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Background: Pulmonary embolism (PE) is a life-threatening event with a broad presentation spectrum ranging from asymptomatic cases to sudden cardiac arrest. It is unclear if right atrial emboli cause PE in patients with atrial fibrillation (AF) or if mild PE itself increases right cardiac pressure provoking AF. Objective: To determine the incidence and predictors of asymptomatic PE in patients undergoing AF ablation. Method and Results: Patients (n = 93) were screened and those with previous or current symptomatic PE or venous thromboembolism, pulmonary hypertension, increased right heart pressures detected on echocardiography, a history of stroke, transient ischemic attack, coagulopathy or cancer and inappropriate contrast for the evaluation of pulmonary arterial tree were excluded. The remaining AF patients (n = 71) underwent guided ablation controlled with 3-dimensional, left atrial and pulmonary venous computed tomography. The asymptomatic PE was defined by using the modified Miller score by 2 independent assessors in 6 patients. Univariate logistic regression showed that age (OR: 1.094, 95% CI 1.007-1.188, p = 0.033), diabetes (OR: 12.000, 95% CI 1.902-75.716, p = 0.008), CHA2DS2-VASc score (OR: 2.800, 95% CI 1.304-6.013, p = 0.008), and pulmonary artery diameter (OR: 1.221, 95% CI 1.033-1.444, p = 0.019) were significantly associated with PE. However, multivariate analysis revealed that the CHA2DS2-VASc score (p = 0.047) remained the exclusive significant predictor for asymptomatic PE. Conclusion: The incidence of random asymptomatic PE in AF patients is high (>8%). The CHA2DS2-VASc score can predict silent PE. Since patients with a high CHA2DS2-VASc score are already anticoagulated, our results do not change clinical practice but are noteworthy in terms of the cause-effect relationship between AF and PE.

In a randomized, double-blind, crossover study of 15 aspirin-naive patients (mean age 48.8 ± 10.2 years) with the metabolic syndrome, statin monotherapy (simvastatin 40 mg daily) was compared to combination therapy (simvastatin 40 mg and ezetimibe 10 mg daily) on biomarkers of inflammation and platelet activity. The addition of ezetimibe to simvastatin over a 4-week period was associated with reduced expression of CD141 (thrombomodulin; p = 0.02), platelet endothelial cell adhesion molecule (p < 0.0001) and CD51/61 (vitronectin receptor; p = 0.048) compared to statin monotherapy. Ezetimibe added to simvastatin improves several indices of platelet reactivity beyond statin monotherapy. However, the clinical relevance of these findings await results of the IMPROVE-IT trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

Context: Extreme rates of vascular and all-cause mortality, especially in the clopidogrel arm of the PLATO (PLATelet Inhibition and Clinical Outcomes) trial, raise concerns of data accuracy and call for independent verification of vital records in the national death registries. Two recently completed acute coronary syndrome (ACS) trials, TRACER and ATLAS ACS 2 (Thrombin Receptor Antagonist for Clinical Event Reduction in ACS and Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with ACS-Thrombolysis in Myocardial Infarction), provide a valuable opportunity to match mortality numbers among 3 similar studies. Objective: To compare the rates of vascular and all-cause mortality in the PLATO, TRACER and ATLAS ACS 2 trials. Results: Despite a shorter mean follow-up (277 days) for the PLATO trial than for the TRACER (502 days) or ATLAS ACS 2 (393 days) trials, both vascular (5.1%) and all-cause (5.9%) mortality in PLATO were higher than in the TRACER (3.2 and 4.9%) or ATLAS ACS 2 (4.1 and 4.5%) control arms, respectively. Adjusting for follow-up duration, rates of vascular (0.0184/day), or all-cause (0.0213/day) mortality in PLATO differ importantly from daily death rates in TRACER (0.0063 and 0.0097) and ATLAS ACS 2 (0.0104 and 0.0115), suggesting that the risk of death in the control PLATO arm was approximately double that of the other trials. The mismatch is particularly striking considering that ATLAS ACS 2 enrolled more STEMI (ST-segment elevation in myocardial infarction) patients (50.9%) than PLATO (38.0%). Conclusions: Both overall and follow-up duration-adjusted mortality rates in PLATO far exceeded the risk of death observed in the two recent ACS trials. The background STEMI rates are not likely to be responsible for the PLATO mortality paradox. These data provide an additional reason to request an independent audit of the deceased PLATO clopidogrel cohort.

