Long-term myocardial adaptations after cardiac rehabilitation in heart failure: a randomized six-year evaluation using magnetic resonance imaging.

OBJECTIVE: To assess exercise capacity and left ventricular function using magnetic resonance imaging (MRI) among patients with chronic heart failure randomized to a residential rehabilitation programme at baseline and six years after participation. DESIGN: Randomized controlled study. SETTING: Residential cardiac rehabilitation centre and community hospital. INTERVENTION: One month of intensive exercise and risk reduction therapy including educational sessions, a low-fat diet, and 2 hours of individually prescribed exercise daily. Control subjects received usual care. Subjects were evaluated at baseline, after completing the one-month residential programme and six years later. SUBJECTS: From an original study group of 50, 16 patients (8 exercise, 8 controls) with chronic heart failure were alive and available for evaluation after six years. MAIN MEASURES: Cardiopulmonary exercise test responses and ventricular size and function using MRI. RESULTS: Peak Vo(2) was 20.0 and 12.4% higher after the rehabilitation programme and six years later, respectively, whereas minimal changes were observed among controls. Left ventricular mass and volumes tended to decrease among subjects in the exercise group, whereas left ventricular mass and volumes tended to increase among control subjects after six years. Ejection fraction increased approximately 20% in both groups. CONCLUSION: Six years after participation in a concentrated residential rehabilitation programme, exercise capacity was preserved and no significant changes were observed in ventricular size or function. These findings provide further support for exercise rehabilitation in chronic heart failure.

BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial.

CONTEXT: It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy. OBJECTIVE: To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy. DESIGN, SETTING, AND PATIENTS: Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008. INTERVENTION: Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy). MAIN OUTCOME MEASURES: Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires. RESULTS: Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction) CONCLUSION: Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43596477.

Effects of exercise training on heart rate recovery in patients with chronic heart failure.

BACKGROUND: Heart rate recovery (HRR) is a marker of vagal tone that is associated with survival, but little is known about the effects of exercise training on HRR in patients with heart failure (HF). METHODS: Twenty-four patients with HF were randomized to a 2-month residential rehabilitation program or to usual care. Symptom-limited exercise testing was performed at baseline and at discharge from the program. Heart rate recovery was expressed as the decline in heart rate from peak exercise through 6 minutes into recovery. In addition, HRR recovery curves were normalized to a range of 1 at peak heart rate and 0 at 6 minutes and adjusted for differences in heart rate reserve, facilitating the comparison of recovery curve shapes between groups. RESULTS: Mean peak oxygen uptake and oxygen uptake at the lactate threshold increased 26% (P < .05) and 39% (P < .001), respectively, in the exercise group, whereas neither of these responses changed significantly among controls. Heart rate recovery was significantly more rapid in the exercise group after training (main effect 12.6 vs 2.6 beat/min in the trained and control groups, respectively, P = .005). The normalized curves showed that the largest improvement in recovery curve shape occurred in the exercise group, but most of the HRR improvement was accounted for by a widening of the difference between peak and resting heart rate. CONCLUSION: Exercise training results in a faster HRR in patients with HF. Heart rate recovery, as a simple marker of autonomic function, is an easily acquired response that may be useful for evaluating patient outcomes in cardiac rehabilitation.

Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial.

CONTEXT: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known. OBJECTIVE: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI. DESIGN, SETTING, AND PARTICIPANTS: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006. INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin. MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up. RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00387231.

Effects of exercise training on left ventricular volumes and function in patients with nonischemic cardiomyopathy: application of magnetic resonance myocardial tagging.

BACKGROUND: Exercise training is now an accepted component of the therapeutic regimen in patients with heart failure and underlying ischemia, but few data are available on the effects of training in patients with nonischemic dilated cardiomyopathy. METHODS: Twenty-four patients (mean age 55 +/- 9 years, mean ejection fraction 26.6% +/- 10%) were randomized to an exercise (n = 12) or a control (n = 12) group. Patients in the exercise group underwent 5 45-minute sessions of supervised training per week. Before and after the 2-month study period, exercise testing with respiratory gas exchange and lactate analysis was performed, left ventricular volumes and ejection fraction were measured with magnetic resonance imaging, and left ventricular rotation and relaxation velocities were measured with a novel magnetic resonance imaging tagging technique. RESULTS: Training resulted in increases in peak oxygen uptake (VO2) (21.7 +/- 4 mL/kg/min to 25.3 +/- 5 mL/kg/min, P <.05) and VO2 at the lactate threshold (12.8 +/- 4 mL/kg/min to 19.0 +/- 5 mL/kg/min, P <.01). No differences were observed within or between groups in left ventricular end-diastolic volume, end-systolic volume, or ejection fraction. Velocity of left ventricular rotation during systole was unchanged in both groups, and relaxation velocity was higher after training in the exercise group (21.2 +/- 5 degrees/s versus 29.7 +/- 12 degrees/s, P <.05). CONCLUSION: Training resulted in increases in peak VO2 and VO2 at the lactate threshold. Left ventricular volumes and systolic function (ie, ejection fraction and rotation velocity) were unchanged with training, suggesting that training in patients with dilated cardiomyopathy does not lead to further myocardial damage. However, the increase in relaxation velocity after exercise training indicates an improvement in diastolic function. The latter finding suggests an additional potential benefit of exercise training in patients with dilated cardiomyopathy.

