Samir Alam

Use of dabigatran for periprocedural anticoagulation in patients undergoing catheter ablation for atrial fibrillation

Background—Pulmonary vein isolation (PVI) for atrial fibrillation is associated with a transient increased risk of thromboembolic and hemorrhagic events. We hypothesized that dabigatran can be safely used as an alternative to continuous warfarin for the periprocedural anticoagulation in PVI. Methods and Results—A total of 999 consecutive patients undergoing PVI were included; 376 patients were on dabigatran (150 mg), and 623 patients were on warfarin with therapeutic international normalized ratio. Dabigatran was held 1 to 2 doses before PVI and restarted at the conclusion of the procedure or as soon as patients were transferred to the nursing floor. Propensity score matching was applied to generate a cohort of 344 patients in each group with balanced baseline data. Total hemorrhagic and thromboembolic complications were similar in both groups, before (3.2% versus 3.9%; P=0.59) and after (3.2% versus 4.1%; P=0.53) matching. Major hemorrhage occurred in 1.1% versus 1.6% (P=0.48) before and 1.2% versus 1.5% (P=0.74) after matching in the dabigatran versus warfarin group, respectively. A single thromboembolic event occurred in each of the dabigatran and warfarin groups. Despite higher doses of intraprocedural heparin, the mean activated clotting time was significantly lower in patients who held dabigatran for 1 or 2 doses than those on warfarin. Conclusions—Our study found no evidence to suggest a higher risk of thromboembolic or hemorrhagic complications with use of dabigatran for periprocedural anticoagulation in patients undergoing PVI compared with uninterrupted warfarin therapy.

Distribution and Risk Profile of Paroxysmal, Persistent, and Permanent Atrial Fibrillation in Routine Clinical Practice Insight From the Real-Life Global Survey Evaluating Patients With Atrial Fibrillation International Registry

Background— There is a paucity of international data on the various types of atrial fibrillation (AF) outside the highly selected populations from randomized trials. This study aimed to describe patient characteristics, risk factors, comorbidities, symptoms, management strategy, and control of different types of AF in real-life practice. Methods and Results— Real-life global survey evaluating patients with atrial fibrillation (RealiseAF) was a contemporary, large-scale, cross-sectional international survey of patients with AF who had ≥1 episode in the past 12 months. Investigators were randomly selected to avoid bias. Among 9816 eligible patients from 831 sites in 26 countries, 2606 (26.5%) had paroxysmal, 2341 (23.8%) had persistent, and 4869 (49.6%) had permanent AF. As AF progressed from paroxysmal to persistent and permanent forms, the prevalence of comorbidities, such as heart failure (32.9%, 44.3%, and 55.6%), coronary artery disease (30.0%, 32.9%, and 34.3%), cerebrovascular disease (11.7%, 10.8%, and 17.6%), and valvular disease (16.7%, 21.2%, and 35.8%), increased, and the prevalence of lone AF decreased. Similarly, there was an increase in mean CHADS2 [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score (1.7, 1.8, and 2.2), and more than half of patients (51.0%, 56.7%, and 67.3%) qualified for oral anticoagulants. Almost 90% of patients received ≥1 antiarrhythmic drug, but >60% had European Heart Rhythm Association symptom scores from II to IV. Furthermore, 40.7% of persistent and 49.8% of permanent AF patients were still in AF with a heart rate >80 beats per minute. Conclusions— This survey disclosed high cardiovascular risks and an unmet need in daily practice for patients with any type of AF, especially those with the permanent form.

Distribution and Risk Profile of Paroxysmal, Persistent, and Permanent Atrial Fibrillation in Routine Clinical Practice: Insight from the RealiseAF International Registry

Background— There is a paucity of international data on the various types of atrial fibrillation (AF) outside the highly selected populations from randomized trials. This study aimed to describe patient characteristics, risk factors, comorbidities, symptoms, management strategy, and control of different types of AF in real-life practice. Methods and Results— Real-life global survey evaluating patients with atrial fibrillation (RealiseAF) was a contemporary, large-scale, cross-sectional international survey of patients with AF who had ≥1 episode in the past 12 months. Investigators were randomly selected to avoid bias. Among 9816 eligible patients from 831 sites in 26 countries, 2606 (26.5%) had paroxysmal, 2341 (23.8%) had persistent, and 4869 (49.6%) had permanent AF. As AF progressed from paroxysmal to persistent and permanent forms, the prevalence of comorbidities, such as heart failure (32.9%, 44.3%, and 55.6%), coronary artery disease (30.0%, 32.9%, and 34.3%), cerebrovascular disease (11.7%, 10.8%, and 17.6%), and valvular disease (16.7%, 21.2%, and 35.8%), increased, and the prevalence of lone AF decreased. Similarly, there was an increase in mean CHADS2 [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score (1.7, 1.8, and 2.2), and more than half of patients (51.0%, 56.7%, and 67.3%) qualified for oral anticoagulants. Almost 90% of patients received ≥1 antiarrhythmic drug, but >60% had European Heart Rhythm Association symptom scores from II to IV. Furthermore, 40.7% of persistent and 49.8% of permanent AF patients were still in AF with a heart rate >80 beats per minute. Conclusions— This survey disclosed high cardiovascular risks and an unmet need in daily practice for patients with any type of AF, especially those with the permanent form.

