Transcatheter edge-to-edge mitral valve repair for mitral regurgitation in patients with cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: There is currently little evidence for transcatheter edge-to-edge mitral valve repair (TEER) for mitral regurgitation (MR) in patients with cardiogenic shock (CS). Therefore, this study investigated the characteristics and outcomes of CS patients who underwent TEER for MR. METHODS: PubMed, EMBASE were searched in July 2023. Case series and observational studies reporting clinical characteristics and outcomes in CS patients with MR who underwent TEER were included. We performed a one-group meta-analysis using a random effects model. RESULTS: A total of 4060 patients from 7 case series and 5 observational studies were included. The mean age was 68.2 (95% confidence interval [CI]: 64.1-72.2) years, and 41.4% of patients (95% CI: 39.1%-43.7%) were female. Pre-TEER, severe MR was present in 85.3% (95% CI: 76.1%-91.3%) of patients. Mean left ventricular ejection fraction was 36.7% (95% CI: 29.2%-44.2%), and 54.6% (95% CI: 36.9%-71.2%) of patients received mechanical circulatory support. The severity of MR post-TEER was less than 2+ in 88% (95% CI: 87%-89%) of patients. In-hospital mortality was 11% (95% CI: 10%-13%), whereas 30-day and 1-year mortality rates were 15% (95% CI: 13%-16%), and 36% (95% CI: 21%-54%), respectively. CONCLUSIONS: This systematic review and meta-analysis assessed the clinical characteristics and outcomes of TEER in CS patients with MR. TEER for MR in patients with CS has been successful in reducing MR in most of the patients, but with a high mortality rate. Randomized controlled trials of TEER for MR and CS are needed.

Prognostic value of left ventricular global longitudinal strain in mitral regurgitation: a systematic review.

Conventional echocardiographic assessment may overestimate the left ventricular (LV) function in mitral regurgitation (MR). LV global longitudinal strain (GLS) is more sensitive marker to detect subclinical LV dysfunction. Multiple studies have investigated the prognostic value of LV-GLS in MR to examine its potential to determine the timing and indication of intervention. This systematic review aimed to assess the prognostic value of LV-GLS in patients with mitral regurgitation (MR) to define its clinical applicability. PUBMED and EMBASE were queried through July 2021 to identify studies investigating the prognostic value of LV-GLS in MR. A total of 24 observational studies with 5267 patients were identified. Sixteen studies investigated for primary MR, 7 studies for secondary MR, and 1 study for both. Most studies included patients who underwent intervention. There was significant heterogeneity in patient population, intervention status, follow-up period, LV-GLS cutoff value, outcomes, and statistical methods among the studies. Meta-analysis was not performed considering the significant variability. With exception to 1 study, all studies demonstrated significant association between impaired LV-GLS and worse clinical and echocardiographic outcomes in primary MR. Prognostic value of LV-GLS in secondary MR was less certain due to inconsistent findings and limited reporting. LV-GLS is a promising parameter of prognostication in primary MR and can be considered as alternative to determine the timing of intervention. However, the optimal cutoff value remains unclear. The prognostic value of LV-GLS in secondary MR is less clear. Further large-scale prospective study is warranted before its routine clinical application.

Outcomes of transcatheter edge-to-edge repair for atrial functional mitral regurgitation: A meta-analysis of observational studies.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) may have potential benefits in the treatment of atrial functional mitral regurgitation (AFMR), but robust evidence is currently lacking. We conducted a systematic review and meta-analysis to investigate the clinical outcomes of TEER for AFMR, including comparisons to ventricular functional MR (VFMR). METHODS: MEDLINE and EMBASE were searched through January 2023 to identify studies eligible for analysis. The primary outcome was postprocedural MR severity. Postprocedural New York Heart Association (NYHA) functional class classification and all-cause mortality were also evaluated. Outcomes were stratified into short term (postprocedure to 6 months) and long term (6 months to 2 years). RESULTS: A total of eight observational studies met the inclusion criteria, enrolling 539 AFMR and 3486 VFMR patients. Postprocedural MR grade ≤2 in the AFMR group was observed in 93.7% (454/491 patients; 95% confidence interval (CI), 91.1%-96.2%, I2 = 24.3%) and 97.1% (89/93 patients; 95% CI, 92.9%-100%, I2 = 26.4%) in short- and long-term follow-up, respectively. There was no difference in the rates of postprocedural MR grade ≤2 between AFMR and VFMR either in short-term (risk ratio [RR], 1.00 [95% CI, 0.95-1.06]; p = 0.90; I2 = 53%) or long-term follow-up (RR, 1.08 [95% CI, 0.89-1.32]; p = 0.44; I2 = 22%). Similarly, no difference was observed between AFMR and VFMR in the rates of postprocedural NYHA class ≤2 or all-cause mortality. CONCLUSION: TEER provides similar clinical outcomes for AFMR and VFMR. A high rate of MR grade ≤2 was observed in patients at both short- and long-term follow-ups. Further prospective studies with TEER versus medical therapy and/or rhythm control for AFMR are warranted.

