Changes in Left Ventricular Ejection Fraction and Clinical Trajectories of Transthyretin Cardiac Amyloidosis with Systolic Dysfunction

Joshua Saef; Trejeeve Martyn; Anusha Ray Dey; Rola Khedraki; Lauren Ives; Patrick Collier; Wael A Jaber; Jerry D Estep; Mazen Hanna; Wai Hong Wilson Tang

doi:10.3390/jcm12237250

Changes in Left Ventricular Ejection Fraction and Clinical Trajectories of Transthyretin Cardiac Amyloidosis with Systolic Dysfunction

J Clin Med. 2023 Nov 23;12(23):7250. doi: 10.3390/jcm12237250.

Authors

Affiliations

¹ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
² Joe DiMaggio Children's Hospital and the Memorial Healthcare Total Heart Center, Hollywood, FL 33021, USA.
³ Department of Medical Science, Brown University, Providence, RI 02912, USA.
⁴ Division of Cardiology, Scripps Clinic and Research Foundation, La Jolla, CA 92037, USA.
⁵ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic Florida, Weston, FL 33331, USA.

Abstract

Background: Transthyretin cardiac amyloidosis (ATTR-CM) is classically thought of as a progressive disease with preserved systolic function. The longitudinal clinical trajectories of ATTR-CM with impaired left ventricular ejection fraction (LVEF) remain unclear.

Methods: This is a single-center retrospective cohort study of consecutive patients with ATTR-CM who underwent two or more echocardiograms with baseline LVEF < 50%. Patients were stratified according to the presence of ≥5% change in LVEF. A Cox proportional hazard model examined hazard of a composite outcome of death, transplant, or LVAD insertion over the two years following diagnosis.

Results: In our study cohort of 179 patients, 62 patients (34.6%) experienced an increase in LVEF while 33 (18.4%) experienced a decrease in LVEF. After adjusting for covariates, patients with a decrease in EF experienced increased hazard of death (HR 2.15, 95% CI 1.05-4.40, p = 0.038) compared to those with stable or an increase in LVEF. Changes in LVEF corresponded with significant differences in NT proBNP trajectories, but initial biomarker levels or clinical staging were not predictive of LVEF trajectory.

Conclusions: in ATTR-CM patients with impaired LVEF, over a third demonstrated improved LVEF over time, while those with a decrease in LVEF had worse long-term outcomes.

Keywords: Transthyretin amyloid cardiomyopathy; heart failure with reduced ejection fraction; prognosis; reverse remodeling.

Grants and funding

This research received no external funding. The Cleveland Clinic Amyloidosis Registry is supposed by M.H.’s Term Chair for Amyloid Heart Disease. J.S. is the recipient of the Karos Research Award for training in clinical investigation. T.M. is supported by a young investigator grant from Ionis Therapeutics Inc. related to amyloidosis research.