L.A. Providência

The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial: study design and rationale

BACKGROUNDnThe protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA*CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features.nnnTRIAL DESIGNnTRA*CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least 1 year. The TRA*CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention.nnnCONCLUSIONnTRA*CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.

Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA·CER) trial

AIMSnThe TRA·CER trial compared vorapaxar, a novel platelet protease-activated receptor (PAR)-1 antagonist, with placebo in 12 944 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS). In this analysis, we explored the effect of vorapaxar on myocardial infarction (MI).nnnMETHODS AND RESULTSnA blinded, independent central endpoint adjudication committee prospectively defined and classified MI according to the universal MI definition, including peak cardiac marker value (creatine kinase-MB [CK-MB] and/or troponin). Because the trial failed to meet its primary endpoint, these analyses are considered exploratory. During a median follow-up of 502 days, 1580 MIs occurred in 1319 patients. The majority (n = 1025, 64.9%) were type 1 (spontaneous) MI, followed by type 4a [percutaneous coronary intervention (PCI)-related] MI (n = 352; 22.3%). Compared with placebo, vorapaxar reduced the hazard of a first MI of any type by 12% [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.79-0.98; P = 0.021] and the hazard of total number of MIs (first and subsequent) by 14% (HR, 0.86; 95% CI, 0.77-0.97; P = 0.014), an effect that was sustained over time. Vorapaxar reduced type 1 MI by 17% (HR, 0.83; 95% CI, 0.73-0.95; P = 0.007). Type 4a MIs were not significantly reduced by vorapaxar (HR, 0.90; 95% CI, 0.73-1.12; P = 0.35). Vorapaxar effect was consistent across MI sizes defined by peak cardiac marker elevations and across key clinical subgroups; however, in patients not treated with thienopyridine at baseline (HR, 0.65; 95% CI, 0.46-0.92) compared with patients who received thienopyridine (HR, 0.91; 95% CI, 0.81-1.02), there was a trend towards a higher effect (Pint = 0.077).nnnCONCLUSIONnThe PAR-1 antagonist vorapaxar was associated with a reduction of MI, including total number of infarctions. This reduction was sustained over time and was mostly evident in type 1 MI, the most common type of MI observed.

Renal artery aneurysm: An endovascular treatment for a rare cause of hypertension

Renal artery aneurysms are a rare cause of secondary hypertension. Endovascular treatment with a polytetrafluoroethylene (PTFE)-coated stent can exclude aneurysms and treat hypertension. We report the case of a 23-year-old man with hypertension diagnosed three years earlier and in whom renal angiography revealed three aneurysms involving the right renal artery. A covered stent was implanted, resulting in successful exclusion of the aneurysm. Ten months after the procedure the patient is asymptomatic and with normal blood pressure without antihypertensive therapy.

Hemoglobina: um mero valor analítico ou um poderoso preditor de risco em doentes com síndromes coronárias agudas?

INTRODUCTIONnAnemia has been shown to be associated with a worse prognosis, especially higher mortality in various pathological conditions. However, few studies have specifically examined its impact in acute coronary syndrome (ACS) patients. The purpose of our study was to assess the association between different quartiles of hemoglobin on admission and short- and long-term prognosis in patients with ACS.nnnMETHODSnWe performed a retrospective analysis of 1303 consecutive ACS patients admitted to a coronary care unit and analyzed the association between baseline hemoglobin and morbidity and mortality, in-hospital and at 12-month follow-up. The population was divided into groups according to quartiles of hemoglobin concentration (Hb): Q1: <10.8g/dl; Q2: 10.8-12.2g/dl; Q3: 12.3-13.2g/dl; Q4: ≥13.3g/dl. Logistic regression analysis was used to identify independent predictors of short- and long-term mortality.nnnRESULTSnHypertension and diabetes mellitus were more common in the lower Hb quartiles, while the prevalence of smoking and physical inactivity increased with higher Hb. A higher proportion of patients in the lower quartiles had congestive heart failure, peripheral artery disease and previous stroke or transient ischemic attack. Anemic patients tended to be older, with worse renal function and left ventricular systolic function. Patients in Q1 had significantly higher levels of troponin I and blood glucose on admission. Anemic patients showed significantly higher in-hospital mortality (Q1: 9.8%; Q2: 6.3%; Q3: 4.1%; Q4: 3.6%, p<0.001), longer hospital stay (Q1: 6.1±4.4; Q2: 5.2±3.0; Q3: 4.9±2.7; Q4 4.3±2.1 days, p<0.001) and higher 1-year mortality (Q1: 23.6%; Q2: 11.6%; Q3: 10.6%; Q4: 5.5%, p<0.001). In multivariate analysis, the only independent predictor of in-hospital mortality was Killip class >1 at admission. The independent predictors of long-term mortality were age ≥69.5 years, Killip class >1 at admission, diabetes mellitus, ST-segment depression on admission ECG and Hb <10.8g/dl.nnnDISCUSSION AND CONCLUSIONSnLow baseline hemoglobin is associated with more comorbidities and can accurately predict 1-year mortality after an acute coronary syndrome.

