Defining electrocardiographic criteria to differentiate non-type 1 Brugada ECG variants from normal incomplete RBBB patterns in the young SCD-SOS cohort.

INTRODUCTION: We assessed the prevalence of non-type 1 Brugada pattern (T1BrP) in children and young adults from the Sudden Cardiac Death-Screening Of risk factorS cohort and the diagnostic yield of nonexpert manual and automatic algorithm electrocardiogram (ECG) measurements. METHODS: Cross-sectional study. We reviewed 14 662 ECGs and identified 2226 with a rSr'-pattern in V1-V2. Among these, 115 were classified by experts in hereditary arrhythmic-syndromes as having or not non-T1BrP, and were compared with measurements of 5 ECG-derived parameters based on a triangle formed by r' -wave (d(A), d(B), d(B)/h, ß-angle) and ST-ascent, assessed both automatically and manually by nonexperts. We estimated intra- and interobserver concordance for each criterion, calculated diagnostic accuracy and defined the most appropriate cut-off values. RESULTS: A rSr'-pattern in V1-V2 was associated with higher PQ interval and QRS duration, male gender, and lower body mass index (BMI). The manual measurements of non-T1BrP criteria were moderately reproducible with high intraobserver and moderate interobserver concordance coefficients (ICC: 0.72-0.98, and 0.63-0.76). Criteria with higher discriminatory capacity were: distance d(B) (0.72; 95% confidence interval [CI]: 0.65-0.80) and ST-ascent (0.87; 95% CI: 0.82-0.92), which was superior to the 4 r'-wave criteria together (area under curve [AUC: 0.74]). We suggest new cut-offs with improved combination of sensitivity and specificity: d(B) ≥ 1.4 mm and ST-ascent ≥ 0.7 mm (sensitivity: 1%-82%; specificity: 71%-84%), that can be automatically measured to allow classification in four morphologies with increasing non-T1BrP probability. CONCLUSION: rSr'-pattern in precordial leads V1-V2 is a frequent finding and the detection of non-T1BrP by using the aforementioned five measurements is reproducible and accurate. In this study, we describe new cut-off values that may help untrained clinicians to identify young individuals who may require further work-up for a potential Brugada Syndrome diagnosis.

High-risk features and predictors of unexplained syncope in the young SCD-SOS cohort.

INTRODUCTION: The Sudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead electrocardiogram (ECG) plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort. METHODS AND RESULTS: We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11 878 individuals, with a mean age of 21 ± 6 (range 6-40) years old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2%, and 14.8% of the individuals had US. Unexplained syncope was independently associated with age < 18 years old (odds ratio [OR] 1.695; 95% confidence interval [CI] 1.26-2.29, p = .001), male gender (OR 1.642; 95% CI 1.22-2.22, p = .001), participation in competitive sports (OR 1.644; 95% CI 1.01-2.66, p = .043), syncope during exertion and/or palpitations preceding syncope (OR 2.556; 95% CI 1.92-3.40, p < .001), syncope after exertion (OR 2.662; 95% CI 1.73-4.10, p < .001), fever context (OR 9.606; 95% CI 4.13-22.34, p < .001), isolated previous syncopal episode (OR 2.780; 95% CI 0.2.06-3.75, p < .001), and history of palpitations requiring medical care (OR 1.945; 95% CI 1.14-3.31, p = .014). We found no ECG predictors of US in this population. CONCLUSIONS: The cumulative incidence of TLOC in children and young adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a nonacute setting.

The efficacy and safety of direct oral anticoagulants plus aspirin in symptomatic lower extremity peripheral arterial disease: a systematic review and meta-analysis of randomized controlled trials.

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). The efficacy and safety of direct oral anticoagulants (DOACs) in this context is evolving. To assess the efficacy and safety of DOAC combined with aspirin compared to the use of antiplatelet agents in patients with symptomatic lower extremity (LE) PAD. We systematically searched PubMed, Embase and Cochrane databases, in September 2020, for randomized controlled trials (RCTs) that were designed to investigate the effect of DOACs in the treatment of PAD. A random-effects meta-analysis was performed targeting ischemic and bleeding events. Three randomized clinical trials were included, providing a total of 9533 patients, and 744 pooled MALE events (316 in DOAC plus aspirin and 428 in control). Only data on rivaroxaban and edoxaban were available. The use of DOAC plus aspirin in PAD patients significantly decreased the rate of MALE (pooled OR 0.70 [0.61-0.83], P < 0.001; I2 = 0%). In terms of safety, there was a significantly higher rate of major bleeding events (pooled OR 1.46 [1.16-1.84], P = 0.001; I2 = 52%). In rivaroxaban-RCTs, the addition of low-dose rivaroxaban to aspirin was still associated with a lower MALE compared to aspirin alone (pooled OR 0.68 [0.53-0.88], P = 0.003; I2 = 28%), but also conferred higher major bleeding rate (pooled OR 1.48 [1.18-1.86], P < 0.001; I2 = 0%). In conclusion, our pooled data suggests that for patients with symptomatic LE-PAD, the use of DOAC combined with aspirin reduced the risk of major ischemic limb events at the expense of an increased risk of major bleeding.

