Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations.

OBJECTIVES: The study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II-III chronic heart failure (CHF). BACKGROUND: Previous studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF. METHODS: The present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured. RESULTS: The patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0+/-2.5 vs. 19.8+/-5.0 ml x kg(-1) x min(-1), p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42+/-0.28 vs. 1.74+/-0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5+/-13.6 vs. 19.5+/-9.4, p <0.05). CONCLUSIONS: There was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF.

Leisure-time physical activity among US adults. Results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of no leisure-time physical activity (LTPA) among US adults is estimated to be between 24% and 30%. Such information, however, usually does not include prevalence estimates for non-Hispanic blacks, Mexican Americans, and the elderly. OBJECTIVE: To assess the prevalence of participation in leisure-time physical activity among US adults. METHODS: Between 1988 and 1991, 9488 adults aged 20 years and older were interviewed in their home as part of the third National Health and Nutrition Examination Survey. A clinic examination in a mobile center was also included. Mexican Americans, non-Hispanic blacks, and the elderly were oversampled to produce reliable estimates for these groups. Questions were asked about the type and frequency of physically active hobbies, sports, and exercises. RESULTS: The prevalence of no LTPA for US adults aged 20 years or older from 1988 through 1991 was 22%. The rate was higher in women (27%) than in men (17%). Mexican-American men (33%) and women (46%) and non-Hispanic black women (40%) had the highest rates of no LTPA. Participation in moderate to vigorous LTPA five or more times per week decreased with age, with the largest decreases observed among non-Hispanic black men and women. In almost all subpopulations, gardening and/or yard work and walking were stated as the two top LTPAs of choice. CONCLUSIONS: Many Americans are inactive or irregularly active during their leisure time. Rates of inactivity are greater for women, older persons, non-Hispanic blacks, and Mexican Americans. Intervention strategies meant to promote lifetime physical activities among all Americans represents a major health priority.

Response of symptomatic myocardial ischemia in ischemic cardiomyopathy to intensive vasodilator therapy.

To determine the cardiovascular protective effects of angiotensin-converting enzyme inhibitors, we examined the response to intensive vasodilator therapy in patients with ischemic cardiomyopathy and ongoing angina pectoris. We found that for patients with ischemic cardiomyopathy and ongoing active angina, intensive vasodilator therapy with angiotensin-converting enzyme inhibition and nitrates improved not only heart failure-related symptoms, but also resulted in a significant improvement in symptomatic ischemia and ischemia-related morbid events.

Electrocardiographic monitoring during cardiac rehabilitation.

STUDY OBJECTIVE: This investigation compares the frequency of cardiac events during ECG-monitored cardiac rehabilitation in patients who meet the American College of Cardiology (ACC) criteria for monitoring, to the frequency of events in patients in the same program who do not meet the ACC criteria. DESIGN AND PATIENTS: Patient charts (n = 289) from a 10-month period were retrospectively reviewed for (1) major and minor cardiovascular events, (2) whether a physician was contacted, and (3) what change, if any, was made in their care plan as a result. RESULTS: There were no sudden deaths, fatal or nonfatal myocardial infarctions, or sustained arrhythmias requiring hospitalizations. The overall rate for minor events (angina, nonsustained arrhythmia, ST segment depression) was 26.6%, with no difference noted between men and women. The rate for a new-onset, asymptomatic event was 3.8%. The rate of minor events was greater in patients who met the ACC criteria vs those who did not (p < 0.01), with no detectable difference noted between the two groups regarding the rate of new-onset, asymptomatic events. Four patients (1.4%) experienced a change in their care plan as a result of ECG monitoring. CONCLUSIONS: The occurrence of a minor cardiovascular event is common during phase 2 cardiac rehabilitation, and existing criteria satisfactorily distinguish those patients at high risk for experiencing such an event. However, the rate for new-onset, asymptomatic events is rare for both patients classified at high risk and those classified not to be at high risk. Also, only four patients experienced a change in therapy secondary to an event identified by ECG monitoring.

Differences in skeletal muscle between men and women with chronic heart failure.

