Change In Exercise Duration Research Articles

Abstract 100

Background and Objective: Exercise intervention can be personalized and delivered digitally to achieve better outcomes in people with diabetes. The study aim was to analyse the effect of supervised exercise prescription delivered as part of Fitterfly diabetes digital therapeutics program in people with diabetes (PWD) after completion of the program. Method: De-identified data of 150 participants (mean age 45.29 ± 10.53 years, 39.3% females) who completed the 90-day program was analyzed. Structured virtual physiotherapy consultations and personalized exercise prescriptions were provided by physiotherapists along with expert-led care by a multidisciplinary team. Participants received access to Fitterfly mobile application for digital logging of meals and physical activity, regular follow-ups from physiotherapists to ensure adherence to the personalized prescription and for reviewing the goals to be achieved during the course of the program. Wilcoxon test was used for the statistical analysis with p < 0.05 considered statistically significant. Results: After completion of the program, significant median improvement in 6-minute walk test and total fitness score by 5.35% (p < 0.001) and 46.86% (p < 0.001) respectively was observed. Participants were categorized based on their activity levels at the beginning of the program, 26% (39/150) of participants were in the sedentary category, 55% (82/150) were in the aerobic category and 19% (29/150) were in the strength training category. After completion of the program, all the participants were following strength training as part of their exercise regimen. Median exercise duration per week in these participants improved by 180 (135,270) min, 70 (0,141.25) min and 60 (0, 142.50) min respectively. Post-program, median HbA1c reduction by -0.8 (-2.00, -0.38) % was observed, with 87.33% (131/150) of the participants showing significant HbA1c reduction. Median weight reduction was found to be -2.5 (-1.00, -4.50) kg and median waist circumference reduction was -4.00 (-7.00, -0.08) cm. Among users who started with HbA1c above recommended level (>7%), 48.39% (45/93) reduced their HbA1c in the recommended range after completion of the program. Conclusion: The study demonstrated improvement in cardiorespiratory and physical fitness, exercise duration and incorporation of strength training in the exercise regimen of the participants. Significant improvement in glycemic control and a significant reduction in body weight and waist circumference was also observed. Virtual supervised exercise guidance as a part of Fitterfly diabetes digital therapeutics program can help in improving safety and adherence to physical activity among people with T2DM for effective diabetes management.

303 Overview of Paternal Programming in Livestock Species

Abstract The concept of developmental programming from a maternal standpoint is well established. Perhaps even more impactful, however, is developmental programming that may arise from paternal contributions when single sires are responsible for breeding multiple females. Research in rodent models has shown that paternal obesity, high fat or low protein diets, exercise, stress, and drug and alcohol exposure can lead to epigenetic modifications in sperm and seminal plasma. Some of these changes withstand the extensive remodeling associated with fertilization and early embryo development, culminating in discernable offspring phenotypes that remain present for multiple generations. Certainly, the observations in rodent models related to alterations in offspring body weight, adiposity, metabolic responses, bone density, and reproductive outcomes and function have implications for the livestock industries if similar paternal programming phenomena exist. Livestock production systems are robust and dynamic and many paradigms exist with potential to alter male germ line epigenome, with specific changes likely related to timing of aberrant conditions relative to spermatogenesis and sperm residence in the epididymis. Within the context of routine management systems, our livestock patriarchs can experience major diet and weight changes, transportation and handling stress, environmental extremes, and/or changes in exercise duration, frequency, and intensity. In addition, livestock managers may embrace the concept of delivering specific quantities and types of feedstuffs, and apply other interventions if proven beneficial. Several research groups using livestock models have revealed that epigenetic machinery delivered in sperm and seminal plasma can be altered. A sheep model demonstrated the feeding rumen-protected methionine to rams from weaning to puberty resulted in epigenetic and phenotypic alterations still present in the F2 generation. This presentation will review the status of literature regarding paternal programming, identify knowledge gaps, and suggest areas for future research efforts with potential to enhance production efficiencies of livestock operations.

