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Background: Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. Methods: PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. Results: A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1–77.04, P < 0.00001; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10–1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14–2.31, P = 0.007; I2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23–1.36, P = 0.20; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52–2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63–1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44–1.51, P = 0.52; I2 = 25%; low certainty) between the two groups. Conclusions: Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload. Systematic Review Registration: This systematic review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), registration number CRD498330. [ABSTRACT FROM AUTHOR]

Context: Palliative care (PC) improves outcomes in noncancer illness. We hypothesized the benefit is driven by studies of heart failure (HF) patients exclusively versus studies of other noncancer illnesses.Objectives: To assess difference in outcomes in trials with HF patients exclusively vs studies of other noncancer chronic illness.Methods: We performed a meta-analysis of studies that assessed association of PC with hospital admissions, emergency department (ED) visits and advance care planning in noncancer chronic illness and compared studies of HF patients versus those with other noncancer chronic illness.Results: Our analysis included 10 HF studies (n = 4,057) and 16 non-HF studies (11 mixed conditions, 3 dementia, 2 COPD, n = 10,235). PC led to reduction in hospital admissions in HF studies (OR = 0.67 [95% CI = 0.48-0.95]) but not in other noncancer illness studies (OR = 0.86 [95% CI = 0.62-1.21]). PC intervention was nonsignificant for change in ED visits in either HF (OR = 0.70 [95% CI = 0.38-1.28]) or other noncancer studies (OR = 0.86 [95% CI = 0.69-1.07]). Increase in advance care planning was noted in both HF (OR = 4.29 [95% CI = 1.44-12.76]) and other studies (OR = 2.67 [95% CI = 1.29-5.52]). Nonsignificant reductions in symptom burden were noted for both HF-studies and non-HF studies, though overall there was a significant improvement in symptom burden (weighted mean difference -1.15 [95% CI = -1.65, -0.65]). Similar results were noted when studies of mixed populations were excluded from the non-HF studies.Conclusion: PC is particularly effective at reducing potentially unwanted hospital admissions for patients with HF compared to other noncancer illnesses. Our findings should further encourage efforts to increase PC access to HF patients. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the safety of uninterrupted versus interrupted direct oral anticoagulation (DOAC) for patients undergoing catheter ablation (CA) of atrial fibrillation (AF). Methods: We conducted a systematic search of MEDLINE and EMBASE for randomized controlled trials (RCT) and observational studies comparing uninterrupted versus interrupted DOAC for patients undergoing CA of AF. Primary outcome was major bleeding. Secondary outcomes included minor bleeding, stroke or transient ischemic attack (TIA) or thromboembolism (TE), silent cerebral ischemic events, and cardiac tamponade. Meta‐analysis was stratified by study design. Risk ratios (RR) with 95% confidence intervals were calculated using random effects model and Mantel–Haenszel method was used to pool RR. Results: A total of 13 studies (7 randomized, 6 observational) comprising 3595 patients were included. The RCT restricted analysis did not show any difference in terms of major bleeding (risk ratio [RR] = 0.79; [0.35–1.79]), minor bleeding (RR = 0.99 [0.68–1.43]), stroke or TIA or TE (RR = 0.80 [0.19–3.32]), silent cerebral ischemic events (RR = 0.64 [0.32–1.28]), and cardiac tamponade (RR = 0.61 [0.20–1.92]). Observational study restricted analysis showed a protective effect of uninterrupted DOAC on silent cerebral ischemic events (RR = 0.45 [0.31–0.67]) and no difference in other outcomes. Conclusions: There is no difference in bleeding and thromboembolic outcomes with uninterrupted versus interrupted DOAC for CA of AF and observational data suggests that uninterrupted DOACs are protective against silent cerebral ischemic lesions. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss the results of their meta-analysis to compare the efficacy and safety of dual versus single antiplatelet therapy following dual antiplatelet therapy (DAPT).

