Impact of procedural variability and study design quality on the efficacy of cell-based therapies for heart failure - a meta-analysis

Background Cell-based therapy has long been considered a promising strategy for the treatment of heart failure (HF). However, its effectiveness in the clinical setting is now doubted. Because previous meta-analyses provided conflicting results, we sought to review all available data focusing on cell type and trial design. Methods and findings The electronic databases PubMed, Cochrane library, ClinicalTrials.gov, and EudraCT were searched for randomized controlled trials (RCTs) utilizing cell therapy for HF patients from January 1, 2000 to December 31, 2020. Forty-three RCTs with 2855 participants were identified. The quality of the reported study design was assessed by evaluating the risk-of-bias (ROB). Primary outcomes were defined as mortality rate and left ventricular ejection fraction (LVEF) change from baseline. Secondary outcomes included both heart function data and clinical symptoms/events. Between-study heterogeneity was assessed using the I2 index. Subgroup analysis was performed based on HF type, cell source, cell origin, cell type, cell processing, type of surgical intervention, cell delivery routes, cell dose, and follow-up duration. Only 10 of the 43 studies had a low ROB for all method- and outcome parameters. A higher ROB was associated with a greater increase in LVEF. Overall, there was no impact on mortality for up to 12 months follow-up, and a clinically irrelevant average LVEF increase by LVEF (2.4%, 95% CI = 0.75−4.05, p = 0.004). Freshly isolated, primary cells tended to produce better outcomes than cultured cell products, but there was no clear impact of the cell source tissue, bone marrow cell phenotype or cell chricdose (raw or normalized for CD34+ cells). A meaningful increase in LVEF was only observed when cell therapy was combined with myocardial revascularization. Conclusions The published results suggest a small increase in LVEF following cell therapy for heart failure, but publication bias and methodologic shortcomings need to be taken into account. Given that cardiac cell therapy has now been pursued for 20 years without real progress, further efforts should not be made. Study registry number This meta-analysis is registered at the international prospective register of systematic reviews, number CRD42019118872.

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Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials

BioMed Research International ◽

10.1155/2017/6274854 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 16

Author(s):

Xiaolong Song ◽

Huiyan Qu ◽

Zongguo Yang ◽

Jingfeng Rong ◽

Wan Cai ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Serum Levels ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cochrane Library ◽

Controlled Trials ◽

Randomized Controlled

Background. Whether additional benefit can be achieved with the use of L-carnitine (L-C) in patients with chronic heart failure (CHF) remains controversial. We therefore performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of L-C treatment in CHF patients. Methods. Pubmed, Ovid Embase, Web of Science, and Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese Biomedical (CBM) database, and Chinese Science and Technology Periodicals database (VIP) until September 30, 2016, were identified. Studies that met the inclusion criteria were systematically evaluated by two reviewers independently. Results. 17 RCTs with 1625 CHF patients were included in this analysis. L-C treatment in CHF was associated with considerable improvement in overall efficacy (OR = 3.47, P<0.01), left ventricular ejection fraction (LVEF) (WMD: 4.14%, P=0.01), strike volume (SV) (WMD: 8.21 ml, P=0.01), cardiac output (CO) (WMD: 0.88 L/min, P<0.01), and E/A (WMD: 0.23, P<0.01). Moreover, treatment with L-C also resulted in significant decrease in serum levels of BNP (WMD: −124.60 pg/ml, P=0.01), serum levels of NT-proBNP (WMD: −510.36 pg/ml, P<0.01), LVESD (WMD: −4.06 mm, P<0.01), LVEDD (WMD: −4.79 mm, P<0.01), and LVESV (WMD: −20.16 ml, 95% CI: −35.65 to −4.67, P<0.01). However, there were no significant differences in all-cause mortality, 6-minute walk, and adverse events between L-C and control groups. Conclusions. L-C treatment is effective for CHF patients in improving clinical symptoms and cardiac functions, decreasing serum levels of BNP and NT-proBNP. And it has a good tolerance.

