George V. Moukarbel

Impact of Time of Presentation on the Care and Outcomes of Acute Myocardial Infarction

Background— Prior studies have demonstrated an inconsistent association between patients’ arrival time for acute myocardial infarction (AMI) and their subsequent medical care and outcomes. Methods and Results— Using a contemporary national clinical registry, we examined differences in medical care and in-hospital mortality among AMI patients admitted during regular hours (weekdays 7 am to 7 pm) versus off-hours (weekends, holidays, and 7 pm to 7 am weeknights). The study cohort included 62 814 AMI patients from the Get With the Guidelines–Coronary Artery Disease database admitted to 379 hospitals throughout the United States from July 2000 through September 2005. Overall, 33 982 (54.1%) patients arrived during off-hours. Compared with those arriving during regular hours, eligible off-hour patients were slightly less likely to receive primary percutaneous coronary intervention (adjusted odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89 to 0.98), had longer door-to-balloon times (median, 110 versus 85 minutes; P<0.0001), and were less likely to achieve door-to-balloon ≤90 minutes (adjusted OR, 0.34; 95% CI, 0.29 to 0.39). Arrival during off-hours was associated with slightly lower overall revascularization rates (adjusted OR, 0.94; 95% CI, 0.90 to 0.97). No measurable differences, however, were found in in-hospital mortality between regular hours and off-hours in the overall AMI, ST-elevated MI, and non–ST-elevated MI cohorts (adjusted OR, 0.99; 95% CI, 0.93 to 1.06; adjusted OR, 1.05; 95% CI, 0.94 to 1.18; and adjusted OR, 0.97; 95% CI, 0.90 to 1.04, respectively). Similar observations were made across most age and sex subgroups and with an alternative definition for arrival time (weekends/holidays versus weekdays). Conclusions— Despite slightly fewer primary percutaneous coronary interventions and overall revascularizations and significantly longer door-to-balloon times, patients presenting with AMI during off-hours had in-hospital mortality similar to those presenting during regular hours.

Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial

AIMS The risk of gastrointestinal (GI) bleeding limits the use of antiplatelet and anticoagulant drugs. Risk factors for GI bleeding in post- myocardial infarction (MI) patients have not been well defined. We sought to identify risk factors for GI bleeding in patients following MI. METHODS AND RESULTS The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) enrolled 14 703 post-MI patients with left ventricular dysfunction and/or heart failure and followed them for a median of 24.7 months. In the present secondary analysis, times from baseline to first GI bleeding were identified from the VALIANT serious adverse event database. Potential risk factors were explored from medical history, demographics, clinical profile, and medications, both at baseline and during follow-up. We also explored the relationship between the occurrence of GI bleeding and subsequent mortality. During follow-up, 98 (0.7%) patients had a serious GI bleeding event. These patients were older, had more comorbidities, were more likely to be taking additional antiplatelet drugs, and had worse left ventricular systolic and renal function. The Kaplan-Meier estimated rate of GI bleeding at 6 months was 0.37% (95% CI 0.27-0.47). In a multivariable Cox model, dual antiplatelet therapy was the most powerful predictor of GI bleeding, with an adjusted hazard ratio of 3.18 (95% CI 1.91-5.29). Other predictors were non-white race, history of alcohol abuse, increasing age, worse New York Heart Association class, anticoagulant therapy, diabetes, lower estimated glomerular filtration rate, and male sex. Gastrointestinal bleeding was associated with increased risk of death [adjusted hazard ratio 2.54 (95% CI 1.66-3.89)]. CONCLUSION Following MI, clinical characteristics can identify patients with increased risk of GI bleeding. The use of dual antiplatelet agents appears to be the most profound risk factor. Whether these patients would benefit from GI prophylaxis therapy remains unknown.