Men with chronic heart failure (CHF) have alterations in their skeletal muscle that are partially responsible for a decreased exercise tolerance. The purpose of this study was to investigate whether skeletal muscle alterations in women with CHF are similar to those observed in men and if these alterations are related to exercise intolerance. Twenty-five men and thirteen women with CHF performed a maximal exercise test for evaluation of peak oxygen consumption (VO(2)) and resting left ventricular ejection fraction, after which a biopsy of the vastus lateralis was performed. Twenty-one normal subjects (11 women, 10 men) were also studied. The relationship between muscle markers and peak VO(2) was consistent for CHF men and women. When controlling for gender, analysis showed that oxidative enzymes and capillary density are the best predictors of peak VO(2.) These results indicate that aerobically matched CHF men and women have no differences in skeletal muscle biochemistry and histology. However, when CHF groups were separated by peak exercise capacity of 4.5 metabolic equivalents (METs), CHF men with peak VO(2) >4.5 METs had increased citrate synthase and 3-hydroxyacyl-CoA dehydrogenase compared with CHF men with peak VO(2) <4.5 METs. CHF men with a lower peak VO(2) had increased capillary density compared with men with higher peak VO(2). These observations were not reproduced in CHF women. This suggests that differences may exist in how skeletal muscle adapts to decreasing peak VO(2) in patients with CHF.

Cardiovascular responses to submaximal arm and leg exercise in cardiac transplant patients.

We examined whether an increase in stroke volume (SV) contributes to the increase in cardiac output that occurs when cardiac transplant patients (CT) exercise between 50% and 75% of maximum. Upright arm and leg exercise was performed by 13 CT and 10 normal controls. Cardiac output (CO2 rebreathing), expired air, and catecholamine measures were obtained at rest and at 50% and 75% of maximum. From rest to 50% of maximum both normals and CT increased heart rate (HR) and SV during arm and leg exercise. In normals, HR (arm = +17 +/- 2 min-1; leg = +21 +/- 3 min-1) was increased further at 75% of maximum but not SV (arm = 3 +/- 4 ml; leg = +2 +/- 8 ml). In CT, further increases in both HR (arm = +9 +/- 1 min-1; leg = +13 +/- 1 min-1) and SV (arm = +12 +/- 5 ml; leg = +12 +/- 3 ml) were observed at 75% of maximum. During leg exercise plasma norepinephrine was increased more in CT than in normals. Between 50% and 75% of maximum, an increase in SV is a more important mechanism for increasing cardiac output during upright arm and leg exercise in CT than in normals.

Prevalence of physical inactivity and its relation to social class in U.S. adults: results from the Third National Health and Nutrition Examination Survey, 1988-1994.

PURPOSE: This study examines the prevalence of physical inactivity during leisure time in a national representative sample of U.S. adults. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey, conducted between 1988 and 1994. A total of 18,825 adults aged 20 yr and older participated in a home interview where information about physical activity, education, income, occupation, employment, and labor force participation was obtained. RESULTS: The prevalence of physical inactivity among U.S. adults was 23%, with more women (28%) than men (17%) reporting being inactive during their leisure time. Additionally, inactivity is more common among in social class such as persons who are less educated, living below the poverty line, living in households with income below 20,000 dollars, and who are retired. In every category of social class, women experienced a higher prevalence of physical inactivity than men. CONCLUSIONS: We conclude that social class is associated with physical inactivity and that more research is needed to better understand the effect that other social and environmental factors have on sedentary behaviors in our society.

Exercise training in a patient with congestive heart failure on continuous dobutamine.

We present a 53-yr-old man with congestive heart failure who underwent 32 wk of exercise training. The patient was on a continuous infusion of dobutamine for 10 months prior to exercise training, which was subsequently discontinued at wk 24 of exercise training. Symptom-limited graded exercise tests were performed at baseline, wk 12, wk 24, and wk 32 of exercise training. While on a continuous infusion of dobutamine, the patient's oxygen consumption and exercise duration were increased during the exercise training period. Additionally, the patient was able to maintain these changes for 8 wk while continuing to exercise after the discontinuation of the dobutamine therapy.

Cardiorespiratory responses during exercise in competitive in-line skaters.