Effect of Breathing Oxygen-Enriched Air on Exercise Performance in Patients with Chronic Obstructive Pulmonary Disease: Randomized, Placebo-Controlled, Cross-Over Trial

Background: Patients with chronic obstructive pulmonary disease (COPD) experience dyspnea and hypoxemia during exercise. Objective: The aim of this study was to evaluate the effects of breathing oxygen-enriched air on exercise performance and associated physiological changes in patients with COPD. Methods: In a randomized, placebo-controlled, single-blind, cross-over trial, 20 patients with COPD (11 women, age 65 ± 6 years, FEV₁ 64 ± 19% pred., resting SpO₂ ≥90%) performed 4 cycle ergospirometries to exhaustion using an incremental exercise test (IET) and a constant work rate (at 75% maximal workload with air) exercise test (CWRET), each with ambient (FiO₂ 0.21) and oxygen-enriched (FiO₂ 0.5) air. The main outcomes were the change in maximal workload in the IET and the change in exercise duration in the CWRET with oxygen versus air. Electrocardiogram, pulmonary gas exchange, thoracic volumes by inductance plethysmography, arterial blood gases, and cerebral and quadriceps muscle tissue oxygenation (CTO and MTO) were additionally measured. Results: In the IET, maximal workload increased from 96 ± 21 to 104 ± 28 W with oxygen. In the CWRET, exercise duration increased from 605 ± 274 to 963 ± 444 s with oxygen. At end-exercise with oxygen, CTO, MTO, PaO₂, and PaCO₂ were increased, while V’E/V’CO₂ was reduced and thoracic volumes were similar. At the corresponding time to end of exercise with ambient air, oxygen decreased heart rate, respiratory rate, minute ventilation, and V’E/V’CO₂, while oxygenation was increased. Conclusion: In COPD patients without resting hypoxemia, breathing oxygen-enriched air improves exercise performance. This relates to a higher arterial oxygen saturation promoting oxygen availability to muscle and cerebral tissue and an enhanced ventilatory efficiency. COPD patients may benefit from oxygen therapy during exercise training.

Comparison of Exercise Performance and Clinical Outcome Between Functional Complete and Incomplete Revascularization

Background and ObjectivesAlthough percutaneous coronary intervention (PCI) is recommended to improve symptoms in patients with stable ischemic heart disease (SIHD), improvement of exercise performance is controversial. This study aimed to investigate changes in exercise duration after PCI according to functional completeness of revascularization by comparing pre- and post-PCI exercise stress test (EST).MethodsPatients with SIHD were enrolled from a prospective PCI registry, and divided into 2 groups: 1) functional complete revascularization (CR) group had a positive EST before PCI and negative EST after PCI, 2) functional incomplete revascularization (IR) group had positive EST before and after PCI. Primary outcome was change in exercise duration after PCI and secondary outcome was major adverse cardiac events (MACE, a composite of any death, any myocardial infarction, and any ischemia-driven revascularization) at 3 years after PCI.ResultsA total of 256 patients (149 for CR group, and 107 for IR group) were eligible for analysis. Before PCI, exercise duration was not significantly different between the functional CR and IR groups (median 540 [interquartile range; IQR, 414, 602] vs. 480 [402, 589] seconds, p=0.091). After PCI, however, the CR group had a significantly higher increment of exercise duration than the IR group (median 62.0 [IQR, 12.0, 141.0] vs. 30.0 [−11.0, 103.5] seconds, p=0.011). The functional CR group also had a significantly lower risk of 3-year MACE (6.2% vs. 26.1%; adjusted hazard ratio, 0.19; 95% confidence interval, 0.09–0.41; p<0.001).ConclusionsFunctional CR showed a higher increment of exercise duration than functional IR.

Hybrid versus traditional cardiac rehabilitation models: a systematic review and meta-analysis.

The common drawbacks of standard cardiac rehabilitation (CR) models include low participation rate, high cost, and dependence on on-site exercise sessions. Therefore, hybrid CR protocols have been developed. We aimed to test whether hybrid CR models are superior or equivalent to the traditional CR models in patients after myocardial infarction, heart failure, and cardiac surgery, using a meta-analysis framework. Data from relevant original studies indexed in the Medline, Scopus, Cochrane Central, and Web of Science data-bases were extracted and analysed. The standardised mean difference (SMD) was used as a summary effect estimate, along with 95% confidence interval (CI). Based on data from 1195 patients, the summary effect size showed similar improvement in functional capacity in hybrid and standard CR programmes (SMD = -0.04, 95% CI -0.18 to 0.09, p = 0.51). No significant difference was detected between the two models in terms of changes in exercise duration (SMD = -0.14, 95% CI -0.51 to 0.24, p = 0.47), systolic (SMD = -0.01, 95% CI -0.14 to 0.12, p = 0.91), and diastolic (SMD = -0.03, 95% CI -0.16 to 0.11, p = 0.7) blood pres-sure, or health-related quality of life (SMD = -0.08, 95% CI -0.23 to 0.07, p = 0.27). In terms of blood lipids, no significant difference was noted between hybrid and traditional CR models in all assessed lipid profile parameters, except for triglycerides (favouring the traditional CR model). Hybrid CR protocols showed comparable efficacy to the traditional model. Further well-designed studies are required to validate these findings, especially regarding the long-term outcomes.

