David Zeltser

Mandatory Electrocardiographic Screening of Athletes to Reduce Their Risk for Sudden Death Proven Fact or Wishful Thinking

OBJECTIVES The purpose of this study was to determine if pre-participation screening of athletes with a strategy including resting and exercise electrocardiography (ECG) reduces their risk for sudden death. BACKGROUND An increasing number of countries mandate pre-participation ECG screening of athletes for the prevention of sudden death. However, the evidence showing that such a strategy actually reduces the risk of sudden death in athletes is limited. We therefore analyzed the impact of the National Sport Law enacted in Israel in 1997-which mandates screening of all athletes with resting ECG and exercise testing-on the incidence of sudden death among competitive athletes. METHODS We conducted a systematic search of the 2 main newspapers in Israel to determine the yearly number of cardiac arrest events among competitive athletes. The size of the population at risk was retrieved from the Israel Sport Authority and was extrapolated to the changes in population size over time. RESULTS There were 24 documented events of sudden death or cardiac arrest events among competitive athletes during the years 1985 through 2009. Eleven occurred before the 1997 legislation and 13 occurred after it. The average yearly incidence of sudden death or cardiac arrest events was 2.6 events per 100,000 athlete-years. The respective averaged yearly incidence during the decade before and the decade after the 1997 legislation was 2.54 and 2.66 events per 100,000 person years, respectively (p = 0.88). CONCLUSIONS The incidence of sudden death of athletes in our study is within the range reported by others. However, mandatory ECG screening of athletes had no apparent effect on their risk for cardiac arrest.

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.

Acute myocardial infarction associated with high dose intravenous immunoglobulin infusion for autoimmune disorders. A study of four cases

OBJECTIVE To report on four patients with autoimmune disorders who developed acute myocardial infarction (MI) during or soon after treatment with high dose intravenous immunoglobulins (IVIG) and to determine the clinical profile of patients prone to this complication. METHODS The clinical history of the four patients is reported with details concerning age, sex, indication for IVIG treatment, risk factors, timing of the MI and outcome. The relevant medical literature has been reviewed. RESULTS The patients, three men and one woman, aged 42–67, received IVIG treatment for different autoimmune disorders. All had a history of atherosclerosis or previous risk factors such as hypertension, stroke, hyperlipidaemia and obesity. Two of the patients suffered a MI after the first infusion of IVIG while the others—after the 5th and 15th pulses. MI occurred during the infusion in two patients and after a few days in the others. All the patients recovered from the acute event. These observations are in concert with sporadic cases of IVIG related thrombosis reported in the medical literature. CONCLUSION In patients with vascular risk factors such as old age, hypertension, history of stroke or coronary artery disease, the possibility of IVIG related vascular complications should be considered and IVIG prescribed with a cautious reweighted risk/benefit consideration.

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

OBJECTIVE To determine the frequency and predictors of pause dependent torsade de pointes among patients with the congenital long QT syndrome and spontaneous ventricular tachyarrhythmias. DESIGN The literature on the “congenital long QT” was reviewed. Articles with illustrations demonstrating the onset of spontaneous polymorphic ventricular arrhythmias in the absence of arrhythmogenic drugs were included. RESULTS Illustrations of 62 spontaneous episodes of torsade de pointes among patients with congenital long QT syndrome were found in the literature. The majority (74%) of documented arrhythmias were “pause dependent”; 82% of these pauses were longer than the basic cycle length by > 100 ms. Age and sex correlated with the mode of arrhythmia initiation. Arrhythmias in infants (⩽ 3 years old) were not pause dependent, while female sex correlated with pause dependent torsade. Using multivariate analysis, age was the only independent predictor of the mode of onset of torsade de pointes. CONCLUSION Available data suggest that the majority of spontaneous arrhythmias in the congenital long QT syndrome are pause dependent. Torsade de pointes that is not preceded by pauses appears to be limited to patient subgroups with severe forms of the disease, like symptomatic infants. These findings have important implications regarding the use of cardiac pacing for arrhythmia prevention.

Prognostic implications of admission inflammatory profile in acute ischemic neurological events

Anuk T, Assayag EB, Rotstein R, Fusman R, Zeltser D, Berliner S, Avitzour D, Shapira I, Arber N, Bornstein NM. Prognostic implications of admission inflammatory profile in acute ischemic neurological events. Acta Neurol Scand 2002: 106: 196–199.

Burnout and Risk of Coronary Heart Disease: A Prospective Study of 8838 Employees

Objective Burnout is a negative affective state consisting of emotional exhaustion, physical fatigue, and cognitive weariness symptoms. This study was designed to evaluate prospectively the association between burnout and coronary heart disease (CHD) incidence and to test the possibility that this association is nonlinear. Methods Participants were 8838 apparently healthy employed men and women, aged 19 to 67 years, who came for routine health examinations at the Tel Aviv Sourasky Medical Center. They were followed up for 3.4 years on average. Burnout was measured by the Shirom-Melamed Burnout Measure. CHD incidence was defined as a composite of acute myocardial infarction, diagnosed ischemic heart disease, and diagnosed angina pectoris. Results During follow-up, we identified 93 new cases of CHD. Baseline levels of burnout were associated with an increased risk of CHD, after adjustment for various risk factors (hazard ratio = 1.41; 95% confidence interval = 1.08–1.85). In addition, we observed a significant threshold effect of burnout on CHD incidence. Participants who scored high on burnout (scores in the upper quintile of the Shirom-Melamed Burnout Measure scores distribution) had a higher risk (hazard ratio = 1.79; 95% confidence interval = 1.05–3.04) of developing CHD on follow-up compared with others. Conclusions Burnout is an independent risk factor for future incidence of CHD. Individuals with high levels of burnout (upper quintile) have a significantly higher risk of developing CHD compared with those with low levels of burnout. Abbreviations CI = confidence interval CHD = coronary heart disease IHD = ischemic heart disease SMBM = Shirom-Melamed Burnout Measure BMI = body mass index ECG = electrocardiogram LDL = low-density lipoprotein

Increased expression of the CD11b/CD18 antigen on the surface of peripheral white blood cells in patients with ischemic heart disease: further evidence for smoldering inflammation in patients with atherosclerosis.

