Martin Juneau

Aspirin, heparin, or both to treat acute unstable angina

We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [+/- SD] of 7.9 +/- 8.0 hours after the last episode of pain), and the study was ended after 6 +/- 3 days, when definitive therapy had been selected. Major end points--refractory angina, myocardial infarction, and death--occurred in 23, 12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P less than 0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina.

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.

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.

Reactivation of Unstable Angina after the Discontinuation of Heparin

BACKGROUND Heparin is an effective, widely used treatment for unstable angina. Among patients enrolled in a double-blind, randomized, placebo-controlled trial comparing intravenous heparin, aspirin, both treatments, and neither during the acute phase of unstable angina, we encountered patients in whom unstable angina was reactivated after heparin was discontinued. METHODS The study population included 403 of the original 479 patients in the trial who had completed six days of blinded therapy without refractory angina or myocardial infarction. After the discontinuation of therapy, clinical events, including reactivation of unstable angina and myocardial infarction occurring within 96 hours after hospitalization, were closely monitored. RESULTS Early reactivation occurred in 14 of the 107 patients who received heparin alone, as compared with only 5 patients in each of the other three study groups (P less than 0.01). These reactivations required urgent intervention (thrombolysis, angioplasty, or coronary-bypass surgery) in 11 patients treated with heparin alone, but in only 2 patients in the other groups combined (P less than 0.01). Four of the six patients who had a myocardial infarction during a reactivation of their disease were in the heparin group. Reactivations in this group occurred in a cluster a mean (+/- SD) of 9.5 +/- 5 hours after the discontinuation of the study drug but were randomly distributed over the initial 96 hours in the other three groups. CONCLUSIONS Although heparin is beneficial in treating unstable angina, the disease process may be reactivated within hours of the discontinuation of this drug. Concomitant therapy with aspirin may prevent this withdrawal phenomenon.

Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina.

BackgroundAntiplatelet therapy with aspirin and antithrombotic therapy with heparin both prevent the complications of unstable angina; however, no definitive data exist on the relative clinical efficacy of the two drugs. Methods and ResultsAspirin (325 mg bid) or heparin (5000-U intravenous bolus followed by a perfusion titrated to the APTT) were compared in a double-blind randomized trial of 484 patients in two cohorts enrolled sequentially. The study was initiated at admission to hospital at a mean of 8.3±7.8 hours after the last episode of pain. End points were assessed 5.7±3.3 days later, when the decision for long-term management was made. Myocardial infarction occurred in 2 (0.8%) of the 240 patients randomized to heparin and in 9 (3.7%) of the 244 randomized to aspirin (P=.035), an odds ratio of 0.22 and a risk difference of 2.9%o (95% confidence limits, 0.3% to 5.6%) with heparin. The only death resulted from a myocardial infarction in an aspirin patient. Survival curves with Cox logistic regression analysis showed that the improvement in survival without myocardial infarction with heparin (P=.035) was independent of other baseline characteristics. ConclusionsThis study documents that heparin prevents myocardial infarction better than aspirin during the acute phase of unstable angina.

Angiotensin Receptor Blockade and Exercise Capacity in Adults With Systemic Right Ventricles A Multicenter, Randomized, Placebo-Controlled Clinical Trial

Background— Pharmacological blockade of the renin-angiotensin system improves exercise tolerance in patients with left ventricular dysfunction, yet its impact on patients with systemic right ventricles (RVs) remains unknown. Methods and Results— A multicenter, randomized, double-blind, placebo-controlled, crossover clinical trial was performed to assess the effects of losartan on exercise capacity and neurohormonal levels in patients with systemic RVs. Of 29 patients studied (age, 30.3±10.9 years), 21 had transposition of the great arteries with a Mustard baffle, and 8 had congenitally corrected transposition of the great arteries. Baseline values were as follows: &OV0312;o2max, 29.8±5.6 mL · kg−1 · min−1 (73.5±12.9% predicted value); RV ejection fraction, 41.6±9.3%; N-terminal pro brain natriuretic peptide (NT-proBNP), 257.7±243.4 pg/mL (normal <125 pg/mL); and angiotensin II, 5.7±4.9 pg/mL (normal <5.0 pg/mL). Comparing losartan to placebo showed no differences in &OV0312;o2max (29.9±5.4 versus 29.4±6.2 mL · kg−1 · min−1; P=0.43), exercise duration (632.3±123.0 versus 629.9±140.7 seconds; P=0.76), and NT-proBNP levels (201.2±267.8 versus 229.7±291.5 pg/mL; P=0.10), despite a trend toward increased angiotensin II levels (15.2±13.8 versus 8.8±12.5 pg/mL; P=0.08). Conclusions— In adults with systemic RVs, losartan did not improve exercise capacity or reduce NT-proBNP levels. Minimal baseline activation of the renin-angiotensin system may explain this lack of benefit and imply an alternative pathophysiological mechanism for the progressive ventricular dysfunction and impaired exercise capacity observed in such patients.

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.