Nordic walking for individuals with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials.

Background Exercise is the cornerstone of rehabilitation programmes for individuals with cardiovascular disease (IwCVD). Although conventional cardiovascular rehabilitation (CCVR) programmes have significant advantages, non-conventional activities such as Nordic walking (NW) may offer additional health benefits. Our aim was to appraise research evidence on the effects of Nordic walking for individuals with cardiovascular disease. Design Systematic review and meta-analysis. Methods A literature search of clinical databases (PubMed, MEDLINE, Scopus, Web of Science, Cochrane) was conducted to identify any randomized controlled trials, including: (i) individuals with cardiovascular disease, (ii) analyses of the main outcomes arising from Nordic walking (NW) programmes. Data from the common outcomes were extracted and pooled in the meta-analysis. Standardized mean differences (SMDs) were calculated and pooled by random effects models. Results Fifteen randomized controlled trials were included and eight trials entered this meta-analysis. Studies focused on coronary artery disease, peripheral arterial disease, heart failure and stroke. In coronary artery disease, significant differences between NW+CCVR and CCVR were found in exercise capacity (SMD: 0.49; p = 0.03) and dynamic balance (SMD: 0.55; p = 0.01) favouring NW+CCVR. In peripheral artery disease, larger changes in exercise duration (SMD: 0.93; p < 0.0001) and oxygen uptake (SMD: 0.64; p = 0.002) were observed following NW compared with controls. In heart failure, no significant differences were found between NW and CCVR or usual care for peak VO2 and functional mobility. In post-stroke survivors, functional mobility was significantly higher following treadmill programmes with poles rather than without (SMD: 0.80; p = 0.03). Conclusions These data portray NW as a feasible and promising activity for individuals with cardiovascular disease. Further studies are necessary to verify whether NW may be incorporated within CCVR for individuals with cardiovascular disease.

The Effects of Respiratory Muscle Training in the Body

Individuals constantly strive to find ways to maintain or boost athletic performance. It is not uncommon for trained individuals to improve performance between the competitive and off-season due to changes in exercise duration and intensity (endurance, strength, power, flexibility, and coordination). An area that is typically neglected is training the lungs and diaphragm. Following a respiratory muscle exercise intervention, it was unknown if participants would maintain or exceed their prior lung capacity. PURPOSE: The purpose of this study was to establish the impact that respiratory endurance and strength training has on participants’ inspiratory vital capacity (IVC), vital capacity (VC), tidal volume (TV), and if as a result a measureable difference was observed in their hemoglobin levels (Hb). METHODS: Participants (N=20, n=10 males, n=10 females) reported to the lab for pre-test measurements, which included screening for respiratory health issues, and were then randomly assigned into a control (CON) or intervention (INV) group. The INV group (age 21.8 ± 2.4 years) was assigned lung strength and endurance exercises five days a week and the CON (age 21.1 ± 1.7 years) group was asked to maintain their normal lifestyle. Both groups were asked to return four weeks later. Testing in the laboratory included: finger prick (Hb), spirometry testing (TV, IVC, VC), and a brief questionnaire. An independent T-test (SPSS v. 21) was used to identify significant differences (p < 0.05) between pre- and post-testing sessions for all participants. All measures are reported as delta change (Δ) ± standard deviation (SD). RESULTS: No significant differences were found following the four week INV. The following changes were observed: (CON [INCREMENT] ± SD : INV [INCREMENT] ± SD): Hb (0.4 ± 1.9 : 0.7 ± 1.1 mg/dL), TV (0.02 ± 0.07 : 0.04 ± .14 L), VC (-0.1 ± .3 : -0.7 ± 1.1 L), and IVC (-0.1 ± 0.3 : 0.3 ± 0.9 L). CONCLUSIONS: Given that the INV group’s Hb, TV, and IVC improved more than the control group (although not significantly), perhaps a longer INV duration may yield greater differences. Further studies involving respiratory muscle strength and endurance training are needed to aid in the understanding of why these specific results occurred.

