Faculty Bibliography

Large randomized clinical trials in cardiovascular disease have proliferated over the past 3 decades, with results that have influenced every aspect of cardiology practice. Despite these advances, there remains a substantial need for more high-quality evidence to inform cardiovascular clinical practice, given the increasing prevalence of cardiovascular disease around the world. Traditional clinical trials are increasingly challenging due to rising costs, increasing complexity and length, and burdensome institutional and regulatory requirements. This review will examine the current landscape of cardiovascular clinical trials in the United States, highlight recently conducted registry-based clinical trials, and discuss the potential attributes of the recently launched pragmatic clinical trial by the Patient-Centered Outcomes Research Institute's National Patient-Centered Clinical Research Network, called the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing the Benefits and Long-term Effectiveness) trial.

This article discusses the controversies surrounding the use of transradial versus transfemoral approaches in the management of patients with ST-segment elevation myocardial infarction, beginning with a review of the benefits of transradial percutaneous coronary intervention (PCI) in this population. The unanswered questions about the mechanism underlying the mortality benefit of transradial PCI are discussed, concluding with recommendations for safe and effective strategies for adoption of the transradial approach to optimize outcomes in these high-risk patients.

Cardiogenic shock is a common clinical condition with high in-hospital mortality. Early application of appropriate interventions for cardiogenic shock-including medical therapies, revascularization, temporary hemodynamic support devices, and durable mechanical circulatory support-may improve outcomes. The number and complexity of therapies for cardiogenic shock are increasing, making time-dependent decision-making more challenging. A multidisciplinary cardiogenic shock team is recommended to guide the rapid and efficient use of these available treatments. © 2015 Wiley Periodicals, Inc.

BACKGROUND:Acute kidney injury (AKI) complicating percutaneous coronary intervention (PCI) is associated with adverse clinical outcomes. To date, no studies have evaluated the association of blood transfusion with AKI in patients undergoing PCI. METHODS AND RESULTS:We used a retrospective cohort study of all patients with acute coronary syndrome undergoing PCI from CathPCI Registry (n=1 756 864). The primary outcome was AKI defined as the rise in serum creatinine post procedure ≥0.5 mg/dL or ≥25% above baseline values. AKI developed in 9.0% of study sample. Patients with AKI were older, more often women, and had high prevalence of comorbidities, including diabetes mellitus, hypertension, and advanced stages of chronic kidney disease at baseline. Blood transfusion was utilized in 2.2% of patients. In the overall sample, AKI developed in 35.1% of patients who received transfusion versus 8.4% of patients without transfusion (adjusted odds ratio, 4.87 [4.71-5.04]). In the subgroup of patients who sustained bleeding event and received transfusion, the rate of AKI was significantly increased across all preprocedure hemoglobin levels versus no blood transfusion. Similar findings were seen in the subgroup of patients with no bleeding event. CONCLUSIONS:Blood transfusion is strongly associated with AKI in patients with acute coronary syndrome undergoing PCI. Further investigation is needed to determine whether a restrictive blood transfusion strategy might improve PCI outcomes by reducing the risk of AKI.

OBJECTIVE:We studied the characteristics of patients with ST segment elevation myocardial infarction (STEMI) after expansion of a STEMI registry as part of the STEMI network programme in a metropolitan city and the surrounding area covering ∼26 million inhabitants. DESIGN:Retrospective cohort study. SETTING:Emergency department of 56 health centres. PARTICIPANTS:3015 patients with acute coronary syndrome, of which 1024 patients had STEMI. MAIN OUTCOME MEASURE:Characteristics of reperfusion therapy. RESULTS:The majority of patients with STEMI (81%; N=826) were admitted to six academic percutaneous coronary intervention (PCI) centres. PCI centres received patients predominantly (56%; N=514) from a transfer process. The proportion of patients receiving acute reperfusion therapy was higher than non-reperfused patients (54% vs 46%, p<0.001), and primary PCI was the most common method of reperfusion (86%). The mean door-to-device (DTD) time was 102±68 min. In-hospital mortality of non-reperfused patients was higher than patients receiving primary PCI or fibrinolytic therapy (9.1% vs 3.2% vs 3.8%, p<0.001). Compared with non-academic PCI centres, patients with STEMI admitted to academic PCI centres who underwent primary PCI had shorter mean DTD time (96±44 min vs 140±151 min, p<0.001), higher use of manual thrombectomy (60.2% vs13.8%, p<0.001) and drug-eluting stent implantation (87% vs 69%, p=0.001), but had similar use of radial approach and intra-aortic balloon pump (55.7% vs 67.2%, and 2.2% vs 3.4%, respectively). In patients transferred for primary PCI, TIMI risk score ≥4 on presentation was associated with a prolonged door-in to door-out (DI-DO) time (adjusted OR 2.08; 95% CI 1.09 to 3.95, p=0.02). CONCLUSIONS:In the expanded JAC registry, a higher proportion of patients with STEMI received reperfusion therapy, but 46% still did not. In developing countries, focusing the prehospital care in the network should be a major focus of care to improve the DI-DO time along with improvement of DTD time at PCI centres. TRIAL REGISTRATION NUMBER:NCT02319473.

