Cardiorespiratory fitness and coronary heart disease risk factors: the LDS Hospital Fitness Institute cohort.

BACKGROUND: Cardiorespiratory fitness is favorably associated with most modifiable coronary heart disease (CHD) risk factors. Findings are limited, however, by few data for women, persons with existing CHD, and low-risk populations. In the present study, we described cross-sectional associations between cardiorespiratory fitness and CHD risk factors in a large cohort of middle-aged men and women, of whom the majority were LDS Church members (Mormons), with and without existing CHD. METHODS AND RESULTS: Comprehensive health examinations were performed on 3232 men (age 45.9+/-10.8 years) and 1128 women (age 43.8+/-12.8 years) between 1975 and 1997. Maximal treadmill exercise testing was used to categorize those with (12% of the men and 10% of the women) and those without CHD into age- and sex-specific cardiorespiratory fitness quintiles. After adjustments for age, body fat, smoking status, and family history of CHD, favorable associations were observed between fitness and most CHD risk factors among men and women, regardless of CHD status. CONCLUSIONS: These data indicate that enhanced levels of cardiorespiratory fitness may confer resistance to elevations in CHD risk factors even in a low-risk sample of middle-aged men and women. Furthermore, these findings reinforce current public health recommendations that advocate increased national levels of physical activity and cardiorespiratory fitness for primary and secondary CHD prevention.

Exercise capacity after heart transplantation: influence of donor and recipient characteristics.

BACKGROUND: For incompletely understood reasons, cardiac transplant recipients achieve only 60% to 70% of predicted values for maximal exercise capacity. The objective was to determine the characteristics of cardiac transplant recipients that are predictive of exercise capacity. METHODS: One hundred ten patients underwent maximal exercise testing using a modified Naughton protocol 26 +/- 1 months after transplantation. Recipient characteristics, resting hemodynamic variables and exercise parameters were compared using univariate and multivariate analyses. RESULTS: The average maximum heart rate was 85% of predicted, and the average peak oxygen consumption (Vo2) was 17.7 +/- 0.3 ml/kg/min (64% of predicted). Pretransplant status, etiology of heart failure, ischemic time, degree of HLA disparity, cumulative corticosteroid exposure, and number of rejection episodes failed to correlate with any exercise parameter. Older recipient age and female gender were associated with greater values for the proportion of the predicted peak Vo2 (p < 0.001 for age; p = 0.001 for gender). Older donor age was the strongest independent predictor of a decreased chronotropic response (p < 0.001) and was a weak predictor of decreased peak Vo2 (p = 0.014). Even in the multivariate analysis, maintenance prednisone dose negatively impacts exercise duration (p = 0.05), peak Vo2 (p = 0.035) and percent of predicted peak Vo2 (p = 0.032). Of all characteristics tested, pulmonary vascular resistance within 24 hours of exercise most powerfully predicts exercise duration (p = 0.002) and peak Vo2 (p = 0.001). CONCLUSIONS: Female recipients and older recipients have a lower absolute exercise capacity, but achieve a greater proportion of their predicted capacity. Recipients of older donor hearts and those receiving chronic corticosteroids have decreased exercise capacity. Pulmonary vascular resistance is inversely correlated with exercise capacity.

Beta-blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy.

BACKGROUND: We investigated the effects of bucindolol, a nonselective, non-ISA beta-blocker with mild-vasodilatory properties, in patients with congestive heart failure from ischemic dilated cardiomyopathy (ISCDC, n = 27) and compared the results with those in subjects with heart failure from idiopathic dilated cardiomyopathy (IDC, n = 22). METHODS AND RESULTS: Patients were randomized in a double-blind fashion to receive 12 weeks' treatment with either bucindolol or placebo, with randomization stratified for IDC or ISCDC: Invasive (right heart catheterization) and noninvasive (echo, MUGA, central venous norepinephrine, exercise treadmill studies, and symptom scores) tests of heart failure severity were determined at baseline and end of the study. For all subjects (ISCDC plus IDC), relative to placebo treatment, bucindolol-treated patients had significant improvement in ejection fraction, left ventricular size and filling pressure, stroke work index, symptom score, and central venous norepinephrine. However, most of these differences could be attributed to improvement in the IDC subgroup, as the only parameter with a statistically significant degree of improvement in the bucindolol-treated ISCDC subgroup was left ventricular size. CONCLUSIONS: We conclude that beta-blockade may produce quantitatively different degrees of response in different kinds of heart muscle disease.