Aims: Intravenous ferric carboxymaltose (FCM) has been shown to improve functional capacity and quality of life in iron deficient heart failure patients. However, FCM's effect on hospitalizations and mortality remains unclear as previous randomized controlled trials (RCTs) and their meta‐analyses have been underpowered to detect significant differences. We sought to conduct an updated meta‐analysis using recently published RCT data. Methods and results: Online databases were searched from inception until November 2020 for RCTs evaluating the effects of FCM on clinical outcomes in iron‐deficient heart failure patients. Outcomes of interest included heart failure hospitalizations, all‐cause mortality, and cardiovascular mortality. Meta‐analysis was performed using a fixed‐effect model and estimates were reported as odds ratios (ORs), hazard ratios, or rate ratios (RRs) along with corresponding 95% confidence intervals (CIs). A total of 1947 patients (n = 1062 in the FCM group; n = 885 in the placebo group) were included. FCM, compared with placebo, significantly reduced the risk of the composite endpoint of time to first heart failure hospitalization or cardiovascular death (hazard ratio = 0.76; 95% CI = 0.63–0.90; I2 = 55%). FCM also significantly reduced the risk of recurrent heart failure hospitalizations (RR = 0.68; 95% CI = 0.54–0.85; I2 = 71%) and recurrent cardiovascular hospitalizations (RR = 0.71; 95% CI = 0.59–0.86; I2 = 56%). However, FCM had no significant effect on the risk of all‐cause (OR = 0.97; 95% CI = 0.73–1.28; I2 = 0%) or cardiovascular mortality (OR = 0.93; 95% CI = 0.69–1.27; I2 = 0%). Conclusions: Ferric carboxymaltose reduces heart failure hospitalizations and cardiovascular hospitalizations with no beneficial effect on all‐cause and cardiovascular mortality in iron‐deficient heart failure patients. These findings reinforce the role of FCM as a therapeutic option in heart failure patients. [ABSTRACT FROM AUTHOR]

Background: The safety and effectiveness of dual therapy (direct oral anticoagulant [DOAC] plus P2Y12 inhibitor) versus triple therapy (vitamin K antagonist plus aspirin and P2Y12 inhibitor) in patients with nonvalvular atrial fibrillation (AF) after percutaneous coronary intervention (PCI) is unclear.Purpose: To examine the effects of dual versus triple therapy on bleeding and ischemic outcomes in adults with AF after PCI.Data Sources: Searches of PubMed, EMBASE, and the Cochrane Library (inception to 31 December 2019) and ClinicalTrials.gov (7 January 2020) without language restrictions; journal Web sites; and reference lists.Study Selection: Randomized controlled trials that compared the effects of dual versus triple therapy on bleeding, mortality, and ischemic events in adults with AF after PCI.Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.Data Synthesis: Four trials encompassing 7953 patients were selected. At the median follow-up of 1 year, high-certainty evidence showed that dual therapy was associated with reduced risk for major bleeding compared with triple therapy (risk difference [RD], -0.013 [95% CI, -0.025 to -0.002]). Low-certainty evidence showed inconclusive effects of dual versus triple therapy on risks for all-cause mortality (RD, 0.004 [CI, -0.010 to 0.017]), cardiovascular mortality (RD, 0.001 [CI, -0.011 to 0.013]), myocardial infarction (RD, 0.003 [CI, -0.010 to 0.017]), stent thrombosis (RD, 0.003 [CI, -0.005 to 0.010]), and stroke (RD, -0.003 [CI, -0.010 to 0.005]). The upper bounds of the CIs for these effects were compatible with possible increased risks with dual therapy.Limitation: Heterogeneity of study designs, dosages of DOACs, and types of P2Y12 inhibitors.Conclusion: In adults with AF after PCI, dual therapy reduces risk for bleeding compared with triple therapy, whereas its effects on risks for death and ischemic end points are still unclear.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Aims: Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF.Methods and Results: Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = -12.21% (-15.47, -8.95); P < 0.001], LA conduit [WMD = -5.68% (-8.56, -2.79); P < 0.001], and pump [WMD = -11.07% (-14.81, -7.34); P < 0.001] emptying fractions compared with controls. LA reservoir [WMD = -13.38% (-16.07, -10.68); P < 0.001], conduit [WMD = -4.09% (-6.77, -1.42); P = 0.003], and pump [WMD = -3.53% (-4.47, -2.59); P < 0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization.Conclusions: Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies. [ABSTRACT FROM AUTHOR]

