Acute effects of exercise on cerebrovascular response and cognitive performance in individuals with stable coronary heart disease.

BACKGROUND: Individuals with coronary heart disease (CHD) exhibit cognitive deficits and cerebrovascular dysfunctions, and are at higher risk of developing dementia. Cognitive function in individuals with CHD has never been studied during acute aerobic exercise. Given the increasing popularity of training at high peak power output (PPO), its impact on cerebrovascular and cognitive functions in individuals with CHD should be further studied. METHOD: Thirty-eight individuals with CHD and 16 healthy controls completed two exercise bouts at 30% and 70% of their individualized PPO on an ergocycle while performing a cognitive task including non-executive and executive conditions. Variations of oxy- deoxy-hemoglobin, and total hemoglobin concentrations were measured on left prefrontal cortex at both PPO using near-infrared spectroscopy. RESULTS: Cognitive task performances were equivalent between groups at all intensity levels. Individuals with CHD exhibited larger variation of deoxyhemoglobin in the executive condition and larger variation in total hemoglobin concentration in all task conditions compared to healthy controls at 70% of PPO. CONCLUSION: Exercising at high intensity seems to have a larger impact on cerebral blood volume in CHD patients compared to healthy age-matched controls. Higher exercise intensity has negative impacts on cerebral blood volume variations during a cognitive task in CHD patients and could potentially lead to other neurocognitive dysfunctions. Other studies are needed to determine if a cognitive task administered during an exercise test could help identify individuals with CHD at higher risk of developing cognitive decline.

Barriers to physical activity in coronary artery disease patients: Development and validation of a new scale.

OBJECTIVE: To develop and validate a self-report questionnaire to measure barriers to regular physical activity (PA) in patients with stable coronary artery disease (CAD). METHODS: Phase 1: 17 patients completed a semi-structured interview. After grouping and reformulating the reported barriers, their pertinence was reevaluated by the patients. Then, a decision algorithm was used to select items. A principal component analysis was performed to determine content validity. Phase 2: 49 patients completed the questionnaire resulting from phase 1 twice, 7 days apart, and questionnaires to evaluate depression, anxiety, and the level of physical activity. Construct validity was evaluated by analysis of Spearman's correlation coefficient between the total score for the questionnaire and a convergent dimension (anxiety), as well as a divergent dimension (Dijon physical activity score). Internal consistency was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated by the intraclass coefficient (ICC). RESULTS: Eleven items were selected after phase 1. The questionnaire presented good face validity and the content validity seemed satisfactory after analysis of the literature by the experts. Construct validity was moderate. Internal consistency was very good (Cronbach's α>0.81). Reproducibility was excellent with an ICC at 0.95. Feasibility was good with less than 3minutes to complete the questionnaire. CONCLUSION: This questionnaire presents good psychometric properties. A further prospective study should evaluate sensitivity to change and help determine a threshold value indicating the need for a specific behavioral strategy to alleviate barriers to physical activity in these patients.

Long-term high-intensity interval training associated with lifestyle modifications improves QT dispersion parameters in metabolic syndrome patients.

BACKGROUND: QT dispersion (QTd) is a marker of myocardial electrical instability, and is increased in metabolic syndrome (MetS). Moderate intensity continuous exercise (MICE) training was shown to improve QTd in MetS patients. OBJECTIVES: To describe long-term effects of MICE and high-intensity interval exercise training (HIIT) on QTd parameters in MetS. METHODS: Sixty-five MetS patients (53 ± 9 years) were assigned to either a MICE (60% of peak power output [PPO]), or a HIIT program (alternating phases of 15-30 s at 80% of PPO interspersed by passive recovery phases of equal duration), twice weekly during 9 months. Ventricular repolarization indices (QT dispersion=QTd, standard deviation of QT = sdQT, relative dispersion of QT = rdQT, QT corrected dispersion = QTcd), metabolic, anthropometric and exercise parameters were measured before and after the intervention. RESULTS: No adverse events were noted during exercise. QTd decreased significantly in both groups (51 vs 56 ms in MICE, P < 0.05; 34 vs 38 ms in HIIT, P < 0.05). Changes in QTd were correlated with changes in maximal heart rate (r = -0.69, P < 0.0001) and in heart rate recovery (r = -0.49, P < 0.01) in the HIIT group only. When compared to MICE, HIIT training induced a greater decrease in weight, BMI and waist circumference. Exercise capacity significantly improved by 0.82 and 1.25 METs in MICE and HIIT groups respectively (P < 0.0001). Lipid parameters also improved to the same degree in both groups. CONCLUSION: In MetS, long-term HIIT and MICE training led to comparable effects on ventricular repolarization indices, and HIIT might be associated with greater improvements in certain cardiometabolic risk factors.