Left atrial functional assessment and mortality in patients with severe aortic stenosis with sinus rhythm.

BACKGROUND: Aortic valve stenosis (AS) is the most common primary valvular heart disease leading to surgical or percutaneous aortic valve replacement (AVR) in Europe and its prevalence keeps growing. While other risk factors in severe AS are well documented, little is known about the prognostic value of left atrial (LA) function in AS. Our aim is to clarify the relationship between LA function measured at severe AS diagnosis (evaluated by means of volumetric assessment) and all-cause mortality during follow-up. METHODS: We retrospectively evaluated patients diagnosed with severe AS for the first time at our echocardiography laboratory. We evaluated LA reservoir, conduit and pump function by measuring LA volumes at different timings of cardiac cycle. Treatment strategy was decided according to heart team consensus and patient decision. We divided patients into groups according to terciles of LA reservoir, conduit and pump function. Primary outcome was defined by the occurrence of all-cause mortality during follow-up. RESULTS: A total of 408 patients were included in the analysis, with a median follow-up time of 45 months (interquartile range 54 months). 57.9% of patients underwent AVR and 44.9% of patients registered the primary outcome during follow-up. Left atrial emptying fraction (LAEF) was the best LA functional parameter and the best overall parameter in discriminating primary outcome (AUC 0.845, 95%CI 0.81-0.88, P < 0.001). After adjustment for clinical, demographic and echocardiographic variables, cumulative survival of patients with LAEF < 37% and LAEF 37 to 53% relative to patients with LAEF ≥54% remained significantly lower (HR 13.91, 95%CI 6.20-31.19, P < 0.001 and HR 3.40, 95%CI 1.57-7.37, P = 0.002, respectively). After adjustment for AVR, excess risk of LAEF < 37% and LAEF 37 to 53% relative to LAEF ≥54% remained significant (HR 11.71, 95%CI 5.20-26.40, P < 0.001 and HR 3.59, 95%CI 1.65-7.78, P = 0.001, respectively). CONCLUSIONS: In patients with a first diagnosis of severe AS, LA function, evaluated by means of volumetric assessment, is an independent predictor of all-cause mortality and a more potent predictor of death compared to classical severity parameters. These data can be useful to identify high-risk patients who might benefit of AVR.

Going beyond classic echo in aortic stenosis: left atrial mechanics, a new marker of severity.

BACKGROUND: There is limited information regarding left atrial (LA) mechanics in aortic valve stenosis (AS). We assessed LA mechanics in AS through speckle-tracking echocardiography (STE) according to severity and prognosis. METHODS: We included 102 patients diagnosed with severe AS (sAS) and 80 patients with moderate AS (mAS), all with preserved ejection fraction and no coronary artery disease. LA mechanics and left ventricular global longitudinal strain (LV-GLS) were assessed by STE. The cohort was followed-up for a median of 30 (IQR 12.6-50) months, and outcomes were determined (combined outcome of HF, death, and aortic valve replacement). RESULTS: In our sample set, values of LV-GLS (- 18.5% vs - 17.1, p = 0.025), E/e' ratio (15.8 vs 18.4, p = 0.03), and global LA mechanics (LA ɛsys, 23% vs 13.8%, p < 0.001) were worse for sAS compared to those for mAS. However, LA ɛsys (AUC 0.85, 95% CI 0.78-0.90, p < 0.001), ɛe (AUC 0.83, 95% CI 0.75-0.88, p < 0.001), and ɛa (AUC 0.80, 95% CI 0.70-0.84, p < 0.001) were the best discriminators of sAS, with sensitivities higher than 85%. LA ɛsys showed a stronger correlation with both aortic valve area (r2 = 0.6, p < 0.001) and mean LV/aortic gradient (r2 = 0.55, p < 0.001) than LV-GLS (r2 = 0.3 and r2 = 0.25, p = 0.01). Either LV-GLS or LA ɛsys, but not the E/e' ratio, TAPSE, or RV/RA gradient, were a significant predictors of the combined outcome. CONCLUSIONS: LA global strain was the best discriminator of severity, surpassing E/e' ratio and LV-GLS, and a significant predictor of prognosis in AS.