CYP2C19*2 and prognosis after an acute coronary syndrome, Insights from a Portuguese center

BACKGROUNDnClopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized.nnnOBJECTIVEnTo investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population.nnnMETHODSnWe performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days.nnnRESULTSnThe median age of the population was 62.0 (51.0-68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three readmissions for MI were documented, all in the slow metabolizers group.nnnCONCLUSIONnIn our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker.

Prognostic implications of left ventricular end-diastolic pressure in acute coronary syndromes with left ventricular ejection fraction of 40% or over

Abstract Introduction There is still debate concerning the impact of left ventricular end-diastolic pressure (LVEDP) on long-term prognosis after an acute coronary syndrome (ACS). Objective To assess LVEDP and its prognostic implications in ACS patients with left ventricular ejection fraction (LVEF) ≥40%. Methods We performed a prospective, longitudinal study of 1329 ACS patients from a single center between 2004 and 2006. LVEDP was assessed at the beginning of the coronary angiogram. Patients with LVEF >40% were included (nxa0=xa0489). The population was divided into three groups: A — LVEDP ≤19xa0mmHg (nxa0=xa0186); B — LVEDP >19 and ≤27xa0mmHg (nxa0=xa0172); and C — LVEDP >27xa0mmHg (nxa0=xa0131). The primary endpoint of the analysis was readmission for congestive heart failure in the year following the index admission. Results Mean LVEDP was 22.8xa0±xa07.8xa0mmHg. The groups were similar age, gender, cardiovascular risk factors, cardiovascular history, and medication prior to admission. There was an association between higher LVEDP and: admission for ST-elevation acute myocardial infarction (35.4 vs. 45.9 vs. 56.7%, pxa0 Conclusion In selected population LVEDP was a significant prognostic marker of future admission for congestive heart failure.

A ressonância magnética cardíaca como uma mais-valia no diagnóstico etiológico de arritmias ventriculares

INTRODUCTIONnCardiac magnetic resonance (CMR) imaging is increasingly important in the diagnostic work-up of a wide range of heart diseases, including those with arrhythmogenic potential.nnnOBJECTIVEnTo assess the added value of CMR in etiological diagnosis of ventricular arrhythmias after an inconclusive conventional investigation.nnnMETHODSnPatients undergoing CMR between 2005 and 2011 for investigation of ventricular arrhythmias were included (n=113). All had documented arrhythmias. Those with a definite diagnosis from a previous investigation and those with evidence of coronary artery disease (acute coronary syndrome, typical angina symptoms, increase in biomarkers or positive stress test) were excluded. CMR results were considered relevant when they fulfilled diagnostic criteria.nnnRESULTSnOf the 113 patients, 57.5% were male and mean age was 41.7 ± 16.2 years. Regarding the initial arrhythmia, 38.1% had ventricular fibrillation/sustained ventricular tachycardia (VF/VT) and 61.9% had less complex ventricular ectopy. CMR imaging showed criteria of a specific diagnosis in 42.5% of patients, was totally normal in 36.3%, and showed non-specific alterations in the remainder. In VF/VT patients, specific criteria were found in 60.4%, and in 31.4% of those with less complex ectopy. The most frequent diagnoses were arrhythmogenic right ventricular dysplasia, ventricular non-compaction and myopericarditis. It is worth noting that, although there was no evidence of previous coronary artery disease, 6.2% of patients had a late gadolinium enhancement distribution pattern compatible with myocardial infarction.nnnCONCLUSIONnCMR gives additional and important information in the diagnostic work-up of ventricular arrhythmias after an inconclusive initial investigation. The proportion of patients with diagnostic criteria was 42.5% (60.0% in those with VF/VT), and CMR was completely normal in 36.6%.