Non-pharmacological strategies in cardiovascular prevention: 2011 highlights.

The clinical efficacy of cardiac rehabilitation programs is clearly recognized. Yet, as regards the three main currently employed strategies (exercise, education, and psychobehavioral support), new ideas regularly appear, stemming from studies aimed at providing proof of their efficacy and innocuousness, along with optimal modes of prescription and, at times, their cost-benefit ratio. This ongoing work, which was initially developed in view of enriching the "What's new in?" section of the Sofmer website, represents a selection of articles that may be non-exhaustive, yet is maximally diversified and as representative as possible of the main 2011 highlights in the field of cardiovascular prevention. Each of the articles selected puts forward an original idea, confirms the existence of an effect that was suspected or has had some impact on clinical practice in the field of non-pharmacological management of cardiovascular disease. In line with the multidisciplinary approach of Physical Medicine and Rehabilitation (PMR), the Sofmer cardiovascular rehabilitation group has associated itself with a wide range of specialists (PMR, cardiologists, exercise physiologists, experts in the science and technology of physical activities), all of whom are involved in clinical research and the management of more and more patients. Our objective was consequently to compile a selection of commented articles most likely to interest the different operatives (doctors, nurses, physiotherapists, dietitians, adapted physical activity instructors, psychologists) working with these patients in rehabilitation units or in phase III associative structures. Their goals may vary: (1) learners may wish to further their knowledge of cardiac rehabilitation techniques; (2) practitioners may be interested in continued education but not have the time for regular bibliographic updates; (3) researchers may be intent on informing themselves on the latest breakthroughs and/or arousing their imagination...Enjoy your reading!

Effects of fasting and/or postprandial glucose on heart rate recovery in patients with coronary heart disease.

AIM: The impact of both fasting and postprandial glycaemia on heart rate recovery (HRR) has not been studied in patients with coronary heart disease (CHD). For this reason, we sought to determine the relationships between HRR and both fasting and postprandial glycaemia. METHODS: A total of 4079 patients with baseline fasting plasma glucose (FPG) levels and 706 patients with 2-hour postprandial glucose (2hPG) levels were identified from the Coronary Artery Surgery Study registry, a database of 24,958 patients with suspected or proven CHD who had undergone cardiac catheterization between 1974 and 1979. Median long-term follow-up was 14.7 years (interquartile range: 9.8-16.2 years). The relationships between HRR and both FPG and 2hPG were studied. RESULTS: In univariate analyses, increasing levels of both FPG and 2hPG were significantly associated with lower HRR. In multivariate models adjusted for age, exercise tolerance in METs, resting heart rate and maximum systolic blood pressure during exercise testing, FPG remained significantly associated with HRR while 2hPG did not. CONCLUSION: Both raised FPG and decreased HRR are independent predictors of total and cardiovascular (CV) mortality in subjects with CHD. Our data suggest that the mortality risk associated with elevated FPG may in part be due to deleterious effects on autonomic regulation of CV function, as reflected by lower HRR. Further studies are required to determine whether or not non-pharmacological and/or pharmacological treatments of increased fasting glucose have a beneficial influence on HRR.

Atrioventricular interval optimization and exercise tolerance.

