Faculty Bibliography

BACKGROUND:Transcatheter aortic valve replacement (TAVR) is a viable alternative to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (SAS) who are at high risk for surgery. We sought to evaluate the outcomes of TAVR vs SAVR in low-intermediate risk patients with SAS. METHODS AND RESULTS/RESULTS:We performed random-effects meta-analysis of randomized controlled trials (RCTs) and propensity-matched observational studies comparing TAVR vs SAVR for low-intermediate risk patients. Five RCTs and 5 observational studies with a total of 6891 patients (3489 TAVR patients; 3402 SAVR patients) were included. Pooled data from RCTs showed no significant differences in all-cause mortality between TAVR and SAVR at 30 days (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.73-1.47) and intermediate-term follow-up (RR, 0.86; 95% CI, 0.67-1.10). A trend toward decreased mortality was found with TAVR using the self-expandable vs balloon-expandable valves (RR, 0.77; 95% CI, 0.52-1.15 and RR, 1.91; 95% CI, 0.25-14.53, respectively) and transfemoral vs transthoracic approach (RR, 0.74; 95% CI, 0.55-1.01 and RR, 2.09; 95% CI, 0.40-11.03, respectively). Compared to SAVR, TAVR was associated with similar risks of stroke (RR, 0.91; 95% CI, 0.74-1.11) and myocardial infarction (RR, 1.00; 95% CI, 0.71-1.41). Furthermore, risks of major vascular complications, moderate-severe paravalvular regurgitation, and new permanent pacemaker implantation were higher with TAVR, whereas SAVR was associated with higher rates of acute kidney injury, atrial fibrillation, and major or life-threatening bleed. Finally, the above results from RCTs were consistent with pooled analyses of observational studies. CONCLUSION/CONCLUSIONS:TAVR appears to be a suitable alternative for patients with SAS who are at low-intermediate risk for SAVR.

BACKGROUND AND OBJECTIVES/OBJECTIVE:We sought to determine the frequency of use and association between prasugrel and outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) in clinical practice. METHODS:PROMETHEUS was a multicenter observational registry of acute coronary syndrome patients undergoing PCI from 8 centers in the United States that maintained a prospective PCI registry for patient outcomes. The primary end points were major adverse cardiovascular events at 90days, a composite of all-cause death, nonfatal myocardial infarction, stroke, or unplanned revascularization. Major bleeding was defined as any bleeding requiring hospitalization or blood transfusion. Hazard ratios (HRs) were generated using multivariable Cox regression and stratified by the propensity to treat with prasugrel. RESULTS:Of 19,914 patients (mean age 64.4years, 32% female), 4,058 received prasugrel (20%) and 15,856 received clopidogrel (80%). Prasugrel-treated patients were younger with fewer comorbid risk factors compared with their counterparts receiving clopidogrel. At 90days, there was a significant association between prasugrel use and lower major adverse cardiovascular event (5.7% vs 9.6%, HR 0.58, 95% CI 0.50-0.67, P<.0001) and bleeding (1.9% vs 2.9%, HR 0.65, 95% CI 0.51-0.83, P<.001). After propensity stratification, associations were attenuated and no longer significant for either outcome. Results remained consistent using different approaches to adjusting for potential confounders. CONCLUSIONS:In contemporary clinical practice, patients receiving prasugrel tend to have a lower-risk profile compared with those receiving clopidogrel. The lower ischemic and bleeding events associated with prasugrel use were no longer evident after accounting for these baseline differences.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease and death, yet little data exist regarding the comparative efficacy of coronary revascularization procedures in CKD patients with multivessel disease. We created a cohort of 4,687 adults who underwent cardiac catheterization, had a serum creatinine value measured within 30 days, and had more than one vessel with ≥50% stenosis. We used Cox proportional hazard regression modeling weighted by the inverse probability of treatment to examine the association between 4 treatment strategies (medical management, percutaneous coronary intervention [PCI] with bare metal stent, PCI with drug-eluting stent, and coronary artery bypass grafting [CABG]) and mortality among patients across categories of estimated glomerular filtration rate; secondary outcome was a composite of mortality, myocardial infarction, or revascularization. Compared with medical management, CABG was associated with a reduced risk of death for patients of any nondialysis CKD severity (hazard ratio [HR] range 0.43 to 0.59). There were no significant mortality differences between CABG and PCI, except a decreased death risk in CABG-treated CKD patients (HR range 0.54 to 0.55). Compared with medical management and PCI, CABG was associated with a lower risk of death, myocardial infarction, or revascularization in nondialysis CKD patients (HR range 0.41 to 0.64). There were similar associations between decreased estimated glomerular filtration rate and increased mortality across all multivessel coronary artery disease patient treatment groups. When accounting for treatment propensity, surgical revascularization was associated with improved outcomes in patients of all CKD severities. A prospective randomized trial in CKD patients is required to confirm our findings.

Oral Antiplatelet Drugs (OAD) have a proven track record in the risk reduction of major cardiovascular events in patients with cardiovascular disease and normal kidney function. However, major gaps exist in our understanding of their effects on thrombosis and bleeding in chronic kidney disease (CKD). Clinical practice guidelines are ambiguous about use of such drugs in CKD patients, because patients with moderate to severe CKD were systematically excluded from clinical trials evaluating the efficacy and safety of OAD. Paradoxically, CKD patients are at high risk of thrombosis and major bleeding events. Thus, choosing the right combination of OAD for cardiovascular protection in these patients is challenging. Patients with CKD exhibit high rates of OAD hyporesponsiveness. It is, therefore, imperative to explore the mechanisms responsible for poor response to OAD in CKD patients in order to use these drugs more safely and effectively. This review explores suggested mechanisms of platelet dysfucntion in CKD patients and the available evidence on the efficacy and safety of oral antiplatelet drugs in patients with renal dysfunction.

