Eric L. Wallace

Meta-analysis of long-term outcomes for drug-eluting stents versus bare-metal stents in primary percutaneous coronary interventions for ST-segment elevation myocardial infarction

The use of drug-eluting stents (DESs) in primary percutaneous coronary intervention (PPCI) has shown early benefit over bare-metal stents (BMSs) in decreasing adverse cardiac events. However, there are concerns regarding the increased risk of late and very late stent thrombosis (ST) after DES use. With the paucity of ST events individual trials may have been underpowered to detect significant differences. We sought to perform a meta-analysis to evaluate the available literature examining the outcomes of DESs and BMSs in PPCI after ≥3 years of follow-up. We analyzed 8 randomized clinical trials (RCTs) and 5 observational studies comparing DESs to BMSs in PPCI. Clinical end-point data were analyzed for RCTs and observational studies separately using random-effect models. RCTs included 5,797 patients in whom first-generation DESs (sirolimus- or paclitaxel-eluting stents) were compared to BMS control arms. Patients receiving DESs had a significantly lower risk of target lesion revascularization (odds ratio [OR] 0.48, confidence interval [CI] 0.37 to 0.61), target vessel revascularization (OR 0.53, CI 0.42 to 0.66), and accordingly major adverse cardiac events (OR 0.69; CI 0.56 to 0.84). Incidence of ST was not different between groups (OR 1.02, CI 0.76 to 1.37). There was no significant difference in mortality (OR 0.88, CI 0.68 to 1.12) or recurrent myocardial infarction (OR 0.97; CI 0.61 to 1.54). Among observational studies (n = 4,650) fewer studies reported on target lesion revascularization and target vessel revascularization, but the trend remained in favor of DESs. A small but statistically significant increase in ST was noted with DES use (OR 1.62, CI 1.18 to 2.21) at ≥3 years of follow up, without evidence of recurrent myocardial infarction. Those receiving DESs had a significantly lower mortality compared to those receiving BMSs (OR, 0.65, 95% CI 0.53 to 0.80, p <0.001). In conclusion, this meta-analysis of RCTs examining the long-term outcomes of first-generation DESs versus BMSs in PPCI, DES use resulted in decreased repeat revascularization with no increase in ST, mortality, or recurrent myocardial infarction.

A retrospective analysis of catheter-based thrombolytic therapy for acute submassive and massive pulmonary embolism

Catheter-based thrombolysis (CBT) is emerging as an option for acute pulmonary embolism (PE). Although prior studies have demonstrated improvement in right ventricular function, little data is available regarding clinical patient outcomes. Our institution adopted CBT as an option for patients with submassive and massive PE and we evaluated its effect on patient outcomes. Two hundred and twenty-one patients who presented to our institution with submassive and massive PE were analyzed over three years by time period; 102 prior to the use of CBT and 119 during the time CBT was performed. The primary outcome was in-hospital major adverse clinical events (a composite of death, recurrent embolism, major bleeding, or stroke). Secondary outcomes were overall and ICU length of stay and individual components of the composite outcome. Mean age was 56.3±16 years with high rates of central PE (57.9%), RV dysfunction (37%), and myocardial necrosis (26%). Mean RV/LV ratio was 1.2. Thirty-two patients were treated with CBT. The composite endpoint occurred more frequently in the CBT era vs the pre-CBT era (21.0% vs 14.7%, p=0.23). After multivariate adjustment, CBT treatment demonstrated no effect on major adverse clinical events (OR 0.84, CI 0.22–3.22, p=0.80). CBT era patients had an unadjusted 37% increase in ICU days and 54% increase in total length of stay (p<0.001). Within the CBT era, CBT treatment resulted in an adjusted 190% increase in overall length of stay (p<0.001). CBT did not demonstrate improvement in hospital outcomes, despite adjustments of PE severity, and was associated with a significant increase in overall and ICU length of stay.

Thromboinflammatory response and predictors of outcomes in patients undergoing transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) has been increasingly used to treat patients with symptomatic aortic stenosis. Despite improvements in valve deployment, patients that have undergone TAVR are at high risk for major adverse events following the procedure. Blood cell numbers, platelet function, and biomarkers of systemic inflammation were analyzed in 58 patients undergoing TAVR with the Edward’s SAPIEN valve. Following valve deployment, platelet count and agonist-induced platelet activity declined and plasma markers of systemic inflammation (interleukin-6 and S100A8/A9) increased. Baseline platelet activity prior to TAVR correlated with perioperative changes plasma interleukin-6 levels. Moreover, perioperative changes in plasma inflammatory markers predicted the decline in platelet count in the days following the TAVR procedure. Additionally, a significant effect of gender on platelet count following TAVR and was observed. Finally, post-procedural mortality was associated with sustained thrombocytopenia after TAVR. Our findings suggest that TAVR elicits a thromboinflammatory state that may contribute to post-procedural thrombocytopenia. Importantly, our results add to the growing body of literature that suggests the thromboinflammatory changes that occur early after TAVR may predict long-term outcomes.

Targeting platelet thrombin receptor signaling to prevent thrombosis.

