Abstract 9692: Sex Differences in Cardiovascular Outcomes of SGLT-2 Inhibitors in Heart Failure Randomized Controlled Trials: A Systematic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A9692-A9692, November 8, 2022. Background:Randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing major adverse cardiovascular events (MACE) in patients with heart failure. A recently published meta-analysis showed that the use of SGLT-2i among women with diabetes resulted in less reduction in MACE vs. men. This study aims to determine sex differences in MACE in patients with chronic heart failure.Methods:We systematically searched the medical database until April 30, 2022, and retrieved all the RCTs using SGLT-2is with specified CV outcomes. We used PRISMA, Preferred Reporting Items for a Review and Meta-analysis. We pooled the hazard ratio (HR) of MACE in both sexes, did a meta-analysis, and analyzed the odds ratio (OR) of MACE based on sex. Statistical analysis was completed with the use of Cochrane Review Manager (RevMan) version 5.4. Results of the pooled hazard ratio (HR) and the 95% confidence interval (CI) were made based on intention-to-treat analysis.Results:Figure 1 shows the results of the meta-analysis of 4 RCTs conducted with SGLT-2is (n=20725) vs. placebo. MACE was significantly lower in males and females taking SGLT-2is (men – HR 0.76; 95% CI 0.69 to 0.83; p=0.00001; women – HR 0.72; 95% CI 0.63 to 0.83; p=0.00001). Pooled data from three of the RCTs (n=7233) revealed a greater reduction in MACE in females vs. males (OR 1.32; 95% CI 1.14 to 1.53; p=0.0002).Conclusion:SGLT-2is reduce the risk of MACE in patients with heart failure, regardless of sex. However, the benefits were more pronounced in females, contrary to the meta-analysis of SGLT-2is in patients with diabetes. This finding may reflect an actual sex difference due to physiologic or behavioral factors or can be due to inadequate statistical power. More sex-based RCTs may help establish these sex differences in cardiovascular outcomes.

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Ottobre 2022

Abstract 11428: A Comparison Between Endothelin Receptor Antagonists and Renal Denervation for Resistant Hypertension: A Systematic Review and Meta-Analysis of Sham and Placebo Controlled Trials

Circulation, Volume 146, Issue Suppl_1, Page A11428-A11428, November 8, 2022. Introduction:Endothelin-1 causes vasoconstriction by activation of calcium flux in smooth muscle cells. Use of endothelin receptor antagonists (ERAs) has remained controversial. Renal denervation (RD) has also been investigated as a treatment option for resistant hypertension (RHTN). The efficacy of these two novel treatment strategies was compared.Methods:Placebo-controlled and sham-controlled randomized clinical trials testing ERA or RD as treatments for RHTN were selected. Prespecified subgroup analyses comparing the efficacy of ERA and RD were conducted for outcomes of 24-hour (hr) blood pressure (BP) and office BP.Results:Nine studies (3 ERA and 6 RD) were identified that included 1,708 participants (816 ERA and 892 RD). Cochran risk of bias assessment showed 72% of the domains to be low risk of bias for the ERA studies and 88% of the domains to be low risk of bias for the RD studies. The raw mean difference (RMD) between ERA and placebo control was statistically significant for 24-hr systolic (SBP) (-8.34 mmHg; 95% CI -11.51 to -5.81, 24-hr diastolic (DBP) (-6.77 mmHg; 95% CI -8.90 to -4.63), office SBP (-4.50 mmHg; 95% CI -6.92 to -2.08), and office DBP (-2.01 mmHg; 95% CI -2.13 to -1.88). The RMD between RD and sham control was not statistically significant for 24-hr SBP (-1.85 mmHg; 95% CI -3.88 to 0.18), 24-hr DBP (-0.67 mmHg; 95% CI -1.84 to 0.51), office SBP (-1.93 mmHg; 95% CI -5.17 to 1.31), and office DBP (-1.55 mmHg; 95% CI -3.43 to 0.33). The interaction between the treatment subgroups was statistically significant for 24-hr SBP and DBP, but not for office SBP and DBP.Discussion:ERAs had greater reduction in 24-hr and office BP compared to RD among patients with RHTN. Despite efficacy in reducing BP in RHTN, use of ERAs remains controversial given the cost and side effect profile. RD does not reduce BP among patients with RHTN. Medications are the optimal treatment for RHTN and sham controlled data showing efficacy is needed prior to widespread use and adoption of RD in RHTN.