Effects of bisoprolol fumarate on left ventricular size, function, and exercise capacity in patients with heart failure: analysis with magnetic resonance myocardial tagging.

BACKGROUND: Recent data suggest that beta-blockers can be beneficial in subgroups of patients with chronic heart failure (CHF). For metoprolol and carvedilol, an increase in ejection fraction has been shown and favorable effects on the myocardial remodeling process have been reported in some studies. We examined the effects of bisoprolol fumarate on exercise capacity and left ventricular volume with magnetic resonance imaging (MRI) and applied a novel high-resolution MRI tagging technique to determine myocardial rotation and relaxation velocity. METHODS: Twenty-eight patients (mean age, 57 +/- 11 years; mean ejection fraction, 26 +/- 6%) were randomized to bisoprolol fumarate (n = 13) or to placebo therapy (n = 15). The dosage of the drugs was titrated to match that of the the Cardiac Insufficiency Bisoprolol Study protocol. Hemodynamic and gas exchange responses to exercise, MRI measurements of left ventricular end-systolic and end-diastolic volumes and ejection fraction, and left ventricular rotation and relaxation velocities were measured before the administration of the drug and 6 and 12 months later. RESULTS: After 1 year, heart rate was reduced in the bisoprolol fumarate group both at rest (81 +/- 12 before therapy versus 61 +/- 11 after therapy; P <.01) and peak exercise (144 +/- 20 before therapy versus 127 +/- 17 after therapy; P <.01), which indicated a reduction in sympathetic drive. No differences were observed in heart rate responses in the placebo group. No differences were observed within or between groups in peak oxygen uptake, although work rate achieved was higher (117.9 +/- 36 watts versus 146.1 +/- 33 watts; P <.05) and exercise time tended to be higher (9.1 +/- 1.7 minutes versus 11.4 +/- 2.8 minutes; P =.06) in the bisoprolol fumarate group. A trend for a reduction in left ventricular end-diastolic volume (-54 mL) and left ventricular end-systolic volume (-62 mL) in the bisoprolol fumarate group occurred after 1 year. Ejection fraction was higher in the bisoprolol fumarate group (25.0 +/- 7 versus 36.2 +/- 9%; P <.05), and the placebo group remained unchanged. Most changes in volume and ejection fraction occurred during the latter 6 months of treatment. With myocardial tagging, insignificant reductions in left ventricular rotation velocity were observed in both groups, whereas relaxation velocity was reduced only after bisoprolol fumarate therapy (by 39%; P <.05). CONCLUSION: One year of bisoprolol fumarate therapy resulted in an improvement in exercise capacity, showed trends for reductions in end-diastolic and end-systolic volumes, increased ejection fraction, and significantly reduced relaxation velocity. Although these results generally confirm the beneficial effects of beta-blockade in patients with chronic heart failure, they show differential effects on systolic and diastolic function.

Effects of high-intensity training on indices of ventilatory efficiency in chronic heart failure.