Background: In orthotopic heart transplant recipients, surveillance with endomyocardial biopsy is crucial to detect acute cellular rejection (ACR) early. ACR is a common and serious complication of transplantation with substantial morbidity and mortality. Speckle tracking echocardiography with global longitudinal strain (GLS) assessment of the left ventricle has emerged as a possible noninvasive screening modality. We have conducted a systematic literature review and meta‐analysis to evaluate the role of GLS in diagnosing ACR. Methods: The following databases were queried: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Embase. We compiled all articles evaluating changes in GLS in comparison to endomyocardial biopsy in ACR dated prior to September 2019. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled by using a random effects model. In order to determine the risk of bias, we used the revised version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. Results: Twelve studies met inclusion criteria of which ten were chosen. These studies encompassed 511 patients and 1267 endomyocardial biopsies. There was a significant difference in GLS between patients who did and did not have ACR proven by biopsy (WMD = 2.18; 95% CI: 1.57‐2.78, P = <.001; I2 = 76%). The overall sensitivity for GLS in detecting ACR was 78% (CI: 63%‐90%, P =.123; I2 = 52.2%) while the overall specificity was 68% (CI: 50%‐83%, P = <.001; I2 = 88.3%). Conclusion: Global longitudinal strain assessment of the left ventricle by speckle tracking echocardiography is useful in detecting ACR and could potentially reduce the burden of frequent endomyocardial biopsies in heart transplant recipients. [ABSTRACT FROM AUTHOR]

Background: The newer P2Y12 inhibitors have better efficacy than clopidogrel. However, whether ticagrelor or prasugrel have a better comparative safety and efficacy profile, especially in the long-term, remains inconclusive. Objective: We compared prasugrel and ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods: MEDLINE and the Cochrane library were queried for randomized controlled trials (RCTs) or observational studies comparing prasugrel with ticagrelor in patients with ACS undergoing PCI. Random-effects pooling was used to calculate odds ratios (ORs) with 95% confidence intervals (CI). Analyses were stratified by duration of follow-up (short term [≤ 3 months] and long term [≥ 1 year]) and study design. Results: In total, 14 studies (six RCTs, eight observational studies), including 40,188 patients, met eligibility criteria. Pooled analysis did not indicate that prasugrel significantly decreased all-cause mortality compared with ticagrelor in the short term (OR 0.49; 95% CI 0.20–1.20; p = 0.11) or long term (OR 0.74; 95% CI 0.48–1.15; p = 0.38). Pooled observational studies showed significantly lower long-term all-cause mortality (OR 0.63; 95% CI 0.43–0.92; p = 0.02) and short-term stent thrombosis (OR 0.46; 95% CI 0.28–0.75; p = 0.002) with prasugrel. No significant difference was observed in the risk of nonfatal myocardial infarction, ischemic stroke, bleeding, or repeat revascularization between the two groups. Results remained similar after stratification according to follow-up and study design. Conclusions: The present analysis suggests that prasugrel might have a better efficacy profile than ticagrelor in patients with ACS undergoing PCI. However, this advantage was only seen in pooled observational studies and is likely to be affected by selection bias. [ABSTRACT FROM AUTHOR]

