Propensity Score Analysis of Possible Medication Effects on Outcomes in Patients With Systemic Right Ventricles

Amrit Misra; Carla P Rodriguez-Monserrate; Kimberlee Gauvreau; Mikael Dellborg; Flavia Fusco; Tripti Gupta; Joseph Kay; Shelby Kutty; Robert M Kauling; Jeremy Nicolarsen; Jolien Roos-Hesselink; Anitha S John; Joshua Wong; Luke J Burchill; Eric V Krieger; Adam M Lubert; Pastora Gallego; Marissa Kuo; Jamil Aboulhosn; Jonathan Cramer; Petra Antonova; David Baker; Payam Dehghani; Alexander R Opotowsky; Alexandra van Dissel; Jasmine Grewal; Elizabeth Yeung; Susan Fernandes; Salil Ginde; Paul Khairy; Frank Han; Isabelle Vonder Muhll; William M Wilson; William Aaron Kay; Stephen Pylypchuk; Berardo Sarubbi; Clare O'Donnell; Fred Rodriguez 3rd; Pavithra S Jayadeva; David S Celermajer; Sangeeta Shah; Timothy Cotts; Christopher DeZorzi; Anthony Magalski; Anne Marie Valente; Craig S Broberg

doi:10.1016/j.jacadv.2024.101443

Propensity Score Analysis of Possible Medication Effects on Outcomes in Patients With Systemic Right Ventricles

JACC Adv. 2024 Dec 13;4(1):101443. doi: 10.1016/j.jacadv.2024.101443. eCollection 2025 Jan.

Authors

Amrit Misra¹, Carla P Rodriguez-Monserrate¹, Kimberlee Gauvreau², Mikael Dellborg³, Flavia Fusco⁴, Tripti Gupta⁵, Joseph Kay⁶, Shelby Kutty⁷, Robert M Kauling⁸, Jeremy Nicolarsen⁹, Jolien Roos-Hesselink^{8

10}, Anitha S John¹¹, Joshua Wong¹², Luke J Burchill¹², Eric V Krieger¹³, Adam M Lubert¹⁴, Pastora Gallego^{10

15}, Marissa Kuo¹⁶, Jamil Aboulhosn¹⁷, Jonathan Cramer¹⁸, Petra Antonova¹⁹, David Baker²⁰, Payam Dehghani²¹, Alexander R Opotowsky¹⁴, Alexandra van Dissel²², Jasmine Grewal²³, Elizabeth Yeung⁶, Susan Fernandes²⁴, Salil Ginde²⁵, Paul Khairy²⁶, Frank Han²⁷, Isabelle Vonder Muhll²⁸, William M Wilson¹², William Aaron Kay²⁹, Stephen Pylypchuk²⁸, Berardo Sarubbi⁴, Clare O'Donnell³⁰, Fred Rodriguez 3rd¹⁶, Pavithra S Jayadeva³¹, David S Celermajer²⁰, Sangeeta Shah³², Timothy Cotts³³, Christopher DeZorzi³⁴, Anthony Magalski³⁴, Anne Marie Valente¹, Craig S Broberg³⁵