Modern pacemakers offer many programming options regarding the AV interval including the ability to vary AV intervals depending on whether atrial activity is paced or spontaneous and to shorten AV intervals with increasing rates. To determine if optimization of these features improves exercise tolerance, 14 patients with intact sinus node function and AV block treated with dual chamber pacemakers were enrolled in a randomized double-blind crossover trial. Doppler echocardiographic measurements of cardiac index and mitral flow were assessed over a range of programmable AV intervals at rest to determine each patient's optimal AV interval. Eleven patients completed serial graded exercise tests with spiroergometry after randomly programming the AV interval three ways in a crossover manner: fixed AV interval = 150 ms without rate adaptation (150/Fixed), fixed AVinterval = 150 ms with rate adaptation (150/R), or optimized AV interval with rate adaptive AV interval shortening (optimized/R). Exercise capacity was determined by maximum oxygen uptake. Ten men and four women, age 64 +/- 8 years, were enrolled. At rest, optimization of the AVintervalimproved the cardiac index by 21% (P < 0.001) and mitral flow by 13.4% (P < 0.001) when compared to least-favorable AV intervals. During exercise, no differences in maximum heart rates were noted. Maximum oxygen uptake was increased in both groups with rate adaptive AVinterval shortening when compared tofixed AVinterval without rate adaptation: 13.9% (adjusted P < 0.04) and 14.6% (adjusted P < 0.02) in optimized/R and 150/R, respectively. No differences were noted between optimized/R and 150/R. In conclusion, rate adaptive AV interval shortening improved exercise tolerance independent of changes in heart rate. However, optimization of the AV interval with Doppler echocardiography at rest did not further improve exercise capacity.

Depression and health-care costs during the first year following myocardial infarction.

OBJECTIVE: Depression in the hospital after myocardial infarction (MI) has been associated with a substantial increase in the long-term risk of cardiac mortality, but little is known about other outcomes. This study uses Quebec Medicare data to examine the relationship between post-MI depression and physician costs, including both out-patient care and hospital readmissions. METHODS: The sample consists of 848 1-year survivors of an acute MI who had completed the Beck Depression Inventory (BDI) in hospital. Two hundred sixty subjects had BDI scores of >/=10 (30.7%), indicative of mild to moderate symptoms of depression. Quebec Medicare data during the index admission for an acute MI and during the year following discharge were compared for the patients with elevated BDI scores and those with normal scores. RESULTS: Total costs, in Canadian dollars (out-patient physician charges plus physician costs during admissions plus estimates of associated direct costs), were about 41% higher (p = 0.004) for patients with elevated BDI scores. The difference was primarily related to out-patient and emergency room visits and readmission costs associated with longer stays in hospital wards, and was not accounted for by use of psychiatric services or readmissions for revascularization. CONCLUSION: Results suggest that, in addition to the survival risks associated with post-MI depression, there are increased health care costs linked to both readmissions and out-patient contacts among depressed patients who survive the first post-MI year. The extent to which the increased use of health care may have reduced depression and enhanced survival remains unclear.

Depression and 1-year prognosis in unstable angina.

BACKGROUND: Depression is common after acute myocardial infarction and is associated with an increased risk of mortality for at least 18 months. The prevalence and prognostic impact of depression in patients with unstable angina, who account for a substantial portion of acute coronary syndrome admissions, have not been examined. METHODS: Interviews were carried out in hospital with 430 patients with unstable angina who did not require coronary artery bypass surgery before hospital discharge. Depression was assessed using the 21-item self-report Beck Depression Inventory and was defined as a score of 10 or higher. The primary outcome was 1-year cardiac death or nonfatal myocardial infarction. RESULTS: The Beck Depression Inventory identified depression in 41.4% of patients. Depressed patients were more likely to experience cardiac death or nonfatal myocardial infarction than other patients (odds ratio, 4.68; 95% confidence interval, 1.94-11.27; P<.001). The impact of depression remained after controlling for other significant prognostic factors, including baseline electrocardiographic evidence of ischemia, left ventricular ejection fraction, and the number of diseased coronary vessels (adjusted odds ratio, 6.73; 95% confidence interval, 2.43-18.64; P<.001). CONCLUSIONS: Depression is common following an episode of unstable angina and is associated with an increased risk of major cardiac events during the following year.