Current guidelines give balloon pulmonary angioplasty (BPA) a Class IIb recommendation for use in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), as its safety and efficacy remain poorly defined. We conducted a systematic review and meta-analysis to evaluate BPA effectiveness. Medline, Cochrane Library and Scopus were searched for original studies from database inception dates until 24th May 2018. Prospective studies reporting outcomes before and after BPA in inoperable CTEPH patients were included. Studies with <20 patients were excluded. Data were pooled using a random effects model represented as weighted mean differences with 95% confidence intervals (CIs). Seventeen noncomparative studies comprising 670 CTEPH patients (mean age 62 years; 68% women) were included. Meta-analysis showed significantly decreased mean pulmonary artery pressure (−14.2 mm Hg [95% CI −18.9, −9.5]), pulmonary vascular resistance (−303.5 dyn·s/cm5 [95% CI −377.6, −229.4]) and mean right atrial pressure (−2.7 mm Hg [95% CI −4.1, −1.3]) after BPA. Six-minute walk distance (67.3 m [95% CI 53.8, 80.8]) and cardiac output (0.2 l/min [95% CI 0.0, 0.3]) were significantly increased following BPA. From 12 studies reporting mortality with median follow-up of 9 months after BPA (range, 1–51 months), pooled incidence of short (≤1 month) and long-term mortality (>1 month) was 1.9% and 5.7%, respectively. This systematic review and meta-analysis suggests mildly improved hemodynamics and overall low mortality rates following BPA in inoperable CTEPH patients. This non-comparative evidence can be used to facilitate decision making until the results of larger, controlled studies become available. • Balloon pulmonary angioplasty (BPA) is a relatively safe procedure. • Significant hemodynamic improvements observed after BPA. • Reperfusion lung injury and reperfusion edema are common complications after BPA. [ABSTRACT FROM AUTHOR]

Aims: Implantable cardioverter-defibrillators (ICDs) implantation in heart failure (HF) patients with reduced ejection fraction improves survival by reducing mortality secondary to arrhythmic events. Whether advanced HF patients treated with continuous-flow left ventricular assist devices (CF-LVADs) derive similar benefit is controversial.Methods and Results: We searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and Scopus from inception through November 2018 for studies examining the association between ICD implantation and all-cause mortality in patients with advanced HF and CF-LVADs. Analyses were performed using a random-effects model. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Heterogeneity and publication bias were formally assessed, using I2 and funnel plots, respectively. Eight observational studies with a total of 6416 patients (ICD group = 3450, no ICD group = 2966) met inclusion criteria. The majority of patients (84.6%) came from the two largest observational studies. There was no difference in mortality in the ICD and no ICD groups (HR 0.96, 95% CI 0.73-1.27, P = 0.79, I2 = 42%), and ICD implantation post-CF-LVAD was not associated with an improvement in mortality (HR 0.87, 95% CI 0.48-1.57, P = 0.64, I2 = 0%). Additionally, there was no significant difference in the likelihood of transplantation (HR 1.10, 95% CI 0.93-1.30, P = 0.28, I2 = 26%) or non-mortality adverse events between the two groups.Conclusion: Implantable cardioverter-defibrillator use was not associated with improved survival in advanced HF patients with CF-LVADs. These findings underscore the need to formally study the efficacy of ICDs in this population in a dedicated randomized controlled study. [ABSTRACT FROM AUTHOR]