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Xinmailong Injection for Improvement of Cardiac Function in Patients with Heart Failure: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6131525 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yuan-long Sun ◽

Yi-ping Li ◽

Ting-ting Qiang ◽

Xiao-fen Ruan ◽

Xiao-long Wang

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Periplaneta Americana ◽

Meta Analysis ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cochrane Library ◽

Ventricular Ejection Fraction ◽

Patients With Heart Failure ◽

Potential Factor

Background. Insect drugs have great potential for treating cardiovascular diseases. Xinmailong (XML) injection, a bioactive composite extracted from Periplaneta americana (a species of cockroach), was wildly used in treating heart failure in China. This meta-analysis aimed to assess the efficacy and safety of XML injection for the improvement of cardiac function in HF. Materials and Methods. Online literature search for relevant studies was performed using databases including PubMed, EMBASE, Cochrane Library, CNKI, and Wanfang. Left ventricular ejection fraction (LVEF), six-minute walk test (6MWT), and brain natriuretic peptide (BNP) were selected as target outcomes. The analysis was performed using Stata 12.0, and sources of heterogeneity were explored by subgroup analysis and metaregression. Results. 32 studies were included in this meta-analysis after meeting the inclusion/exclusion criteria. The results demonstrated that additional use of XML improved LVEF (WMD = 5.82, 95% CI: 5.52–7.13, P < 0.00001 ) and 6MWT (WMD = 51.48, 95% CI: 35.83–67.13, P < 0.00001 ) and reduced BNP (WMD = −172.84, 95% CI: −205.79 to −139.89, P < 0.00001 ). The results of subgroup analyses and metaregression suggested that XML injection has more cardiac function improvement for middle-aged HF patients than youth, and greater LVEF and 6MWT improvement were associated with higher average age. Conclusions. XML plus conventional treatment demonstrated a significant effect in reducing cardiac dysfunction in HF patients, and age is a potential factor of higher efficacy. Given the heterogeneity and bias of the included RCTs, large, prospective, rigorous trials are still needed.

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Abstract 17223: Castle of Stone or Straw, Radiofrequency Ablation of Atrial Fibrillation in Heart Failure?

Circulation ◽

10.1161/circ.138.suppl_1.17223 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Brian D McCauley ◽

Esseim Sharma ◽

John Dudley ◽

Antony Chu

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Catheter Ablation ◽

Sinus Rhythm ◽

Meta Analysis ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Prospective Trials

Introduction: Based on the data from CASTLE-AF trial, in patient with Atrial Fibrillation (AF) and heart failure (HF) catheter ablation may offer a significant reduction in both death, and hospitalization, while promoting maintenance of sinus rhythm as well as improvement in left ventricular ejection fraction (LVEF). This multi-center randomized trial is hailed as a paradigm shifting study in catheter ablation, however it is not without fault. One of the critiques of the CASTLE-AF trial was the high frequency of crossover between the treatment arms. To help sort out this potential source of confounding, we performed a systematic meta-analysis of prospective trials for catheter ablation in AF in patients with Class II through IV heart failure. Hypothesis: The reduction in death, and hospitalization, as well as the maintenance in sinus rhythm and improvement in LVEF seen CASTLE-AF trial are support by other similarly designed AF ablation trials. Methods: Using the inclusion/exclusion criteria from the CASTLE-AF trial, we performed a systematic meta-analysis of 28 published studies. Randomized and non-randomized observational studies comparing the impact of catheter ablation of AF in HF. Studies were identified using the Cochrane Library, EMBASE, and PubMed. Results: A total of 29 studies were identified (n =2,339). Mean follow-up was 25 (95% confidence interval, 18-40) months. Efficacy in maintaining sinus rhythm at follow-up end was 60% (43%-76%). Left ventricular ejection fraction improved significantly during follow-up by 15% (P<0.001). Conclusions: Following our meta-analysis, we found data to support the findings of improved LVEF and maintenance of sinus rhythm reported in the CASTLE-AF trial. However, due to differences in study design, we were unable to further validate the reduction in both hospitalization and death seen in CASTLE-AF. We recommend future prospective trials be conducted without cross over to further explore this topic.