PURPOSE OF REVIEW/OBJECTIVE:Ischemic and non-ischemic injury to the heart causes deleterious changes in ventricular size, shape, and function. This adverse remodeling is mediated by neurohormonal and hemodynamic alterations and is reflected in non-invasive measures of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). These measures are closely linked to cardiovascular outcomes and have become key surrogate endpoints for evaluating the therapeutic efficacy of contemporary treatments for heart failure with reduced ejection fraction (HFrEF). In this review, we critically evaluate recent published data (2015-2016) from randomized clinical trials (RCTs) and observational studies of HFrEF therapies to assess the role of ventricular remodeling on outcomes. RECENT FINDINGS/RESULTS:These data highlight the benefits of certain guideline-directed medical therapies (GDMT) such as cardiac resynchronization therapy, surgical revascularization, and mechanical circulatory support on remodeling, while revealing the limitations of other therapies-routine mitral valve repair for patients with moderate ischemic mitral regurgitation and adjuncts to percutaneous coronary intervention in patients with ST elevation myocardial infarction (cyclosporine A and bioabsorbable cardiac matrix). The new angiotensin receptor blocker/neprilysn inhibitor, sacubitril/valsartan, demonstrates convincing improvements in clinical outcomes with a study of remodeling parameters to follow; the new cardiac myosin activator, omecamtiv mecarbil, demonstrates improvement in remodeling parameters without a clear early clinical benefit. The concepts and contemporary trials reviewed in this paper reinforce the value of non-invasive measures of ventricular remodeling (LVEF, LVESV, and LVEDV) as important metrics across a range of cardiovascular therapies. Global non-invasive measures of cardiovascular remodeling have roughly paralleled or preceded hard clinical outcomes. Additionally, the capacity for reverse remodeling in HFrEF with GDMT motivates continued research in the fields of implementation science, diagnostic imaging, and gene-based therapeutics.

Despite a high rate of early revascularization and use of intra-aortic balloon pump counterpulsation therapy, the prognosis of patients with cardiogenic shock has remained poor. In the hopes of improving outcomes, clinicians are increasingly turning to percutaneous left and right mechanical circulatory support devices. Until recently, the evidence base for these devices had consisted only of observational data, meta-analyses, and small feasibility trials. In this article, we describe the contemporary outcomes of patients with cardiogenic shock, the hemodynamics of cardiogenic shock, and hemodynamic effects of percutaneous mechanical circulatory support devices. We then use this discussion to provide clinicians with a useful framework for understanding when selecting between or while managing patients with a percutaneous mechanical circulatory support devices. We critically review the recently published data for and against the use of commercially available devices-the intra-aortic balloon pump counterpulsation, the Impella system, the TandemHeart, and venous-arterial extracorporeal membrane oxygenation-and highlight gaps in our understanding. Given such gaps, a consensus multidisciplinary approach that combines expertise from interventional cardiologists, heart failure specialists, cardiac surgeons, and cardiac anesthesiologists may help pair the right patient with the right device at the right time.

BACKGROUND:Patients with chronic kidney disease (CKD) are at increased risk for bleeding, transfusion, and dialysis after cardiac catheterization. Whether rates of these complications are increased in this high-risk population undergoing transradial access compared with transfemoral access is unknown. METHODS AND RESULTS/RESULTS:value for trend=0.04: non-CKD: HR, 0.99; 95% CI, 0.73-1.34; GFR 45-59 mL/min: HR, 0.93; 95% CI, 0.70-1.23; GFR 30-44 mL/min: HR, 0.73; 95% CI, 0.51-1.03; GFR 15-29 mL/min: HR, 0.43; 95% CI, 0.20-0.90). CONCLUSIONS:Among patients undergoing cardiac catheterization in the VA health system, transradial access was associated with lower risk for postprocedure transfusion within 48 hours among patients with more-severe CKD, and with lower risk of progression to end-stage renal disease at 1 year compared with transfemoral access. These data provide additional evidence that transradial access may provide significant benefit in this high-risk population.

Dual antiplatelet therapy (DAPT) is prescribed to millions of patients worldwide following coronary stenting. DAPT is indicated to lower the risk of ischemic events, such as myocardial infarction, including stent thrombosis, ischemic stroke, or death from cardiovascular causes. A significant number of these patients undergo noncardiac surgery and may require DAPT interruption. This poses a significant clinical dilemma because DAPT interruption exposes patients to the potential risk of stent thrombosis, perioperative myocardial infarction, or both. Conversely, continuing DAPT may be associated with excess bleeding complications. Observational data in this area are conflicting, and there are no randomized clinical trials to guide practitioner decision making. On the basis of predominantly consensus recommendations, various strategies for managing DAPT during the perioperative period have been proposed. This review presents 3 commonly encountered clinical scenarios that lead into an evidence-based discussion of practical strategies for managing perioperative antiplatelet therapy in patients following percutaneous coronary intervention.