Symptoms, functional status and quality of life in patients with controlled and uncontrolled atrial fibrillation: data from the RealiseAF cross-sectional international registry

Background Rate control and rhythm control are accepted management strategies for atrial fibrillation (AF). Objective RealiseAF aimed to describe the success of either strategy and the impact of control on symptomatic status of patients with AF. Methods This international, observational, cross-sectional survey of patients with any history of AF in the previous year, recorded AF characteristics, management and frequency of control (defined as sinus rhythm or AF with resting heart rate ≤80 bpm). Results Overall, 9665 patients were evaluable for AF control, with 59.0% controlled (sinus rhythm 26.5%, AF ≤80 bpm 32.5%) and 41.0% uncontrolled. Symptom prevalence in the previous week was lower in controlled than uncontrolled AF (55.7% vs 68.4%; p<0.001) and similar for patients in sinus rhythm versus AF ≤80 bpm (54.8% vs 56.4%; p=0.23). At the visit, AF-related functional impairment (EHRA class >I) was seen in 67.4% of patients with controlled AF and 82.1% of patients with uncontrolled AF (p<0.001). Quality-of-life (QoL, measured using EQ-5D) was better for patients with controlled versus uncontrolled AF using the Visual Analogue Scale (mean (SD) score 67.1 (18.4) vs 63.2 (18.9); p<0.001), single index utility score (median 0.78 vs 0.73; p<0.001), or five dimensions of well-being (all p<0.001). Irrespective of AF control, cardiovascular events had led to hospitalisation in the past year in 28.1%. Conclusion AF control is not optimal. Control appears to be associated with fewer symptoms and better QoL, but even patients with controlled AF have frequent symptoms, functional impairment, altered QoL and cardiovascular events. New treatments are needed to improve control and minimise the functional and QoL burden of AF.

Relation Between Iron-Overload Indices, Cardiac Echo-Doppler, and Biochemical Markers in Thalassemia Intermedia

Cardiovascular impairment is a major cause of morbidity and mortality in patients with thalassemia intermedia. In this study, echocardiographic assessment of left heart condition was performed in patients with thalassemia intermedia, and its relation to hematologic variables--amino terminal pro-brain natriuretic peptide (NT-proBNP), ferritin, hemoglobin--and liver iron concentration (LIC) was investigated. Echocardiographic assessment was performed using pulse-wave Doppler and tissue Doppler imaging. Data from 74 patients with thalassemia intermedia--35 men, 39 women, mean age 26.5 years (8 to 63)--were randomly selected and evaluated. Blood samples were collected for NT-proBNP levels in a random subgroup of 19 patients. Mean baseline values were hemoglobin 8.4 g/dl (4.9 to 13.1), serum ferritin 902.6 ng/ml (15 to 4,140), LIC 9.0 mg Fe/g (0.5 to 32.1), and NT-proBNP 113.5 pg/ml (16.4 to 371). Correlation between LIC and pulmonary artery systolic pressure was significant, suggesting that iron loading in the liver is indicative of cardiovascular sequelae. NT-proBNP was significantly correlated with the ratio of the left ventricular early rapid filling wave to early diastolic velocity at the mitral annulus (r = 0.50, p = 0.04) and hemoglobin (r = -0.49, p = 0.03), but not with other characteristics assessed. In conclusion, this study has highlighted the importance of using tissue Doppler imaging rather than pulse-wave Doppler to characterize left ventricular diastolic dysfunction in patients with thalassemia intermedia. Demonstration of the correlation of LIC and pulmonary artery systolic pressure independent of left ventricular filling pressures supports our hypothesis that left ventricular diastolic dysfunction does not contribute to the increased pulmonary artery systolic pressure in patients with thalassemia intermedia.

