Episode #50: Inside the RESOLVE-HCM Trial: A New Approach to Non-Obstructive HCM

In this episode of BeatWise The Podcast, I am joined by Professor Joseph Selvanayagam to explore cardiac metabolism in hypertrophic cardiomyopathy (HCM), the evolving treatment landscape in HCM, and the findings of the RESOLVE-HCM trial investigating perhexiline in non-obstructive disease.We explore the heterogeneity of HCM, including the differences between obstructive and non-obstructive forms of the condition, why symptoms are not always explained by LV outflow tract obstruction alone, and how treatment strategies are beginning to move beyond symptom management toward disease-modifying therapies.We also discuss the role of myocardial energetics and metabolic dysfunction in HCM, how perhexiline works as a CPT1 inhibitor to shift myocardial metabolism toward more oxygen-efficient glucose use, and why this may be particularly relevant in non-obstructive HCM where treatment options remain limited.Professor Selvanayagam takes us inside the design of the randomized, double-blind RESOLVE-HCM trial, including the use of cardiac MRI imaging and maximal LV wall thickness as the primary endpoint over 12 months. We review the trial findings, where several endpoints including diastolic function, NT-proBNP, and quality-of-life measures favored perhexiline, with mental health quality-of-life outcomes reaching statistical significance.We also explore the importance of therapeutic drug monitoring given perhexiline’s narrow therapeutic index, the risks of hepatotoxicity and neurotoxicity, and the future direction of metabolic therapies in cardiomyopathy.Key topics discussed: Obstructive vs non-obstructive HCMWhat drives symptoms in hypertrophic cardiomyopathyThe evolution of HCM therapiesCardiac metabolism and myocardial energeticsHow perhexiline worksThe RESOLVE-HCM trialCardiac MRI endpoints in HCM researchTherapeutic drug monitoring and safetyDisease-modifying therapies in cardiomyopathyEPISODE HIGHLIGHTS:00:00 Welcome to Beatwise00:27 Why metabolism matters01:59 Meet Professor Selvanayagam02:29 HCM types and symptoms04:29 Treatment landscape update05:42 Why RESOLVE-HCM07:20 How perhexiline works08:44 Trial design and imaging12:53 RESOLVE-HCM results14:43 Clinical use and safety17:15 Future trials and wrap up18:54 Final takeawaysIf you enjoyed this episode, please like, rate, and subscribe to Beatwise The Podcast. Your support helps me reach more listeners and continue providing valuable content.Don't forget to follow me on social media @sarah.theheartdoc for the latest updates, behind-the-scenes content, and more engaging discussions. Stay connected and be part of our growing community! Hosted on Acast. See acast.com/privacy for more information.