This study describes the cardiorespiratory responses of 12 male (age = 30 +/- 6 yr) competitive in-line skaters during peak and submaximal skating. We hypothesized that velocities of 22.5 and 27.4 km.h-1 would elicit heart rate (HR) and oxygen consumption (VO2) responses consistent with the American College of Sports Medicine's guidelines for developing cardiorespiratory fitness. Using a 644-m indoor cement course, subjects completed 10 trials comprised of various velocities, stroke frequencies, and body positions. At 22.5 km.h-1, HR and VO2 were 74 and 51% of peak, respectively. At 27.4 km.hr-1, HR and VO2 were 85 and 72% of peak, respectively. When compared to the College's guidelines, regression analysis revealed a leftward shift in the VO2-HR relationship, evidenced by a disproportionately higher HR at a VO2 approximating 60 vs 80% of peak. At 22.5 km.h-1 our skaters self-selected a stroke frequency which resulted in less of an increase in both HR and VO2, when compared to the imposed stroke frequencies of 50 min-1 and 70 min-1. Also, skating at 27.4 km.h-1 in the bent vs upright position resulted in less of an increase in HR and VO2. Competitive in-line skaters are capable of safely skating at velocities sufficient to stimulate an increase in cardiorespiratory fitness. These athletes select a stroke frequency and utilize a body position which results in favorable HR and VO2 responses.

Assessment of body composition in heart transplant patients.

Orthotopic heart transplantation (OHT) recipients often experience increased body weight (BW) following surgery. Using hydrostatic weighing (HW), this study assessed the body density (BD) and body composition of 17 white and seven black male OHT patients. It examined the cross-validity of the Jackson and Pollock seven and three site skinfold (SF) regression equations for predicting BD in these patients. We hypothesized that both prednisone (P) dose and months post-operative (MPO) would be inversely related to BD. The average of the last five of ten HW trials was used in computing BD. BW and % body fat (BF) were 88.5 +/- 17.8 kg (mean +/- SD) and 33.5 +/- 9.4%, respectively. The correlation coefficient between hydrostatically determined BD and BD determined via two of the three intercept revised Jackson and Pollock SF equations was r = 0.89, SE = 0.009. A polynomial regression model for BD using P dose and MPO provided a correlation coefficient of r = 0.71, SE = 0.015. Partial correlation techniques incorporating SF, age, MPO, and P dose indicated that neither P dose or MPO provided any significant additive effect, above SF and age, when predicting BD. We conclude that in OHT patients receiving glucocorticoids, the intercept revised Jackson and Pollock SF regression equations are generally applicable and associated with a SE of +/- 4 BF percentage points. Up to 49 months after OHT, both P dose and MPO are inversely related to BD but provide no additive value above SF for predicting BD.

Changes in functional health status of older women with heart disease: evaluation of a program based on self-regulation.

OBJECTIVES: This study involving 570 women aged 60 years or older with heart disease, assessed the effects of a disease management program on physical functioning, symptom experience, and psychosocial status. METHODS: Women were randomly assigned to control or program groups. Six to eight women met weekly with a health educator and peer leader over 4 weeks to learn self-regulation skills with physical activity as the focus. Evaluative data were collected through telephone interviews, physical assessments, and medical records at baseline and 4 and 12 months post baseline. RESULTS: At 12 months, compared with controls, program women were less symptomatic (p < .01), scored better on the physical dimension of the Sickness Impact Profile (SIP; p < 0.05), had improved ambulation as measured by the 6-minute walk (p < 0.01), and lost more body weight (p < .001). No differences related to psychosocial factors as measured by the SIP were noted. CONCLUSION: A self-regulation-based program that was provided to older women with heart disease and that focused on physical activity and disease management problems salient to them, improved their physical functioning and symptom experience. Psychosocial benefit was not evident and may be a result of measurement error or due to insufficient program time spent on psychosocial aspects of functioning.

The impact of beta-receptor blocker addition to high-dose angiotensin-converting enzyme inhibitor-nitrate therapy in heart failure.