Comparison of intracardiac and transoesophageal echocardiography for guidance of percutaneous left atrial appendage occlusion: A meta-analysis.

AIMS: We performed a meta-analysis to compare the safety and efficacy of intracardiac echocardiography (ICE) vs transoesophageal echocardiography (TOE) for the guidance of percutaneous left atrial appendage occlusion (LAAO). METHODS AND RESULTS: A comprehensive search of the literature was performed, from inception to December 2018 using MEDLINE, Cochrane Library, and Google Scholar electronic databases, and references from articles. Publications comparing ICE and TOE for the guidance of percutaneous LAAO were included in the analysis. The co-primary endpoints were procedural success and procedure-related complications. Secondary endpoints included procedural and fluoroscopy times and the volume of contrast media used. Five studies were included in the analysis, providing a total of 1122 patients. Procedural success was similar with both techniques (pooled odd ratio [OR] 1.46, 95% confidence interval [CI] 0.77-2.75, P = 0.24, I2  = 0%), with a trend for less procedure-related complications in the ICE group (pooled OR 0.57, 95% CI 0.31-1.05, P = 0.07, I2  = 0%). Neither procedural (mean difference -1.64 minutes, 95% CI -16.42 to 13.14, P = 0.83, I2  = 96%) nor fluoroscopy times (mean difference + 1.29 minutes, 95% CI -1.38 to 3.97, P = 0.34, I2  = 76%) varied significantly between groups. There was a reduction in the volume of contrast media used in the ICE group (mean difference -9.71 mL, 95% CI -14.61 to -4.81, P > 0.01, I2  = 0%). CONCLUSION: Intracardiac echocardiography is a safe and effective alternative to TOE for guidance of percutaneous LAAO.

Two-dimensional speckle tracking cardiac mechanics and constrictive pericarditis: systematic review.

Transthoracic echocardiography has a pivotal role in the diagnosis of constrictive pericarditis (CP). In addition to the classic M-mode, two-dimensional and Doppler indices, newer methodologies designed to evaluate myocardial mechanics, such as two-dimensional speckle tracking echocardiography (2DSTE), provide additional diagnostic and clinical information in the context of CP. Research has demonstrated that cardiac mechanics can improve echocardiographic diagnostic accuracy of CP and aid in differentiating between constrictive and restrictive ventricular physiology. 2DSTE can also be used to assess the success of pericardiectomy and its impact on atrial and ventricular mechanics. In the course of this review, we describe cardiac mechanics in patients with CP and summarize the influence of pericardiectomy on atrial and ventricular mechanics assessed using 2DSTE.

Aortic Valve Disease and Vascular Mechanics: Two-Dimensional Speckle Tracking Echocardiographic Analysis.

PURPOSE: Degenerative aortic valve disease (AVD) is a complex disorder that goes beyond valve itself, also undermining aortic wall. We aimed to assess the ascending aortic mechanics with two-dimensional speckle tracking echocardiography (2DSTE) in patients with aortic regurgitation (AR) and hypothesized a relationship with degree of AR. Aortic mechanics were then compared with those of similarly studied healthy controls and patients with aortic stenosis (AS); finally, we aimed to assess the prognostic significance of vascular mechanics in AVD. METHODS: Overall, 73 patients with moderate-to-severe AR and 22 healthy subjects were enrolled, alongside a previously examined cohort (N = 45) with moderate-to-severe AS. Global circumferential ascending aortic strain (CAAS) and strain rate (CAASR) served as indices of aortic deformation; corrected CAAS was calculated as CAAS/pulse pressure (PP). Median clinical follow-up was 438 days. RESULTS: In patients with severe (vs. moderate) AR, CAASR (1.53 ± 0.29/sec vs. 1.90 ± 0.62/sec, P < 0.05) and corrected CAAS (0.14 ± 0.06%/mmHg vs. 0.19 ± 0.08%/mmHg, P < 0.05) were significantly lower, whereas CAAS did not differ significantly. Measurers of aortic mechanics (CAAS, corrected CAAS, CAASR) differed significantly (all P < 0.01) in patients with AS and AR and in healthy subjects, with lower values seen in patients with AS. In follow-up, survival rate of AVD patients with baseline CAASR >0.88/sec was significantly higher (log rank, 97.4% vs. 73.0%; P = 0.03). CONCLUSIONS: Quantitative measures of aortic mechanics were lower for AS patients, suggesting a more significant derangement of aortic elastic properties. In the context of AVD, vascular mechanics assessment proved useful in gauging clinical prognosis.