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Ottobre 2022

Abstract 10070: Valve-in-Valve Transcatheter Mitral Valve Replacement versus Redo Surgical Mitral Valve Replacement-Sytemetaic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A10070-A10070, November 8, 2022. Introduction:Data on comparative outcomes between valve in valve transcatheter mitral valve replacement (ViV-TMVR) versus redo-surgical mitral valve replacement (SMVR) for degenerated bioprosthetic valves remain limited.Hypothesis:ViV TMVR is associated with lower in-hospital mortality and complication rates compared with redo SMVR.Methods:The MEDLINE (PubMed, Ovid) and Cochrane databases were queried with various combinations of medical subject headings (MeSH) to identify relevant articles. Eight studies evaluating comparative outcomes (ViV TMVR vs Redo SMVR) for patients with degenerated bioprosthetic valves were included in the analysis.Results:A total of 5,161 patients with degenerated prosthetic mitral valves underwent ViV TMVR (n = 1163) and redo SMVR (n = 3998) were included in the study. The mean age of patients was 76 versus 66 years for ViV TMVR versus the redo SMVR group, respectively (p

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Ottobre 2022

Abstract 14647: Effects of an App-Based Exercise Intervention Program on Exercise Capacity for Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A14647-A14647, November 8, 2022. Introduction:Mobile-based healthcare is considered a strategy that can overcome time and space constraints and increase the participation rate of a heart health program; however, a review of the elements of exercise prescription, such as frequency, intensity, time, and type (FITT), has been insufficient. Therefore, a systematic review and meta-analysis were performed to identify the FITT elements of an app-based exercise heart health intervention that was effective in improving the exercise capacity of patients with Acute Coronary Syndrome (ACS).Methods:A literature search was conducted for papers published up to November 2021. We searched for randomized controlled trials (RCTs) evaluating the effectiveness of an exercise-based heart health program using a smartphone app for adult inpatients initially diagnosed with ACS, who received primary percutaneous coronary intervention or medication treatment. With the help of our librarians, we searched MEDLINE, EMBASE, and Cochrane CENTRAL. Literature selection, bias evaluation, and data collection were independently performed by two researchers. Cochrane Risk of Bias 2 was used to evaluate the quality of literature; the level of evidence was evaluated using GRADE, and CMA Version 3.0 was used for the meta-analysis. Effect size for exercise capacity was calculated using standardized mean difference.Results:Seven RCTs were identified. The study results suggested that using an app-based exercise heart health program was effective in improving the exercise capacity of patients in Phase III of cardiac rehabilitation post-ACS. As a confirmed exercise prescription factor, the app was found to be effective in improving exercise capacity when aerobic exercise was performed for approximately 30 minutes at least three to five times a week. The effect size for exercise capacity was 0.42 (95% CI, 0.24-0.60; I2, 45.00;p

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Ottobre 2022

Abstract 13292: Rural-Urban Differences in Mortality Rate of Myocardial Infarction and Heart Failure: A Systematic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A13292-A13292, November 8, 2022. Introduction:Studies indicate that living in a rural area may be associated with worse health outcomes. However, it is unclear whether rurality is associated with mortality in patients with acute myocardial infarction (AMI) and heart failure (HF). This systematic review and meta-analysis aimed to evaluate rural-urban differences in mortality rate after AMI or HF.Methods:A systematic search was conducted for studies published till May 1, 2022 in PubMed, Embase and CENTRAL. Included studies compared mortality rates after hospital admission for AMI or HF in rural versus urban areas. Follow up ranged between 30 days and 3 years. Adjusted Odds ratios (aORs) were pooled with a random-effects model.Results:Six cohort studies were identified, which included 785,156 patients (128,990 in rural vs. 656,166 in urban) with AMI and 1,159,000 patients (192,749 in rural vs. 966,251 in urban) with HF. Compared with urban, patients admitted with AMI in rural areas had higher mortality rates (16% vs 14%, aOR 1.12, 95% Confidence Interval (CI) 1.05-1.20;p=0.0003,I2=75%). Compared with urban, patients admitted with HF in rural areas had higher mortality rates (21% vs 18%, aOR 1.19, 95% CI 1.03-1.38;p=0.02,I2=90%). (Figure)Conclusions:Among patients with AMI or HF, living in rural areas is associated with an increased risk of mortality. Clinical and policy efforts are needed in order to reduce disparities in rural health.