Effect of Weight Loss After Weight Loss Surgery on Plasma N-Terminal Pro-B-Type Natriuretic Peptide Levels

Natriuretic peptides have multiple beneficial cardiovascular effects. Previous cross-sectional studies have indicated that obese subjects have lower natriuretic peptide concentrations than those of normal weight. It is not known whether this relative natriuretic peptide deficiency is reversible with weight loss. We studied 132 obese subjects undergoing weight loss surgery with serial measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations at preoperative, early (1 to 2 months), and late postoperative (6 months) points. In addition, 20 subjects also underwent echocardiography at baseline and 6 months after surgery. Significant weight loss was observed after surgery (median body mass index 45.1, 41.0, and 32.9 kg/m(2) for the 3 corresponding points, analysis of variance p <0.001). The median NT-proBNP levels increased substantially (31.6, 66.9, and 84.9 pg/ml; p <0.001). The average intrasubject increase in NT-proBNP at the 2 postoperative points was 3.4 and 5.0 times the preoperative level (p <0.001 for both points vs preoperatively). In the multivariate regression models adjusted for clinical characteristics and insulin resistance, the strongest predictor of the change in NT-proBNP level 6 months after weight loss surgery was the change in weight (p = 0.03). Echocardiography showed a mean intrasubject reduction in left ventricular mass index of 18% (p <0.001) and mild improvements in diastolic function, with no change in ejection fraction. In conclusion, we have demonstrated that weight loss is associated with early and sustained increases in NT-proBNP concentrations, despite evidence of preserved systolic and improved diastolic function. These findings suggest a direct, reversible relation between obesity and reduced natriuretic peptide levels.

Antiplatelet Therapy and Proton Pump Inhibition: Clinician Update

A 77-year-old man with history of diabetes mellitus and coronary artery disease presented with angina and evidence of ischemia despite maximal medical therapy. He underwent a percutaneous coronary intervention with a drug-eluting stent and was started on long-term dual antiplatelet therapy with aspirin and clopidogrel. His medical history was significant for an episode of gastrointestinal (GI) bleeding in the setting of using nonsteroidal antiinflammatory drugs. Dual antiplatelet therapy, typically the addition of an ADP receptor antagonist to aspirin, has become the cornerstone of management of patients with acute coronary syndromes and after percutaneous coronary intervention. However, along with the reduction of thrombotic outcomes, this therapeutic strategy has the untoward effect of increasing the risk of bleeding events, including GI bleeding.1 The use of gastroprotective strategies, most notably proton pump inhibitors (PPIs), has become a widely adopted and recommended practice in this patient population.2 Currently, the most commonly prescribed ADP receptor antagonist is clopidogrel, a prodrug that undergoes activation by the cytochrome P450 system, in particular CYP2C19. The importance of this reaction on the overall platelet inhibitory effects of clopidogrel is highlighted by the fact that patients with reduced-function CYP2C19 alleles exhibit a reduced response to clopidogrel compared with those with the wild-type alleles. This finding might translate into increased risk of adverse events after acute coronary syndromes and percutaneous coronary intervention. Given that PPIs are inhibitors of CYP2C19, coupled with reports suggesting a clinically significant interaction,3 regulatory agencies issued a cautionary statement advising against the combined use of PPIs (specifically omeprazole and esomeprazole) and clopidogrel.4 Aspirin causes direct damage to the gastric epithelium and inhibits prostaglandin production by the gastric mucosa, leading to ulcerations and an estimated 2-fold increased risk of GI bleeding with low-dose aspirin alone.1 The risk increases with the additional use of …

Catheter Ablation and Antiarrhythmic Drug Therapy as First- or Second-Line Therapy in the Management of Atrial Fibrillation Systematic Review and Meta-Analysis

