The effect of an educational intervention on coronary artery bypass graft surgery patients' participation rate in cardiac rehabilitation programs: a controlled health care trial.

BACKGROUND: Cardiac rehabilitation has a beneficial effect on the prognosis and quality of life of cardiac patients, and has been found to be cost-effective. This report describes a comprehensive and low cost educational intervention designed to increase the attendance at cardiac rehabilitation programs of patients who have undergone coronary artery bypass graft surgery. METHODS/DESIGN: A controlled prospective intervention trial. The control arm comprised 520 patients who underwent coronary artery bypass graft surgery between January 2004 and May 2005 in five medical centers across Israel. This group received no additional treatment beyond usual care. The intervention arm comprised 504 patients recruited from the same cardiothoracic departments between June 2005 and November 2006. This group received oral and written explanations about the advantages of participating in cardiac rehabilitation programs and a telephone call two weeks after hospital discharge intended to further encourage their enrollment. The medical staff attended a one-hour seminar on cardiac rehabilitation. In addition, it was recommended that referral to cardiac rehabilitation be added to the letter of discharge from the hospital. Both study groups were interviewed before surgery and one-year post surgery. A one-year post-operative interview assessed factors affecting patient attendance at cardiac rehabilitation programs, as well as the structure and content of the cardiac rehabilitation programs attended. Anthropometric parameters were measured at pre- and post-operative interviews;- and medical information was obtained from patient medical records. The effect of cardiac rehabilitation on one- and three-year mortality was assessed. DISCUSSION: We report a low cost yet comprehensive intervention designed to increase cardiac rehabilitation participation by raising both patient and medical staff awareness to the potential benefits of cardiac rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00356863.

Statins have an early antiplatelet effect in patients with acute myocardial infarction.

Statins confer an antiplatelet effect in hypercholesterolemic subjects and in stable coronary artery disease patients. We explored the antiplatelet effects of statins in ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. Of 120 STEMI patients, 80 (67%) received statins while 40 (33%) did not. Ex vivo platelet reactivity was studied on admission and 72 hours later by conventional aggregometry and under flow conditions (Impact R). Measures of platelet reactivity under flow conditions included aggregate size and surface coverage, signifying platelet aggregation and adhesion respectively. The effect of statins on platelet function under flow conditions and platelet aggregation was studied in?vitro in platelets from 10 STEMI patients. Platelets from each patient were incubated in?vitro with lovastatin or PBS as a control. The effect of lovastatin in the presence of a nitric oxide synthase inhibitor (L-NMMA) was also studied. Patients treated with statins were compared with those who did not have significantly lower ADP-induced platelet aggregation on the 4th day (56 ± 18% vs. 64 ± 17%, p=0.02). Platelet deposition under flow conditions as measured by surface coverage was reduced from admission to 72 hours later among statin-treated patients (19 ± 28% reduction, p<0.01), but was unchanged in non-treated patients (for comparison p<0.01). The extent of platelet inhibition was unrelated to patient characteristics, including lipid profile and type of statin administered (lipophylic vs. hydrophilic). In the in vitro study platelet incubation with statin compared with PBS resulted in a lower aggregate-size (29 ± 9 µm(2) vs. 39 ± 15 µm(2), p<0.01), and lower surface coverage (8.5 ± 4% vs. 12 ± 4%, p<0.01). The effect of the statin on both parameters was significantly blunted by L-NMMA. Incubation with statin also resulted in a reduction in collagen-induced platelet aggregation (31 ± 20% vs. 54 ± 25%, p<0.01). We concluded that in acute myocardial infarction patients, statins have an early antiplatelet effect, in addition to that afforded by standard antiplatelet therapy.

Time-resolved MR angiography of the calf arteries using a phased array cardiac coil: comparison of visibility with standard three-step bolus chase MR angiography.