Abstract W P381: Type and Duration of Exercise in the SAMMPRIS Trial

Background: Previous analyses of SAMMPRIS trial data showed that good risk factor control resulted in a significant reduction in the risk of vascular events (stroke, MI, and vascular death), with exercise as the most important predictor of good outcome. We sought to determine the type and duration of exercise that SAMMPRIS patients reported during the trial. Methods: In SAMMPRIS, 451 patients with recent TIA or stroke attributed to 70-99% intracranial stenosis were randomized to aggressive medical management (AMM) alone or percutaneous transluminal angioplasty and stenting plus AMM at 50 USA sites. AMM included a telephonic lifestyle modification program, INTERVENT, that was provided free of charge to all subjects during their participation in the study. We analyzed self-reported data collected by INTERVENT on the patients’ type and duration of exercise from baseline (n= 394) to 4 years (n=34). We calculated the mean duration for each exercise type at each time period and then compared the change in exercise duration from baseline using paired t-tests and Wilcoxon signed rank tests. Results: Data from subjects who completed the INTERVENT questionnaires were included in these analyses. As shown in the Figure, walking was the most common form of exercise at all time points, as measured by both the duration of exercise and the number of patients performing the exercise. The mean duration of walking and other aerobic activities increased significantly from baseline to all other time points. Conclusions: The type of self-reported exercise performed by SAMMPRIS patients included mostly walking or other aerobic activity and increased significantly during follow-up. Given that exercise was protective against recurrent vascular events, future secondary prevention stroke trials should encourage and monitor exercise participation and neurologists should encourage physical activity in clinical practice.

Effect of resveratrol on exercise capacity: a randomized placebo-controlled crossover pilot study.

To assess the effect on exercise capacity and tolerability of resveratrol, 13 healthy, sedentary adult volunteers were enrolled in a randomized crossover study comparing resveratrol and placebo over two 4-week periods, with a 2-week time between periods when subjects received no treatment. No significant changes in exercise duration or aerobic capacity (peak oxygen uptake) were observed. Gastrointestinal side effects were more common during resveratrol treatment (77% vs. 15%, p = 0.0048). A small reduction in fasting glucose and small but statistically significant increases in liver enzymes, total cholesterol, and triglycerides were observed, although mean results remained within normal limits. There was no change in complete blood count, inflammatory markers, renal function, or other measures of liver function.

Cardiac Resynchronization Therapy in Patients With Heart Failure and a QRS Complex &lt;120 Milliseconds

Background— Although the benefits of cardiac resynchronization therapy are well established in selected patients with heart failure and a prolonged QRS duration, salutary effects in patients with narrow QRS complexes remain to be demonstrated. Methods and Results— The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial is a randomized, double-blind, 12-center study that was designed to compare the effects of active and inactive cardiac resynchronization therapy in patients with severe left ventricular dysfunction and a QRS duration &lt;120 milliseconds. The trial was interrupted prematurely by the Data Safety and Monitoring Board because of futility and safety concerns after 85 patients were randomized. Changes in exercise duration after 12 months were no different in patients with and without active cardiac resynchronization therapy (−0.7 minutes [95% confidence interval (CI), −2.9 to 1.5] versus 0.8 minutes [95% CI, −1.2 to 2.9]; P =0.31]. Similarly, no significant differences were observed in left ventricular end-systolic volumes (−6.4 mL [95% CI, −18.8 to 5.9] versus 3.1 mL [95% CI, −9.2 to 15.5]; P =0.28) and ejection fraction (3.3% [95% CI, 0.7–6.0] versus 2.1% [95% CI, −0.5 to 4.8]; P =0.52). Moreover, cardiac resynchronization therapy was associated with a significant reduction in the 6-minute walk distance (−11.3 m [95% CI, −31.7 to 9.7] versus 25.3 m [95% CI, 6.1–44.5]; P =0.01), an increase in QRS duration (40.2 milliseconds [95% CI, 34.2–46.2] versus 3.4 milliseconds [95% CI, 0.6–6.2]; P &lt;0.0001), and a nonsignificant trend toward an increase in heart failure–related hospitalizations (15 hospitalizations in 5 patients versus 4 hospitalizations in 4 patients). Conclusions— In patients with a left ventricular ejection fraction ≤35%, symptoms of heart failure, and a QRS duration &lt;120 milliseconds, cardiac resynchronization therapy did not improve clinical outcomes or left ventricular remodeling and was associated with potential harm. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00900549.