Small-sample reproducibility estimates: an example using rebreathing measurements.

We developed a statistical technique to estimate the reproducibility of a parameter from a population in which only two repeated measurements can be made in a single individual. The following data were analyzed: acetylene cardiac output (Qc), lung tissue volume (Vti), and carbon monoxide diffusing capacity (DLCO) measured by rebreathing techniques in a population of 86 healthy subjects (51 men and 35 women). Each subject was measured twice with a computerized rebreathing system using a test gas of 10% He-0.3% C18O-0.7% C2H2-25% O2-balance N2 while sitting at rest. The estimated coefficients of variation for repeated measurements were 6.8, 10.3, and 5.7% for Qc, Vti, and DLCO, respectively. Chebyshev's inequality was used to estimate the imprecision for a single measurement of these parameters and for averages of two or more repeated values. A single measurement of Qc would be within 14.2% of a "true" mean 90% of the time, whereas an average of three consecutive measurements would be within 8.2% of the true mean 90% of the time. Single measurements of Vti and DLCO were found to be within 21.7 and 12.0%, respectively, of the true mean 90% of the time. When three consecutive measurements are averaged, Vti is within 12.6% and DLCO is within 6.9% of the true mean 90% of the time. We conclude that 1) rebreathing Qc is as reproducible as other measurements of cardiac output, 2) rebreathing measurements of DLCO are as reproducible as those made by the single-breath technique, and 3) an average of two to three measurements of Vti should be made to obtain values with a reasonable degree of precision.

Long-term beta-blocker vasodilator therapy improves cardiac function in idiopathic dilated cardiomyopathy: a double-blind, randomized study of bucindolol versus placebo.

PURPOSE: Bucindolol is a potent nonselective beta-blocking agent with vasodilatory properties. In this study, we evaluated the effects of long-term bucindolol therapy in the treatment of heart failure from idiopathic dilated cardiomyopathy. PATIENTS AND METHODS: Patients were eligible for enrollment if they had symptomatic heart failure, idiopathic dilated cardiomyopathy, and left ventricular ejection fraction less than 0.40. All patients received an initial test dose of 12.5 mg bucindolol orally every 12 hours for two or three doses. Patients tolerating the test dose were randomly assigned (double-blind) to receive bucindolol or placebo in a 3:2 ratio. Study medication was begun at a dose of 12.5 mg orally every 12 hours and gradually increased over a 1-month period until either a maximum tolerated dose or a target dose of 100 mg every 12 hours was reached. Study medication was then continued for an additional 2 months. RESULTS: A total of 24 patients were enrolled into the study. Twenty-three patients tolerated bucindolol test challenge; 14 were randomized to receive bucindolol, and nine were randomly assigned to receive placebo. The placebo group (age 56 +/- 2 years) was significantly older than the bucindolol group (46 +/- 3 years), but by all other clinical and hemodynamic parameters the two groups were comparable. Twenty-two of 23 patients completed the study. Patients treated with bucindolol had significant improvements in clinical heart failure symptoms and in resting hemodynamic function, including an increase of left ventricular ejection fraction (0.26 +/- 0.02 to 0.35 +/- 0.09, p = 0.003), cardiac index (2.2 +/- 0.1 to 2.5 +/- 0.4 L/minute/m2, p = 0.014), and left ventricular stroke work index (25 +/- 3 to 35 +/- 7 g.m/m2, p = 0.002) and a decrease in pulmonary artery wedge pressure (17 +/- 3 to 10 +/- 5 mm Hg, p = 0.005) and heart rate (86 +/- 3 to 75 +/- 9 beats/minute, p = 0.012). Patients treated with bucindolol also had a significant increase in exercise left ventricular ejection fraction (0.26 +/- 0.03 to 0.32 +/- 0.14, p = 0.015) and reduction in questionnaire-measured symptoms (p = 0.007) and New York Heart Association functional class (p less than 0.001). However, total treadmill exercise duration and maximal oxygen consumption with exercise did not change. No changes in rest or exercise parameters were observed in the placebo-treated group. Central venous plasma norepinephrine concentration decreased significantly in the bucindolol-treated group (423 +/- 79 to 212 +/- 101 pg/mL, p = 0.010), but was unchanged in the placebo-treated group. CONCLUSION: Bucindolol is well tolerated in patients with idiopathic dilated cardiomyopathy and congestive heart failure, and therapy for 3 months is associated with improved resting cardiac function, improved heart failure symptoms, and a reduction in venous norepinephrine concentration.