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Ottobre 2022

Abstract 14258: Left Bundle Branch Pacing for Cardiac Resynchronization Therapy in Heart Failure: A Systematic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A14258-A14258, November 8, 2022. Introduction:: Cardiac resynchronization therapy (CRT) using a biventricular pacemaker (BVP) reduced mortality and rehospitalizations in patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) of less than 35% and concomitant left bundle branch block. However, 10-30% of BVP patients fail to show a clinical or echocardiographic response. Recently left bundle branch pacing (LBBP) has been studied as a more physiological alternative to BVP. The aim of this study is to summarize the available evidence on LBBP.Hypothesis:LBBP is an effective and feasible alternative option for CRT.Methods:Unrestricted searches of the PubMed, EMBASE, and Cochrane databases from inception till June 1, 2022, for studies examining the role of LBBP for CRT in HF patients. Data were analyzed using Revman 5.3 software. Mean Difference (MD), Odds Ratio (OR), and 95% Confidence interval (CI) were calculated using the random-effects model.Results:A total of 8 observational studies (3 single-armed, and 5 comparative studies) examined 756 HF patients who underwent CRT (551 LBBP vs 205 BVP). LBBP was successful in 87% of patients. Compared to baseline, LBBP was associated with a reduction in QRS duration (MD -53.5, 95%CI -69.77, -37.24), an increase in LVEF (MD 17%, 95%CI 13.38, 20.6), and a reduction in NYHA class (MD -1.4, 95%CI -1.56, -1.05). Compared to BVP, LBBP was associated with a significant reduction in QRS duration (MD -22.68, 95%CI -31, -14.35), improvement in LVEF (MD 7.58, 95%CI 5.21, 9.95), and a decrease in NYHA class (MD -0.55, 95% CI -0.73, -0.37) during a mean follow-up of 9.2 months. The super response rate, which is defined as an increase in LVEF of more than 20% or LVEF at or above 50% after CRT, was higher in LBBP compared to BVP (OR 2.98, 95%CI 1.65, 5.32).Conclusions:LBBP is a feasible and effective alternative for CRT. LBBP was associated with better electrical ventricular synchrony than BVP which was also translated into better echocardiographic and clinical outcomes in the short term. Our findings need to be further validated in larger randomized controlled trials with a long-term follow-up.

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Ottobre 2022

Abstract 12626: A Systematic Review and Meta-analysis of Factors Associated With Long-Term Mortality in Adults After Coronary Artery Bypass Graft Surgery

Circulation, Volume 146, Issue Suppl_1, Page A12626-A12626, November 8, 2022. Background:With an ageing and increasingly multi-morbid population, the use of coronary artery bypass grafting (CABG) is expected to increase. As short-term CABG mortality rates have decreased, estimating long-term outcomes for patients with specific risk factors has become more relevant. Previous single observational studies have identified risk factors for adverse long-term outcomes, such as older age and diabetes.Purpose:Understanding the pre-operative characteristics that affect late mortality post-CABG can lead to effective risk stratification and enhancement of secondary prevention programmes, thereby aiming to improve long-term prognosis after the procedure.Methods:MEDLINE, Embase, Google Scholar, and Cochrane electronic databases were searched to identify all relevant articles evaluating associations between pre-operative risk factors and long-term mortality (≥5 years ) post-CABG. Studies with

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Ottobre 2022

Abstract 15618: Contemporary and Emerging Training Pathways for Acute Care Cardiology: A Systematic Review