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Effect of ivabradine in heart failure: a meta-analysis of heart failure patients with reduced versus preserved ejection fraction

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0700 ◽

2021 ◽

pp. 1-16

Author(s):

Noémi Tóth ◽

Alexandra Soós ◽

Alex Váradi ◽

Péter Hegyi ◽

Benedek Tinusz ◽

...

Keyword(s):

Heart Failure ◽

Heart Rate ◽

Clinical Trials ◽

Ejection Fraction ◽

Meta Analysis ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cochrane Library ◽

Preserved Ejection Fraction ◽

Ventricular Performance

In clinical trials of heart failure reduced ejection fraction (HFrEF), ivabradine seemed to be an effective heart rate lowering agent associated with lower risk of cardiovascular death. In contrast, ivabradine failed to improve cardiovascular outcomes in heart failure preserved ejection fraction (HFpEF) despite the significant effect on heart rate. This meta-analysis is the first to compare the effects of ivabradine on heart rate and mortality parameters in HFpEF versus HFrEF. We screened three databases: PubMed, Embase, and Cochrane Library. The outcomes of these studies were mortality, reduction in heart rate, and left ventricular function improvement. We compared the efficacy of ivabradine treatment in HFpEF versus HFrEF. Heart rate analysis of pooled data showed decrease in both HFrEF (–17.646 beats/min) and HFpEF (–11.434 beats/min), and a tendency to have stronger bradycardic effect in HFrEF (p = 0.094) in randomized clinical trials. Left ventricular ejection fraction analysis revealed significant improvement in HFrEF (5.936, 95% CI: [4.199–7.672], p < 0.001) when compared with placebo (p < 0.001). We found that ivabradine significantly improves left ventricular performance in HFrEF, at the same time it exerts a tendency to have improved bradycardic effect in HFrEF. These disparate effects of ivabradine and the higher prevalence of non-cardiac comorbidities in HFpEF may explain the observed beneficial effects in HFrEF and the unchanged outcomes in HFpEF patients after ivabradine treatment.

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Clinical Efficacy and Safety of Qishen Yiqi Dropping Pill Combined with Conventional Western Medicine in the Treatment of Chronic Heart Failure: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6612653 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Lisheng Chen ◽

Ruilin Wang ◽

Honghong Liu ◽

Shizhang Wei ◽

Manyi Jing ◽

...

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Chronic Heart Failure ◽

Clinical Efficacy ◽

Western Medicine ◽

Methodological Quality ◽

Meta Analysis ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cochrane Library

Objective. The systematic review was designed to evaluate the safety and efficacy of Qishen Yiqi dropping pill combined with conventional Western medicine in the treatment of chronic heart failure (CHF). Methods. Relevant randomized controlled trials (RCTs) investigating the clinical efficacy of Qishen Yiqi dropping pill combined with conventional Western medicine in treating CHF were widely searched in electronic databases, including PubMed, Cochrane Library, EMBASE, CBM, CNKI, Read-show database, VIP database, and WanFang up to December 26, 2020. The methodological quality of each trial was assessed according to the Cochrane Reviewers’ Handbook 5.0. Meta-analysis was performed by using Review Manager 5.3. Results. Twenty-one RCTs (N = 2162) that met the criteria were included in the review for the assessment of methodological quality. Meta-analysis showed that compared with the conventional Western medicine (control group), Qishen Yiqi dropping pill combined with conventional Western medicine (experience group) significantly improved clinical efficiency, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), brain natriuretic peptide level (BNP), 6 min-walk distance (6-MWD), and adverse reactions. Conclusion. Qishen Yiqi dropping pill combined with conventional Western medicine are better than conventional Western medicine alone to improve the indicators of patients with CHF, which provides a certain basis for the treatment of CHF.