Social support, depression, and mortality during the first year after myocardial infarction.

BACKGROUND: We previously reported that depression after myocardial infarction (MI) increases the long-term risk of cardiac mortality. Other research suggests that social support may also influence prognosis. This article examines the interrelationships between baseline depression and social support in terms of cardiac prognosis and changes in depression symptoms over the first post-MI year. METHODS AND RESULTS: For this study, 887 patients completed the Beck Depression Inventory (BDI) and the Perceived Social Support Scale (PSSS) at about 7 days after MI. Some 32% had BDIs > or =10, indicating mild to moderate depression. One-year survival status was determined for all patients. Follow-up interviews, including the BDI, were conducted with 89% of survivors. There were 39 deaths (35 cardiac). Elevated BDI scores were related to cardiac mortality (P=0.0006), but PSSS scores and other measures of social support were not. There was a significant interaction between depression and the PSSS (P=0. 016). The relationship between depression and cardiac mortality decreased with increasing support. Furthermore, residual change score analysis revealed that among 1-year survivors who had been depressed at baseline, higher baseline social support was related to more improvement in depression symptoms than expected. CONCLUSIONS: Post-MI depression is a predictor of 1-year cardiac mortality, but social support is not directly related to survival. However, very high levels of support appear to buffer the impact of depression on mortality. Furthermore, high levels of support predict improvements in depression symptoms over the first post-MI year in depressed patients. High levels of support may protect patients from the negative prognostic consequences of depression because of improvements in depression symptoms.

Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.

BACKGROUND: The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina. METHODS AND RESULTS: We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction. CONCLUSIONS: Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.

Value of exercise electrocardiography in the detection of restenosis after coronary angioplasty in patients with one-vessel disease.

Exercise treadmill testing (ETT) is considered an unreliable method for detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The studies on which this belief is based have used quantitative coronary angiography (QCA) as a reference. The inherent limitations of angiography have been demonstrated by intravascular ultrasound (IVUS). To determine the value of ETT for detecting restenosis when IVUS criteria are used to define restenosis, we studied 29 patients with angiographically documented 1-vessel coronary disease (<35% stenosis in all nondilated segments) who underwent angioplasty. ETT was performed < or =2 weeks before follow-up angiography and IVUS imaging. Only patients without any abnormalities precluding an accurate reading of the ST segment during ETT were included. Restenosis was defined as a > or =50% diameter stenosis by QCA criteria and as a cross-sectional area narrowing of > or =75% by IVUS. The ETT was positive in 12 patients and restenosis was documented by QCA and IVUS in 38% and 48% of cases, respectively. Sensitivity, specificity, and positive and negative predictive values of ETT when QCA was used as a reference were 55%, 67%, 50%, and 71%, respectively. This corresponded to an accuracy of 62% when compared with QCA. Sensitivity, specificity, and positive and negative predictive values were 79%, 93%, 92%, and 82% when ETT was compared with IVUS, with an accuracy of 86% (p = 0.002). Thus, ETT is a reliable noninvasive method for detecting the presence of restenosis after PTCA in patients with 1-vessel coronary artery disease. The presence of > or =75% cross-sectional narrowing shown by IVUS is well correlated with > or =1-mm ST-segment depression at follow-up ETT after PTCA.

Sauna-induced myocardial ischemia in patients with coronary artery disease.