Maintenance immunosuppression in heart transplantation: insights from network meta-analysis of various immunosuppression regimens.

Previous studies have reported superiority of mechanistic target-of-rapamycin (mTOR) antagonists (mTA) over calcineurin inhibitors (CNI) as part of maintenance immunosuppression (IS) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). MEDLINE and EMBASE were searched through October 2019 for studies comparing maintenance IS with mTA + antimetabolites (AM), CNI + mTA or CNI + AM post HT. The main outcomes were all-cause mortality, CAV, acute rejection, CMV infections, and change in eGFR. To compare different IS antagonists, a random-effects network meta-analysis was performed. We used p-scores to rank best treatments per outcome. Our search identified fifteen eligible studies (5 studies comparing mTA + AM vs. CNI + AM, 9 comparing CNI + mTA vs. CNI + AM, 1 comparing mTA + AM vs. CNI + mTA, 8 using everolimus and 7 sirolimus as mTA) reporting the selected outcomes. We did not identify any statistical difference in all-cause mortality among the three IS regimens without heterogeneity among studies. CAV rates were significantly lower with CNI + mTA (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.3-0.92). Acute rejection rates were significantly lower with CNI + AM (OR 0.26, 95% CI 0.12-0.56) and with CNI + mTA (OR 0.16, 95% CI 0.07-0.33) compared with mTA + AM without significant heterogeneity (I2 = 43%, p = 0.9). CMV infections were significantly lower with mTA + AM (OR 0.13, 95% CI 0.03-0.46) and with CNI + mTA (OR 0.27, 95% CI 0.2-0.38) compared with CNI + AM without heterogeneity. mTA + AM led to higher eGFR compared with CNI + AM (9.06 ml/min/1.73 m2, 95% CI 3.15-14.97) and CNI + Mta (9.64 ml/min/1.73 m2, 95% CI 0.91-18.36), but the heterogeneity among studies was significant. CNI + mTA ranked better for CAV (p = 0.78), and acute rejection (p = 0.99) while mTA + AM for CMV infection (p = 0.94) and improvement in renal function (p = 0.93) than other regimens. Different IS regimens have similar effects on survival post HT, but CNI + mTA was associated with lower CAV rates, and acute rejection, while mTA + AM with less CMV infection post HT.

The risk of stent thrombosis of dual antithrombotic therapy for patients who require oral anticoagulant undergoing percutaneous coronary intervention: insights of a meta-analysis of randomized trials.

Recent meta-analyses investigating dual antithrombotic therapy (DAT) versus triple antithrombotic therapy (TAT) among patients who require oral anticoagulants especially with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raised the concern of stent thrombosis (ST) and myocardial infarction (MI), however, these meta-analyses did not include all randomized trials who require oral anticoagulants. We aimed to investigate the efficacy of DAT versus TAT in these patients undergoing PCI. Our data showed the risk of ST was not significantly different in DAT vs. TAT (HR [95%CI]: 1.50 [0.97-2.34], p = .07; I2 = 0%) and MI (HR [95%CI]: 1.17 [0.95-1.45], p = .14; I2 = 0%).

Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis.

BACKGROUND: Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients. METHODS: We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized. RESULTS: Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]). CONCLUSIONS: In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.

Network meta-analysis of anticoagulation strategies for venous thromboembolism in patients with cancer.