Background: Despite the use and purported benefits of balloon atrial septostomy (BAS), its safety, efficacy, and therapeutic role in the setting of advanced pulmonary arterial hypertension (PAH) are not well defined.Objective: The goal of this study was to conduct a systematic review and meta-analysis to better determine the evidence supporting the use of BAS in PAH.Methods: MEDLINE, Scopus, Cochrane Library, and Clinicaltrials.gov were searched from inception through May 2018 for original studies reporting outcomes with PAH prior to and following BAS. Studies comparing BAS vs other septostomy procedures were excluded. Weighted mean differences and 95% CIs were pooled by using a random effects model.Results: Sixteen studies comprising 204 patients (mean age, 35.8 years; 73.1% women) were included. Meta-analysis revealed significant reductions in right atrial pressure (-2.77 mm Hg [95% CI, -3.50, -2.04]; P < .001) and increases in cardiac index (0.62 L/min/m2 [95% CI, 0.48, 0.75]; P < .001) and left atrial pressure (1.86 mm Hg [95% CI, 1.24, 2.49]; P < .001) following BAS, along with a significant reduction in arterial oxygen saturation (-8.45% [95% CI, -9.93, -6.97]; P < .001). The pooled incidence of procedure-related (48 h), short-term (≤ 30 day), and long-term (> 30 days up to a mean follow-up of 46.5 months) mortality was 4.8% (95% CI, 1.7%, 9.0%), 14.6% (95% CI, 8.6%, 21.5%), and 37.7% (95% CI, 27.9%, 47.9%), respectively.Conclusions: The present analysis suggests that BAS is relatively safe in advanced PAH, with beneficial hemodynamic effects. The relatively high postprocedural and short-term survival with less impressive long-term survival suggest a bridging role for BAS; its contribution to this change needs to be verified by using a comparator group. [ABSTRACT FROM AUTHOR]

Objectives: To compare percutaneous mitral valve repair (PMVR) with optimal medical therapy (OMT) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR).Background: Many patients with HF and FMR are not suitable for surgical valve replacement and remain symptomatic despite maximal OMT. PMVR has recently emerged as an alternative solution.Methods: We performed a systematic review and a meta-analysis to address this question. Cochrane CENTRAL, MEDLINE, and Scopus were searched for randomized (RCT) and nonrandomized studies comparing PMVR with OMT in patients with HF and FMR. Primary endpoint was all-cause midterm mortality (at 1 and 2 years). Secondary endpoints were 30-day mortality and cardiovascular mortality and HF hospitalizations, at maximum follow-up. Studies including mixed cohort of degenerative and functional MR were allowed initially but were excluded in a secondary sensitivity analysis for each of the study's end points. This meta-analysis was performed following the publication of two RCTs (MITRA-FR and COAPT).Results: Eight studies (six observational, two RCTs) comprising 3,009 patients were included in the meta-analysis. In comparison with OMT, PMVR significantly reduced 1-year mortality (RR: 0.70 [0.56, 0.87]; p=0.002; I2=47.6%), 2-year mortality (RR: 0.63 [0.55, 0.73]; p<0.001; I2=0%), and cardiovascular mortality (RR: 0.32 [0.23, 0.44]; p<0.001; I2=0%). No significant difference between PMVR+OMT and OMT was noted in HF hospitalization (HR: 0.69 [0.40, 1.20]; p=0.19; I2=85%) and 30-day mortality (RR: 1.13 [0.68, 1.87]; p=0.16; I2=0%).Conclusions: In comparison with OMT, PMVR significantly reduces 1-year mortality, 2-year mortality, and cardiovascular mortality in patients with HF and severe MR. [ABSTRACT FROM AUTHOR]

Background Current guidelines do not support the use of serial natriuretic peptide (NP) monitoring for heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) treatment, despite some studies showing benefit. We conducted an updated meta-analysis to address whether medical therapy in HFpEF or HFrEF should be titrated according to NP levels. Methods MEDLINE, Scopus and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) comparing NP versus guideline directed titration in HF patients through December 2017. The key outcomes of interest were mortality, HF hospitalizations and all-cause hospitalizations. Risk ratios and 95% confidence intervals were pooled using random effects model. Sub-group analyses were performed for type of NP used, average age and acute or chronic HF. Results Eighteen trials including 5116 patients were included. Meta-analysis showed no significant difference between the NP-guided arm versus guideline directed titration in all-cause mortality (RR = 0.91 [0.81, 1.03]; p  = 0.13), HF hospitalizations (RR = 0.81 [0.65, 1.01]; p  = 0.06), and all cause hospitalizations (RR = 0.93 [0.86, 1.01]; p  = 0.09). The results were consistent upon subgroup analysis by biomarker type (NT-proBNP or BNP) and type of heart failure (acute or chronic and HFrEF or HFpEF). Sub-group analysis suggested that NP-guided treatment was associated with decreased all-cause hospitalizations in patients younger than 72 years of age. Conclusion The available evidence suggests that NP-guided therapy provides no additional benefit over guideline directed therapy in terms of all-cause mortality and HF-related hospitalizations in acute or chronic HF patients, regardless of their ejection fraction. [ABSTRACT FROM AUTHOR]