BACKGROUND: The natural history of heart failure is one of continued worsening of cardiac function. Beta-receptor blocker therapy has been effective in improving clinical status and left ventricular function in patients with heart failure. Similarly, high doses of angiotensin-converting enzyme (ACE) inhibitors with nitrates partially reverse the ventricular remodeling of heart failure. HYPOTHESIS: We tested the hypothesis that beta-blocker therapy added to high-dose ACE inhibitor-nitrates would potentiate the reversal of heart failure. METHODS: Thirteen patients, aged 52 +/- 8 years, with moderate to severe heart failure, 12 of whom were referred for transplant consideration, with heart failure duration of 4.8 +/- 2.2 years, were prospectively followed for 12 months. Baseline echocardiographic ejection fraction was 19 +/- 8%, and presenting New York Heart Association class was 2.9 +/- 0.7. Angiotensin-converting enzyme inhibitors and nitrates were uptitrated over 6 months to a final dose of lisinopril 53 +/- 31 mg/day, and isosorbide dinitrate 217 +/- 213 mg/day. At 6 months, beta-blocker therapy with atenolol was initiated and titrated to a final dose of 46 +/- 23 mg/day. Two-dimensional Doppler echocardiography and metabolic stress testing were performed at baseline, at 6 months on lisinopril-nitrates only, and at 12 months on combined ACE inhibitor-nitrate and beta-blocker therapy. RESULTS: New York Heart Association classification improved from 2.9 +/- 0.7 to 1.8 +/- 0.8 on lisinopril-nitrates (p < 0.05), and to 1.5 +/- 0.5 with the addition of beta blockade (p = NS). On follow-up, peak oxygen consumption rose from 17 +/- 7 ml O2/kg/min at baseline to 21 +/- 5 ml O2/kg/min at 6 months on lisinopril-nitrates (p = 0.06) without further change on beta blockade. Ejection fraction rose from 19 +/- 8 to 33 +/- 14% on lisinopril-nitrates at 6 months (p = 0.005) and to 36 +/- 18% on beta blockade at 12 months (p = NS). CONCLUSION: High-dose ACE inhibitor-nitrate therapy significantly improved patient clinical status and left ventricular systolic function in heart failure. The addition of beta-receptor blockade over and above high-dose ACE inhibitor-nitrates was well tolerated but had no further impact on symptomatic status, exercise tolerance, or left ventricular systolic function. The potential for pharmacologic reversal of heart failure remodeling may be finite despite the use of complementary therapies. Larger placebo-controlled and randomized trials of beta-receptor blockade added to high-dose ACE inhibitor-nitrate therapy are needed to confirm these observations.

Reverse remodeling in heart failure with intensification of vasodilator therapy.

BACKGROUND: Heart failure therapy with beta-receptor blockade has been shown to effect a partial reversal of left ventricular (LV) remodeling in heart failure. HYPOTHESIS: We tested the hypothesis that, in the absence of beta blockade, uptitration of angiotensin-converting enzyme (ACE) inhibitor and nitrate therapy over conventional dosages would improve symptoms as well as LV function in patients with severe heart failure. METHODS: For patients with nonischemic or ischemic cardiomyopathy, intensive high-dose angiotensin-converting enzyme inhibitor and nitrate therapy was uptitrated. Echocardiograms were obtained semiannually and evaluated in a blinded fashion. Of 99 patients in the study, aged 55 +/- 13 years, with heart failure for 5.2 +/- 3.1 years, 74 were men, 69 were Caucasian, and 34 had ischemic cardiomyopathy. The final dosage of enalapril was 40 +/- 23 mg/day of isosorbide dinitrate it was 153 +/- 127 mg/day. RESULTS: Initial New York Heart Association classification improved from 2.8 +/- 0.9 to 1.7 +/- 0.9 (p < 0.001) in 2.7 years of follow-up. Of the 99 patients, 72 further improved their ejection fraction. For the whole group, ejection fraction increased from 21 +/- 9% to 30 +/- 13% in 6 months (p < 0.001), with a reduction in LV end-diastolic size from 6.6 +/- 0.9 to 6.3 +/- 1.0 cm (p = 0.002), a decrease in the severity of mitral regurgitation from mild/moderate to only mild. Resting heart rate declined with no change over time in systemic systolic blood pressure. Final ejection fraction for nonischemic patients (n = 65) was 36 +/- 16% versus 23 +/- 9% for the ischemic population. CONCLUSIONS: Uptitration of high-dose ACE inhibitor and nitrate therapy to higher doses is well tolerated in severe heart failure, further improves both clinical status and LV systolic function, and is more effective in nonischemic than in ischemic cardiomyopathy.

Cardiovascular symptoms in coronary-artery disease patients are strongly correlated with emotional distress.