Effect of Bisoprolol on Respiratory Function and Exercise Capacity in Chronic Obstructive Pulmonary Disease

Cardioselective β blockers are considered to have little impact on lung function at rest in patients with chronic obstructive pulmonary disease (COPD). However, their effects on dynamic hyperinflation, an important mechanism contributing to symptoms and exercise tolerance in patients with COPD, have not been evaluated. Twenty-seven patients with moderate to severe COPD (forced expiratory volume in 1 second 52 ± 13% predicted) completed pulmonary function tests, echocardiography, maximal exercise tests, and cycle endurance tests at baseline. Inspiratory capacity was measured at 2-minute intervals during the cycle endurance test to quantify dynamic hyperinflation. Pulmonary function and cycle endurance testing were repeated after 14 days of bisoprolol 10 mg/day and 14 days of placebo in a randomized, double-blind, placebo-controlled, crossover trial. The extent of dynamic hyperinflation at peak isotime exercise with bisoprolol and placebo was compared. Peak isotime was defined as the latest time point that was reached during the 2 cycle endurance tests. Changes in inspiratory capacity from rest to peak isotime were different with bisoprolol compared to placebo (-0.50 ± 0.35 vs -0.41 ± 0.33 L, p = 0.01). Exercise duration tended to be lower with bisoprolol compared to placebo (305 ± 125 vs 353 ± 172 seconds, p = 0.11). The magnitude of change in exercise duration between the bisoprolol and placebo conditions was correlated with the magnitude of change in inspiratory capacity (r = 0.57, p <0.01). In conclusion, bisoprolol was associated with modest worsening dynamic hyperinflation, whereas exercise duration remained unchanged in patients with moderate to severe COPD. The magnitude of these effects was small and should not contraindicate the use of bisoprolol in patients with COPD.

Effect of theophylline on exercise capacity in COPD patients treated with combination long-acting bronchodilator therapy: a pilot study

BackgroundMany patients with chronic obstructive pulmonary disease continue to experience significant functional limitation despite the use of both long-acting anticholinergic and beta-agonist inhalers. Theophylline is a widely available medication which may further improve lung function and exercise performance. Previous studies evaluating the effects of theophylline on exercise capacity in chronic obstructive pulmonary disease (COPD) have demonstrated heterogeneous results.MethodsWe performed a randomized placebo-controlled double-blind pilot study assessing the effects of theophylline on constant load exercise duration and lung function, involving 24 COPD patients already treated with long-acting inhaled beta-agonist and long-acting anti-cholinergic bronchodilator therapy.ResultsAnalyzable data was available in 10 of 12 subjects in the treatment arm and 11 of 12 subjects in the control arm. Theophylline was associated with a 26.1% (95% confidence interval [CI]: −17.3–69.5) improvement in exercise duration compared to placebo. Four of 10 treated patients demonstrated an improvement in exercise duration exceeding the minimum clinically important difference of 33%, compared to 1 of 11 controls (P = 0.15). Furthermore, peak ventilation was reduced by 11.1%, (95% CI: 0.77–21.5) which may suggest improvements in gas exchange. There were no significant observed differences in resting lung function nor measures of dyspnea between the two treatment groups.ConclusionsOur study demonstrated a trend, but not a statistically significant improvement in exercise duration and a reduction in peak ventilation with theophylline. Based on the observed mean differences and standard deviations in this pilot study, a randomized controlled trial would require 45 subjects in each arm to detect a significant change in exercise duration.

Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons

At some level, carboxyhemoglobin (COHb) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in both normal and ischemic heart patients. At high COHb levels in normal subjects, brain function is also affected and behavioral performance is impaired.These are findings from published experiments that are, due to ethical or practical considerations, incomplete in that higher or lower ranges of COHb, and exercise have not been well studied. To fill in this knowledge base, a whole-body human physiological model was used to make estimates of physiological functioning by the simulation of parametric exposures to CO and various exercise levels. Ischemic heart disease was simulated by introducing a stenosis in the left heart arterial supply. Brain blood flow was also limited by such a stenosis. To lend credibility to such estimation, the model was tested by simulating experiments from the published literature. Simulations permitted several new conclusions. Increases in COHb produced the largest decreases in exercise duration when exercise was least strenuous and when COHb was smallest. For ischemic heart disease subjects, the greatest change in exercise duration produced by COHb increase was when ischemia and COHb was smallest. Brain aerobic metabolism was unaffected until COHb exceeded 25%, unless the maximum brain blood supply was limited by a stenosis greater than 50% of normal. For higher levels of stenosis, aerobic brain metabolism was reduced for any increase in COHb level, implying that behavior would be impaired with no “threshold” for COHb.

Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis

To determine the clinical effectiveness and cost-effectiveness of enhanced external counterpulsation (EECP) compared with usual care and placebo for refractory stable angina and heart failure, and to undertake analyses of the expected value of information to assess the potential value of future research on EECP. Major electronic databases were searched between November 2007 and March 2008. A systematic review of the literature was undertaken and a decision model developed to compare EECP treatment with no treatment in adults with chronic stable angina. Five studies were included in the review. In the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP), time to greater than or equal to 1-mm ST segment depression (exercise-induced ischaemia) was statistically significantly improved in the EECP group compared with the control group (sham EECP), mean difference (MD) 41 seconds [95% confidence interval (CI) 9.10-73.90]. However, there was no statistically significant difference between the EECP and control groups in the change in exercise duration from baseline to end of treatment, self-reported angina episodes or daily nitroglycerin use, and the clinical significance of the limited benefits was unclear. There was also a lack of data on long-term outcomes. There were more withdrawals due to adverse events in the EECP group than in the control group, as well as a greater proportion of patients with adverse events [relative risk (RR) 2.13, 95% CI 1.35-3.38]. The three non-randomised studies compared EECP with elective percutaneous coronary intervention (PCI) and usual care. There was a high risk of selection bias in all three studies and the results should be treated with considerable caution. The study comparing an EECP registry with a PCI registry reported similar 1-year all-cause mortality in both groups. In the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial, patients with heart failure were randomised to EECP or to usual care (pharmacotherapy only). At 6 months post treatment, the proportion of patients achieving at least a 60-second increase in exercise duration was higher in the EECP group (RR 1.39, 95% CI 0.89-2.16), but the proportion with an improvement in peak VO2 was similar in both groups. The clinical significance of this is unclear. The proportion of patients in the EECP group with an improvement in New York Heart Association classification was higher (RR 2.25, 95% CI 1.25-4.06) at 6 months, as was mean exercise duration, MD 34.6 (95% CI -4.86 to 74.06). There were more withdrawals in the EECP group than in the control group as a result of adverse events (RR 1.05, 95% CI 0.67-1.66). There were limitations in the generalisability of results of the trial and, again, a lack of data on long-term outcomes. The review of cost-effectiveness evidence found only one unpublished study but demonstrated that the long-term maintenance of quality of life benefits of EECP is central to the estimate of its cost-effectiveness. The incremental cost-effectiveness ratio of EECP was 18,643 pounds for each additional quality-adjusted life-year (QALY), with a probability of being cost-effective of 0.44 and 0.70 at cost-effectiveness thresholds of 20,000 pounds and 30,000 pounds per QALY gained respectively. Results were sensitive to the duration of health-related quality of life (HRQoL) benefits from treatment. The results from a single randomised controlled trial (MUST-EECP) do not provide firm evidence of the clinical effectiveness of EECP in refractory stable angina or in heart failure. High-quality studies are required to investigate the benefits of EECP, whether these outweigh the common adverse effects and its long-term cost-effectiveness in terms of quality of life benefits.

Clinical relevance of constant power exercise duration changes in COPD

The endurance time during constant high work-rate exercise (t(LIM)) is used to assess exercise capacity in patients with chronic obstructive pulmonary disease and as an outcome measure for pulmonary rehabilitation. Our study was designed to establish the minimum clinically important difference for the t(LIM). t(LIM) was measured in 105 patients (86 males) before and after an 8-week outpatient pulmonary rehabilitation programme. Subjects were asked to identify, from a five-point Likert scale, the perceived change in their exercise performance immediately upon completion of the exercise tests. The scale ranged from "better" to "worse". The mean+/-sd age was 64+/-5 yrs, forced expiratory volume in 1 s (FEV(1)) 47+/-10% and FEV(1)/forced vital capacity 54.7+/-16.3%. Baseline t(LIM) at 75% of the peak work rate was 397+/-184 s, which increased by 62+/-63% after rehabilitation. In subjects who felt their exercise tolerance was "slightly better", the mean improvement was 34% in the relative improvement over the baseline value (95% CI 29-39)% or 101 (86-116) s compared with 121 (109-134)% in those who reported that their exercise tolerance was "better" and 8 (2-14)% in those who felt their exercise tolerance was "about the same". Minimum clinically important improvement for t(LIM) averaged approximately 33% of baseline. Patients were able to distinguish at least one further additional level of benefit at 120% of baseline.