Current guidelines offer a choice of P2Y12 receptor antagonist among clopidogrel, prasugrel or ticagrelor on top of aspirin (ASA) for dual antiplatelet therapy (DAPT) in patients after acute coronary syndromes (ACS). However, the comparative risks of gastrointestinal (GI) adverse events during DAPT are not clear. Two large ACS trials (TRITON and PLATO) provide a valuable opportunity to directly match the risks of GI complications among current antiplatelet regimens. We compared the rates of GI adverse events after prasugrel and ticagrelor versus clopidogrel based on the Food and Drug Administration (FDA) clinical safety reviews. When compared with ticagrelor, clopidogrel is safer with regard to GI-related risks including fewer overall GI/anal bleeding events and spontaneous GI hemorrhagic episodes, less nausea, vomiting, dyspepsia and diarrhea, and a lower rate of presence of Helicobacter pylori. Among GI symptoms, only constipation was more common after clopidogrel than following ticagrelor. There were extrahepatic risks observed with ticagrelor but not with prasugrel when compared to clopidogrel. Prasugrel unquestionably caused more bleeding from the GI tract and GI malignancies than clopidogrel. However, the entire spectrum of GI effects of prasugrel is much less well known and mostly based on sponsor analysis rather than FDA-verified numbers. Among 3 DAPT options on top of ASA, clopidogrel seems to represent the safest alternative, although comprehensive data on direct prasugrel-associated GI effects are lacking or inconclusive.

Background: There was an excess of new solid neoplasms (112 vs. 69), and cancer deaths (24 vs. 15) after prasugrel in the TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition). These cancers usually occur after 4 months following prasugrel, and women are especially at risk. The hypothesis has been offered that prasugrel, but not aspirin or clopidogrel, causes indirect modulation of tumor growth, and/or enhanced metastatic dissemination due to instability of platelet-tumor cell aggregates via the inability to keep cancer locally within the platelet thrombi due to excessive chronic platelet inhibition. Case Report: A 70-year old female diabetic patient underwent drug-eluting stent implantation. The patient received a loading dose of prasugrel (60 mg), followed by prasugrel 10 mg/daily as well as aspirin (81 mg/daily). After 4 months on dual antiplatelet therapy she expectorated blood when coughing. A lung X-ray and CT scan revealed numerous lung nodules later diagnosed as unclassified pleomorphic and spindle cell malignant solid neoplasm. The patient died following multiple brain metastasis. Conclusion: Female gender, duration of prasugrel exposure, rare unclassified neoplasm pathology type and a tumor of a highly metastatic and aggressive nature in the index patient should be regarded with caution. The effects of novel antiplatelet agents on the onset of cancer should be tested in future mega-trials.

Background: It has been shown that mitral stenosis (MS) impairs left ventricular (LV) systolic function; however, this issue has not been studied comprehensively. We aimed to evaluate the role of 2D strain in the assessment of subclinical LV systolic dysfunction in patients with MS. Methods: Seventy-two patients with isolated MS (mild, moderate and severe) and 31 healthy control subjects constituted the study population. 2D echocardiography images were obtained from LV apical 4-chamber (4C), long axis (LAX), and 2-chamber (2C) views. Peak longitudinal strain and strain rate (Sr) were obtained from 4C, LAX, and 2C views. Global strain and Sr were calculated by averaging the three apical views. Results: There were no significant differences in LV ejection fraction and LV systolic or diastolic dimensions between the groups. Patients with MS had significantly lower LV longitudinal strain and Sr measurements than the control group. In addition, there were no significant differences in MS subgroups with respect to LV strain and Sr measurements. Conclusion: We demonstrated that patients with MS had lower LV functions using 2D strain imaging, and this is independent of the hemodynamic severity of MS. In the detection of subclinical LV dysfunction in patients with MS, 2D strain imaging appears to be useful.

Acute renal infarction due to emboli represents a very rare but significant threat for kidney loss, and the clinical presentation is challenging. The differential diagnosis of massive renal thrombi includes all other causes of abdominal pain, and they can be easily misdiagnosed as renal colic due to nephrolithiasis. Although there are a few case reports regarding the possibility that cardiac emboli may cause acute kidney infarction, intracardiac thrombi within the ventricular cavity diagnosed by echocardiography as a cause of such renal artery occlusion have never been reported in patients with cardiomyopathy. Herein, we describe a 39-year-old male with a history of ischemic dilated cardiomyopathy. He was admitted to our hospital with left upper abdominal pain and vomiting. After serial examinations and tests, the diagnosis of acute renal infarction due to intracardiac thrombus embolization as a result of severely reduced cardiac function was made.