Integrating sex and gender in studies of cardiac resynchronization therapy: a systematic review.
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ABSTRACT: Aims
To examine the prevalence, temporal changes, and impact of the National Institute of Health (NIH) Sex as a Biological Variable (SABV) policy on sex and gender reporting and analysis in cardiac resynchronization therapy (CRT) cohort studies.Methods and results
We searched MEDLINE, EMBASE, and Web of Science for cohort studies reporting the effectiveness and safety of CRT in heart failure patients from January 2000 to June 2020, with no language restrictions. Segmented regression analysis was used for policy analysis. We included 253 studies. Fourteen per cent considered sex in the study design. Outcome data disaggregated by sex were only reported in 17% of the studies. Of the studies with statistical models (n = 173), 57% were adjusted for sex. Sixty-eight per cent of those reported an effect size for sex on the outcome. Sex-stratified analyses were conducted in 13% of the studies. Temporal analysis shows an increase in sex reporting in background, statistical models, study design, and discussion. Besides statistical models, NIH SABV policy analysis showed no significant change in the reporting of sex in study sections. Gender was not reported or analysed in any study.Conclusions
There is a need to improve the study design, analysis, and completeness of reporting of sex in CRT cohort studies. Inadequate sex integration in study design and analysis may potentially hinder progress in understanding sex disparities in CRT. Deficiencies in the integration of sex in studies could be overcome by implementing guidance that already exists.
SUBMITTER: Dewidar O
PROVIDER: S-EPMC8788138 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Cardiac resynchronization therapy (CRT) confers morbidity and mortality benefits to selected patients with heart failure. This systematic review examined effects of CRT in CKD patients (estimated GFR [eGFR] <60 ml/min per 1.73 m(2)). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:MEDLINE and Scopus (from 1990 to December 2012) and conference proceedings abstracts were searched for relevant observational studies and randomized controlled trials (RCTs). Studies comparing the following outcomes were included: (1) CKD patients with and without CRT and (2) CKD patients with CRT to non-CKD patients with CRT. Mortality, eGFR, and left ventricular ejection fraction data were extracted and pooled when appropriate using a random-effects model. RESULTS:Eighteen studies (14 observational studies and 4 RCTs) were included. There was a modest improvement in eGFR with CRT among CKD patients (mean difference 2.30 ml/min per 1.73m(2); 95% confidence interval, 0.33 to 4.27). Similarly, there was a significant improvement in left ventricular ejection with CRT in CKD patients (mean difference 6.24%; 95% confidence interval, 3.46 to 9.07). Subgroup analysis of three RCTs reported lower rates of death or hospitalization for heart failure with CRT (versus other therapy) in the CKD population. Survival outcomes of CKD patients (compared with the non-CKD population) with CRT differed among observational studies and RCTs. CONCLUSIONS:CRT improves left ventricular and renal function in the CKD population with heart failure. Given the increasing use of cardiac devices, further studies examining the effects of CRT on mortality in CKD patients, particularly those with advanced kidney disease, are warranted.
| S-EPMC3731896 | biostudies-other
Project description:BackgroundEvidence from randomized trials is conflicting on the effects of cardiac resynchronization therapy (CRT) by sex, and differences in access are unknown. We examined sex differences in the implantation rates and outcomes in patients treated with CRT using cohort studies.MethodsWe followed a pre-specified protocol (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42020204804). MEDLINE, Embase, and Web of Science were searched for cohort studies from January 2000 to June 2020 that evaluated the response to CRT in patients ≥ 18 years old and reported sex-specific information in any language.ResultsWe included 97 studies (1,172,654 men and 486,553 women). Men received CRT more frequently than women (median ratio, 3.16; 25th to 75th interquartile range, 2.48-3.62). In the unadjusted analysis, men had a greater long-term all-cause mortality rate after CRT, compared with women (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.38-1.63; P < 0.001). Adjustment for confounders did not affect the strength or direction of association (HR, 1.45; 95% CI, 1.32-1.59; P < 0.001). Women achieved a greater rate of improvement in left ejection fraction compared with men (HR, 4.66; 95% CI, 4.23-5.13; P < 0.001). Men had a lower risk of a pneumothorax (relative risk, 0.21; 95% CI, 0.13-0.34; P < 0.001]); otherwise, there were no differences in complications.ConclusionsWe found in this large meta-analysis that men were more often implanted with CRT than women, yet men had a higher long-term all-cause mortality following CRT, compared with women, and smaller improvement in left ventricular ejection fraction. Reasons for this difference in implantation rates of CRT in real-world practice need to be investigated.
| S-EPMC8767135 | biostudies-literature
Project description:BackgroundCardiac resynchronization therapy (CRT) is beneficial in patients who have heart failure with reduced ejection fraction or arrhythmic events. However, most randomized controlled trials (RCTs) showing survival benefits primarily enrolled older white men. This study aims to evaluate CRT efficacy by sex, race, and age in RCTs.MethodsFive electronic databases (CINAHL, Embase, Emcare, Medline, and PubMed) were searched from inception to July 12, 2021 for RCTs with CRT in adult patients. Data were analyzed for clinical outcomes including all-cause or cardiovascular (CV) death, worsening heart failure (HF), and HF hospitalization (HFH) according to sex, race, and age.ResultsAmong six RCTs with up to moderate risk of bias, 54% (n = 3,630 of 6,682; mean age 64 years, 22% female, 8% black patients) had CRT device implantation. All-cause death (odds ratio [OR], 0.51; P = 0.053) was reduced in female versus male CRT patients, whereas CV death, HFH, or all-cause death with worsening HF or HFH did not differ significantly. No difference was seen in CRT patients for all-cause death and worsening HF (OR, 1.32; P = 0.46) among white vs black patients or for all-cause death and HFH (OR, 1.19; P = 0.55) among ≥ 65 versus < 65 years.ConclusionsWhereas all-cause death was lower in female CRT patients, other reported outcomes did not significantly differ by sex, race, or age. Only 6 studies partially reported outcomes. Thus, enhanced reporting and analyses are required to overcome such paucity of data to evaluate the impact of these factors on clinical outcomes in distinct patient cohorts with CRT indication.