PURPOSE: Sauna bathing is a popular recreational activity that is generally considered to be safe. However, there have been case reports of adverse cardiac events. We sought to determine whether sauna use caused myocardial ischemia in patients with coronary artery disease. METHODS: Sixteen patients with proven coronary artery disease were submitted to three conditions (rest, exercise, and sauna bathing) with continuous electrocardiographic (ECG) monitoring and regular blood pressure measurements. During each condition, patients were injected with Tc-99 sestamibi followed by nuclear scintigraphic imaging. Perfusion defect scores were calculated in 15 patients. RESULTS: Sauna bathing was well tolerated. There was a mean (+/- SD) increase in heart rate of 32% +/- 20% in the sauna (resting mean heart rate = 60 +/- 9 beats per minute vs sauna mean heart rate = 79 +/- 11 beats per minute, P <0.001) and a 13% +/- 6% drop in systolic blood pressure (resting mean systolic blood pressure = 142 +/- 14 mm Hg vs sauna mean systolic blood pressure = 123 +/- 15 mm Hg, P <0.001). There were no arrhythmias or ECG changes in the sauna. Compared with rest, there was significant ischemia during sauna bathing (average perfusion defect score at rest = -0.44 vs average sauna score = -0.93, P <0.001). The perfusion defect score in the sauna was worse than the resting score in 14 of the 15 patients. Sauna-associated perfusion defect scores were highly correlated with exercise-induced scores (R2 = 0.65, P <0.001). CONCLUSION: In patients with stable coronary artery disease, sauna use is clinically well tolerated but is associated with scintigraphically demonstrated myocardial ischemia.

Gender, depression, and one-year prognosis after myocardial infarction.

OBJECTIVE: The purpose of this study was to assess gender differences in the impact of depression on 1-year cardiac mortality in patients hospitalized for an acute myocardial infarction (MI). METHODS: Secondary analysis was performed on data from two studies that used the Beck Depression Inventory (BDI) to assess depression symptoms during hospitalization: a prospective study of post-MI risk and a randomized trial of psychosocial intervention (control group only). The sample included 896 patients (283 women) who survived to discharge and received usual posthospital care. Multivariate logistic regression analysis was used to assess the risk of 1-year cardiac mortality associated with baseline BDI scores. RESULTS: There were 290 patients (133 women) with BDI scores > or =10 (at least mild to moderate symptoms of depression); 8.3% of the depressed women died of cardiac causes in contrast to 2.7% of the nondepressed. For depressed men, the rate of cardiac death was 7.0% in contrast to 2.4% of the nondepressed. Increased BDI scores were significantly related to cardiac mortality for both genders [the odds ratio for women was 3.29 (95% confidence interval (CI) = 1.02-10.59); for men, the odds ratio was 3.05 (95% CI = 1.29-7.17)]. Control for other multivariate predictors of mortality in the data set (age, Killip class, the interactions of gender by non-Q wave MI, gender by left ventricular ejection fraction, and gender by smoking) did not change the impact of the BDI for either gender. CONCLUSIONS: Depression in hospital after MI is a significant predictor of 1-year cardiac mortality for women as well as for men, and its impact is largely independent of other post-MI risks.

Effect of a short-term primary prevention program on endothelium-dependent vasodilation in adults at risk for atherosclerosis.

