis

Aims: The acute response to therapeutic afterload reduction differs between heart failure with preserved (HFpEF) versus reduced ejection fraction (HFrEF), with larger left ventricular (LV) stroke work augmentation in HFrEF compared to HFpEF. This may (partially) explain the neutral effect of HFrEF-medication in HFpEF. It is unclear whether such differences in hemodynamic response persist and/or differentially trigger reverse remodeling in case of long-term afterload reduction. Methods and results: A systematic search was performed, identifying 21 clinical trials investigating renin-angiotensin-aldosterone system (RAAS) inhibitors, beta-blockers and sodium-glucose cotransport 2 inhibitors that report data on afterload reduction, stroke volume and reverse remodeling in HFpEF and/or HFrEF. In both HFpEF and HFrEF, meta-analyses revealed limited long-term change in systolic/diastolic blood pressure (-5.6/-3.2 and -4.6/-1.4 mmHg, respectively) and LV afterload reduction (arterial elastance: -0.039 and -0.055 mmHg/mL, respectively). Long-term treatment did not result in increase in stroke volume, with the exception of beta-blockers in HFrEF. Indexed LV mass decreased slightly in both HFpEF and HFrEF (-2.8 and -2.3 g/m2, respectively). In HFrEF, treatment reduced LV end-diastolic and end-systolic volume (-8 and -6 ml, respectively), whereas in HFpEF there was no relevant change. Conclusion: Contrary to acute heart failure studies, long-term afterload reduction had little effect on blood pressure and stroke volume augmentation in both HFpEF and HFrEF. On the other hand, reverse remodeling was clearly present in HFrEF, but was essentially absent in HFpEF.