Noninvasive evaluation of world class athletes engaged in different modes of training.

This study evaluated by noninvasive methods the cardiac structure and functional characteristics of world class athletes participating in different types of training programs. Fourteen subjects, including 4 strength-trained (discus and shot put), 4 endurance-trained (long distance runners), 4 decathlon-trained (strength and endurance), 2 wheelchair athletes and 31 college-age control subjects were evaluated using electrocardiography, M-mode echocardiography and maximal oxygen consumption. M-mode echocardiography measurements of left ventricular structure and function were compared before and after normalization for lean body weight. As expected, endurance athletes had greater maximal O2 consumption than the other groups (p less than 0.05). Before normalization for lean body weight, there were no significant differences in end-diastolic dimensions. After normalization, the endurance, wheelchair and control subjects had end-diastolic dimensions larger than those of strength athletes. Strength athletes appeared to have a much larger posterior wall and septal thickness than all groups except the decathlon athletes. However, when normalized, there was no difference among any of the groups. Previous investigators have attempted to determine "normalcy" of cardiac hypertrophy by looking at the ratio of left ventricular wall thickness to left ventricular radius. In the present study, the thickness to radius ratio in strength athletes was 33% greater than that in endurance athletes. It appears that the left ventricular wall thickness in the strength athletes occurred without a concomitant increase in left ventricular radius and that the left ventricular hypertrophy of world class athletes is related to the total increase in lean body weight. However, ventricular dimensions may be related more to the type of overload experienced.

Turbine flowmeter vs. Fleisch pneumotachometer: a comparative study for exercise testing.

The purpose of this study was to investigate the characteristics of a newly developed turbine flowmeter (Alpha Technologies, model VMM-2) for use in an exercise testing system by comparing its measurement of expiratory flow (VE), O2 uptake (VO2), and CO2 output (VCO2) with the Fleisch pneumotachometer. An IBM PC/AT-based breath-by-breath system was developed, with turbine flowmeter and dual-Fleisch pneumotachometers connected in series. A normal subject was tested twice at rest, 100-W, and 175-W of exercise. Expired gas of 24-32 breaths was collected in a Douglas bag. VE was within 4% accuracy for both flowmeter systems. The Fleisch pneumotachometer system had 5% accuracy for VO2 and VCO2 at rest and exercise. The turbine flowmeter system had up to 20% error for VO2 and VCO2 at rest. Errors decreased as work load increased. Visual observations of the flow curves revealed the turbine signal always lagged the Fleisch signal at the beginning of inspiration or expiration. At the end of inspiration or expiration, the turbine signal continued after the Fleisch signal had returned to zero. The "lag-before-start" and "spin-after-stop" effects of the turbine flowmeter resulted in larger than acceptable error for the VO2 and VCO2 measurements at low flow rates.

Occurrence of exercise-induced and spontaneous wide complex tachycardia during therapy with flecainide for complex ventricular arrhythmias: a probable proarrhythmic effect.

Flecainide acetate, a new antiarrhythmic agent, possesses favorable pharmacokinetic and hemodynamic properties and demonstrates highly favorable antiarrhythmic activity in patients with ventricular arrhythmias. However, the proarrhythmic potential of flecainide deserves further evaluation. In 7 (13%) of 55 consecutive patients treated with oral flecainide, 200 to 600 mg/day, for complex ventricular arrhythmias (including sustained ventricular tachycardia in 14), we observed the appearance of new or more sustained exercise-induced (five patients) or spontaneous (two patients) wide complex tachycardia. The mechanism of wide complex tachycardia appeared to be ventricular tachycardia in all seven. In our series, episodes were self-remitting or successfully treated. In four patients, wide complex tachycardia did not recur during exercise testing during alternative antiarrhythmic therapy (three patients) or no antiarrhythmic therapy (one patient). These observations raise the possibility of flecainide-related proarrhythmia, manifested as an increased propensity to exercise (activity)-induced wide complex tachycardia, which was not reliably predicted by results of Holter recordings or programmed electrical stimulation. Patients with complex ventricular arrhythmias beginning long-term treatment with oral flecainide should be considered for treadmill exercise testing together with ambulatory monitoring as part of the initial assessment of drug efficacy.

