Dan Justo

Torsade de pointes due to noncardiac drugs: Most patients have easily identifiable risk factors

Numerous medications, including drugs prescribed for noncardiac indications, can lead to QT prolongation and trigger torsade de pointes. Although this complication occurs only rarely, it may have lethal consequences. It is therefore important to know if patients with torsade de pointes associated with noncardiac drugs have risk factors that are easy to identify. We reviewed reports of drug-induced torsade de pointes and analyzed each case of torsade de pointes associated with a noncardiac drug for the presence of risk factors for the long QT syndrome that can be easily identified from the medical history or clinical evaluation (female gender, heart disease, electrolyte disturbances, excessive dosing, drug interactions, and history of familial long QT syndrome). We identified 249 patients with torsade de pointes caused by noncardiac drugs. The most commonly identified risk factor was female gender (71%). Other risk factors were frequently present (18%-41%). Virtually all patients had at least 1 of these risk factors, and 71% of patients had 2 or more risk factors. Our study suggests that almost all patients with torsade de pointes secondary to noncardiac drugs have risk factors that can be easily identified from the medical history before the initiation of therapy with the culprit drug.

Prevalence and Predictors of Concomitant Carotid and Coronary Artery Atherosclerotic Disease

OBJECTIVES The purpose of this research was to evaluate the relationship between coronary and carotid atherosclerotic disease using current guidelines for the definition of carotid artery stenosis (CAS). BACKGROUND The reported prevalence of concomitant coronary and carotid atherosclerotic disease has varied among studies due to differences in study populations and methodologies used. METHODS We performed a retrospective analysis of prospectively collected data obtained between January 2007 and May 2009 from consecutive patients undergoing same-day coronary angiography and carotid Doppler studies. Spearman correlations and multinomial logistic regression models were used to identify independent correlates of CAS. RESULTS The study included 1,405 patients (age 65 ± 11 years, 77.2% male), of whom 12.8% had significant CAS (peak systolic velocity [PSV] >125 cm/s) and 4.6% had severe CAS (PSV >230 cm/s). Mild CAS (PSV <125 cm/s and the presence of a sonographic atherosclerotic lesion) was present in 58%. The severity of CAS and the extent of coronary artery disease (CAD) were significantly correlated (r = 0.255, p < 0.001). Independent predictors of severe CAS defined by PSV were the presence of left-main or 3-vessel CAD, increasing age, a history of stroke, smoking status, and diabetes mellitus. CONCLUSIONS The degree of internal carotid artery (ICA) stenosis is related to the extent of CAD, though the prevalence of clinically significant ICA stenosis is lower in specific CAD subsets than previously reported.

Thrombosis associated with acute cytomegalovirus infection: A meta-analysis

BACKGROUND Thrombosis associated with acute cytomegalovirus (CMV) infection has been reported in the medical literature almost 100 times thus far. Still, the clinical characteristics of patients with both conditions have never been systematically reviewed and described. METHODS A literature search was conducted for all (n=97) reports concerning thrombosis associated with acute CMV infection. The current knowledge concerning this unique association and previous clinical experience are presented here. RESULTS The incidence of thrombosis among acute CMV infection hospitalized patients was 6.4%, and the incidence of acute CMV infection among thrombosis hospitalized patients was 1.9-9.1%. Most (n=64; 65.9%) reported patients were immunocompetent. Mean age of reported patients was 39.7 ± 14.9 years. Female-male ratio was 1:1. DVT/PE, splanchnic vein thrombosis and splenic infarction were the most prevalent thromboses associated with acute CMV infection. While DVT/PE was more prevalent among immunocompromised patients, splanchnic vein thrombosis was more prevalent among immunocompetent patients. Inherited predispositions for thrombosis were significantly more prevalent among immunocompetent patients. Immunocompromised patients were treated with antiviral agents significantly more often. Duration of anticoagulation therapy varied significantly between reported patients. In-hospital mortality rates were 4.9-22.2%. CONCLUSIONS We believe physicians should be alert for symptoms and signs of thrombosis in patients with acute CMV infection, and for symptoms and signs of acute CMV infection in patients with thrombosis.