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The prolactine hypothesis for peripartum cardiomyopathy: has it found its feet for good?

European Heart Journal ◽

10.1093/ehjci/ehaa946.2069 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J.P Sousa ◽

L Puga ◽

J Lopes ◽

C Saleiro ◽

R Gomes ◽

...

Keyword(s):

Heart Failure ◽

Survival Benefit ◽

Meta Analysis ◽

Left Ventricular ◽

Prolactin Secretion ◽

Peripartum Cardiomyopathy ◽

Left Ventricular Ejection ◽

Cochrane Library ◽

Ventricular Ejection Fraction ◽

The Impact

Abstract Background Peripartum cardiomyopathy (PPCM) is a rare but serious condition that affects childbearing women. Dopamine agonists (DAs) may represent a specific therapy, potentially facilitating left ventricular recovery, through inhibition of prolactin secretion. However, their therapeutic value in this setting has not been fully demonstrated. Purpose To perform a meta-analysis aimed at evaluating the extent to which DAs are able to interfere with the natural history of PPCM. Methods We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library, Google Scholar, Scopus and DARE for both randomized controlled trials (RCTs) and observational studies addressing the impact of DAs on main outcomes of PPCM patients, published up until February 1, 2020. Endpoints were those of mortality, recovery from heart failure and, likewise, the degree to which left ventricular ejection fraction (LVEF) was restored. All analyses were conducted under a DA plus optimized medical therapy (OMT) vs. OMT alone design, while results were pooled using traditional meta-analytic techniques, under a random-effects model. Odds ratios (ORs) were computed for the first two outcomes, whereas mean difference (MD) was calculated to quantify LVEF restoration. Results 2 RCTs, 2 prospective cohort, 1 prospective case-control and 2 retrospective cohort studies, encompassing 452 patients, were regarded as eligible for quantitative evaluation. 180 patients were allocated to the DA arm, which was mostly represented by bromocriptine; in fact, only 1 study, including 24 patients, specified cabergolin utilization. Overall, 5 papers including 295 patients reported 42 deaths, whereas 5 papers comprising 305 patients detailed 220 heart failure recoveries, thus unveiling that LVEF restoration was the norm. The addition of a DA to OMT provided no signal of a survival benefit (OR 0.71, 95% CI 0.27–1.87, p=0.49, i2=27%). On the other hand, the incorporation of a DA into the therapeutic regimen narrowly missed significance for the heart failure recovery endpoint (OR 2.68, 95% CI 0.98–7.31, p=0.05, i2=56%). Furthermore, DAs were demonstrated to incrementally improve LVEF by 15% (MD 15.00, 95% CI 10.24–19.76, p<0.00001, i2=77%). Adverse events, including thromboembolic ones, were rare, though adjunct anticoagulation was broadly reported. Conclusion In PPCM patients, the addition of a DA to OMT seems to be both effective at incrementally improving LVEF and safe, even though not reaching survival benefit status. These findings appear to corroborate the so-called prolactin hypothesis for PPCM pathophysiology. Funding Acknowledgement Type of funding source: None

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Biomarkers-based personalized follow-up in chronic heart failure improves patient’s outcomes and reduces care associate cost

Health and Quality of Life Outcomes ◽

10.1186/s12955-021-01779-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Antonio Leon-Justel ◽

Jose I. Morgado Garcia-Polavieja ◽

Ana Isabel Alvarez-Rios ◽

Francisco Jose Caro Fernandez ◽

Pedro Agustin Pajaro Merino ◽

...

Keyword(s):

Heart Failure ◽

Hospital Admissions ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Secondary Outcome ◽

Ventricular Ejection Fraction ◽

Number Of Patients ◽

Ed Visits ◽

The Impact

Abstract Background Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). Methods This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. Results Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. Conclusions A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.

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