LV Unloading and Myocardial Recovery: An Exciting Future in the Continuum of Remission to Recovery

At the 2^nd annual THT 2023 conference, experts discussed what’s known and what’s cooking in the area of left ventricular unloading and myocardial recovery.

Dr. Douglas Mann from Washington University School of Medicine in St. Louis set the stage with a ten-minute deep dive into the physiology of ventricular load. After a recall of the principles of the Frank-Starling curve for the audience, a discussion of the different molecular level signal transduction patterns that occur as a result of increasing load/stress of the myocytes eventually leading to cardiac hypertrophy, ensued. He elaborated upon the stretch activated pathways including Integrins, transient receptor potential (TRP) channels and sodium hydrogen exchanger (NHE) implicated in cardiac hypertrophy.

Dr. Stravos Drakos from University of Utah Health Sciences Center followed with a review of the results of the RESTAGE-HF trial challenging the prevailing dogma “The failing human heart cannot improve after severe injury”. Guided by predictors of response before LVAD implantation, myocardial recovery incidence of up to 50% is achievable! He emphasized that reverse remodelling after LVAD is not “all or none” with 10% being responders, 30% partial responders and 60% non-responders. He raised the important question of sustainability after LVAD weaning and presented data supporting this being comparable to post-transplant survival.

What about the implications of unloading in acute MI? Dr. Navin Kapur from Tufts Medical Center in Boston and the Cardiogenic Shock Working Group presented the results of the STEMI-DTU Pilot trial emphasizing a fascinating paradigm shift from door-to-balloon to door-to-unload in the management of acute MI patients showing safety and feasibility as well as promising reduction in infarct size and microvascular obstruction. The results of the ongoing pivotal trial will surely be exciting!

Next, Dr. Veli Topkara from Columbia University got to the GENES of the matter! Only a small proportion of heart failure (HF) mRNAs and differentially methylated DNA regions normalize after LVAD implantation; highlighting the reality that there is persistent dysregulation at the transcriptional level. This opens the door to possible transcriptional targets to achieve recovery.

The session was concluded by Dr. Jane Wilcox from Northwestern Medical Center in Chicago. She drew parallels (in terminology) with oncology by introducing concepts of HF remission and relapse. She alluded to the role of unloading when HF remission turns into HF relapse with the trial design of the Impella-BTR trial. Will temporary unloading serve as a platform for neurohormonal therapy for these patients? More to come on this.

These thrilling glimpses into the future drove a stimulating discussion by the panelists, Dr. Daniel Burkhoff, Dr. Jennifer Cowger and Dr. Robert Mentz along with the speakers on how much recovery would be considered enough, multi-center collaboration and shared decision making placing the patient at the center.

Dr. Sonu Abraham is a cardiology fellow at Lahey Hospital and Medical Center, Burlington, Massachusetts and served as a CardioNerds Conference Scholar for the 2023 Technology and Heart Failure Therapeutics (THT23).

References:

1. Kapur N, Moses J, Faraz H, et al. TCT-34 Reduction of Infarct Size in Anterior ST-Segment Elevation Myocardial Infarction (STEMI) With LAD Occlusion and LV Unloading Using a Micro-axial Pump for 30 Minutes Before PCI: Per-Protocol Analysis of the STEMI Door to Unload (DTU) Pilot Study. J Am Coll Cardiol. 2022 Sep, 80 (12_Supplement) B14–B15.
2. Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF) Emma J. Birks, Stavros G. Drakos, Snehal R. Patel et al. 2020;142:2016–2028
3. Reverse Remodeling with Left Ventricular Assist Devices. Daniel Burkhoff, Veli K. Topkara, Gabriel Sayer, Nir Uriel. Circulation Research. 2021;128:1594–1612
4. Use of the Impella BTR™ in Patients with Heart Failure: An Early Feasibility Study (BTR EFS). https://clinicaltrials.gov/ct2/show/NCT05291884