BACKGROUND: Endothelium-dependent vasodilation is impaired in asymptomatic subjects with risk factors for atherosclerosis. PURPOSE: To determine whether a three-month integrative primary prevention program can improve endothelial function in asymptomatic subjects with risk factors for atherosclerosis. PATIENTS AND METHODS: Twenty-two asymptomatic middle-aged men and women (13 men and nine women) aged 55 +/- 7 years with sedentary lifestyle and dyslipidemia (low density lipoprotein [LDL] level greater than 3.4 mmol/L) underwent an exercise test, determination of fasting blood lipid levels and noninvasive measurement of brachial artery reactivity before and three months after the beginning of a prevention program. The program consisted of exercise training (three times per week) and National Cholesterol Education Program step 1 diet in all subjects. A smoking cessation program was offered when applicable (six patients). Brachial artery diameter was measured by using high resolution ultrasound at rest, during reactive hyperemia (flow-mediated dilation [FMD], which is endothelium-dependent) and after sublingual nitroglycerin (NTG) (endothelium-independent vasodilation). RESULTS: After three months, peak oxygen uptake increased significantly from 25.4 +/- 4.9 to 27.5 +/- 4.8 mL/kg/min (P < 0.005), and LDL level decreased significantly from 4.48 +/- 0.92 to 4.00 +/- 0.83 mmol/L (P < 0.005). FMD and NTG responses assessed as percentage of diameter change from baseline, however, did not change (FMD 5.4 +/- 4.3% before and 5.1 +/- 3.9% at three months, not significant; NTG 8.4 +/- 3.8% before and 7.4 +/- 4.5% at three months, not significant). CONCLUSIONS: Short-term application of the currently recommended lifestyle intervention in adults with coronary risk factors did not improve vascular endothelial function. Longer and more aggressive programs may be needed to improve vascular function in subjects with risk factors for atherosclerosis.

Intravenous diltiazem in acute myocardial infarction. Diltiazem as adjunctive therapy to activase (DATA) trial.

OBJECTIVES: This study was defined as a pilot investigation of the usefulness and safety of intravenous diltiazem as adjunctive therapy to tissue plasminogen activator in acute myocardial infarction, followed by oral therapy for 4 weeks. BACKGROUND: Experimental studies have documented that calcium antagonists protect the myocardial cell against the damage caused by coronary artery occlusion and reperfusion, yet no benefits have been conclusively demonstrated in acute myocardial infarction (AMI) in humans. METHODS: In this pilot study, 59 patients with an AMI treated with tissue-type plasminogen activator (t-PA) were randomized, double blinded, to intravenous diltiazem or placebo for 48 h, followed by oral therapy for 4 weeks. The primary objective was to detect an effect on indices of regional left ventricular function and perfusion. Patients were also closely monitored for clinical events, coronary artery patency and indices of infarct size and of left ventricular function. RESULTS: Creatine kinase elevation, Q wave score, global and regional left ventricular function and coronary artery patency at 48 h were not significantly different between the diltiazem and placebo groups. A greater improvement observed in regional perfusion and function with diltiazem was likely explained by initial larger defects. Diltiazem, compared to placebo, reduced the rate of death, reinfarction or recurrent ischemia at 35 days from 41% to 13% (p=0.027) and prevented the need for an urgent intervention. The rate of death or myocardial infarction was reduced by 65% (p=0.15). These benefits could not be explained by differences in baseline characteristics such as age, site and extent of infarction, time of inclusion or concomitant therapy. Heart rate and blood pressure were reduced throughout the study with active diltiazem treatment. Side effects of diltiazem were bradycardia and hypotension that required transient or permanent discontinuation of the study drug in 27% of patients, vs. 17% of patients with placebo. CONCLUSIONS: A protective effect for clinical events related to early postinfarction ischemia and reinfarction was suggested in this study, with diltiazem administered intravenously with t-PA followed by oral therapy for 1 month, with no effect on coronary artery patency and left ventricular function and perfusion.

Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction.

BACKGROUND: Increases in life stress have been linked to poor prognosis, after myocardial infarction (MI). Previous research suggested that a programme of monthly screening for psychological distress, combined with supportive and educational home nursing interventions for distressed patients, may improve post-MI survival among men. Our study assessed this approach for both men and women. We aimed to find out whether the programme would reduce 1-year cardiac mortality for women and men. METHODS: We carried out a randomised, controlled trial of 1376 post-MI patients (903 men, 473 women) assigned to the intervention programme (n = 692) or usual care (n = 684) for 1 year. All patients completed a baseline interview that included assessment of depression and anxiety. Survivors were also interviewed at 1 year. FINDINGS: The programme had no overall survival impact. Preplanned analyses showed higher cardiac (9.4 vs 5.0%, p = 0.064) and all-cause mortality (10.3 vs 5.4%, p = 0.051) among women in the intervention group. There was no evidence of either benefit or harm among men (cardiac mortality 2.4 vs 2.5%, p = 0.94; all-cause mortality 3.1 vs 3.1%, p = 0.93). The programme's impact on depression and anxiety among survivors was small. INTERPRETATION: Our results do not warrant the routine implementation of programmes that involve psychological-distress screening and home nursing intervention for patients recovering from MI. The poorer overall outcome for women, and the possible harmful impact of the intervention on women, underline the need for further research and the inclusion of adequate numbers of women in future post-MI trials.