Cancer-associated thrombosis (CAT) is a common complication in patients with malignancy. Although direct oral anticoagulants (DOACs) have emerged as a treatment option for CAT, there have not been head-to-head comparisons of these agents. We searched MEDLINE and EMBASE from inception to April 2020 for studies comparing the effect of different long-term anticoagulation strategies for venous thromboembolism (VTE) in patients with cancer. We performed a network meta-analysis comparing the antithrombotic strategies in the selected studies using random-effects model. We identified a total of 20 studies [9 randomized control trials (RCTs) and 11 subgroup analyses from other unique RCTs] with total of 6699 patients for inclusion in our analysis. There was no significant difference in recurrent VTE, all-cause death, major bleeding and clinically relevant non-major bleeding among DOACs. When DOACs were combined, recurrent VTE was significantly decreased in DOACs compared to low-molecular weight heparin (LMWH) and Vitamin K antagonist (VKA) [RR (95% CI) 0.75 (0.59-0.94); RR (95% CI) 0.51 (0.39-0.66), respectively] without significant increase in major bleeding or clinically relevant non-major bleeding. In patients with CAT, there was no significant difference in recurrent thrombotic event among different DOACs. Bleeding risk was comparable among all anticoagulation strategies. When DOACs were combined, DOACs were associated with a significant decrease in recurrent VTE with comparable bleeding risk to LMWH and VKA.

Transcatheter versus surgical aortic valve replacement in patients with chronic obstructive pulmonary disease.

Although a number of studies compared mortality after transcatheter aortic valve implantation (TAVI) with that after surgical aortic replacement (SAVR) in patients with chronic obstructive pulmonary disease (COPD), no meta-analysis of them has been conducted to date. To determine whether TAVI or SAVR is associated with better postprocedural survival in patients with COPD, a meta-analysis of all studies currently available was performed. Design. To identify all comparative studies of TAVI with SAVR in patients with COPD, PubMed and Web of Science were searched through January 2020. Studies meeting the following criteria were included in the present meta-analysis: the design was an observational comparative study or a randomized controlled trial; the study population was patients with COPD; patients were assigned to TAVI versus SAVR; and outcomes included all-cause mortality. Adjusted (if unavailable, unadjusted) odds or hazard ratios with their confidence intervals (CIs) of mortality for TAVI versus SAVR were extracted from each study. Study-specific estimates were combined in the random-effects model. Results. Six eligible studies with a total of 4771 patients with COPD were identified and included in the present meta-analysis. The meta-analysis indicated significantly lower early (in-hospital or 30-day) mortality after TAVI than after SAVR (odds ratio, 0.69; 95% CI, 0.53-0.90; p = .006) but no significant difference in midterm (1-year to 5-year) mortality between TAVI and SAVR (hazard ratio, 1.07; 95% CI, 0.79-1.44; p = .68). Conclusions. In patients with COPD, TAVI was associated with reduced early mortality, while midterm mortality appeared similar, as compared with SAVR.

P2Y12 inhibitor monotherapy versus aspirin monotherapy after short-term dual antiplatelet therapy for percutaneous coronary intervention: Insights from a network meta-analysis of randomized trials.

BACKGROUND: A number of trials have assessed the efficacy and safety of short-term dual antiplatelet therapy (DAPT) in patients who undergo percutaneous coronary intervention (PCI). However, whether to continue aspirin or a P2Y12 inhibitor after a short course of DAPT is actively debated. METHODS: PUBMED and EMBASE were searched through March 2020 for randomized controlled trials evaluating short-term DAPT (≤6 months) when compared with longer-term (≥12 months) DAPT among patients undergoing PCI. The ischemic outcomes were all-cause death, myocardial infarction, stent thrombosis, and stroke. The safety outcome was major and/or clinically relevant bleeding. The primary objective was to investigate the outcomes with aspirin monotherapy (Aspirin group) versus P2Y12 inhibitor monotherapy (P2Y12i group) after short-term DAPT. RESULTS: Our search identified 17 eligible trials enrolling a total of 54,625 patients comparing different DAPT duration. Either of the 2 monotherapy groups did not increase the risk of ischemic outcomes when compared with the long-term DAPT group, without difference between the Aspirin versus the P2Y12i groups. However, both monotherapy groups significantly reduced bleeding when compared with long-term DAPT (Aspirin group: hazard ratio [95% CI]: 0.62 [0.45-0.86], P=.004 and P2Y12i group: 0.68 [0.50-0.93], P=.015). There was no difference in bleeding between the Aspirin versus P2Y12i groups (hazard ratio=0.91 [0.58-1.43], P=.70). CONCLUSIONS: Among patients undergoing PCI, short-term DAPT with continuation of either aspirin or P2Y12i reduced bleeding without increasing ischemic outcomes when compared with long-term DAPT. The choice of antiplatelet therapy after short-term DAPT should be evaluated in well-powered trials.