A randomized trial of low-dose beta-blockade therapy for idiopathic dilated cardiomyopathy.

Beta-blockade therapy to improve survival in idiopathic dilated cardiomyopathy (IDC) has been both advocated and criticized. However, randomized studies have not been performed. Thus, 50 patients with IDC were randomized in pairs to standard therapy (C) alone or with beta blockade (BB). Beta-blockade therapy with metoprolol was titrated from 12.5 to 50 mg twice daily as tolerated (final average dose, 61 mg/day). Groups were comparable in age (C, 50 +/- 15 years; BB, 51 +/- 13 years), gender (C, 76% male; BB, 56% male), entry functional class (C, 2.8 +/- 0.8; BB, 2.7 +/- 0.7), and left ventricular ejection fraction (C, 27 +/- 12%; BB, 29 +/- 10%). Follow-up averaged 19 months (range 1 to 38). One subject in each group was lost to follow-up. There were 3 early BB dropouts (within 2 days) due to low-output syndrome (2 patients) or fatigue (1 patient). Eleven patients died. By intention to treat, 5 BB and 6 C patients died (difference not significant). By actual treatment, 3 BB patients died, including 2 late dropouts (at 0.2, 10 and 17 months), and 8 C patients died (at 2, 9, 9, 15, 18, 24, 29 and 32 months, p = 0.12). In additional, functional evaluation on follow-up (functional class, San Diego questionnaire and exercise time) all tended to favor those receiving BB. Low-dose BB is tolerated in 80% of IDC patients on a long-term basis. Those continuing to take BB have a good prognosis. Mortality in C patients, however, is less than in some retrospective studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous aminophylline upon the incremental exercise performance of healthy men.

Aminophylline increases the contractile force of fatiguing muscles. The effects of aminophylline upon maximal exercise performance are not defined. 6 healthy men performed incremental bicycle ergometry before and after receiving intravenous aminophylline (6 mg/kg). Maximal oxygen uptake, maximum work rate, and maximum minute ventilation were unchanged following aminophylline. Heart rate measured at rest and at 50-watt increments of work rate was significantly increased following aminophylline (p less than 0.03). The heart rate response to incremental exercise (delta HR/delta VO2) was unchanged by aminophylline. We conclude that aminophylline does not increase maximal exercise performance of healthy men.

Heritability of cardiac size: an echocardiographic and electrocardiographic study of monozygotic and dizygotic twins.

Because of the uncertainty as to the extent to which cardiac size is determined by exercise training vs genetic endowment, this study investigated familial (genetic plus common family environment) vs nonfamilial influences on cardiac size. College-age monozygotic twins (group 1, 31 sets), dizygotic twins (group 2, 10 sets), siblings of like sex (group 3, six sets), and nonrelated subjects (group 4, 15 sets) underwent echocardiographic and electrocardiographic tests, measurement of maximum oxygen uptake (VO2max), and evaluation of pulmonary and body composition; mean intrapair differences of the four groups were compared. Mean intrapair differences in cardiac size varied as much for subjects in group 1 as for those in groups 2 and 3. However, subjects in groups 1, 2, and 3 had less variation (p less than .05) than those in group 4. After the initial testing, 14 pairs of monozygotic twins, five sets of dizygotic twins, and six sets of siblings underwent 14 weeks of exercise training (both members participated) and all tests were repeated. After exercise training, subjects in group 1 still had as much intrapair variability in cardiac size as those in groups 2 and 3. The data suggest cultural familial influences are more important in determining cardiac size than nonfamilial influences or even genetic influences alone.

Long-term follow-up after intracoronary streptokinase for myocardial infarction: a randomized, controlled study.