BACKGROUND: Measures of ventilatory inefficiency, such as the slope of the relation between ventilation and carbon dioxide production ((Equation is included in full-text article.)slope) and the oxygen uptake efficiency slope (OUES) have recently been shown to be strong prognostic markers in patients with heart failure. Little is known regarding the effects of exercise training on these indices. METHODS: Fifty heart failure patients (mean age = 55 ± 6 years, ejection fraction = 33 ± 6%) referred to a residential cardiac rehabilitation program were randomized to a 2-month high-intensity training program (n = 24) or to a control group (n = 26). Before and after the study period, maximal cardiopulmonary exercise testing was performed, and markers of ventilatory inefficiency were determined. RESULTS: Training increased peak oxygen uptake ((Equation is included in full-text article.); 23%), exercise time (29%), and peak workload (28%), whereas no changes were observed in controls (all P < .05 between groups). No differences were observed in the (Equation is included in full-text article.)slope in either group. However, the ventilatory equivalent for oxygen ((Equation is included in full-text article.)ratio) was reduced at matched work rates throughout exercise (P < .01). The OUES increased by 12% in the exercise groups (P = .003) and 4% in controls. At baseline, trained patients had an OUES that was 69% of the age-predicted value and this improved to 78% after training (P = .004). The change in OUES was significantly related to the change in peak (Equation is included in full-text article.)with training (r = 0.63, P = .001). CONCLUSION: High-intensity training resulted in marked improvements in exercise capacity in patients with heart failure. Training improved the OUES and reduced the (Equation is included in full-text article.)ratio, but the (Equation is included in full-text article.)slope was unchanged. Among measures of ventilatory inefficiency, the OUES may be more sensitive to training than the (Equation is included in full-text article.)slope.

Effects of exercise training on myocardial energy metabolism and ventricular function assessed by quantitative phosphorus-31 magnetic resonance spectroscopy and magnetic resonance imaging in dilated cardiomyopathy.

OBJECTIVES: The present study investigated changes in cardiac energy metabolism and function in patients with dilated cardiomyopathy (DCM) before and after exercise training (ET) with phosphorus-31 magnetic resonance spectroscopy (MRS) in combination with magnetic resonance imaging (MRI). BACKGROUND: Exercise training might have a beneficial role on myocardial function and oxidative metabolism in DCM, but it is unclear whether the additional load on the failing heart leads to deterioration of cardiac energy metabolism. METHODS: Twenty-four patients were randomized to an exercise (age 53 +/- 12 years) or a control (age 56 +/- 6 years) group. Supervised ET was performed for 2 months, followed by 6 months of self-regulated training. At baseline and 2 and 8 months, maximal exercise testing along with quantitative MRS and MRI studies were performed. RESULTS: The effectiveness of ET was demonstrated by a 17% increase in peak oxygen uptake (p < 0.05). Exercise training improved left ventricular (LV) end-systolic volume (p < 0.05) and LV ejection fraction (30 +/- 15% vs. 37 +/- 15%; p < 0.01) but not right ventricular parameters. The improvement in cardiac function was not accompanied by changes in cardiac high-energy phosphate concentrations; phosphocreatine, adenosine triphosphate, and the phosphocreatine/adenosine triphosphate ratio were all unchanged after training. CONCLUSIONS: The observation that LV function improved and LV energy metabolism remained unchanged suggests that the beneficial effect of ET on LV function is achieved without adversely affecting metabolism. These findings lend further support for the use of ET as an adjunct therapy in DCM.

Exercise capacity, physical activity patterns and outcomes six years after cardiac rehabilitation in patients with heart failure.

OBJECTIVE: To determine the short- and long-term effects of an intensive, concentrated rehabilitation programme in patients with chronic heart failure. DESIGN: Randomized controlled trial, with one-month and six-year evaluations. SETTING: Residential rehabilitation centre in Switzerland. SUBJECTS: Fifty patients with chronic heart failure, randomized to exercise or control groups. INTERVENTIONS: A rehabilitation programme lasting one month, including educational sessions, a low-fat diet, and 2 hours of individually prescribed exercise daily. MAIN MEASURES: Exercise test responses, health outcomes and physical activity patterns. RESULTS: Peak Vo(2) increased 21.4% in the exercise group during the rehabilitation programme (P<0.05), whereas peak Vo(2) did not change among controls. After the six-year follow-up period, peak Vo(2) was only slightly higher than that at baseline in the trained group (7%, NS), while peak Vo(2) among controls was unchanged. During long-term follow-up, 9 and 12 patients died in the exercise and control groups, respectively (P = 0.63). At six years, physical activity patterns tended to be higher in the exercise group; the mean energy expenditure values over the last year were 2,704 +/- 1,970 and 2,085 +/- 1,522 kcal/week during recreational activities for the exercise and control groups, respectively. However, both groups were more active compared to energy expenditure prior to their cardiac event (P<0.001). CONCLUSIONS: Six years after participation in a residential rehabilitation programme, patients with chronic heart failure had slightly better outcomes than control subjects, maintained exercise capacity and engaged in activities that exceed the minimal amount recommended by guidelines for cardiovascular health.

Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study.