Circulation, Volume 146, Issue Suppl_1, Page A15618-A15618, November 8, 2022. Introduction:Several studies have described trends toward increasing complexity and illness-severity of patients admitted to the cardiac intensive care units (CICU). This has necessitated the development of training pathways in critical care cardiology (CCC). Hybrid training in combinations of interventional cardiology (IC), advanced heart failure and transplant cardiology (AHFTC), and CCC have also gained interest. This review sought to outline current and proposed pathways for hybrid training in acute cardiovascular care.Methods:We performed a systematic review of articles describing training pathways for dual certification in CCC, as well as hybrid models for training in a combination of IC, CCC, and AHFTC. PubMed, EMBASE, and CINAHL were searched from 01/01/2000 to 04/28/2022. Pathways through pediatric and adult non-internal medicine specialties were excluded.Results:Of 2,236 citations, 18 studies were included in the final analysis. Most pathways included sequential CCC training, i.e. traditional cardiovascular fellowship and 1-2 additional years of critical care medicine, although integrated 4-year programs were noted to be emerging. Hybrid models for advanced training in two or more complementary subspecialties, including CCM, AHFTC, and IC, have been described, each with their own strengths and limitations. Additional expertise in advanced therapies such as mechanical circulatory support, the longitudinal AHFTC practice, and the combination of procedural and intensivist skills for management of diseases such as acute coronary syndromes were the stated benefits of these combined models. Alternatively, some advocate for incorporating focused CC training into a single year of IC or AHFTC fellowship. However, this may limit the time required to gain expertise in all areas of advanced training and is insufficient for board certification in CCM.Conclusion:Despite the growing need, there are limited dedicated pathways to train the contemporary acute care cardiologists. Further study is needed to consolidate training to encourage the growth and development of this field.

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Ottobre 2022

Abstract 9736: Steerable versus Non-Steerable Sheath Technology in Atrial Fibrillation Ablation: A Systematic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A9736-A9736, November 8, 2022. Introduction:Catheter placement and stability are well-known challenges in atrial fibrillation (AF) ablation. As a result, steerable sheaths were developed to improve catheter stabilization and maintain proper catheter-tissue contact. The purpose of this systematic review and meta-analysis is to see if employing a steerable sheath influences procedure outcome.Method:We performed a comprehensive literature search for studies that evaluated the efficacy and safety of Steerable Sheaths (SS) compared to Non-Steerable Sheaths (NSS) in AF ablation. The primary outcome was the rate of atrial arrhythmia (AA) freedom by the time of the last follow-up. The secondary outcomes were the procedure-related complications and procedural characteristics. Risk ratio (RR) or the mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model.Results:A total of 10 studies, including 967 AF patients (mean age: 59.2±11.1 years, 516 patients managed with SS vs. 454 with NSS), were included. SS group showed a higher rate of freedom of AA compared to NSS (RR: 1.19; 95% CI 1.09, 1.29; P < 0.001). Both techniques had similar rate for procedural-related complication (RR: 1.09, 95% CI 0.50, 2.39; P = 0.83). The SS strategy had a shorter procedure time (MD -10.6 (min.), 95% CI -20.97, -0.20; P = 0.05) but comparable fluoroscopic and radiofrequency application times to the NSS group.Conclusions:The steerable sheaths for AF catheter ablation not only reduced the total procedure time but also significantly increased the rate of successful ablation while maintaining a similar safety profile when compared to the traditional non-steerable sheaths.

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Ottobre 2022

Abstract 12334: A Systematic Review and Meta-analysis Curriculum for Internal Medicine Residents Interested in Cardiology

Circulation, Volume 146, Issue Suppl_1, Page A12334-A12334, November 8, 2022. Introduction:Internal Medicine (IM) residents face major challenges in conducting original research due to inadequate instruction in research methodology and lack of mentorship during the traditional research electives offered during residency.Hypothesis:A novel systematic review curriculum (SRC) can improve resident satisfaction and research productivity.Methods:8 IM residents interested in cardiology were selected to participate in a 4-week elective focused on conducting systematic reviews and meta-analyses. Didactic lectures, online tutorials, and problem-based exercises were delivered by a multidisciplinary team of educators including a clinical researcher, librarian, and biostatistician.Results:Demographics are presented (Table 1). As compared to 16 residents that underwent traditional research electives, the SRC participants reported higher satisfaction, completed a mentored research project within 4 weeks, presented 4 posters at AHA annual meeting 2020, and finished manuscripts for publication (Figure 1).Conclusions:A focused research curriculum delivered by multidisciplinary educators is better than a traditional research elective and improves resident satisfaction.