BACKGROUND:Bioabsorbable cardiac matrix (BCM) is a novel device that attenuates adverse left ventricular (LV) remodeling after large myocardial infarctions in experimental models. OBJECTIVES:This study aimed to analyze whether BCM, compared with saline control, would result in less LV dilation and fewer adverse clinical events between baseline and 6 months. METHODS:In an international, randomized, double-blind, controlled trial, 303 subjects with large areas of infarction despite successful primary percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) were randomized 2:1 to BCM or saline injected into the infarct-related artery 2 to 5 days after primary PCI. The primary outcome was mean change from baseline in LV end-diastolic volume index (LVEDVI) at 6 months. Secondary outcomes included change in Kansas City Cardiomyopathy Questionnaire score, 6-minute walk time, and New York Heart Association functional class at 6 months. The primary safety endpoint was a composite of cardiovascular death, recurrent MI, target-vessel revascularization, stent thrombosis, significant arrhythmia requiring therapy, or myocardial rupture through 6 months. RESULTS:In total, 201 subjects were assigned to BCM and 102 to saline control. There was no significant difference in change in LVEDVI from baseline to 6 months between the groups (mean change ± SD: BCM 14.1 ± 28.9 ml/m(2) vs. saline 11.7 ± 26.9 ml/m(2); p = 0.49). There was also no significant difference in the secondary endpoints. The rates of the primary safety outcome were similar between the 2 groups (BCM 11.6% vs. saline 9.1%; p = 0.37). CONCLUSIONS:Intracoronary deployment of BCM 2 to 5 days after successful reperfusion in subjects with large myocardial infarction did not reduce adverse LV remodeling or cardiac clinical events at 6 months. (IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction [PRESERVATION I]; NCT01226563).

OBJECTIVES/OBJECTIVE:We evaluated outcomes associated with transradial vs. transfemoral approaches and vorapaxar in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the TRACER trial. BACKGROUND:Vorapaxar reduces ischemic events but increases the risk of major bleeding. METHODS:We compared 30-day and 2-year major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization) and noncoronary artery bypass graft (CABG)-related bleedings in 2,192 transradial and 4,880 transfemoral patients undergoing PCI after adjusting for confounding variables, including propensity for transradial access. RESULTS:Overall, 30-day GUSTO moderate/severe and non-CABG TIMI major/minor bleeding occurred less frequently in transradial (0.9% vs. 2.0%, P = 0.001) vs. transfemoral (1.1% vs. 2.5%, P = 0.005) patients. A similar reduction was seen at 2 years (3.3% vs. 4.7%, P = 0.008; 3.3% vs. 4.9%, P < 0.001, respectively). Transradial was associated with an increased risk of ischemic events at 30 days (OR 1.38, 95% CI 1.11-1.72; P = 0.004), driven primarily by increased periprocedural myocardial infarctions. At 2 years, rates of MACE were comparable (HR 1.14, 95% CI 0.98-1.33; P = 0.096). Although bleeding rates were higher with vorapaxar in transfemoral vs. transradial patients, there was no significant treatment interaction. Also, the access site did not modulate the association between vorapaxar and MACE. CONCLUSIONS:Transradial access was associated with lower bleeding rates and similar long-term ischemic outcomes, suggesting transradial access is safer than transfemoral access among ACS patients receiving potent antiplatelet therapies. Because of the nonrandomized allocation of arterial access, these results should be considered exploratory. © 2015 Wiley Periodicals, Inc.