Background: The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding.Methods and Results: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79).Conclusions: Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice. [ABSTRACT FROM AUTHOR]

Background: Despite the publication of several randomized clinical trials comparing catheter ablation (CA) with medical therapy (MT) in patients with atrial fibrillation (AF), the superiority of one strategy over another is still questioned by many. In this meta-analysis of randomized controlled trials, we compared the efficacy and safety of CA with MT for AF.Methods: We systematically searched MEDLINE, EMBASE, and other online sources for randomized controlled trials of AF patients that compared CA with MT. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular hospitalizations and recurrence of atrial arrhythmia. Subgroup analyses stratified by the presence of heart failure with reduced ejection fraction, type of AF, age, and sex were performed. Risk ratios (RRs) with 95% CIs were calculated using a random effects model, and Mantel-Haenszel method was used to pool RR.Results: Eighteen randomized controlled trials comprising 4464 patients (CA, n=2286; MT, n=2178) were included. CA resulted in a significant reduction in all-cause mortality (RR, 0.69; 95% CI, 0.54-0.88; P=0.003) that was driven by patients with AF and heart failure with reduced ejection fraction (RR, 0.52; 95% CI, 0.35-0.76; P=0.0009). CA resulted in significantly fewer cardiovascular hospitalizations (hazard ratio, 0.56; 95% CI, 0.39-0.81; P=0.002) and fewer recurrences of atrial arrhythmias (RR, 0.42; 95% CI, 0.33-0.53; P<0.00001). Subgroup analyses suggested that younger patients (age, <65 years) and men derived more benefit from CA compared with MT.Conclusions: CA is associated with all-cause mortality benefit, that is driven by patients with AF and heart failure with reduced ejection fraction. CA reduces cardiovascular hospitalizations and recurrences of atrial arrhythmia for patients with AF. Younger patients and men appear to derive more benefit from CA. [ABSTRACT FROM AUTHOR]

Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype. Methods and Results Cochrane CENTRAL, Medline, and Scopus databases were searched for randomized or nonrandomized studies that assessed the association between anticoagulation and outcomes in patients with PAH. Hazard ratios (HRs) for mortality were pooled using the random effects model. Subgroup analyses were performed for type of PAH and study design. Twelve nonrandomized studies, at moderate risk of bias, were included. These consisted of 2512 patients (1342 receiving anticoagulation and 1170 controls). Anticoagulation significantly reduced mortality in the overall PAH cohort (HR, 0.73 [0.57, 0.93]; P=0.001; I2=64%). On subgroup analysis, a significant mortality reduction was seen in idiopathic PAH patients (HR, 0.73 [0.56, 0.95]; P=0.02; I2=46%), whereas no significant difference was observed in connective tissue disease-related PAH (HR, 1.16 [0.58, 2.32]; P=0.67; I2=71%). Sensitivity analysis specific to scleroderma-associated PAH demonstrated a significant increase in mortality with anticoagulant use (HR, 1.58 [1.08, 2.31]; P=0.02; I2=9%). Conclusions This meta-analysis shows that use of anticoagulation may improve survival in idiopathic PAH patients, while increasing mortality when used in scleroderma-associated-PAH patients. Currently, no randomized clinical trials have been published, and until randomized data are available, anticoagulant use in PAH should be tailored to PAH subtype. [ABSTRACT FROM AUTHOR]