BACKGROUND: Standard bolus chase MR angiography (MRA) is increasingly replacing digital subtraction angiography (DSA) in the diagnostic evaluation of peripheral vascular disease. However, a major limitation of bolus chase MRA is the relatively poor visibility of the calf arteries. PURPOSE: To evaluate the feasibility of visualizing the calf arteries and the visibility quality of an 8-channel cardiac phased array coil using time-resolved imaging of contrast kinetics (TRICKS) MRA compared with standard bolus chase MRA on a 1.5 Tesla MRI scanner. MATERIAL AND METHODS: MRA findings of 59 sequential patients (mean age 57.8 years, range 14-83 years; 41 men) were retrospectively evaluated. All examinations included preliminary TRICKS for the lower leg using a surface 8-channel cardiac coil, followed by a 3-step MRA of the abdominal aorta, thigh, and lower leg using a body coil. Images yielded by both methods were separately evaluated by consensus of two radiologists unaware of the patients' clinical data. Visibility of the calf arteries (popliteal, tibialis anterior, tibialis posterior, tibioperoneal trunk, and peroneal) for both sides was subjectively classified as 'diagnostic' or 'non-diagnostic'. Descriptive statistics for image diagnostic quality were assessed. RESULTS: A total of 575 calf arterial segments were evaluated. Visibility of all calf arteries was significantly better with TRICKS than with the standard bolus chase MRA (P < 0.001). The improvement of calf artery visibility with TRICKS was more pronounced in patients with peripheral vascular disease compared to those with arteritis, vascular malformation and popliteal entrapment syndrome. CONCLUSION: Using a cardiac coil for MRA of the lower extremities resulted in visibility comparable to that of a dedicated leg coil, with diagnostic superiority for the TRICKS method compared to the standard bolus chase method.

The effect of active immunization on varicella-related hospitalizations in Israel.

The purpose of this study is to report on the impact of introduction of the varicella vaccine "Varilix" on hospitalizations due to varicella, following licensure in Israel in June, 2000. Data on children hospitalized throughout Israel with the diagnosis of varicella were collected from 1998 until 2003. The national rate of varicella-related hospitalizations decreased during the period 2001-2002. However in 2003 an increase in hospitalization occurred. Based on an assumption that at least 22,000 vaccinations per year were administered, we estimate that there is a greater than 60% reduction in the risk for hospitalization in the immunized population (RR = 0.32; 0.10-1.00). In summary, no national trend in reduction of hospitalization has yet been observed, but a significant reduction in hospitalization is apparent for vaccinated children.

Analysis of polymorphic patterns in candidate genes in Israeli patients with prostate cancer.

BACKGROUND: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known. OBJECTIVES: To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters. METHODS: Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters. RESULTS: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner. CONCLUSIONS: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Antiplatelet effect of thienopyridine (clopidogrel or prasugrel) pretreatment in patients undergoing primary percutaneous intervention for ST elevation myocardial infarction.

Although previous retrospective studies have suggested the clinical benefits of clopidogrel pretreatment in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the antiplatelet effect of thienopyridines during a narrow door-to-balloon time frame has not been evaluated. Seventy-nine consecutive patients with STEMI were treated with either 600 mg of clopidogrel (n = 49) or 60 mg of prasugrel (n = 30) loading on admission. All patients underwent PPCI with a door-to-balloon time of 48 ± 20 minutes. Adenosine diphosphate (ADP)-induced platelet aggregation (PA) was determined by light transmission aggregometry before thienopyridine loading, at PPCI, and after 72 hours. Baseline ADP-induced PA was comparable in clopidogrel- and prasugrel-treated patients (79 ± 10% vs 76 ± 9%, p = 0.2). Although ADP-induced PA was reduced significantly in both clopidogrel- and prasugrel-treated patients (p <0.01 for both), it was significantly lesser in prasugrel-treated patients (63 ± 18% vs 74 ± 12%, p = 0.002). Yet, <50% of the prasugrel-treated patients achieved adequate platelet inhibition (ADP-induced PA <70%) at PPCI. Prasugrel-treated patients, compared with clopidogrel-treated patients, were more likely to have Thrombolysis In Myocardial Infarction myocardial perfusion grade of ≥2 (79% vs 49%, p = 0.01), lower Thrombolysis In Myocardial Infarction frame count (10.2 ± 5.7 vs 13.6 ± 7.2, p = 0.03), and a numerically greater incidence of early ST-segment resolution >50% (26 of 30 [87%] vs 35 of 49 [71%], p = 0.1), suggesting better myocardial reperfusion. In conclusion, overall, prasugrel compared with clopidogrel pretreatment resulted in greater platelet inhibition at PPCI, but even with prasugrel, only <50% of the patients achieved early adequate platelet response.