Coronary angiography after out-of-hospital cardiac arrest without ST-segment elevation: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis. The optimal timing and role of early coronary angiography (CAG) in OHCA patients without ST-segment elevation remains unclear. The goal of this study is to compare an early CAG versus delayed CAG strategy in OHCA patients without ST elevation. METHODS: We systematically searched PubMed, Embase and Cochrane databases, in June 2022, for randomised controlled trials (RCTs) comparing early versus delayed early CAG. A random effects meta-analysis was performed. RESULTS: A total of seven RCTs were included, providing a total of 1625 patients: 816 in an early strategy and 807 in a delayed strategy. In terms of outcomes assessed, our meta-analysis revealed a similar rate of all-cause mortality (pooled odds ratio [OR] 1.22 [0.99-1.50], P  = 0.06, I 2  = 0%), neurological status (pooled OR 0.94 [0.74-1.21], = 0.65, I 2  = 0%), need of renal replacement therapy (pooled OR 1.11 [0.78-1.74], P  = 0.47, I 2  = 0%) and major bleeding events (pooled OR 1.51 [0.95-2.40], P  = 0.08, I 2  = 69%). CONCLUSION: According to our meta-analysis, in patients who experienced OHCA without ST elevation, early CAG is not associated with reduced mortality or an improved neurological status.

Computed tomography imaging in preprocedural planning of transcatheter valvular heart interventions.

Cardiac Computed Tomography (CCT) has become a reliable imaging modality in cardiology providing robust information on the morphology and structure of the heart with high temporal and isotropic spatial resolution. For the past decade, there has been a paradigm shift in the management of valvular heart disease since previously unfavorable candidates for surgery are now provided with less-invasive interventions. Transcatheter heart valve interventions provide a real alternative to medical and surgical management and are often the only treatment option for valvular heart disease patients. Successful transcatheter valve interventions rely on comprehensive multimodality imaging assessment. CCT is the mainstay imaging technique for preprocedural planning of these interventions. CCT is critical in guiding patient selection, choice of procedural access, device selection, procedural guidance, as well as allowing postprocedural follow-up of complications. This article aims to review the current evidence of the role of CCT in the preprocedural planning of patients undergoing transcatheter valvular interventions.

One-shot diagnostic and prognostic assessment in intermediate- to high-risk acute pulmonary embolism: the role of multidetector computed tomography.

INTRODUCTION: Contrast-enhanced multidetector computed tomography (MDCT) is useful for the diagnosis of pulmonary embolism (PE). However, current guidelines do not support its use for risk assessment in acute PE patients. OBJECTIVES: We compared the prognostic impact of MDCT-derived indices regarding medium-term mortality in a population of intermediate- to high-risk PE patients, mostly treated by thrombolysis. METHODS: Thirty-nine consecutive patients admitted to an intensive care unit with acute PE were studied. All patients had a pulmonary MDCT on admission to the emergency room as part of the diagnostic algorithm. We assessed the following MDCT variables: right ventricular/left ventricular diameter (RV/LV) ratio, arterial obstruction index, pulmonary artery-to-aorta diameter ratio and azygos vein diameter. A 33-month follow-up was performed. RESULTS: Mean age was 59.1±19.6 years, with 80% of patients receiving thrombolysis. Follow-up all-cause mortality was 12.8%. Of the MDCT-derived variables, only the RV/LV ratio had significant predictive value, being higher in patients who suffered the endpoint (1.6±0.5 vs. 1.9±0.4, p=0.046). Patients with an RV/LV ratio ≥1.8 had 11-fold higher medium-term all-cause mortality (3.8% vs. 38.8%, p<0.001). Regarding this endpoint, the c-statistic was 0.78 (95% CI, 0.60-0.96) for RV/LV ratio and calibration was good (goodness-of-fit p=0.594). No other radiological index was predictive of mortality. CONCLUSIONS: MDCT gives the possibility, in a single imaging procedure, of diagnosing and assessing the prognosis of patients with intermediate- to high-risk PE. Although further studies are needed, the simple-to-calculate RV/LV ratio has good discrimination and calibration for predicting poorer outcomes in patients with acute PE.