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Ottobre 2022

Abstract 11096: Impact of Rhythm versus Rate Control in Atrial Fibrillation on All-Cause Mortality, Hospitalization and Stroke: A Systematic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A11096-A11096, November 8, 2022. Introduction:Many randomized controlled trials (RCTs) compared rate control vs rhythm control therapy in patients with atrial fibrillation (AF). In this study, we systematically reviewed these RCTs and performed a meta-analysis of the outcomes comparing the two therapies.Methods:We searched PubMed, Medline, EMBASE, and SCOPUS databases until April 30, 2022 for all RCTs investigating AF rate vs rhythm control. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) for constructing and reporting this review. We assigned I2 >50% as an indicator of statistical heterogeneity among the RCTs. We analyzed all-cause mortality, stroke rate, heart failure (HF) hospitalization, and total hospitalization between the two groups. We estimated the risk ratios (RR) with a random-effects model using the Mantel-Haenszel technique and calculated the 95% confidence intervals (CI). A P-value

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Ottobre 2022

Abstract 10566: Hypothermia as an Adjunctive Therapy to Percutaneous Intervention in St-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Control Trials

Circulation, Volume 146, Issue Suppl_1, Page A10566-A10566, November 8, 2022. Introduction:In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of Therapeutic hypothermia (TH). However, results from previous studies are contradictory.Method:We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcome was the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door to balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model.Results:A total of 10 RCTs, including 706 patients (mean age: 58±9.6 years, 364 patients managed with adjunctive TH vs. 342 with standard PCI), were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its individual components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door to balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation.Conclusions:According to our meta-analysis of published RCTs, the benefit of TH in STEMI patients is modest, with a marginal safety profile and potential for care delays. Larger-scale RCTs are needed to further clarify our results.

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Ottobre 2022

Abstract 15477: Timely PCI Shows Beneficial Long-Term Outcomes in Late Presentation With STEMI: A Systematic Review and Meta-Analysis Between 2012 and 2022

Circulation, Volume 146, Issue Suppl_1, Page A15477-A15477, November 8, 2022. Introduction:Approximately 8-40% of ST-elevation Myocardial Infarction (STEMI) present later than 12 hours after symptom onset. Current ACC/AHA guidelines recommend primary percutaneous coronary intervention (PCI) for STEMI after 12 hours of symptom onset only in the setting of cardiogenic shock or severe acute heart failure, (Class Ia, LOE B) or persistent ischemic symptoms (Class IIa, LOE B). There are limited data comparing long-term outcomes among patients with a late STEMI presentation managed with PCI versus medical therapy (MT).Objective:To compare long-term outcomes among patients treated with PCI versus MT who have late presentation of STEMIMethods:We followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to extract data from PubMed/Medline, Cochrane, Embase, and Clinicaltrials.gov databases by using the search terms “late” or “delayed” or “ >12 hours” presentation with STEMI from 01/2012 through 12/2022. Included studies reported at least one of the following outcomes: all-cause mortality, reinfarction, heart failure, major adverse cardiac events (MACE), and stroke. Studies reporting delays in PCI due to COVID-19 positive status or COVID-19 enforced protocols were excluded to prevent the impact of pragmatic barriers on treatment. Relative risk (RR) was calculated using random effects model if heterogeneity was >50%, otherwise, fixed effects model was usedResults:Seven studies (n=11,576, delayed PCI n=6,248, and medical therapy n=5,319) were included in our analysis. The median follow-up was 12 months (1-60 months). Overall, among patients with STEMI and PCI >12 hour after presentation had lower incidence of MACE (27% vs. 30%, RR 0.85, 95% CI 0.76-0.69, I2=30%, p=0.007) compared to MT alone, which was driven by a significantly reduced all-cause mortality with PCI (4.4% vs. 17%, RR 0.38, 95% CI 0.17-0.85, I2=95%, p=0.01). No significant differences were observed in the incidence of recurrent MI and heart failure hospitalizations.Conclusion:Our study suggests favorable outcomes of PCI in STEMI with presentation >12 hours compared with medical therapy. Further prospective studies are needed to validate our findings.

