Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature

Navkaranbir S. Bajaj, Kartik Gupta, Nitin Gharpure, Mike Pate, Lakshay Chopra, Rajat Kalra, Sumanth D. Prabhu

Research output: Contribution to journalArticlepeer-review


Aims: Immunomodulation in heart failure (HF) has been studied in several randomized controlled trials (RCTs) with variable effects on cardiac structure, function, and outcomes. We sought to determine the effect of immunomodulation on left ventricular ejection fraction (LVEF), LV end-diastolic dimension (LVEDD), and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF) through meta-analyses and trial sequential analyses (TSAs) of RCTs. Methods and results: PubMed, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov were systematically reviewed to identify RCTs that studied the effects of immunomodulation in patients with HFrEF. The primary endpoint in this analysis was change in LVEF. Secondary outcomes were changes in LVEDD and all-cause mortality. TSA was used to quantify the statistical reliability of data in the cumulative meta-analyses. Nineteen RCTs with 1341 HFrEF subjects were eligible for analyses. The aetiology of HF, specific immunomodulation strategy, and treatment duration were variable across trials. Immunomodulation led to a greater improvement in LVEF [mean difference: +5.7% 95% confidence interval (CI): 3.0–8.5%, P < 0.001] and reduction in LVEDD (mean difference: −3.7 mm, 95% CI: −7.0 to −0.4 mm, P = 0.028) than no immunomodulation in meta-analyses and TSAs. We observed a non-significant decrease in all-cause mortality among those on immumomodulation (risk ratio: 0.7, 95% CI: 0.4–1.3, P = 0.234), but the Z-curve for cumulative treatment effect of immunomodulation in the TSA did not cross the boundary of futility. Conclusions: Immunomodulation led to improved cardiac structure and function in patients with HFrEF. While these benefits did not translate into a significant improvement in mortality, our analysis suggests that larger studies of targeted immunomodulation are needed to understand the true benefits.

Original languageEnglish (US)
Pages (from-to)1319-1330
Number of pages12
JournalESC Heart Failure
Issue number3
StatePublished - Jun 1 2020

Bibliographical note

Funding Information:
Dr. Bajaj is supported by Walter B. Frommeyer, Jr. Fellowship in Investigative Medicine awarded by the University of Alabama at Birmingham, American College of Cardiology Presidential Career Development Award, and National Center for Advancing Translational Research of the National Institutes of Health under award number UL1TR001417. Dr. Prabhu is supported by NIH-NHLBI R01 grants HL125735 and HL147549 and a Department of Veterans Affairs?VA Merit Award I01 BX002706.The content of the manuscript does not necessarily represent the views of NIH, VA, ACC and/or UAB.

Publisher Copyright:
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology


  • Anti-cytokine therapy
  • Heart failure
  • Immunomodulation
  • Inflammation
  • Left ventricular ejection fraction

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Review


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