Outcome of Surgical Myectomy After Unsuccessful Alcohol Septal Ablation for the Treatment of Patients With Hypertrophic Obstructive Cardiomyopathy

We sought to determine the outcome of myectomy after unsuccessful alcohol ablation. Alcohol septal ablation results in symptomatic improvement and a reduction in dynamic obstruction in most hypertrophic obstructive cardiomyopathy patients. However, a few patients remain with severe symptoms and obstruction and need surgery. The outcome of these cases is not well known. The medical records of 375 patients who underwent alcohol ablation at our institution were reviewed. Twenty patients (5.3%, mean age 53 +/- 18 years, 17 women) subsequently needed surgical myectomy. The New York Heart Association (NYHA) functional class, angina class, exercise duration, left ventricular outflow tract (LVOT) gradient, ejection fraction, and septal thickness were tabulated. The anatomy and distribution of the septal perforator arteries were examined. After ablation, NYHA functional class (3 to 2.5; p < 0.05) and LVOT gradient (93 +/- 23 mm Hg to 71 +/- 26 mm Hg; p < 0.05) were slightly improved, without a change in exercise duration (171 +/- 124 s to 168 +/- 148 s; p > 0.5). Myectomy was performed at 19 +/- 15 months after ablation. There was no operative mortality, but permanent pacing was needed in 2 patients after surgery, and 3 other cases needed pacing before, or as a complication of, alcohol ablation. A significant improvement was noted, with the NYHA functional class decreasing to 1, exercise duration increasing to 423 +/- 171 s, and LVOT gradient decreasing to 6 +/- 11 mm Hg (all p < 0.05 versus post-alcohol ablation). Myectomy can be successfully performed after failed alcohol ablation, but with a higher incidence of heart block than in cases where only surgery is performed. Otherwise, alcohol ablation does not appear to adversely affect surgical outcome.

A Blinded, Randomized, Placebo-Controlled Trial of Percutaneous Laser Myocardial Revascularization to Improve Angina Symptoms in Patients With Severe Coronary Disease

This study was a randomized, patient- and evaluator-blinded, placebo-controlled trial in patients treated using percutaneous myocardial laser revascularization. Previous studies using similar therapies have been confounded by placebo bias. A total of 298 patients with severe angina were randomly assigned to receive low-dose or high-dose myocardial laser channels or no laser channels, blinded as a sham procedure. The primary end point was the change in exercise duration from baseline examination to six months. The incidence of 30-day death, stroke, myocardial infarction, coronary revascularization, or left ventricular perforation occurred in two patients in the placebo, eight patients in the low-dose, and four patients in the high-dose groups (p = 0.12); 30-day myocardial infarction incidence was higher in patients receiving either low-dose or high-dose laser (nine patients) compared with placebo (no patients, p = 0.03). At six months, there were no differences in the change in exercise duration between those receiving a sham (28.0 s, n = 100), low-dose laser (33.2 s, n = 98), or high-dose laser (28.0 s, n = 98, p = 0.94) procedure. There were also no differences in the proportion of patients improving to better than Canadian Cardiovascular Society class III angina symptoms at six months. The follow-up visual summed stress single-photon-emission computed tomography scores were not significantly different from baseline in any group and were no different between groups. The modest improvement in angina symptoms assessed by the Seattle Angina Questionnaire also was not statistically different among the arms. Treatment with percutaneous myocardial laser revascularization provides no benefit beyond that of a similar sham procedure in patients blinded to their treatment status.

Randomized comparison of T-type versus L-type calcium-channel blockade on exercise duration in stable angina: Results of the Posicor Reduction of Ischemia During Exercise (PRIDE) trial