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Ottobre 2022

Abstract 11273: Comparison of Outcome Between Type 2 versus Type 1 Myocardial Infarction: A Systematic Review and Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A11273-A11273, November 8, 2022. Introduction:Unlike type 1 myocardial infarction (T1MI) which is caused by plaque rupture and erosion, type 2 myocardial infarction (T2MI) is due to the mismatch between supply-demand of oxygen. To date, there were limited studies available and consequently, the outcomes of patients with T1MI compared to T2MI remained inconclusive.Hypothesis:We aimed to compare the outcomes of T1MI and T2MI patients in terms of mortality and adverse cardiovascular outcomes.Methods:We performed a systematic literature search of databases for relevant articles from inception until March 20, 2022.Results:340,802 patients had T1MI while the remaining 52,855 patients had T2MI. Mean age was similar between both groups (T1MI: 69.4 years, T2MI: 71.8 years) while proportion of female was found to be more higher in T2MI (61% vs 38%). Our analysis revealed that patients with T1MI had a significantly lower odds of all-cause mortality (OR 0.44, 95%CI 0.34 to 0.56, p

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Ottobre 2022

Abstract 11279: Reporting of Diversity and Inclusion in Clinical Trials of Exercise Therapy for Peripheral Vascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Circulation, Volume 146, Issue Suppl_1, Page A11279-A11279, November 8, 2022. Introduction:Exercise therapy serves as a cornerstone of treatment for all patients with peripheral arterial disease (PAD); however, data suggest that women and minority groups with PAD suffer from disparate outcomes.Hypothesis:Randomized controlled trials (RCTs) of exercise therapy for PAD will demonstrate high rates of reporting and recruitment of women and minority groups.Methods:Databases were queried for RCTs that assessed the role of exercise therapy for PAD (Figure 1).Results:Only 2/47 (4%) of studies reported details of racial and ethnic subgroups (Figure 2). A meta-analysis of participation among non-white participants showed high heterogeneity (pooled effect 32%, I2 74%, p

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Ottobre 2022

Abstract 12442: A Systematic Review And Network Meta-analysis In HfpEF Pharmacologic Treatment

Circulation, Volume 146, Issue Suppl_1, Page A12442-A12442, November 8, 2022. Introduction:Heart failure with preserved ejection fraction (HFpEF) remains a highly prevalent condition with significant morbidity and mortality but limited treatment options. Sodium glucose cotransporter-2 inhibitors (SGLT2i), angiotensin-receptor neprilysin inhibitors (ARNi) and mineralocorticoid receptor antagonists (MRA) are moderately to weakly guideline supported. Yet, the potential gain with combination therapies has not been elucidated.Hypothesis:This study sought to estimate and compare the aggregate treatment benefit of medical therapies for HFpEF.Methods:We performed a systematic reviewed and network meta-analysis, using MEDLINE, Cochrane, and the Web of Science databases for randomized controlled studies from inception to May 2022. We included patients with heart failure and left ventricular ejection fraction >40%, treated with any of the following therapies: angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), beta-blockers (BB), MRA, digoxin, ARNi, SGLT2i, and vericiguat. Our analysis assumed additive benefits of each therapy. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HHF); secondary outcome was all-cause mortality.Results:We identified 14 studies with a total of 26,556 patients, mean age 71 (±8.8), 49% females and mean ejection fraction of 57% (±8%). Mean follow-up time was 24 months. MRA and SGLT2i, were the individual components that reduced the primary outcome [HR =0.82 (95% CI 0.67-0.99 and 0.78 (95% CI 0.68 – 0.91), respectively], while the combination of ACE-i/ARB, BB, MRA and SGLT2i was the only beneficial [HR 0.53 (95% CI 0.30 – 0.95]. None of the explored combinations or individual components were associated with decreased all-cause mortality.Conclusions:In patients with HFpEF, MRA and SGLT2i alone as well as a combination of ACE-i/ARB, BB, MRA and SGLT2i were associated with decreased risk of CV mortality and HHF.

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Ottobre 2022