Takotsubo cardiomyopathy and QT interval prolongation: who are the patients at risk for torsades de pointes? ☆

OBJECTIVES QT interval prolongation is prevalent among patients with Takotsubo cardiomyopathy (TC), whereas torsades de pointes (TdP) has rarely been reported in these patients. We studied all peer-reviewed reports on TC-associated QT interval prolongation and all peer-reviewed reports on TC-associated TdP to characterize the clinical circumstances leading to TdP in patients with TC. METHODS The literature search yielded 14 reports on TC-associated TdP and 26 reports on TC-associated QT interval prolongation. Overall, 15 patients with TC-associated TdP and 86 patients with TC-associated QT interval prolongation were reported. We systematically reviewed each report and recorded the risk factors for TdP as well as the clinical circumstances of TC. RESULTS The prevalence of the male sex was higher among patients with TC-associated TdP relative to patients with TC-associated QT interval prolongation (26.7% vs 5.8%; P = .01). There was a trend in the mean maximal corrected QT interval being longer among patients with TC-associated TdP relative to patients with TC-associated QT interval prolongation (679.9 +/- 230.6 vs 555.9 +/- 63.8 milliseconds; P = .06). There were no differences between patients with TC-associated TdP and patients with TC-associated QT interval prolongation in mean age, maximal troponin levels, and lowest ejection fraction. Overall, 12 (80.0%) patients with TC-associated TdP had risk factors for TdP other than the female sex and systolic dysfunction, including suspicion of congenital long QT syndrome, bradycardia, hypokalemia, recent conversion from atrial fibrillation to sinus rhythm, and using QT prolonging agents. CONCLUSIONS Men with TC-associated QT interval prolongation are at risk for TdP. Most patients with TC-associated TdP have risk factors for TdP other than the female sex and systolic dysfunction.

Platelet counts and platelet activation markers in obese subjects.

Objective. In this work we studied the correlation between platelet count, platelet activation, and systemic inflammation in overweight, obese, and morbidly obese individuals. Methods and subjects. A total of 6319 individuals participated in the study. Complete blood counts, high sensitivity C-reactive protein (hs-CRP) serum levels, and body mass index (BMI) were measured during routine checkups. Platelet activation markers were studied among 30 obese (BMI = 41 ± 8 kg/m2) and 35 nonobese (BMI = 24 ± 3 kg/m2) individuals. Platelet activation status was evaluated by flow cytometry using specific antibodies against the activated platelet membrane glycoprotein IIb/IIIa, p-selectin (CD-62 p), and binding of Annexin-V to platelet anionic phospholipids. Results. Overweight, obese, and morbidly obese females had significantly elevated platelet counts ( P < .0001) compared with normal-weight females. No significant elevation of platelet counts was observed in the male subgroups. A significant age adjusted correlation between BMI and platelet counts ( P < .0001) was found among females. This correlation was attenuated (P = .001) after adjustment for hs-CRP concentrations. The flow cytometry analysis of platelets showed no significant differences in activation marker expression between nonobese and obese individuals. Discussion. Obesity may be associated with elevated platelet counts in females with chronic inflammation. Obesity is not associated with increased platelet activation.

Incidence of cytomegalovirus-associated thrombosis and its risk factors: a case-control study.

INTRODUCTION Cytomegalovirus (CMV)-associated thrombosis has been reported sporadically in the medical literature until now. However, thrombosis incidence and its risk factors have never been studied in a cohort of patients with acute CMV infection. MATERIALS AND METHODS A retrospective case-control study. Medical charts and imaging study reports of all consecutive patients diagnosed with acute CMV infection during the years 2005-2006 in a tertiary medical center were reviewed for the presence of arterial and/or venous thromboses, and their acquired as well as inherited predispositions. The control group included age-matched and sex-matched consecutive patients, in whom acute CMV infection was excluded. Laboratory tests used for acute CMV infection diagnosis/exclusion were also matched, including serology, antigenemia, and PCR. RESULTS Included were 140 patients with acute CMV infection (study group) and 140 consecutive matched patients in whom acute CMV infection was excluded (control group). Among the control group, none of the patients had thrombosis, while among the study group, nine (6.4%; p=0.003) patients had thrombosis: five (3.6%; p=0.025) patients had arterial thrombosis and four (2.9%; p=0.045) patients had venous thrombosis. Binary logistic regression analysis showed that acute CMV infection was independently associated with thrombosis among the whole cohort (p=0.004), while use of oral contraceptives/hormones or pregnancy were independently associated with thrombosis among patients with acute CMV infection (p=0.043). CONCLUSIONS Thrombosis in patients with acute CMV infection is not rare. Acute CMV infection is associated with thrombosis independent of other risk factors for thrombosis. We hope to raise physicians awareness to the association between acute CMV infection and thrombosis.