Ressonância magnética cardíaca de perfusão em stress : a experiência de um centro nacional

INTRODUCTION AND OBJECTIVESnMyocardial ischemia can be assessed with cardiac magnetic resonance perfusion imaging (MRPI). This study aimed to analyze the clinical utility of MRPI in the diagnosis of significant coronary artery disease.nnnMETHODSnFifty-five patients were examined with a 1.5 T MR scanner (Siemens Symphony), with a first pass of 0.10 mmol/kg gadolinium chelate, at rest and during adenosine vasodilatation (140μg/kg/min for 4min) using an inversion recovery steady-state free precession sequence. The results were compared with coronary angiography and with SPECT myocardial perfusion images. Agreement for qualitative diagnosis was measured by the kappa coefficient, taking statistical significance as 95%. Minimum clinical follow-up was 12 months.nnnRESULTSnIn 19 patients (34.5%) MRPI was negative for myocardial ischemia and necrosis, in 17 (30.9%) it was negative for ischemia but positive for necrosis, in 7 (12.7%) only ischemia was present and in 12 (21.8%) the ischemic area was larger than the necrotic area. The correlation between MRPI and coronary angiography for ischemia detection by coronary artery territory was very good: left anterior descending and right coronary - k=0.8571 (0.59-1), circumflex - k=0.8108 (0.59-1). By contrast, there was no correlation in terms of myocardial ischemia detection between MRPI and SPECT.nnnCONCLUSIONSnMRPI is able to diagnose significant coronary disease in a high risk population, by detection of myocardial ischemia.

CHADS2 e CHA2DS2VASc como preditores de fonte cardioembólica em prevenção secundária cerebrovascular

INTRODUCTION AND OBJECTIVESnCardioembolism is one of the most common causes of ischemic stroke, with an estimated prevalence of 20-30%, and correct diagnosis is essential given the therapeutic implications. Although stroke risk scores (CHADS2 and more recently CHA2DS2-VASc) have been validated in heterogeneous populations of patients with atrial fibrillation, their accuracy has not been ascertained for secondary stroke prevention. We set out to assess the sensitivity and specificity of the CHADS2 and CHA2DS2-VASc stroke risk scores as predictors of cardioembolic sources, documented by transesophageal echocardiography (TEE) in a population with ischemic stroke.nnnMETHODSnThe CHADS2 and CHA2DS2-VASc scores were applied to all patients admitted to the stroke unit/neurology ward of a Portuguese tertiary hospital with atrial fibrillation (diagnosed previously or during or after admission) who underwent TEE between January and August 2011. The presence of a cardioembolic source was defined as the observation by TEE of spontaneous echo contrast in the left atrium and atrial appendage or thrombi in the left cardiac chambers.nnnRESULTSnWe studied 94 patients, 66.0% male, mean age 64.4 years (standard deviation 14.2). A cardioembolic source was detected in 20 patients. ROC curve analysis identified as predictors of cardioembolic source CHADS2 score ≥4 (sensitivity of 75.0%, specificity of 66.0%, p=0.014) and CHA2DS2-VASc score ≥5 (sensitivity of 83.3%, specificity of 58.0%, p=0.009).nnnCONCLUSIONSnBoth scores showed acceptable sensitivity as predictors of embolic risk in the context of secondary prevention of cardioembolic stroke. The CHA2DS2-VASc score has higher sensitivity than CHADS2 but lower specificity.

Distrofia muscular de Emery-Dreifuss : a propósito de um caso clínico

Emery-Dreifuss muscular dystrophy type 1 (EDMD1) is a familial disease with X-Linked recessive transmission, caused by a mutation in a nuclear envelope protein, emerin. Clinical manifestations usually occur in adolescence and include contractures, muscle atrophy and weakness, and cardiac conduction disturbances. We describe the case of a young male, aged 16, with first-degree atrioventricular (AV) block and limited extension of both forearms. He had elevated CK, and cardiac monitoring showed severe conduction tissue disease, with significant sinus pauses, chronotropic incompetence and periods of AV dissociation during exercise. Immunohistochemical staining using an emerin antibody showed absence of the protein in a fragment of muscle tissue and genetic study identified a mutation associated with EDMD1. Study of his brother, aged 21, also established a diagnosis of EDMD1. Both individuals received a permanent pacemaker but musculoskeletal manifestations at that time did not warrant any other intervention: Screening for certain genetic diseases, including muscular dystrophies, is mandatory following identification of conduction abnormalities in young people.