Background—The optimal management of atrial fibrillation remains unclear. We performed a meta-analysis of randomized controlled trials to examine the safety and the efficacy of catheter ablation (CA) when compared with antiarrhythmic drug therapy both as first- and second-line therapy for the maintenance of sinus rhythm in atrial fibrillation. Methods and Results—Several databases were searched from inception to March 2014, which yielded 11 studies with 1481 patients with atrial fibrillation. The outcomes measured were recurrence of atrial tachyarrhythmia and the incidence of adverse events. A subgroup analysis was done to evaluate the efficacy of CA as first- or second-line therapy. There was recurrence of atrial tachyarrhythmia in 222 of 785 (28%) patients who underwent CA and in 451 of 696 (65%) patients who were on antiarrhythmic drug therapy (relative risk, 0.40; 95% confidence interval, 0.31−0.52; P=0.00001). Subgroup analysis revealed a beneficial effect of CA both as a first-line (relative risk, 0.52; 95% confidence interval, 0.30−0.91; P=0.02) and as a second-line (relative risk, 0.37; 95% confidence interval, 0.29−0.48; P<0.00001) therapeutic modality. There was a significantly higher incidence of major adverse events in the CA group when compared with those in the antiarrhythmic drug therapy group (relative risk, 2.04; 95% confidence interval, 1.10–3.77; P=0.02, I2=0%). Conclusions—CA seems to be superior to antiarrhythmic drug therapy in drug naïve, resistant, and intolerant patients with atrial fibrillation. However, it should be performed in carefully selected patients after weighing the risks and benefits of the procedure.

The impact of kidney function on outcomes following high risk myocardial infarction: findings from 27 610 patients

Renal dysfunction is associated with poor cardiovascular outcome. We investigated the relationship of kidney function and long‐term cardiovascular outcomes in patients with high risk myocardial infarction.

Practical echocardiographic approach for risk stratification of patients with acute pulmonary embolism

Acute pulmonary embolism remains a common cause of mortality. Early diagnosis and appropriate risk stratification is necessary to individualize treatment strategy. Computed tomography scan of the pulmonary arteries is routinely used to diagnose acute pulmonary embolism and in some cases is useful to assess right ventricular dilation. In patients with acute pulmonary embolism, right ventricular dilation and dysfunction indicates a high-risk situation where immediate administration of thrombolytic agent, catheter-directed thrombolysis, or surgical embolectomy could be considered. A bedside 2D echocardiogram at the time of presentation could provide additional morphological, functional, and hemodynamic parameters including right ventricular dilation, McConnell’s sign, reduced tricuspid annular plane systolic excursion (TAPSE), interventricular septal flattening, abnormal right ventricular hemodynamics and in rare cases thrombi in the inferior vena cava, right atrium or ventricle en route to pulmonary arteries may also be visualized. This additional information is useful for selection of appropriate treatment modality. Thus, our objective is to provide a practical echocardiographic approach for risk stratification of patients with acute pulmonary embolism.

Aortic pseudoaneurysm compressing the left coronary artery

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Disruption of Coronary Vasomotor Function: The Coronary Spasm Syndrome

Abnormal coronary vasoconstriction, or coronary spasm, can be the result of several factors, including local and neuroendocrine aberrations. It can manifest clinically as a coronary syndrome and plays an important role in the genesis of myocardial ischemia. Over the past half century, coronary angiography allowed the in vivo demonstration of spasm in patients who fit the initial clinical description of the condition as reported by Prinzmetal et al. Several clinical, basic, and more recently, genetic studies have provided insight into the pathogenesis, manifestations, and therapy of this condition. It is not uncommonly encountered in patients with coronary syndromes and absence of clearly pathologic lesions on angiography. Provocation tests utilizing pharmacologic and nonpharmacologic stimuli combined with imaging (echocardiography or coronary angiography) can help make the correct diagnosis. The use of calcium channel blockers and long-acting nitrates is currently considered standard of care and the overall prognosis appears to be good. The recent discovery of genetic abnormalities predisposing to abnormal spasm of the coronaries has stimulated interest in the development of targeted therapies for the management of this condition.

Isolated Pulmonary Valve Endocarditis

Endocarditis of only the pulmonary valve is a very rare finding and is often missed during echocardiographic evaluation due to limited views of the pulmonary valve and a low index of suspicion. We report 2 cases of pulmonary valve endocarditis (PVE), highlighting the importance of echocardiography in the assessment of the infected pulmonary valve. In addition, we review the published case reports of isolated PVE from 1979 to 2013 in order to study the role of echocardiography in the diagnosis of pulmonary valve masses.