Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Bajaj NS

PROVIDER: S-EPMC7261557 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Bajaj Navkaranbir S NS Gupta Kartik K Gharpure Nitin N Pate Mike M Chopra Lakshay L Kalra Rajat R Prabhu Sumanth D SD

ESC heart failure 20200321 3

<h4>Aims</h4>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.<h4>Methods and results</h4>Pu ...[more]

PMID: 32198851

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Project description:AimsThis study aims to assess long-term changes in left ventricular ejection fraction (LVEF) together with echocardiographic markers of cardiac remodelling and their association with prognosis and patient-reported quality of life (QoL).Methods and resultsWe conducted a retrospective analysis of serial echocardiograms performed between January 2009 and December 2019 in 1089 patients (median age 63 years, 71.0% men) enrolled in the Mazankowski Heart Function Clinic Registry who had at least two echocardiograms separated by ≥12 months. We classified the patients into four subgroups by their baseline and LVEF trajectories: persistent heart failure with reduced ejection fraction (persistent HFrEF, n = 364), recovered ejection fraction (HFrecEF, n = 325), transient recovery in ejection fraction (HFtrecEF, n = 117), and preserved ejection fraction (HFpEF, n = 283); 4490 echocardiograms were included in the present analysis, with 4.1 ± 1.8 echocardiograms available per patient during follow-up. Reductions in echocardiographic markers of cardiac remodelling, including LVIDd [adjusted odds ratio (aOR): 2.22, 95% confidence interval (CI) 1.75-2.86], LVIDs (aOR: 2.44, 95% CI 2.00-2.94), left ventricular mass index (aOR: 1.15, 95% CI 1.09-1.22), E/e' ratio (aOR: 1.15, 95% CI 1.02-1.30), left atrial volume index (aOR: 1.10, 95% CI 1.03-1.16), along with an increase in the maximum recommended daily dose of renin-angiotensin system inhibitors (aOR: 1.04, 95% CI 1.01-1.07) and mineralocorticoid-receptor antagonists (aOR: 1.06, 95% CI 1.01-1.11) at 2 years, strongly predicted the HFrecEF classification, which was further sustained at 5 years of follow-up. However, changes in these parameters were mostly absent in patients experiencing only a transient recovery in LVEF (HFtrecEF), closely resembling patients with persistent HFrEF. In the multivariable analysis, HFrecEF patients had lower risk of all-cause mortality alone [adjusted hazard ratio (aHR): 0.46, 95% CI 0.23-0.93], and composite all-cause (aHR: 0.59, 95% CI 0.49-0.73), cardiovascular (aHR: 0.47, 95% CI 0.36-0.61), and heart failure (aHR: 0.50, 95% CI 0.35-0.70) related hospitalizations with mortality than patients with persistent HFrEF. QoL assessed through the shortened Kansas City Cardiomyopathy Questionnaire-12 at the end of follow-up was greater in patients with HFrecEF by 5.2, 12.4, and 9.4 points than persistent HFrEF, HFtrecEF, and HFpEF, respectively.ConclusionsPatients with HFrecEF experienced progressive normalization in echocardiographic markers of cardiac remodelling characterized by reductions in left ventricular dimensions and mass in tandem with reductions in left atrial volume and E/e' ratio, which is associated with better prognosis and QoL.

Dataset Information

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

Aims

Methods and results

Conclusions

Publications

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

Similar Datasets

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