BACKGROUND This study examined the availability of the CD11b/CD18 and CD62L antigens on the surface of peripheral blood leukocytes in patients with ischemic heart disease. METHODS AND RESULTS The study population included 45 patients with angiographically documented ischemic heart disease admitted to our department of internal medicine and the cardiology department during 1 month (December 1997). Sixty-six healthy members of the hospital medical staff served as control subjects. Another 39 post-trauma patients who were admitted to the emergency room were also evaluated. Patients with ischemic heart disease had significantly (P <.002) higher concentrations of CD11b/CD18 antigen on the surface of their polymorphonuclear leukocytes and monocytes (mean fluorescence intensity of 203 +/- 81 and 261 +/- 75, respectively) compared with the control group (mean fluorescence intensity 158 +/- 68 and 211 +/- 74, respectively) and to the group of patients with acute stress (mean fluorescence intensity of 146 +/- 70 and 200 +/- 22, respectively). CONCLUSIONS The presence of increased concentration of CD11b/CD18 suggests that circulating leukocytes are activated in patients with ischemic heart disease. This activation probably reflects the presence of an inflammatory response involving the atherosclerotic lesion and is not merely a result of acute stress.

INFLAMET: an image analyzer to display erythrocyte adhesiveness/aggregation

Background: Due to a lack of simple, inexpensive, and real-time methodology, the state of erythrocyte adhesiveness/aggregation is not measured in daily practice by most clinicians. Methods: We measured the state of erythrocyte adhesiveness/aggregation before and following the administration of intravenous high-dose gamma globulins in 18 patients with various autoimmune diseases using a simple slide test and image analysis system (INFLAMET). Results: A significant (P=0.01) increment in the state of erythrocyte adhesiveness/aggregation (from 2+/-3 to 8+/-9 arbitrary units) was noted in the entire study group despite a significant (P=0.008) decrement (from 350+/-97 to 323+/-127 mg%) in the concentration of fibrinogen and no significant change in the erythrocyte sedimentation rate (32+/-30 mm/h before and 35+/-29 mm/h following administration of gamma globulin). Conclusions: By using a simple slide test and image analysis, we were able to provide relevant rheological information that was not available from either of the routine indirect tests, i.e. the Westergren erythrocyte sedimentation rate and the concentration of fibrinogen.

Increased erythrocyte adhesiveness and aggregation in peripheral venous blood of women with pregnancy-induced hypertension

OBJECTIVE To study the state of erythrocyte adhesiveness/aggregation in the peripheral blood of women with pregnancy‐induced hypertension as well as in matched controls using a simple slide test and image analysis. METHODS We recruited 25 women with pregnancy‐inducedhypertension. Twenty‐five age‐ and gestational age‐matched normotensive volunteers took part in the study and served as controls. Blood smears were evaluated by an image analysis system (INFLAMET). Quantitative measures of erythrocyte aggregation were used to describe the state of erythrocyte adhesiveness/aggregation such as vacuum radius, which measures the spaces between the aggregated erythrocytes. The number of participants was established by power analysis (given αof 0.05 and 80% power and considering a minimum difference to detect 4 μm in vacuum radius with a standard deviation of approximately 5). RESULTS A significant (P = .002) increment in the state of erythrocyte aggregation was noted in the study group compared with the controls, the vacuum radius values being 16.1 ± 1.3 and 10.3 ± 1.2, respectively. Erythrocyte sedimentation rate but not fibrinogen concentration was significantly elevated in the study group. The increased aggregation correlated significantly with fibrinogen concentration, systolic, and diastolic blood pressures. CONCLUSION We observed increased aggregability of red blood cells in hypertensive conditions of pregnancy. Our findings are significant in that they reveal blood pressure‐related increment in red cell adhesiveness/aggregation despite there being no significant increment in clotable fibrinogen concentrations.

The erythrocyte adhesiveness/aggregation test (EAAT): A new biomarker to reveal the presence of low grade subclinical smoldering inflammation in individuals with atherosclerotic risk factors

BACKGROUND Multiple acute phase proteins and atherosclerotic risk factors increase the aggregability of erythrocytes. METHODS AND RESULTS We used a simple slide test and image analysis to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of 222 women and 221 men with no, one, two or more atherosclerotic risk factors. The degree of erythrocyte adhesiveness/aggregation correlated significantly with the concentration of commonly used variables of the acute phase response. We also showed that individuals with low erythrocyte adhesiveness/aggregation tend to be younger and to have fewer risk factors for atherosclerosis, including diabetes mellitus, hypertension, hyperlipidemia and smoking. CONCLUSIONS The association between increased erythrocyte adhesiveness/aggregation, higher concentrations of acute phase proteins, and increased atherosclerotic risk factors points to a possible clinical applicability of the erythrocyte adhesiveness/aggregation test (EAAT) to reveal the presence of both low-grade subclinical smoldering inflammation and morbid biology in individuals with risk factors for atherosclerosis.