Platelets contribute fundamentally to ischemic heart disease, and antiplatelet therapy has been critical to reducing acute thrombotic complications of atherosclerotic disease. Thrombin, by acting on protease activated receptors (PAR), is one of the most potent platelet activators. PAR-1 antagonists may therefore provide more comprehensive antithrombotic effects. We review the pathophysiology of atherothrombosis, platelet activation by thrombin, the role of platelet protease activated receptors (PAR), and the clinical data supporting their use.

The Effect of Rosuvastatin on Platelet-Leukocyte Interactions in the Setting of Acute Coronary Syndrome

Statins have been used in the treatment of coronary artery disease for 2 decades. In addition to long-term protective effects elicited by lowering cholesterol, statins are postulated to have acute benefits in the setting of acute coronary syndromes (ACS) and vascular injury. In the JUPITER (

Anti-Thrombotic Effects of Statins in Acute Coronary Syndromes: At the Intersection of Thrombosis, Inflammation, and Platelet-Leukocyte Interactions

HMG CoA reductase inhibitors, or statins, are standard of care for preventing cardiovascular disease in at-risk populations. Statins are a well-established therapy proven to reduce long-term cardiovascular mortality and morbidity for prevention of secondary cardiovascular events and have become guideline-recommended therapy following acute myocardial infarction. Emerging data from clinical trials over the last decade indicates that statin therapy may provide broad beneficial effects beyond their primary lipid lowering mechanisms. In coronary heart disease, statins have demonstrated a unique ability to target several cellular pathways, which appear to play an underappreciated role in acute inflammation and subsequent thrombosis. Herein, we review the potential mechanisms where statins may act as antithrombotic agents in the setting of acute coronary syndromes and discuss the clinical implications of these findings.

Long-Term Outcomes and Causes of Death in Patients With Renovascular Disease Undergoing Renal Artery Stenting.

Renovascular disease (RVD) can lead to hypertension and chronic kidney disease (CKD). Patients with advanced peripheral arterial disease (PAD) have a 5-year mortality of ∼30%. Rate and causes of death in patients with significant RVD, who share similar risk factors with patients having PAD, are not well defined. We assessed consecutive patients with RVD who underwent renal artery stenting at our institution over 6 years. Specific causes of death were ascertained, and the probability of survival was estimated. Cox models were fit to identify predictors of outcomes. We identified 281 patients with RVD who underwent renal stenting. Follow-up was available for all patients (median 5.1 years). All-cause mortality was 24.2% at 5 years and 33.7% at 7 years (compounded annualized death rate: 5.5%). Of the 68 deaths, 36 (52.9%) were cardiovascular (13.2% acute myocardial infarction, 13.2% stroke, 11.8% sudden death, and 10.3% congestive heart failure) and 32 (47.1%) deaths had noncardiovascular causes. In patients with RVD undergoing stenting, cardiovascular events are the most common causes of death. Compared to patients with advanced PAD, RVD may have a lower 5-year mortality.

Fibrinolytic Therapy Versus Primary Percutaneous Coronary Interventions for ST-Segment Elevation Myocardial Infarction in Kentucky: Time to Establish Systems of Care?

Background Fibrinolytic therapy is recommended for ST-segment myocardial infarctions (STEMI) when primary percutaneous coronary intervention (PPCI) is not available or cannot be performed in a timely manner. Despite this recommendation, patients often are transferred to PPCI centers with prolonged transfer times, leading to delayed reperfusion. Regional approaches have been developed with success and we sought to increase guideline compliance in Kentucky. Methods A total of 191 consecutive STEMI patients presented to the University of Kentucky (UK) Chandler Medical Center between July 1, 2009 and June 30, 2011. The primary outcome was in-hospital mortality and the secondary outcomes were major adverse cardiovascular events, extent of myocardial injury, bleeding, and 4) length of stay. Patients were analyzed by presenting facility—the UK hospital versus an outside hospital (OSH)—and treatment strategy (PPCI vs fibrinolytic therapy). Further analyses assessed primary and secondary outcomes by treatment strategy within transfer distance and compliance with American Heart Association guidelines. Results Patients presenting directly to the UK hospital had significantly shorter door-to-balloon times than those presenting to an OSH (83 vs 170 minutes; P < 0.001). This did not affect short-term mortality or secondary outcomes. By comparison, OSH patients treated with fibrinolytic therapy had a numeric reduction in mortality (4.0% vs 12.3%; P = 0.45). Overall, only 20% of OSH patients received timely reperfusion, 13% PPCI, and 42% fibrinolytics. In a multivariable model, delayed reperfusion significantly predicted major adverse cardiovascular events (odds ratio 3.87, 95% confidence interval 1.15–13.0; P = 0.02), whereas the presenting institution did not. Conclusions In contemporary treatment of STEMI in Kentucky, ongoing delays to reperfusion therapy remain regardless of treatment strategy. For further improvement in care, acceptance of transfer delays is necessary and institutions should adopt standardized protocols in association with a regional system of care.

Tearing Into the Heart

![Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5][![Graphic][6] ][6] A 48-year-old man was brought to our emergency department after a high-speed motor vehicle accident. A nongated computed tomography scan with contrast of the chest was suspicious

Images in CardiologyTearing Into the Heart: Dissociation of Aortic Cusp With Rupture of the Interventricular Septum

![Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5][![Graphic][6] ][6] A 48-year-old man was brought to our emergency department after a high-speed motor vehicle accident. A nongated computed tomography scan with contrast of the chest was suspicious