Erectile Dysfunction Might Be Associated With Chronic Periodontal Disease: Two Ends of the Cardiovascular Spectrum

INTRODUCTION Both chronic periodontal disease (CPD) and erectile dysfunction (ED) are associated with cardiovascular disease and its risk factors, including smoking and diabetes mellitus. However, the association between ED and CPD has never been studied. AIM To study the association between ED and CPD. MAIN OUTCOME MEASURES. Prevalence of ED, prevalence of CPD, ED severity. METHODS The study population consisted of 305 men who filled the Sexual Health Inventory for Men (SHIM) questionnaire in order to detect ED and assess its severity, and underwent a pair of standardized posterior dental bitewing radiographs in order to detect CPD. SHIM questionnaire scores 21 or less represented ED. Alveolar bone loss of >or=6 mm represented CPD. RESULTS The mean age of included men was 39.5 +/- 6.7 years. Overall, 70 (22.9%) men had ED and 13 (4.3%) had CPD. CPD was significantly more prevalent among men with mild ED (P = 0.004) and moderate to severe ED (P = 0.007) in comparison to men without ED. CONCLUSIONS ED might be associated with CPD. These preliminary findings are consistent with theories that associate these conditions with systemic inflammation, endothelial dysfunction, and atherosclerosis.

C-reactive protein serum levels as an early predictor of outcome in patients with pandemic H1N1 influenza A virus infection

BackgroundData for predicting which patients with pandemic influenza A (H1N1) infection are likely to run a complicated course are sparse. We retrospectively studied whether the admission serum C-reactive protein (CRP) levels can serve as a predictor of illness severity.MethodsIncluded were all consecutive adult patients who presented to the emergency department (ED) between May-December, 2009 with a flu-like illness, a confirmed diagnosis of pandemic influenza A (H1N1) infection and a serum CRP level measured within 24 hours of presentation. Patients with a proven additional concurrent acute illness (e.g., bacteremia) were excluded. We used the ROC curve analysis, Kaplan-Meier curves and the Cox proportional hazard model to evaluate the predictive ability of CRP as a prognostic factor.ResultsSeventeen (9%) of the 191 enrolled patients were admitted to the intensive care unit (ICU), of whom eight (4%) required mechanical ventilation and three (2%) died. The median admission serum CRP levels were significantly higher among patients who required subsequent ICU care and mechanical ventilation than among patients who did not (123 mg/L and 112 mg/L vs. 40 mg/L, p < .001 and 43 mg/L, p = .017, respectively). A Cox proportional hazard model identified admission serum CRP levels and auscultatory findings over the lungs as independent prognostic factors for ICU admission. Admission serum CRP levels were the only independent prognostic factor for mechanical ventilation. Thirty days after presenting to the ED, none of the patients with admission serum CRP level <28 mg/L (lower tertile) required either ICU admission or mechanical ventilation. At the same time point, 19% of the patients with admission serum CRP level ≥70 mg/L (upper tertile) needed to be admitted to the ICU and 8% of the same upper tertile group required mechanical ventilation. The differences in the rates between the lower vs. upper tertile groups were significant (Log-Rank p < .001 for ICU and p < .024 for mechanical ventilation).ConclusionsIn our study group, serum CRP levels obtained in the early ED admission stage from patients presenting with pandemic H1N1 influenza A infection were found to serve as a useful gauge for predicting disease course and assisting in patient management.

Vitamin D deficiency prevalence and cardiovascular risk in Israel

Eur J Clin Invest 2011; 41 (3): 263–268

Relation of Educational Level to Inflammation-Sensitive Biomarker Level

It is a well-established finding that cardiovascular morbidity varies among groups of different socioeconomic status. Inflammatory processes have been proposed as a possible mediator of this variance. Level of education is an important indicator of socioeconomic status, inversely related to levels of inflammatory biomarkers. Whether this association was significant in a subpopulation of highly educated individuals was questioned. This cross-sectional study enrolled attendees of an executive health screening program intended specifically for executive and high-wage personnel from September 2002 to November 2007. A detailed questionnaire, anthropometric measurements, and laboratory data were used to determine self-reported years of education and cardiovascular risk factors. Linear regression models included high-sensitivity C-reactive protein, fibrinogen, erythrocyte sedimentation rate, and white blood cell count as dependent variables and were adjusted for multiple potential confounders. Data for 8,998 subjects (5,757 men, 3,241 women) with a mean age of 44 years (range 18 to 84) were analyzed. More than two-thirds reported >or=14 years of schooling, and >2,900 reported >or=17 years of schooling. We found a statistically significant inverse association between number of school years and high-sensitivity C-reactive protein, fibrinogen, and erythrocyte sedimentation rate. Higher levels of education were associated with lower prevalences of diabetes and current smoking in both genders and lower prevalences of hypertension and dyslipidemia in women. In conclusion, level of education was inversely associated with inflammatory biomarkers and prevalence of cardiovascular risk factors, even within highly educated populations.