Affiliations

¹ Boston Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Adult Congenital Heart Disease Unit, Monaldi Hospital, Napoli, Italy.
⁵ Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁶ Colorado Adult and Teen Congenital Heart (C.A.T.C.H.) Program, Colorado University School of Medicine, Denver, Colorado, USA.
⁷ Helen B. Taussig Heart Center, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
⁸ Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.
⁹ Providence Adult and Teen Congenital Heart Program, Providence Spokane, Spokane, Washington, USA.
¹⁰ European Reference Network for Rare, Low Prevalence and Complex Disease of the Heart- ERN-Guard Heart, Amsterdam, the Netherlands.
¹¹ Division of Pediatric Cardiology, Children's National Hospital, Washington, DC, USA.
¹² Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia.
¹³ University of Washington Medical Center and Seattle Children's Hospital, Seattle, Washington, USA.
¹⁴ Cincinnati Children's Hospital Medical Center, Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹⁵ Adult Congenital Heart Disease Unit, Hospital Universitario Virgen Del Rocio, Sevilla, Spain.
¹⁶ Division of Cardiology, Department of Medicine, Emory University Hospital, Atlanta, Georgia, USA.
¹⁷ Division of Cardiology, Department of Medicine, Ahmanson/UCLA Adult Congenital Heart Disease Center, UCLA Medical Center, Los Angeles, California, USA.
¹⁸ Children's Hospital, Omaha & University of Nebraska Medical Center, Omaha, Nebraska, USA.
¹⁹ Department of Cardiovascular Surgery, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic.
²⁰ Department of Cardiology, University of Sydney and Royal Prince Alfred Hospital, Sydney, Australia.
²¹ Department of Cardiology, Regina General Hospital, Regina, Saskatchewan, Canada.
²² Division of Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands.
²³ St.Paul's Hospital, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada.
²⁴ Stanford University, School of Medicine, Departments of Pediatrics and Medicine, Palo Alto, California, USA.
²⁵ Division of Cardiology, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
²⁶ Department of Medicine, Montreal Heart Institute, Montreal Heart Institute, Montreal, Quebec, Canada.
²⁷ Department of Cardiology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
²⁸ Internal Medicine/Cardiology, University of Alberta, Edmonton, Alberta, Canada.
²⁹ Division of Cardiology, Krannert Institute of Cardiology, Indianapolis, Indiana, USA.
³⁰ Green Lane Paediatric and Congenital Cardiac Service, Auckland City Hospital, Auckland, New Zealand.
³¹ Peter Munk Cardiac Center, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada.
³² Ochsner Medical Center, New Orleans, Los Angeles, USA.
³³ Division of Cardiology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
³⁴ Division of Cardiology, Saint Luke's Mid America Heart Institute Hospital, Kansas City, Missouri, USA.
³⁵ Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA.

Abstract

Background: Patients with systemic right ventricle (SRV), either d-transposition of the great arteries following an atrial switch procedure or congenitally corrected transposition of the great arteries, develop severe right ventricular dysfunction, prompting appropriate medical therapy. However, the efficacy of beta-blockers and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (ACEI) in SRV patients is unproven.

Objectives: The objective of this study was to determine the effects of ACEI/ARB and beta-blockers on outcomes in SRV patients after accounting for likely cofounders affecting their use.

Methods: From a retrospective, multicenter study on heart failure-related outcome in individuals with SRV, those who were taking an ACEI/ARB, beta-blocker, or both of these medication were identified. We performed a propensity analysis to match them to those not using these medications at their initial visit. Matching was based on a propensity score, which captured co-morbidities, demographics, and baseline echocardiographic parameters. Primary outcome of death, transplant, or mechanical circulatory support, and secondary outcomes of heart failure hospitalizations/atrial arrhythmias were analyzed respectively.

Results: We identified 393 patients taking ACEI/ARB or beta-blocker, or taking both a beta-blocker and ACEI/ARB (62.1% male, median age 31.3 years) and 484 patients (56.4% male, median age of 26.0 years) who were neither on a beta-blocker nor on ACEI/ARB at the time of initial clinic visit. Median follow-up was ∼8 years. After propensity matching, medication use was not associated with decreased mortality, heart failure hospitalizations, or arrhythmias. Hazard ratios remained positive for beta blockers, implying potential harm rather than benefit.

Conclusions: In this large multicenter propensity-matched observational study, patients with SRV taking beta-blockers or ACEI/ARB did not have a benefit in survival or reduced hospitalization. The likelihood of demonstrating favorable effects in larger studies appears remote.

Keywords: congenital heart diseas; congestive heart failure; systemic right ventricle; transposition of the great arteries.