| S-EPMC8712541 | biostudies-literature
Project description:Systolic heart failure is a major problem for Americans today, with 550,000 new cases diagnosed per year, and ultimately contributes to 287,000 deaths annually. While pharmacologic therapy has drastically improved outcomes in patients with systolic heart failure, hospitalizations from systolic heart failure continue to increase and remain a major cost burden. In response to this unmet need, recent years have seen dramatic improvements in device-based therapy targeting one cause of systolic dysfunction: dyssynchronous ventricular contraction. Cardiac resynchronization therapy aims to restore mechanical synchrony by electrically activating the heart in a synchronized manner. This review summarizes the rationale for cardiac resynchronization therapy, evidence for its use, current guidelines, and ongoing and future directions for research.
| S-EPMC3096278 | biostudies-other
Project description:ObjectiveThis systematic review aimed to evaluate the performance of echocardiography-based programming in comparison with the intracardiac electrocardiogram (IEGM)-based method for the optimization of cardiac resynchronization therapy (CRT).MethodsA literature review was conducted using digital databases to systematically identify the studies reporting CRT optimization through echocardiography compared with IEGM. Detailed patient-level study characteristics including the type of study, sample size, therapy, the New York Heart Classification (NYHA) status, lead placement, and other parameters were abstracted. Finally, postprogramming outcomes were extracted for each article.ResultsIn a total of 11 studies, 919 patients were recruited for the final analysis. Overall, 692 (75.29%) were males. The mean duration of the QRS complex in our study population ranged from 145.2 ± 21.8 ms to 183 ± 19.9 ms. There was an equal improvement in the NYHA class between the two methods while the left ventricular ejection fraction (LVEF) demonstrated an improvement by IEGM. Many studies supported IEGM to increase the 6-minute walk test and left ventricular outflow tract velocity time interval (LVOT VTI) when compared to echocardiography. The mean time for echocardiography-based optimization was 60.15 min while that of IEGM-based optimization was 6.65 min.ConclusionIEGM is an alternative method for CRT optimization in improving the NYHA class, LVEF, and LVOT VTI, and is less time-consuming when compared to the echocardiography-based methods.
| S-EPMC10023891 | biostudies-literature
Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall.
2010-01-05 | GSE14338 | GEO
Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall.
2010-01-05 | GSE14327 | GEO
Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall. Complementary study to GSE14327. While GSE14327 was designed as a 1-color microarray experiment, this series was carried out following a 2-color design (anterior and lateral LV wall labeled with Cy3 and Cy5, respectively, including dye swaps).
2010-05-16 | E-GEOD-14338 | biostudies-arrayexpress
Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall. Designed as a 1-color experiments, samples from anterior and lateral left ventricular myocardium from non-failing, DHF and CRT animals were labeled with Cy3 and hybridized onto Agilent 44K long oligonucleotide arrays.
2010-05-16 | E-GEOD-14327 | biostudies-arrayexpress
Project description:Patients with conventional pacemakers or implanted defibrillators are often considered for cardiac resynchronization therapy (CRT). Our aim was to summarize the available evidences regarding the clinical benefits of upgrade procedures. A systematic literature search was performed from studies published between 2006 and 2017 in order to compare the outcome of CRT upgrade vs. de novo implantations. Outcome data on all-cause mortality, heart failure events, New York Heart Association (NYHA) Class, QRS narrowing and echocardiographic parameters were analysed. A total of 16 reports were analysed comprising 489,568 CRT recipients, of whom 468,205 patients underwent de novo and 21,363 upgrade procedures. All-cause mortality was similar after CRT upgrade compared to de novo implantations (RR 1.19, 95% CI 0.88-1.60, p = 0.27). The risk of heart failure was also similar in both groups (RR 0.96, 95% CI 0.70-1.32, p = 0.81). There was no significant difference in clinical response after CRT upgrade compared to de novo implantations in terms of improvement in left ventricular ejection fraction (?EF de novo - 6.85% vs. upgrade - 9.35%; p = 0.235), NYHA class (?NYHA de novo - 0.74 vs. upgrade - 0.70; p = 0.737) and QRS narrowing (?QRS de novo - 9.6 ms vs. upgrade - 29.5 ms; p = 0.485). Our systematic review and meta-analysis of currently available studies reports that CRT upgrade is associated with similar risk for all-cause mortality compared to de novo resynchronization therapy. Benefits on reverse remodelling and functional capacity improved similarly in both groups suggesting that CRT upgrade may be safely and effectively offered in routine practice. CLINICAL TRIAL REGISTRATION:Prospero Database-CRD42016043747.
| S-EPMC5756552 | biostudies-literature