Anti-SARS-CoV-2 vaccine-induced myocarditis - real but, in general, rare and mild: A consensus statement from the Studies Committee of the Portuguese Society of Cardiology.

Acute myocarditis (especially) and pericarditis have been consistently associated with the administration of vaccines against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), generating anxiety in the general population, uncertainty in the scientific community and obstacles to ambitious mass vaccination programs, especially in foreign countries. Like some of its European counterparts, the Portuguese Society of Cardiology (SPC), through its Studies Committee, decided to take a position on some of the most pressing questions related to this issue: (i) How certain are we of this epidemiological association? (ii) What is the probability of its occurrence? (iii) What are the pathophysiological bases of these inflammatory syndromes? (iv) Should their diagnosis, treatment and prognosis follow the same steps as for typical idiopathic or post-viral acute myopericarditis cases? (v) Is the risk of post-vaccine myocarditis great enough to overshadow the occurrence of serious COVID-19 disease in unvaccinated individuals? In addition, the SPC will issue clinical recommendations and offer its outlook on the various paths this emerging disease may take in the future.

Tricuspid repair in mitral regurgitation surgery: a systematic review and meta-analysis.

BACKGROUND: Concomitant tricuspid repair in MR surgery is indicated in patients with severa tricuspid regurgitation, however, concomitant repair in less-than-severe TR patients is still a matter of debate. METHODS: In December 2021, we systematically searched PubMed, Embase and Cochrane databases for randomised control trials (RCTs) comparing isolated MR surgery versus MR surgery with concomitant TR annuloplasty. Four studies were included, resulting in 651 patients (323 in the prophylactic tricuspid intervention group and 328 in the no tricuspid intervention group). RESULTS: Our meta-analysis showed a similar all-cause mortality and perioperative mortality for concomitant prophylactic tricuspid repair when compared with no tricuspid intervention (pooled odds ratio (OR), 0.54; 95% confidence interval (CI): 0.25-1.15, P = 0.11; I2 = 0% and pooled OR, 0.54; 95% CI: 0.25-1.15, P = 0.11; I2 = 0%, respectively) in patients undergoing MV surgery. despite a significantly lower TR progression (pooled OR, 0.06; 95% CI: 0.02-0.24, P < 0.01; I2 = 0%). Additionally, similar New York Heart Association (NYHA) classes III and IV were identified in both concomitant prophylactic tricuspid repair and no tricuspid intervention, despite a lower trend in the tricuspid intervention group (pooled OR, 0.63; 95% CI: 0.38-1.06, P = 0.08; I2 = 0%). CONCLUSIONS: Our pooled analyses suggested that TV repair at the time of MV surgery in patients with moderate or less-than-moderate TR did not impact on perioperative or postoperative all-cause mortality, despite reducing TR severity and TR progression following the intervention.

Early surgical intervention versus conservative management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis.

OBJECTIVE: Timing of intervention for patients with asymptomatic severe aortic stenosis (AS) remains controversial. To compare the outcomes of early aortic valve replacement (AVR) versus watchful waiting (WW) in patients with asymptomatic severe AS. METHODS: We systematically searched PubMed, Embase and Cochrane databases, in December 2021, for studies comparing early AVR with WW in the treatment of asymptomatic severe AS. Random-effects meta-analysis was performed. RESULTS: Twelve studies were included in which two were randomised clinical trials. A total of 4130 patients were included, providing a 1092 pooled death events. Our meta-analysis showed a significantly lower all-cause mortality for the early AVR compared with WW group, although with a high amount of heterogeneity between studies in the magnitude of the effect (pooled OR 0.40; 95% CI 0.35 to 0.45, p<0.01; I²=61%). An early surgery strategy displayed a significantly lower cardiovascular mortality (pooled OR 0.33; 95% CI 0.19 to 0.56, p<0.01; I²=64%) and heart failure hospitalisation (pooled OR 0.19; 95% CI 0.10 to 0.39, p<0.01, I²=7%). However, both groups had similar rates of stroke (pooled OR 1.30; 95% CI 0.73 to 2.29, p=0.36, I²=0%) and myocardial infarction (pooled OR 0.49; 95% CI 0.19 to 1.27, p=0.14, I²= 0%). CONCLUSIONS: This study suggests that for patients with asymptomatic severe AS an early surgical intervention compared with a conservative WW strategy was associated with a lower heart failure hospitalisation and a similar rate of stroke or myocardial infarction, although with significant risk of bias. PROSPERO REGISTRATION NUMBER: CRD42021291144.