Percutaneous coronary intervention or coronary artery bypass graft surgery for left main coronary artery disease: A meta-analysis of randomized trials.

We aimed to investigate long-term (≥5 years) outcomes of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) using a meta-analysis from updated published randomized trials. Our data showed that the risk of all-cause death as well as cardiovascular death, myocardial infarction, and stroke was similar between PCI and CABG, whereas PCI had significantly higher rates of repeat revascularization compared to CABG. Decisions for PCI versus CABG for LMCAD should be based on weighing the upfront morbidity and mortality risk of CABG with late risk of repeat revascularization with PCI and taking into consideration patient preference.

Mortality in patients undergoing revascularization with paclitaxel eluting devices for infrainguinal peripheral artery disease: Insights from a network meta-analysis of randomized trials.

OBJECTIVES: We aimed to evaluate whether paclitaxel eluting devices increased the risk of death in patients undergoing revascularization for infrainguinal peripheral artery disease using network meta-analyses. METHODS: PUBMED and EMBASE were searched through April 2020 for randomized trials in patients with infrainguinal peripheral artery disease who underwent revascularization with or without a paclitaxel eluting device (balloon/stent). Short-term mortality defined as death at 6-12 months, and long-term mortality defined as death at >12 months after revascularization. RESULTS: Our search identified 57 eligible randomized controlled studies enrolling a total of 9,362 patients comparing seven revascularization strategies (balloon angioplasty vs. bare metal stent vs. covered stent vs. paclitaxel eluting stent vs. other drug eluting stent vs. paclitaxel-coated balloon vs. bypass surgery). Overall, paclitaxel eluting stent and paclitaxel-coated balloons did not increase short-term mortality (eg, vs. balloon angioplasty: paclitaxel-coated balloon OR [95% CI] 1.21 [0.88-1.66], p = .24; paclitaxel eluting stent OR [95%CI] 1.01 [0.63-1.63], p = .97, respectively). In addition, paclitaxel eluting stent did not show significant increase in long-term mortality (eg, vs. balloon angioplasty: OR [95%CI] 1.06 [0.70-1.59], p = .79). However, paclitaxel-coated balloon showed significant increase in long-term mortality compared to balloon angioplasty and bypass (vs. balloon angioplasty: OR [95% CI] 1.48 [1.06-2.07], p = .021; vs. bypass: OR [95%CI] 1.73 [1.05-2.84], p = .031, respectively). CONCLUSIONS: In this meta-analysis of randomized trials, there was no significant increase in mortality with paclitaxel eluting stent, but there was increased risk of long-term mortality in paclitaxel-coated balloon for the treatment of infrainguinal peripheral artery disease.

Prognostic impact of baseline C-reactive protein levels on mortality after transcatheter aortic valve implantation.