Influence of CYP2C9 and VKORC1 Polymorphisms on Warfarin and Acenocoumarol in a Sample of Lebanese People

The authors assessed the impact of CYP2C9*2, CYP2C9*3, and/or VKORC1−1639G>A/1173C>T single‐nucleotide polymorphisms on oral anticoagulants in a Lebanese population. This study recruited 231 Lebanese participants on long‐term warfarin or acenocoumarol maintenance therapy with an international normalized ratio (INR) monitored at the American University of Beirut Medical Center. CYP2C9 and VKORC1 variant alleles were screened by real‐time PCR. Plasma R‐ and S‐warfarin and R‐ and S‐acenocoumarol levels were assayed using high‐performance liquid chromatography. The variant allele frequencies of CYP2C9*2, CYP2C9*3, and VKORC1 −1639G>A/1173C>T were 15.4%, 7.8%, and 52.4%, respectively. Fifty‐five participants were excluded from analysis because of nontherapeutic INR values at recruitment, leaving 43 participants taking warfarin and 133 taking acenocoumarol. There was a significant decrease in the weekly maintenance dose of both drugs with CYP2C9 and VKORC1 variants when compared with wild‐type patients. CYP2C9*2 had the least impact on the response to both drugs. The concentrations of R‐ and S‐warfarin in plasma were significantly correlated with CYP2C9 genotypes. For acenocoumarol, time to reach target INR was more prolonged in patients carrying any CYP2C9 variant allele but failed to reach statistical significance because of low numbers of patients. There was no association between allelic variants and bleeding events. This is the first pharmacogenetic study of oral anticoagulants in Arabs. The authors showed that both CYP2C9 and VKORC1 polymorphisms are common in Lebanon and influence warfarin and acenocoumarol dose requirements, with the CYP2C9*2 polymorphism having less effect on acenocoumarol, the most commonly used oral anticoagulant in Lebanon.

Hydatid cyst of the heart: Diagnosis by two-dimensional echocardiography and computed tomography

4. Arthur A, Cottom D, Evans R, Spencer H: Myocardial infarction in a newborn infant. J Pediatr 73:110, 1968. 5. Fletcher MA, Meyer M, Kirkpatrick SE, Papelbaum S, Gluck L, Benirschke K: Myocardial infarction associated with umbilical cord hematoma. J Pediatr 89:806, 1976. 6. Richart R, Benirschke K: Myocardial infarction in the perinatal period: Report of two cases in newborn infants. J Pediatr 55:706, 1959. 7. Mueller RF, Sybert VP, Johnson J, Brown ZA, Chen W-J: Evaluation of a protocol for post-mortem examination of stillbirths. N Engl J Med 309:587, 1983.

High residual platelet reactivity on clopidogrel: its significance and therapeutic challenges overcoming clopidogrel resistance

Over the last decade, dual antiplatelet therapy has been the mainstay of the management of Acute Coronary Syndrome, with clopidogrel therapy providing clear benefits over aspirin monotherapy and becoming the agent of choice for the prevention of stent thrombosis. While newer antiplatelet agents have now become available, clopidogrel is still widely used due to its low cost and efficacy. However, many patients still experience recurrent ischemic events. A poor response of the platelets to clopidogrel, called High Residual Platelet Reactivity (HRPR), has been incriminated to account for this dilemma. Despite the absence of a universal definition of HRPR or the gold standard test to quantify it, persistent high platelet reactivity has consistently been associated with recurrence of ischemic events. Clopidogrel metabolism is highly variable, and genetics, comorbidities and drug interactions can affect it. In this article we review all definitions of HRPR, explore the available tests to quantify it, the clinical outcomes associated with it, as well as strategies that have shown success in overcoming it.

Resistance to aspirin and clopidogrel therapy

Introduction:  Despite increasing evidence on the roles of aspirin and clopidogrel in decreasing morbidity and mortality from cardiovascular disease, resistance to therapy remains an emerging clinical entity. The aim of this review was to revisit current knowledge of the mechanisms, laboratory evaluation, clinical impact and management of resistance to aspirin and clopidogrel therapy.

Parental consanguinity and family history of coronary artery disease strongly predict early stenosis

BACKGROUND Coronary artery disease (CAD) is a multifactorial disease with acquired and inherited components. AIM We investigated the roles of family history and consanguinity on CAD risk and age at diagnosis in 4284 patients. The compounded impact of diabetes, hyperlipidemia, hypertension, smoking, and BMI, which are known CAD risk factors, on CAD risk and age at diagnosis was also explored. METHODS CAD was determined by cardiac catheterization. Logistic regression and stratification were performed to determine the impact of family history and consanguinity on risk and onset of CAD, controlling for diabetes, hyperlipidemia, hypertension, smoking, and BMI. RESULTS Family history of CAD and gender significantly increased the risk for young age at diagnosis of CAD (p<0.001). Consanguinity did not promote risk of CAD (p=0.38), but did affect age of disease diagnosis (p<0.001). The mean age at disease diagnosis was lowest, 54.8 years, when both family history of CAD and consanguinity were considered as unique risk factors for CAD, compared to 62.8 years for the no-risk-factor patient category (p<0.001). CONCLUSIONS Family history of CAD and smoking are strongly associated with young age at diagnosis. Furthermore, parental consanguinity in the presence of family history lowers the age of disease diagnosis significantly for CAD, emphasizing the role of strong genetic and cultural CAD modifiers. These findings highlight the increased role of genetic determinants of CAD in some population subgroups, and suggest that populations and family structure influence genetic heterogeneity between patients with CAD.