Prognostic implications of nonobstructive coronary artery disease in patients undergoing coronary computed tomographic angiography for acute chest pain.

Coronary computed tomographic angiography can detect nonobstructive atherosclerotic lesions that would not otherwise have been detected with functional cardiac imaging. Currently, limited data exist regarding the clinical significance of these lesions in patients with acute chest pain. The aim of our study was to examine the prognostic significance of these nonobstructive findings in a patient population presenting with acute chest pain. We evaluated 959 consecutive patients who underwent coronary computed tomographic angiography for investigation of acute chest pain. The patients were classified as having normal (n = 545), nonobstructive coronary artery disease (CAD; defined as any narrowing <50% diameter stenosis; n = 312), or obstructive CAD (narrowing of ≥50% diameter stenosis; n = 65). Follow-up data for a minimum of 12 months (mean 27 ± 11) was obtained for any major adverse coronary events consisting of death, nonfatal acute coronary syndrome, and coronary revascularization. Compared to patients with normal coronary arteries, those with nonobstructive CAD were older and had a greater prevalence of CAD risk factors. The incidence of major adverse coronary events was equally low among both these groups (0.6% vs 1.3%, for the normal and nonobstructive groups, respectively, p = 0.2). In conclusion, patients with either nonobstructive CAD or normal findings, as evaluated by coronary computed tomographic angiography, for acute chest pain during an intermediate-term follow-up period had equally benign clinical outcomes.

Relation of aspirin failure to clinical outcome and to platelet response to aspirin in patients with acute myocardial infarction.

Aspirin failure, defined as occurrence of an acute coronary syndrome despite aspirin use, has been associated with a higher cardiovascular risk profile and worse prognosis. Whether this phenomenon is a manifestation of patient characteristics or failure of adequate platelet inhibition by aspirin has never been studied. We evaluated 174 consecutive patients with acute myocardial infarction. Of them, 118 (68%) were aspirin naive and 56 (32%) were regarded as having aspirin failure. Platelet function was analyzed after ≥72 hours of aspirin therapy in all patients. Platelet reactivity was studied by light-transmitted aggregometry and under flow conditions. Six-month incidence of major adverse coronary events (death, recurrent acute coronary syndrome, and/or stroke) was determined. Those with aspirin failure were older (p = 0.002), more hypertensive (p <0.001), more hyperlipidemic (p <0.001), and more likely to have had a previous cardiovascular event and/or procedure (p <0.001). Cumulative 6-month major adverse coronary events were higher in the aspirin-failure group (14.3% vs 2.5% p <0.01). Patients with aspirin failure had lower arachidonic acid-induced platelet aggregation (32 ± 24 vs 45 ± 30, p = 0.003) after aspirin therapy compared to their aspirin-naive counterparts. However, this was not significant after adjusting for differences in baseline characteristics (p = 0.82). Similarly, there were no significant differences in adenosine diphosphate-induced platelet aggregation and platelet deposition under flow conditions. In conclusion, our results suggest that aspirin failure is merely a marker of higher-risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy.

Lifestyle intervention in obese Arab women: a randomized controlled trial.

BACKGROUND: Few randomized controlled trials on lifestyle interventions have been reported in non-Western populations; none have been reported in Arab populations. METHODS: From 2 Muslim Arab communities in Israel, obese, nondiabetic women aged 35 to 54 years with 1 or more components of the metabolic syndrome were randomized to either an intensive (n = 100) or a moderate (control) (n = 101) 12-month lifestyle intervention. Women in the intensive intervention had 11 individual and 11 group counseling sessions per year with a dietitian and 22 physical activity group sessions per year. Women in the moderate intervention had 3 individual and 2 group dietary counseling sessions per year and no guided physical activity. Cultural issues were addressed in the design and conduct of both interventions. The primary outcome measure was change in the metabolic syndrome and its components. RESULTS: At 12 months, the intensive intervention group had median declines of 3.0 mg/dL (to convert to millimoles per liter, multiply by 0.0555) in fasting plasma glucose and 4.5 mg/dL (to convert to millimoles per liter, multiply by 0.0113) in triglyceride levels compared with median increases of 1 mg/dL in fasting plasma glucose and 5.8 mg/dL in triglyceride levels in the moderate intervention group (P = .01 and P = .02, respectively). The median waist circumference decreased by 5.4 cm in the intensive intervention group and by 3.1 cm in the moderate intervention group (P = .10). The prevalence of the metabolic syndrome decreased by 4.0% in the intensive intervention group and increased by 5.2% in the moderate intervention group (P = .12). CONCLUSION: The 12-month culturally sensitive intensive lifestyle intervention was effective in improving some of the metabolic syndrome components in obese Arab women. Trial Registration clinicaltrials.gov Identifier: NCT00273572.