BACKGROUND: The relationship of cardiovascular events and cardiovascular symptoms is unclear, and physical symptoms, including most cardiovascular symptoms, are known to be influenced by emotional distress. OBJECTIVE: Authors examined the relative strength of association of multiple measures of emotional distress and accepted cardiac risk factors with five common cardiac symptoms (chest pain, fatigue, palpitations, presyncope, and dyspnea). METHOD: The authors tested the association of multiple cardiovascular symptoms with various measures of emotional distress (i.e., the scales of the Symptom Checklist-90-Revised) and the putative risk factors for disease status in 109 patients with documented coronary artery disease. RESULTS: Measures of emotional distress were stronger correlates of patient-rated distress due to the symptoms than were traditional risk factors. CONCLUSION: Treatment of emotional distress may be a viable strategy for symptom-control in cardiovascular disease.

Exercise testing and training of patients with heart failure due to left ventricular systolic dysfunction.

Reducing the exercise intolerance and symptoms experienced by patients with chronic heart failure remains an important focus in their clinical care. A clear shortcoming exists; however, with respect to an appreciation that in addition to standard medical therapy, selected patients with stable heart failure also can benefit from a moderate exercise training program. Improvements in central transport, regional blood flow, and skeletal muscle histology and biochemistry all likely account for the increase in exercise capacity and delay in fatigue that these patients experience. Additionally, the autonomic imbalance that is characteristic of these patients is improved. Although the number of patients with heart failure participating in an exercise program is increasing, much work still exists relative to incorporating this treatment method into the care plans established by physicians and physician extenders.

Exercise training in heart failure.

Patients with heart failure challenge the clinician with a constellation of difficult clinical, pathophysiologic, and psychologic issues. As a result, until recently, exercise training was not considered a safe and effective treatment strategy to be used in these patients. However, in the past 10 years, data from both randomized and nonrandomized trials showed that regular exercise training in patients with stable Class II and III heart failure can safely improve exercise tolerance, attenuate an overactivated sympathetic nervous system, partially reverse skeletal muscle abnormalities, and enhance health-related quality of life. These outcomes are achievable with a relatively moderate dose of physical activity, such as 30 to 60 minutes of walking or cycling 3 to 5 days per week at an intensity equivalent to 60% to 70% of peak oxygen consumption. Sufficiently powered trials are needed to assess morbidity, mortality, and cost-effectiveness endpoints relative to exercise training in patients with heart failure.

Normal skeletal muscle Na(+)-K(+) pump concentration in patients with chronic heart failure.

Intrinsic changes in skeletal muscle are being increasingly suspected as part of the underlying cause of exercise intolerance in patients with chronic heart failure (CHF). The objective of the present study was to determine whether differences existed between CHF patients and age-matched healthy controls in the concentration of skeletal muscle Na(+)-K(+)-ATPase (adenosine triphosphatase), a cation pump that functions to restore Na(+)-K(+) gradients and protect membrane excitability. Moreover, given the potency for physical activity in altering long-term regulation of the pump, an additional objective was to examine the role of activity level in pump expression in CHF patients. Na(+)-K(+)-ATPase concentration (pmol/g wet wt) determined in the vastus lateralis muscle of 27 CHF males (ejection fraction, 23 +/- 1.6%), using the vanadate facilitated [(3)H] ouabain binding technique, was not different (264 +/- 10) from 10 sedentary controls (268 +/- 19,P > 0.05). Similarly, no differences (P > 0.05) could be found between female patients (228 +/- 16, n = 7) and controls (243 +/- 13, n = 9). Differences between untrained control (294 +/- 20, n = 7), chronically active (251 +/- 20, n = 9), and trained (252 +/- 16, n = 6) CHF groups in Na(+)-K(+) pump expression were also insignificant. This study indicates that long-term regulation of Na(+)-K(+)-ATPase concentration is not altered in moderate CHF patients, regardless of the history of regular activity. However, the positive correlations (P < 0.05) that were observed between peak aerobic power (VO(2) peak) and Na(+)-K(+)-ATPase (r = 0.422) and VO(2) peak and maximal citrate synthase activity (r = 0.404) suggests a role for the skeletal muscle in explaining exercise intolerance in CHF patients.