AIMS: To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. METHODS AND RESULTS: In a randomized multicentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n = 26) or risk factor control-only (RFC, n = 28). They were followed yearly for 11.2 +/- 2.2 years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P < 0.001). In addition, MED patients had consistently lower rates of exercise-induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (-0.7%, P = 0.597) in contrast to RFC patients in whom it decreased over time (-6.0%, P = 0.006). CONCLUSION: Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered.

Maintenance of exercise capacity and physical activity patterns 2 years after cardiac rehabilitation.

BACKGROUND: The benefits of exercise training for postmyocardial infarction and postcoronary artery bypass surgery patients are well established, but little is known about the effects of rehabilitation in the months or years following the program. The purpose of this study was to assess exercise capacity, blood lipids, and physical activity patterns 2 years after completing a concentrated residential rehabilitation program in Switzerland. METHODS: Seventy-eight patients (86% males, mean age = 56 +/- 10, mean ejection fraction = 64% +/- 12%) were referred to a residential rehabilitation program after a myocardial infarction or coronary artery bypass surgery between January 2001 and June 2001. Patients lived at the center for 1 month, during which time they underwent educational sessions, consumed a low-fat diet, and exercised 2 hours daily. Two years after completing the program, patients returned to the hospital and underwent a maximal exercise test, an assessment of recent and adulthood physical activity patterns, and evaluation of blood lipids. RESULTS: During the 2-year follow-up period, there were 5 deaths, and 70 of the remaining 73 patients returned for repeat testing. Mean exercise capacity increased 27% during the rehabilitation program (P < .01). Gains in exercise capacity during rehabilitation were maintained after the follow-up period; mean exercise capacity after 2 years was 34% higher compared with that at baseline (P < .01). At the 2-year evaluation, patients were expending a mean of 3127 +/- 1689 kcals/wk during recreational activities compared with 977 +/- 842 kcals/wk during adulthood prior to their cardiac event (P < .001). Between the completion of rehabilitation and the 2-year follow-up, total cholesterol, total cholesterol/high-density lipoprotein ratio, and triglycerides increased significantly. CONCLUSIONS: Two years after a cardiac event and participation in a concentrated residential rehabilitation program, patients maintained their exercise capacity and engaged in physical activities that exceed the levels recommended by guidelines for cardiovascular health. These observations suggest that a relatively intensive rehabilitation program provided a catalyst to maintain physical activity patterns and exercise tolerance in the 2 years following a cardiac event.

An evaluation of training responses using self-regulation in a residential rehabilitation program.

BACKGROUND: The efficacy of exercise training for patients with cardiovascular disease is well established. Given recent changes in reimbursement patterns for cardiac rehabilitation and therefore a greater need for self-monitoring, home programs, and the like, a need exists to determine the capability of patients to regulate their own exercise intensity and assess the efficacy of self-regulated exercise. This study assessed the training responses of a group instructed to train at an intensity they perceived as "somewhat hard," and compared their responses to standardized methods of exercise prescription. METHODS: A total of 78 patients (86% male; mean age, 56 +/- 10 years; mean ejection fraction, 64% +/- 12%) referred to a residential rehabilitation program after myocardial infarction or bypass surgery were randomized to three different groups, for which exercise intensity was prescribed using different methods. For group 1, 70% of heart rate reserve was maintained using precise, continuous electronic heart rate-controlled resistance on a cycle ergometer. Group 2 gauged their own exercise intensity according to a level they perceived as "somewhat hard" (13 on the Borg scale) and were given no feedback in terms of heart rate or work rate. For group 3, exercise intensity was determined using both objective (heart rate reserve and work rate targeted to 60% to 80% of maximal exercise) and subjective (Borg scale 12 to 14) indices. The subjects exercised daily for 1 month. Training frequency, duration, and mode were equivalent between the groups. RESULTS: The exercise capacity of the three groups was increased significantly after the training period: 33.7% in group 1, 22.9% in group 2, and 31.2% in group 3 (P <.005 for all). Other measures of the training response also were similar between the groups, including a significant increase in work rate at a perceived exertion of 13 and maximal watts achieved. The magnitude of the training response was not different between the groups. There were no complications during training. CONCLUSIONS: The training response was similar between the three methods used to monitor exercise intensity. Thus, patients are able to gauge their own exercise intensity reasonably when instructed to exercise at a perceived exertion of 13. This suggests that close heart rate monitoring may not always be necessary for many stable patients with cardiovascular disease to achieve the benefits of a rehabilitation program.