The number of meta-analyses published annually has increased more than 20-fold between 1994 (n = 386) and 2014 (n = 8203). In examining how much of this increase in meta-analysis publication has genuinely represented novel contributions to clinical medicine and public health, it became clear that there was an abundance of redundant and disorganized meta-analyses, creating confusion and generating considerable debate. Ironically, meta-analyses, which should prevent redundant research, have become a victim of it. Recently, 17 meta-analyses were published based on the results of only 3 randomized controlled trials that studied the role of transcatheter closure of patent foramen ovale for prevention of cryptogenic stroke. In our search of the published literature, we identified at least 10 topics that were the subject of 10 meta-analyses. In the context of overlapping meta-analyses, one questions what needs to be done to put this "runaway train" back on track. In this review we examine the practice of redundant meta-analyses and the reasons for its disturbing "popularity." The registration of systematic reviews should be mandatory in prospective registries, such as PROSPERO, and the PRISMA checklist should be updated to incorporate new evidence and mandate the reference of previously published reviews and rationale for any new study. [ABSTRACT FROM AUTHOR]

Background: For low-risk patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) the recommended optimal discharge timing is inconsistent in guidelines. The European Society of Cardiology guidelines recommend early discharge within 48-72 h, while the American College of Cardiology guidelines do not recommend a specific discharge strategy. In this systematic review and meta-analysis we compared outcomes with early discharge (≤3 days) versus late discharge (>3 days).Methods: Randomized controlled trials (RCTs) and observational studies were selected after searching MEDLINE and EMBASE database. Meta-analysis was stratified according to study design. Outcomes were reported as random effects risk ratios (RR) with 95% confidence intervals.Results: Seven RCTs comprising 1780 patients and 4 observational studies comprising 39,288 patients were selected. The RCT-restricted analysis did not demonstrate significant differences in terms of all-cause mortality (RR, 0.97 [0.23-4.05]) and major adverse cardiac events (MACE) (RR, 0.84 [0.56-1.26]). Conversely, observational study restricted analysis showed that early vs late discharge strategy was associated with a reduction in all-cause mortality (RR, 0.40 [0.23-0.71]) and MACE (RR, 0.45 [0.26-0.78]). There were no significant differences in hospital readmissions between early vs late discharge in both RCT or observational study analyses.Conclusions: Early discharge strategy in appropriately selected low-risk patients with STEMI undergoing PCI is safe and it has the potential to improve cost of care. [ABSTRACT FROM AUTHOR]

Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents.Methods: Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model.Results: In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding.Conclusions: The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events. [ABSTRACT FROM AUTHOR]

Introduction: Catheter ablation has shown to reduce mortality in patient with atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction. Its effect on mortality in patients without HF has not been well elucidated. Methods: Thirteen randomized controlled trials encompassing 3856 patients were selected using PubMed, Embase and the CENTRAL till April 2019. Estimates were reported as random effects risk ratio (RR) with 95% confidence intervals (CI). Results: Compared with medical therapy, catheter ablation did not reduce the risk of all-cause mortality (RR, 0.86, 95% CI, 0.62-1.19, P=0.36; I²=0), stroke (RR, 0.55, 95% CI, 0.18-1.66, P=0.29; I²=0), need for cardioversion (RR, 0.84, 95% CI, 0.66-1.08, P=0.17; I²=0) or pacemaker (RR, 0.59, 95% CI, 0.34-1.01, P=0.06; I²=0). However, ablation reduced the RR of cardiac hospitalization (0.37, 95% CI, 0.18-0.77, P=0.01; I²=86), and recurrent atrial arrhythmia (0.46, 95% CI, 0.35-0.60, P<0.001; I²=87). There were non-significant differences among treatment groups with respect to major bleeding (RR, 1.89, 95% CI, 0.59-6.08, P=0.29; I²=15), and pulmonary vein stenosis (RR, 3.00, 95% CI, 0.83-10.87, P=0.09; I²=0), but had significantly higher rates of pericardial tamponade (RR, 4.46, 95 % CI, 1.70-11.72, P<0.001; I²=0). Conclusions: Catheter ablation did not improve survival compared with medical therapy in patients with AF without HF. Catheter ablation reduced cardiac hospitalization and recurrent atrial arrhythmia at the expense of pericardial tamponade. [ABSTRACT FROM AUTHOR]