Comparison of myocardial reperfusion in patients with fasting blood glucose < or =100, 101 to 125, and >125 mg/dl and ST-elevation myocardial infarction with percutaneous coronary intervention.

Diabetes and impaired fasting glucose (FG) were associated with worse outcomes in patients with acute myocardial infarction (MI). Because the underlying mechanism is not entirely clear, 376 consecutive patients with ST-elevation MI who underwent primary percutaneous coronary intervention (PPCI) were investigated. Patients were divided into 3 groups based on FG < or =100, FG of 101 to 125, and FG >125 mg/dl or previously diagnosed diabetes mellitus (DM) and studied for electrocardiographic signs of myocardial reperfusion (both spontaneous and after PPCI) and clinical outcomes. Clinical reperfusion was less likely with increasing FG: FG < or =100 mg/dl, 26%; FG of 101 to 125, 19%; and FG >125 and/or DM, 16% (p for trend = 0.03). Accordingly, angiographic TIMI grade 3 flow on initial angiography was 22% for FG < or =100 mg/dl, 13% for FG of 101 to 125, and 14% for FG >125 and/or DM (p for trend = 0.05). Despite similar TIMI flow after PPCI, early ST-segment resolution (> or =70%) was noted in 76%, 63%, and 60% in patients with FG < or =100 mg/dl, FG of 101 to 125, and FG >125 and/or DM, respectively (p for trend <0.01). Peak creatine phosphokinase (CPK) increased gradually, whereas left ventricular ejection fraction decreased with increased FG. Worse outcomes were observed with increasingly higher FG for heart failure (9%, 23%, and 26%; p for trend <0.01), cardiogenic shock (5%, 7%, and 13%; p for trend = 0.02), in-hospital mortality (1%, 2%, and 6%; p for trend = 0.01), and long-term mortality (2.5%, 4.5%, and 12%; p for trend <0.01) for patients with FG < or =100 mg/dl, FG of 101 to 125, and FG >125 and/or DM, respectively. In conclusion, increased FG and previously diagnosed DM were associated with less spontaneous reperfusion and less myocardial reperfusion after PPCI, resulting in worse clinical outcomes.

Modulation of ventricular fibrillation in isolated perfused heart by dofetilide.

The authors studied the involvement of IKr potassium current in ventricular fibrillation during perfusion. Electrophysiologic parameters were measured before and after dofetilide administration (2.5, 7.5, and 12.5 x 10-7 M, n = 8) in isolated perfused feline hearts. During pacing, these parameters included epicardial conduction time, refractoriness, and the fastest rate for 1:1 pacing/response capture. During 8 minutes of electrically induced tachyarrhythmias, they included heart rate and normalized entropy reflecting the degree of organization. In all groups, arrhythmia rate was slower in the right ventricle than in the left ventricle. Dofetilide decreased the arrhythmia rate more than it increased organization, reduced its maintenance, or increased difficulty in initiation. Refractoriness was prolonged in a reverse use-dependent way which was less than 1:1 pacing/response capture. Unexpectedly, a moderate prolongation of conduction time was observed. Inverse correlation was found between the arrhythmia rate and changes in refractoriness and conduction time and between the degree of organization and refractoriness (both ventricles) and conduction time (right ventricle). Dofetilide, which intensively blocks IKr current and unexpectedly suppressed conduction, has different quantitative effects on fibrillation features. These changes in fibrillation suggest that these effects are mainly associated with refractoriness prolongation and do not seem to be attenuated by conduction suppression.

Effects of adrenaline on electrophysiological parameters during short exposure to global ischemia. A ventricular fibrillation study in isolated heart.