OBJECTIVES: To determine whether baseline C-reactive protein (CRP) levels can predict mortality after transcatheter aortic valve implantation (TAVI), we performed a meta-analysis of currently available studies. METHODS: All studies investigating the prognostic impact of baseline (preprocedural) CRP levels on all-cause mortality after TAVI were identified by means of searching PubMed and Google Scholar through May 2019. For each study, (preferentially, adjusted rather than unadjusted) odds/hazard ratios (ORs/HRs) with corresponding 95% confidence intervals of mortality per standard-deviation (SD) (or unit) increase in CRP levels or those for high vs low CRP levels. RESULTS: Our search identified 14 eligible studies including a total of 3449 patients undergoing TAVI and reporting early (in-hospital to 3-month) and midterm (1-year to 3-year) all-cause mortality after TAVI. Pooled analyses demonstrated associations of high-baseline CRP levels with a marginal, but statistically nonsignificant increase in early mortality (pooled OR/HR per SD increase in CRP levels, 2.72; P = .09 and pooled OR/HR for high vs low CRP levels, 3.32; P = .07) and a statistically significant increase in midterm mortality after TAVI (pooled OR/HR per SD increase in CRP levels, 1.45; P < .0001 and pooled OR/HR for high vs low CRP levels, 1.78; P < .00001). Excluding HRs for high-sensitivity CRP, combining ORs/HRs of 1-year mortality, pooling HRs of ≥2-year mortality, and combining adjusted HRs did not alter the primary results. CONCLUSION: High-baseline CRP levels may predict increased midterm, but not early, mortality after TAVI.

Racial disparities in in-hospital outcomes after left ventricular assist device implantation.

BACKGROUND: Previous studies of patients undergoing various cardiac surgeries demonstrated worse outcomes among African-American (AA) patients. It remains unclear if the race is a predictor of outcomes among left ventricular assist device (LVAD) recipients. METHODS: Patients who underwent LVAD implantation between 2010 and 2017 were identified using the National Inpatient Sample. The race was classified as Caucasians vs AA vs Hispanics, and endpoints were in-hospital outcomes, length of stay, and cost. Procedure-related complications were identified via the International Classification of Diseases-9 (ICD-9) and ICD-10 coding and analysis performed via mixed-effect models. RESULTS: A total of 27 132 adults (5114 unweighted) underwent LVAD implantation in the U.S. between 2010 and 2017, including Caucasians (63.8%), AA (23.8%), and Hispanics (6%). The number of LVAD implantations increased in both Caucasians and AA during the study period. AA LVAD recipients were younger, with higher rates of females and mostly comorbidities, but lower rates of coronary artery disease and bypass grafting compared to Caucasians and Hispanics. Medicaid and median income at the lowest quartile were more frequent among AA LVAD recipients. We did not identify differences in stroke, bleeding complications, tamponade, infectious complications, acute kidney injury requiring hemodialysis, and in-hospital mortality among racial groups. AA LVAD recipients had lower rates of routine discharge than Caucasians and Hispanics, longer length of stay than Caucasians, but similar cost of hospitalization. After adjustment for clinical comorbidities, race was not a predictor of in-hospital mortality. CONCLUSION: We identified differences in clinical characteristics but not in in-hospital complications among LVAD recipients of a different races.

Baseline left ventricular diastolic dysfunction affects midterm mortality after transcatheter aortic valve implantation.

OBJECTIVES: To determine whether preprocedural left ventricular (LV) diastolic dysfunction impairs midterm mortality after transcatheter aortic valve implantation (TAVI) for patients with severe aortic stenosis (AS), we performed a meta-analysis of currently available evidence. METHODS: We identified all studies investigating impact of preprocedural severity of LV diastolic dysfunction on midterm (≥1-year) all-cause mortality after TAVI for patients with AS through a search of databases (MEDLINE and EMBASE) until September 2019. From each study, we extracted an adjusted (if unavailable, unadjusted) hazard ratio (HR) of midterm mortality. We pooled study-specific estimates in the random-effects model. RESULTS: Ten eligible studies with a total of 2380 patients with AS undergoing TAVI were identified. In accordance with pooled analyses, higher-grade preprocedural LV diastolic dysfunction was associated with significantly worse midterm all-cause mortality after TAVI compared to lower-grade dysfunction (HR for grade II vs I, 1.15; P = .002; HR for grade III vs I, 1.35; P = .001; HR for grade III vs II; 1.16, P = .002; HR for grade II-III vs I, II-III vs 0-I, or III vs I-II, 1.34; P < .00001 [primary meta-analysis]; HR per grade, 1.16; P = .003). No funnel plot asymmetry for the primary meta-analysis (for grade II-III vs I, II-III vs 0-I, or III vs I-II) was identified, which probably indicated no publication bias (P = .381 by the linear-regression test). CONCLUSION: Higher-grade preprocedural LV diastolic dysfunction was associated with worse midterm all-cause mortality after TAVI for patients with AS compared to lower-grade dysfunction.