Background Mibefradil is a T-type calcium-channel antagonist and arterial vasodilator with negative chronotropic effects. It is not known if T-type calcium-channel blockade is superior to L-type calcium-channel blockade in patients with stable angina pectoris. Methods A multicenter, randomized, double-blind trial was conducted in patients with documented coronary disease and stable angina to compare a 360 mg dose of diltiazem CD with 100 mg dose of mibefradil. The primary end point was change in time to symptom-limited exercise termination from baseline to 8 weeks. Secondary efficacy parameters included time to onset of persistent ST-segment depression, time to awareness of angina, and change in exercise duration from baseline to 2 and 4 weeks of treatment. Results A total of 121 patients were randomized to mibefradil and 113 to diltiazem CD. At 8 weeks, the increase in exercise duration was 24.5 seconds greater in the mibefradil group (P =.017; 95% CI 4.4-44.7 seconds). At 8 weeks, time to development of ≥1 mm ST-segment depression was greater by 45.3 seconds (P =.0025; 95% CI 16.2-74.5) with mibefradil, but time to development of angina was not significantly different. Conclusion T-type calcium-channel antagonism with mibefradil improved treadmill exercise parameters compared with diltiazem in patients with chronic stable angina. Further investigation and development of antagonists of T-type calcium channels with fewer adverse drug interactions is warranted and may be promising in the management of ischemic heart disease. (Am Heart J 2002;144:60-7.)

Effects of the repeated administration of adenosine and heparin on myocardial perfusion in patients with chronic stable angina pectoris

The mechanism by which ischemia stimulates angiogenesis is unknown. Adenosine is released during myocardial ischemia and may be a mediator of this process. Experimental data suggest that heparin may enhance this effect. The purpose of this open-labeled, placebo-controlled trial was to determine whether repeated intravenous administration of adenosine and heparin could mimic physiologic angiogenesis and reduce the amount of exercise-induced myocardial ischemia in patients with coronary artery disease. Subjects with chronic stable angina refractory to conventional medical therapy and not suitable for revascularization received either adenosine (140 μg/kg/min for 6 minutes) and heparin (10,000 U bolus), (n = 14), or placebo, (n = 7) daily for 10 days. All patients underwent baseline and follow-up exercise testing with thallium-201 single-photon emission computed tomography myocardial perfusion imaging. A semiquantitative assessment of the extent and severity of the perfusion abnormalities was calculated by 2 blinded investigators. There was no significant change in exercise duration or in the peak heart rate systolic blood pressure product associated with adenosine and heparin compared with placebo treatment. There was, however, a 9% reduction in the extent (60.6 ± 4.0 vs 54.9 ± 4.1, p = 0.03) and a 14% improvement in severity (41.5 ± 3.2 vs 35.7 ± 2.9, p = 0.01) of the myocardial perfusion abnormalities seen in patients who received adenosine and heparin compared with placebo. Thus, in this pilot study, repeated administration of adenosine and heparin reduced the amount of exercise-induced ischemia in patients with chronic stable angina refractory to conventional treatment.

Medium-term effects of beta-blockade on left ventricular mechanics: A double-blind, placebo-controlled comparison of nebivolol and atenolol in patients with ischemic left ventricular dysfunction

The aim of this study was to compare the effects on left ventricular function and exercise tolerance of a selective beta 1-antagonist (atenolol) with those of another selective beta 1-antagonist with vasodilator properties (nebivolol) in patients with ischemic left ventricular dysfunction but no overt congestive heart failure. Beta blockers are widely used in ischemic heart disease, but their effects on left ventricular mechanics and exercise tolerance are poorly defined in the subgroup of patients with significant systolic dysfunction but without clinical evidence of ischemia or congestive heart failure. Angiographic and symptom-limited exercise data were obtained at baseline and after an 8–10-week double-blind treatment with placebo (n = 10), 50 mg atenolol daily (n = 10), or 2.5 mg (n = 10) or 5 mg (n = 10) nebivolol daily. When compared to placebo, both atenolol and nebivolol reduced resting heart rate and improved left ventricular ejection fraction (from 33.9 to 39.2% with atenolol and from 36.5 to 40.8% with nebivolol, both P < .05) while lowering mean systolic wall stress. Only nebivolol, however, produced a parallel downward shift of the pressure-volume relationship during early diastolic filling and improved the early peak filling rate when compared to placebo (+ 10%, P < .05). When compared to baseline, maximal exercise duration increased by 7 and 13 seconds with placebo and atenolol, respectively (both NS vs baseline), and increased by 44 seconds with nebivolol ( P = .0077 vs baseline). Both atenolol and nebivolol decreased maximal exercise heart rate; the reduction was more pronounced with atenolol. Prolonged beta 1-adrenoceptor blockade leads to a significant increase in left ventricular ejection fraction in patients with ischemic left ventricular dysfunction. The dissociation between the changes in resting left ventricular function and the changes in exercise duration suggests that in this clinical setting, the changes in systolic function may have less impact on functional capacity than an improvement in diastolic distensibility during the rapid filling phase.