BACKGROUND: The mechanisms by which adrenaline may enhance defibrillation success rate, is poorly understood. OBJECTIVES: To study electrophysiological effects of adrenaline during short exposure to global ischemia. METHODS: In isolated perfused feline hearts, coronary perfusion was eliminated repeatedly for 1 min with 10 min reperfusion intervals. Treatment included: (1) continuous perfusion alone-control, (2) global ischemia alone, (3) adrenaline (10(-7) M) during perfusion, (4) adrenaline (10(-7) M) during global ischemia (n = 10), in separate hearts, (5) control and higher adrenaline concentration (1 x 10(-6) M), (6) during perfusion, (7) during global ischemia (n = 9). Measurements during pacing included: (1) diastolic threshold of excitability; (2) refractoriness; (3) epicardial conduction time; and (4) all tissue resistivity to indirectly detect changes in passive properties of conduction. Measurements during 1 min (or 90 sec) of electrically induced ventricular fibrillation included-all tissue resistivity and, based on maximal entropy spectral analysis and normalized entropy, rate of arrhythmia and degree of arrhythmia organization. RESULTS: Adrenaline (10(-7) M) during global ischemia vs control caused spontaneous arrhythmia termination, increased threshold significantly but reduced conduction time. Higher adrenaline concentration (1 x 10(-6) M) during global ischemia improved the passive properties of conduction and arrhythmia organization and reduced arrhythmia rate. Global ischemia alone increased conduction time but had a deleterious effect on passive properties. Adrenaline (10(-7) M) during perfusion improved conduction, but did so less than during global ischemia. Higher adrenaline concentration during perfusion (10(-6) M) improved arrhythmia organization and caused spontaneous arrhythmia termination but again less than during global ischemia. CONCLUSIONS: During short periods of global ischemia adrenaline improved the passive properties of conduction and arrhythmia organization, reduced arrhythmia rate and increased its spontaneous termination. Such changes may be operative in improving defibrillation success.

Stunting of growth as a major feature of anorexia nervosa in male adolescents.

OBJECTIVE: To assess growth retardation in male adolescent patients who have a diagnosis of anorexia nervosa (AN) and the effect of weight restoration on catch-up growth. METHODS: Medical charts of all male adolescent AN patients (n = 12) who were admitted to the Pediatric Psychosomatic Department at the Sheba Medical Center from January 1, 1994, to December 31, 1998, were reviewed. Height and weight measurements were obtained before the onset of AN, at admission, and thereafter routinely during hospitalization and follow-up. RESULTS: Eleven patients exhibited growth retardation during the course of their illness, as evident in a decrease in their height standard deviation score (SDS). The mean height SDS at the time of admission (-0.81 +/- 0.93) was significantly lower than the premorbid SDS (-0.21 +/- 0.91). Weight restoration resulted in accelerated linear growth (up to 2 cm/mo) in all patients. Positive weight gain (weight gain rate >1 kg/y) was associated with a mean height gain of 6.97 +/- 6.48 cm/y, whereas weight loss or failure to gain weight (weight gain rate

Refractoriness and conduction interaction during modulation of non-ischemic ventricular fibrillation by flecainide.

PURPOSE: To study refractoriness and conduction interaction during modulation of non-ischemic ventricular fibrillation (VF) by flecainide. METHODS: Isolated feline and rabbit hearts were used. (a) In the feline hearts (n = 8), electrophysiological parameters were measured before and after flecainide administration (0.6, 1.2 x 10(-6) M). During pacing the parameters were: epicardial conduction time, refractoriness and 1:1 pacing/response capture. During 8 min of electrically-induced tachyarrhythmias they included heart rate and normalized entropy reflecting the degree of organization. (b) In rabbit hearts (n = 4), three-dimensional mapping was performed before and after flecainide administration (2 x 10(-6) M). To follow changes in organization, local RR-intervals and differences in activation time between adjacent epicardial electrodes were measured immediately and 80 sec after VF induction. RESULTS: In feline hearts with flecainide, fibrillation was more difficult to induce, more frequently terminated spontaneously and was slower and more organized; conduction time was markedly lengthened, and refractoriness less than 1:1 capture, was moderately prolonged. An inverse correlation was observed between arrhythmia properties, rate and organization, and changes in refractoriness and conduction time. In rabbit, the number of wave fronts was reduced, RR-intervals were prolonged but at the same time activation time differences between adjacent electrodes were smaller following flecainide administration. CONCLUSIONS: It is suggested that flecainide modulation of VF properties is associated with conduction suppression and refractoriness prolongation, which act in a synergistic, additive way.