High-Intensity Interval Training in Cardiac Rehabilitation

High-intensity interval training (HIIT) is frequently used in sports training. The effects on cardiorespiratory and muscle systems have led scientists to consider its application in the field of cardiovascular diseases. The objective of this review is to report the effects and interest of HIIT in patients with coronary artery disease (CAD) and heart failure (HF), as well as in persons with high cardiovascular risk. A non-systematic review of the literature in the MEDLINE database using keywords ‘exercise’, ‘high-intensity interval training’, ‘interval training’, ‘coronary artery disease’, ‘coronary heart disease’, ‘chronic heart failure’ and ‘metabolic syndrome’ was performed. We selected articles concerning basic science research, physiological research, and randomized or non-randomized interventional clinical trials published in English.To summarize, HIIT appears safe and better tolerated by patients than moderate-intensity continuous exercise (MICE). HIIT gives rise to many short- and long-term central and peripheral adaptations in these populations. In stable and selected patients, it induces substantial clinical improvements, superior to those achieved by MICE, including beneficial effects on several important prognostic factors (peak oxygen uptake, ventricular function, endothelial function), as well as improving quality of life. HIIT appears to be a safe and effective alternative for the rehabilitation of patients with CAD and HF. It may also assist in improving adherence to exercise training. Larger randomized interventional studies are now necessary to improve the indications for this therapy in different populations.

Improvement in Exercise Capacity in Asymptomatic and Mildly Symptomatic Adults After Atrial Septal Defect Percutaneous Closure

Background—Controversy exists as to whether secundum atrial septal defects (ASDs) in asymptomatic or mildly symptomatic New York Heart Association (NYHA) class I or II adult patients should be closed. Methods and Results—Thirty-seven patients (24 females; mean age 49.4 years, range 19 to 76) with a mean pulmonary to systemic flow ratio (Qp:Qs) of 2.1 (1.2 to 3.4) had a maximal oxygen uptake (Vo2max) determination and echocardiographic measurement of right ventricular dimensions before and 6 months after elective percutaneous closure of ASD. At baseline, mean Vo2max was 23.5±6.4 mL/kg per minute and was higher in the 15 NYHA I patients than in the 22 NYHA II patients (27±6.9 versus 20.8±4.6 mL/kg per minute;P =0.0015). Vo2max increased significantly at 6 months (23.5±6.4 to 26.9±6.9 mL/kg per minute;P <0.0001). Improvement was as marked in NYHA I (+22%;P <0.0001) as in NYHA II patients (+12%;P <0.0001), in patients with Qp:Qs 1.2 to 2.0 (+16%;P <0.0001) as in those with Qp:Qs >2 (+12%;P <0.0001), and in patients ≥40 years of age (+14%;P <0.0001) as in those <40 years of age (+16%;P <0.0001). Compared with 15 of 37 patients before closure, 35 of 37 patients were in NYHA I at 6 months. Right ventricular dimensions decreased significantly (P <0.0001). Conclusions—Adult ASD patients significantly increase their functional capacity after percutaneous defect closure. This is observed even in patients classified as asymptomatic, in those with lesser shunts, and in older patients. These findings suggest that ASD closure in an adult population should be considered even in the absence of symptoms.

Symptom-limited versus low level exercise testing before hospital discharge after myocardial infarction.

OBJECTIVE This study was undertaken to compare a low level and a symptom-limited test performed before hospital discharge after an uncomplicated myocardial infarction. BACKGROUND Exercise testing after myocardial infarction provides useful prognostic information. Usually either a low level test is performed before hospital discharge or a symptom-limited test is performed at 3 weeks. METHODS The study group comprised 202 patients with an uncomplicated myocardial infarction; 58 patients had a non-Q wave infarction and 115 patients had received thrombolytic therapy. Both a low level and a symptom-limited exercise test were performed in 200 of the 202 study patients in randomized order on consecutive days, a mean of 7.4 +/- 2.3 days after infarction. RESULTS The symptom-limited test required a considerably greater effort than the low level test: exercise duration was 554 +/- 209 versus 389 +/- 125 s (p less than 0.0001), and peak work load was 5.7 +/- 1.8 versus 4.2 +/- 1.1 METs (p less than 0.0001). The peak heart rate was higher during the symptom-limited test (121 +/- 20 vs. 108 +/- 14 beats/min, p less than 0.0001), as was the rate-pressure product. The number of patients who developed ST segment depression greater than or equal to 1 mm increased from 56 during the low level test to 89 during the symptom-limited test (p less than 0.0001). ST segment depression greater than or equal to 2 mm occurred in 22 patients during the low level test and in 41 patients during the symptom-limited test, an 86% increase (p less than 0.0001). The number of patients with either angina or ST depression greater than or equal to 1 mm increased from 66 to 105 (p less than 0.0001) with the symptom-limited test. Exercise test results were similar for patients with a Q wave or a non-Q wave infarction. Exercise duration was longer and exercise-induced ST depression less frequent in patients who had received thrombolytic therapy. CONCLUSIONS A symptom-limited exercise test performed before hospital discharge after uncomplicated myocardial infarction provides a significantly greater cardiovascular stress than does a low level test and is associated with an ischemic response nearly twice as frequently. The prognostic significance of a positive response at higher work loads has not been defined.