Conclusion
Coronary microvascular disease–HFpEF may be a distinct HFpEF endotype with coronary microvascular dysfunction being the underlying mechanism leading to impaired myocardial reserve. We have scrutinized the role of subendocardial ischaemia and impaired lusitropy in the development of CMD–HFpEF and have explored the challenges in demonstrating causality between CMD and HFpEF. We have also discussed the role of gender in CMD–HFpEF and have explored the limitations of the contemporary HFpEF therapeutic trials targeting the NO–cGMP–PKG pathway. Further longitudinal and mechanistic studies are required to verify the proposed mechanistic link between CMD and HFpEF. A better understanding of the common pathophysiology may pave the way for the development of therapeutic agents that can improve these patients' quality of life and cardiovascular outcomes.
Funding
The authors' work is supported by grants from the Medical Research Council (MR/T029390/1), British Heart Foundation (FS/16/49/32320, CH/1999001/11735, and RE/18/2/34213), the UK National Institute for Health Research (through the Biomedical Research Centre award to King's College London and Guy's and St Thomas' Hospital), and the Fondation Leducq.
Eur Heart J. 2021;42(43):4431-4441. © 2021 Oxford University Press
Copyright 2007 European Society of Cardiology. Published by Oxford University Press. All rights reserved.