Background: There is inconsistency in the literature regarding the clinical effects of proton pump inhibitors (PPI) when added to dual antiplatelet therapy (DAPT) in subjects with coronary artery disease (CAD). We performed meta-analysis stratified by study design to explore these differences.Methods and Results: 39 studies [4 randomized controlled trials (RCTs) and 35 observational studies) were selected using MEDLINE, EMBASE and CENTRAL (Inception-January 2018). In 221,204 patients (PPI = 77,731 patients, no PPI =143,473 patients), RCTs restricted analysis showed that PPI did not increase the risk of all-cause mortality (Risk Ratio (RR): 1.35, 95% Confidence Interval (CI), 0.56-3.23, P = 0.50, I2 = 0), cardiovascular mortality (RR: 0.94, 95% CI, 0.25-3.54, P = 0.92, I2 = 56), myocardial infarction (MI) (RR: 0.97, 95% CI, 0.62-1.51, P = 0.88, I2 = 0) or stroke (RR: 1.11, 95% CI, 0.25-5.04, P = 0.89, I2 = 26). However, PPI significantly reduced the risk of gastrointestinal (GI) bleeding (RR: 0.32, 95% CI, 0.20-0.52, P < 0.001, I2 = 0). Conversely, analysis of observational studies showed that PPI significantly increased the risk of all-cause mortality (RR: 1.25, 95% CI, 1.11-1.41, P < 0.001, I2 = 82), cardiovascular mortality (RR: 1.25, 95% CI, 1.03-1.52, P = 0.02, I2 = 71), MI (RR: 1.30, 95% CI, 1.16-1.47, P < 0.001, I2 = 82) and stroke (RR: 1.60, 95% CI, 1.43-1.78, P < 0.001, I2 = 0), without reducing GI bleeding (RR: 0.74, 95% CI, 0.45-1.22, P = 0.24, I2 = 79).Conclusion: Meta-analysis of RCTs endorsed the use of PPI with DAPT for reducing GI bleeding without worsening cardiovascular outcomes. These findings oppose the negative observational data regarding effects of PPI with DAPT. [ABSTRACT FROM AUTHOR]

Background: The optimal preventive strategy for contrast induced acute kidney injury (CIAKI) in patients undergoing cardiac catheterization remains uncertain.Objective: We conducted Bayesian network meta-analysis (NMA) to compare different preventive strategies for CIAKI in these cohorts.Methods: Forty-nine randomized controlled trials were extracted using MEDLINE, EMBASE and CENTRAL data bases (inception-1st December 2017). We calculated median of the odds ratio (OR) with the corresponding 95% credible interval (CrI). The ranking probability of each treatment was based on SUCRA (surface under the cumulative ranking curve).Results: In NMA of 28,063 patients [normal saline (NS: 9716 patients), sodium bicarbonate (NaHCO3: 4484 patients), statin (2542 patients), N-acetylcysteine (NAC: 3006 patients), NAC + NaHCO3 (774 patients), NS + NAC (3807 patients), NS + NaHCO3 (135 patients) and placebo (3599 patients)], statins reduced the relative risk of CIAKI compared with NS (OR: 0.50; 95% CrI, 0.25-0.99), and placebo (OR: 0.44; 95% CrI, 0.24-0.83). Subgroup analyses showed that in patients receiving low osmolar contrast, statins reduced the relative risk of CIAKI by 58% versus NS, and 51% versus placebo. There were no significant differences across all the treatments in terms of risk of hemodialysis or all-cause mortality. Statins had the highest probability for reducing the risk of CIAKI (SUCRA, 0.86), risk of hemodialysis (SUCRA, 0.88) and all-cause mortality (SUCRA, 0.81).Conclusion: Statins were the superior preventive strategy for reducing the risk of CIAKI compared with NS alone and placebo. [ABSTRACT FROM AUTHOR]