Pharmacokinetics and safety of single intravenous and oral doses of dolasetron mesylate in healthy women.

Twenty-four healthy women received 2.4 mg kg-1 dolasetron mesylate (1.8 mg kg-1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0.08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0.08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2 = 0.23 h) to MDL 74156 (mean t1/2 = 8.05 and 9.12 h after intravenous and oral administration respectively). MDL 74156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non-significant changes in PR, QRS, and QTc intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men.

Safety and feasibility of a self-monitored, home-based phase II exercise program for high risk patients after cardiac surgery.

OBJECTIVE: To determine the safety and effectiveness of a self-monitored, home-based phase II exercise program for high risk patients after cardiac surgery. METHODS: High risk patients were defined as those presenting with severe left ventricular dysfunction with an ejection fraction less than 35%, severe ventricular arrhythmias, incomplete revascularization, abnormal response to a standard walking test or significant (grade 3/4) valvular regurgitation persisting postoperatively. Eighty patients (mean age 58.5 +/- 8.9 years) were randomly assigned to two groups. The experimental group (n = 37) received a home program of aerobic training with an intensity gradually increasing from 1.5 to 4.0 multiples of resting oxygen consumption (METs). This program was started at discharge from the hospital and lasted eight weeks. The control group (n = 43) received general guidelines for progressive increase of their activity level. Functional capacity was measured at discharge by the 6 min walking test and between the sixth and eighth week following discharge by a symptom-limited exercise test, according to the Naughton protocol. RESULTS: No cardiovascular complications occurred during the training program. At the final evaluation, there was no significant difference between the experimental and control groups regarding aerobic capacity (5.1 +/- 1.8 versus 4.9 +/- 1.6 METs respectively, P = 0.61), nor peak rate-pressure product (22.8 +/- 4.9 versus 23.6 +/- 5.2 beats/min x mmHg x 10(3) respectively, P = 0.54).

Clinical efficacy and safety of once-daily diltiazem in patients with stable angina pectoris switched from twice-daily diltiazem.

The maintenance of angina control was assessed in this multicenter (three sites), randomized, double-blind, parallel-group study. Patients with stable angina pectoris receiving twice-daily sustained-release (SR) diltiazem were switched to equivalent doses of once-daily controlled-delivery (CD) diltiazem or to diltiazem SR. Patients who were switched from diltiazem SR to diltiazem CD (n = 28) experienced a 5% increase in time to termination (p = 0.0004) on the exercise tolerance test (ETT), as well as an 8% improvement in time to onset of angina (p < 0.0001) on the ETT. A similar trend was observed in patients randomized to diltiazem SR (n = 7), which suggested a training effect, and, therefore, equal efficacy between diltiazem SR and diltiazem CD. During exercise testing in the diltiazem SR baseline phase, 77% of the patients did not experience angina, whereas 60% of the patients did not experience ST-segment depression. Following transfer to diltiazem CD, 79 and 61% of patients, respectively, remained angina- and ST-segment depression free. No significant changes in the number of angina attacks, nitroglycerin use, or any hemodynamic-related parameters were observed following transfer to diltiazem CD. Eleven percent of the patients receiving diltiazem CD experienced treatment-related adverse events, which were limited to headache and abdominal pain; these adverse events did not lead to discontinuation of treatment. These findings suggest that patients whose angina is controlled with twice-daily diltiazem SR can be safely and effectively switched to an equivalent daily dose of the once-daily diltiazem CD.