Conservative management of pneumopericardium: A case of unexpected success.

A 79-year-old male with severe aortic stenosis was admitted with syncope and cranioencephalic traumatism with major nasal hemorrhage. While being prepared for surgical aortic valve replacement, a high-degree atrioventricular block was detected and a definite pacemaker was implanted.

Sudden death in young South European population: a cross-sectional study of postmortem cases.

To describe the annual incidence and the leading causes of sudden non-cardiac and cardiac death (SCD) in children and young adult Portuguese population. We retrospectively reviewed autopsy of sudden unexpected deaths reports from the Portuguese National Institute of Legal Medicine and Forensic Sciences' database, between 2012 and 2016, for the central region of Portugal, Azores and Madeira (ages 1-40: 26% of the total population). During a 5-year period, 159 SD were identified, corresponding to an annual incidence of 2,4 (95%confidence interval, 1,5-3,6) per 100.000 people-years. Victims had a mean age of 32 ± 7 years-old, and 72,3% were male. There were 70,4% cardiac, 16,4% respiratory and 7,5% neurologic causes of SD. The most frequent cardiac anatomopathological diagnosis was atherosclerotic coronary artery disease (CAD) (33,0%). There were 15,2% victims with left ventricular hypertrophy, with a diagnosis of hypertrophic cardiomyopathy only possible in 2,7%. The prevalence of cardiac pathological findings of uncertain significance was 30,4%. In conclusion, the annual incidence of SD was low. Atherosclerotic CAD was diagnosed in 33,0% victims, suggesting the need to intensify primary prevention measures in the young. The high prevalence of pathological findings of uncertain significance emphasizes the importance of molecular autopsy and screening of first-degree relatives.

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

BACKGROUND: Clopidogrel 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. OBJECTIVE: To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population. METHODS: We 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. RESULTS: The 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. CONCLUSION: In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker.

Platelet aggregation at discharge: a useful tool in acute coronary syndromes?

INTRODUCTION: Inhibition of platelet aggregation appears two hours after the first dose of clopidogrel, becomes significant after the second dose, and progresses to a steady-state value of 55% by day seven. Low response to clopidogrel has been associated with increased risk of stent thrombosis and ischemic events, particularly in the context of stable heart disease treated by percutaneous coronary intervention. OBJECTIVE: To stratify medium-term prognosis of an acute coronary syndrome (ACS) population by platelet aggregation. METHODS: We performed a prospective longitudinal study of 70 patients admitted for an ACS between May and August 2009. Platelet function was assessed by ADP-induced platelet aggregation using a commercially available kit (Multiplate(®) analyzer) at discharge. The primary endpoint was a combined outcome of mortality, non-fatal myocardial infarction, or unstable angina, with a median follow-up of 136.0 (79.0-188.0) days. RESULTS: The median value of platelet aggregation was 16.0U (11.0-22.5U) with a maximum of 41.0U and a minimum of 4.0U (normal value according to the manufacturer: 53-122U). After ROC curve analysis with respect to the combined endpoint (AUC 0.72), we concluded that a value of 18.5U conferred a sensitivity of 75.0% and a specificity of 68% to that result. We therefore created two groups based on that level: group A - platelet aggregation <18.5U, n=44; and group B - platelet aggregation ≥18.5U, n=26. The groups were similar with respect to demographic data (age 60.5 [49.0-65.0] vs. 62.0 [49.0-65.0] years, p=0.21), previous cardiovascular history, and admission diagnosis. There were no associations between left ventricular ejection fraction, GRACE risk score, or length of hospital stay and platelet aggregation. The groups were also similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6 vs. 46.2%, p=0.15) and statin therapy. The variability in platelets and hemoglobin was also similar between groups. Combined event-free survival was higher in group A (96.0 vs. 76.7%, log-rank p<0.01). Platelet aggregation higher than 18.5U was an independent predictor of the combined event (HR 6.75, 95% CI 1.38-32.90, p=0.02). CONCLUSION: In our ACS population platelet aggregation at discharge was a predictor of medium-term prognosis.