Faculty Bibliography

Background Although current guidelines recommend dual antiplatelet therapy (DAPT) for 3 to 6 months following transcatheter aortic valve replacement (TAVR), there are no studies directly comparing outcomes of different durations of DAPT following TAVR. Methods and Results PubMed, EMBASE, and Cochrane Database were searched through November 2020 to identify clinical studies that investigated single antiplatelet therapy versus DAPT use following TAVR. Studies using oral anticoagulants and antiplatelet therapy concomitantly were excluded. The DAPT group was subdivided by the duration of DAPT. We extracted the risk ratios (RRs) of major or life-threatening bleeding, stroke, and all-cause mortality. Four randomized controlled trials, 2 propensity-score matched studies, and 1 observational study were identified, yielding a total of 2498 patients who underwent TAVR assigned to the single antiplatelet therapy group (n=1249), 3-month DAPT group (n=485), or 6-month DAPT group (n=764). Pooled analyses demonstrated that when compared with the single antiplatelet therapy group, the rates of major or life-threatening bleeding were significantly higher in the 3- and 6-month DAPT groups (RR [95% CI]=2.13 [1.33-3.40], P=0.016; RR [95% CI]=2.54 [1.49-4.33], P=0.007, respectively) with no difference between the 3-month DAPT versus 6-month DAPT groups. The rates of stroke and all-cause mortality were similar among the 3 groups. Conclusions In this network meta-analysis of antiplatelet therapy following TAVR, single antiplatelet therapy with aspirin had lower bleeding without increasing stroke or death when compared with either 3- or 6-month DAPT.

The concept of a direct association between coronary graft patency and clinical status is generally accepted. However, the relationship is more complex and variable than usually thought. Key issues are the lack of a common definition of graft occlusion and of a standardized imaging protocol for patients undergoing coronary bypass surgery. Factors like the type of graft, the timing of the occlusion, and the amount of myocardium at risk, as well as baseline patients' characteristics, modulate the patency-to-clinical status association. Available evidence suggests that graft occlusion is more often associated with non-fatal events rather than death. Also, graft failure due to competitive flow is generally a benign event, while graft occlusion in a graft-dependent circulation is associated with clinical symptoms. In this systematic review, we summarize the evidence on the association between graft status and clinical outcomes.

BACKGROUND:Mechanical circulatory support (MCS) with Impella or intra-aortic balloon pump (IABP) is used for high-risk percutaneous coronary intervention (PCI) and/or for cardiogenic shock (CS) due to acute myocardial infarction. We aimed to investigate the efficacy and safety of Impella or IABP when compared with no MCS using a network meta-analysis of randomized controlled trials (RCTs). METHODS:EMBASE and MEDLINE were searched through February 2020 for RCT evaluating efficacy of Impella vs. IABP vs. no MCS in patients undergoing high-risk PCI or CS. The primary efficacy outcome was 30 day or in-hospital all-cause mortality whereas the primary safety outcomes were major bleeding and vascular complications. RESULTS:= 1.5%). CONCLUSIONS:Neither Impella nor IABP decreased all-cause short-term mortality when compared with no MCS for high-risk PCI and/or CS. Moreover, Impella increased major bleeding compared with no MCS.

A patient with coronavirus disease 19 (COVID-19) developed acute myocardial infarction (AMI) complicated by extensive coronary thrombosis and cardiogenic shock. She underwent percutaneous coronary intervention and placement of a mechanical circulatory support device but subsequently died from shock. This report illustrates the challenges in managing patients with COVID-19, AMI, and cardiogenic shock.

INTRODUCTION/BACKGROUND:Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (<5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome. METHODS:The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12-70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30-90 mL/min/1.73 m2, and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values >200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. RESULTS:A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (n = 77) or placebo (n = 80). The average age at screening was 39.2 years, and 23 (15%) were <18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m2, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was -4.9 mL/min/1.73 m2 despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. DISCUSSION/CONCLUSION/CONCLUSIONS:CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.

BACKGROUND:Potent P2Y12 inhibitors reduce cardiovascular events but increase bleeding in patients presenting with acute coronary syndrome (ACS). Elderly patients are at increased risk of bleeding and whether the benefit-risk ratio of potent P2Y12 inhibitors remains favorable is not known. OBJECTIVES/OBJECTIVE:To investigate the efficacy and safety of potent P2Y12 inhibitors versus clopidogrel in elderly patients with ACS. METHODS:PUBMED and EMBASE were searched through July 2020 for randomized control trials (RCTs) or subgroup analyses of RCTs investigating potent P2Y12 inhibitors (prasugrel or ticagrelor) or clopidogrel in elderly (age ≥ 65 years) patients with ACS. The primary outcome was major adverse cardiovascular events (MACE). RESULTS:=0%). In a subgroup analysis, ticagrelor reduced all-cause mortality (HR: 0.73; 95% CI [0.55-0.98]) and cardiovascular death (HR: 0.70; 95% CI [0.54-0.90]) compared with clopidogrel. CONCLUSIONS:Among elderly patients with ACS, potent P2Y12 inhibitors reduce cardiovascular death but increase bleeding with no difference in MACE or all-cause death when compared with clopidogrel. Further RCTs are needed to refine P2Y12 inhibitor selection for elderly patients with ACS.

In the era of evidence-based medicine, systematic reviews and meta-analyses are considered at the top of evidence hierarchy. Despite the almost exponential increase in the number of published meta-analyses over the course of the last decades, only a small minority of them is of high quality, with major flaws involving every aspect of the meta-analytic process. The strength of a meta-analysis is closely linked to the quality of the included studies. Once preliminary phases are completed, it is vital that selected papers undergo a thorough quality assessment, using the most appropriate tools among those available. Analytical approaches must be tailored to the nature of the extracted data and the specific purpose of the meta-analysis. Appraisal of heterogeneity is a key step to inform subgroup or meta-regression analyses. The solidity of the results of the main analysis (especially in meta-analyses of observational studies or studies with high heterogeneity) should be tested by means of pertinent sensitivity analyses. Finally, the investigators should be aware of the possibility of publication bias and make efforts to assess it using qualitative and quantitative methods. The aim of the second part of this expert review is to provide guidance on how to appropriately perform trial level meta-analyses, with particular focus on the quality assessment of the included studies, the choice of the appropriate statistical approach, the methods to deal with heterogeneity (including subgroup, meta-regression and sensitivity analyses), and the appraisal of publication bias.

The number of cardiac surgical meta-analyses and systematic reviews published in the last decades has constantly increased, paralleling the exponential growth observed in virtually all other medical fields. However, meta-analyses are open to methodological flaws if best practices are not strictly followed. Assessment of the appropriateness of the research question is a crucial first step. Once a protocol has been developed, this should be registered before the work is initiated. The cornerstone of any systematic review or meta-analysis is a rigorous, comprehensive, and most of all reproducible search which follows a prespecified and clear strategy. Eligibility criteria must be discussed and agreed upon in advance to guide final study selection, which ultimately lays the foundation for subsequent data extraction. In case of missing or partially reported data, the authors of the original paper should be contacted. Adherence to rigorous methodological rules at each of these stages will warrant availability of good quality data for formal statistical analyses. The aim of the first part of this expert review is to discuss the limits and pitfalls of the meta-analytic approach and provide guidance on how to perform trial level meta-analyses, with particular reference to the identification of an appropriate research question, the definition and registration of the protocol, the search strategy, the study selection and the data abstraction.