Intracoronary streptokinase (SK) may have beneficial effects on the in-hospital course of acute myocardial infarction (MI), but long-term outcome is unknown. We evaluated the outpatient course of 50 MI patients, randomly treated with either SK (n = 24) or standard therapy (n = 26), who presented within 2.7 +/- 0.7 hours of symptoms. Coronary reperfusion occurred in 19 (79%) SK patients. Survivors were followed for a mean of 18.7 months (range 11 to 28.5); information was current in 48 patients (96%). Both groups received antiplatelet therapy for 3 months. A total of five deaths occurred in the control group and two in the SK group, including one posthospital death in each. Nonfatal MIs totaled five in control patients and three in SK patients, including five posthospital MIs (three control, one SK). Differences in major events (death or nonfatal MI) favoring SK did not quite reach statistical significance (10 control vs 5 SK). Bypass surgery was performed in seven SK and four control patients (NS). Angina occurred in more control (15) than SK (six) patients (p less than 0.01), and more control patients used long-acting nitrates (14 control, three SK; p less than 0.01). Palpitations were noted by nine control and one SK patient (p less than 0.01), and documented late arrhythmias were present in four control patients and no SK survivors (p less than 0.05). Symptoms suggestive of heart failure were present in seven control and one SK patient (p less than 0.01); two control patients were hospitalized for failure. Use of beta blockers, calcium channel blockers, and other cardiac medications did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized trial of intravenous and intracoronary streptokinase in patients with acute myocardial infarction.

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less than .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p less than .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 +/- 5.0 and 11.5 +/- 4.3 hr for creatine kinase MB isoenzyme and 31.7 +/- 11.8 and 28.1 +/- 12.7 hr for lactic dehydrogenase (LDH). Peak LDH-1 level was lower in patients receiving intravenous drug than in the historical control group (p less than .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug = 5, historical control = 4, intracoronary drug = 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of aminophylline upon the exercise performance of patients with stable chronic airflow obstruction.

To assess the effects of aminophylline upon the exercise performance of patients with chronic airflow obstruction (CAO), we performed ramp exercise tests (1 W/3 s) on six CAO subjects before and after intravenous aminophylline (6 mg X kg-1). The subjects had airflow obstruction (mean FEV1/FVC = 0.53) which did not improve following the inhalation of aerosolized isoetharine. After intravenous aminophylline, maximal oxygen uptake, maximal work rate and exercise duration increased (p less than 0.03) and the subjective dyspnea scores during exercise decreased (p less than 0.05). These changes were not accompanied by increases of FEV1 or peak expiratory flow rate, but maximal inspiratory pressure and peak inspiratory flow rate during exercise increased (p less than 0.05). These observations suggest that aminophylline acutely improves the maximal exercise performance of CAO subjects by mechanisms other than bronchodilation.

Effect of O2, N2, and CO2 composition on nonlinearity of Fleisch pneumotachograph characteristics.

Although the Fleisch pneumotachograph has many advantages, its flow-conductance characteristics are nonlinear and sensitive to changes in gas composition. The purpose of this study was to assess the effect of different O2, N2, and CO2 compositions on the nonlinearity of the Fleisch pneumotachograph flow-conductance characteristics, by use of a recently developed computerized calibration method. Hospital-grade O2 was mixed with room air to obtain seven gas mixtures (containing O2 percentages of 20.9, 28.3, 38.7, 52.8, 66.7, 78.7, and 99.6%). Within the accuracy of the applied method, the measured flow-conductance curves of the pneumotachograph had the same shape. Relative flow resistance of gas mixtures to room air was directly proportional to their O2 composition. Two O2-N2-CO2 mixtures were also tested. Their relative flow resistance compared with room air was proportional to the viscosity ratios. We concluded that the change in O2, N2, and CO2 composition does not affect the nonlinearity of the Fleisch pneumotachograph flow-conductance characteristics. However, the relative flow resistance compared with room air does change in a predictable way.

"Anaerobic threshold": problems of determination and validation.

Despite the popularity of the concept of "anaerobic threshold" (AT), the noninvasive detection criteria remain subjective, and invasive validations of AT have been based on lactate data of arterial, mixed venous, venous, and capillary blood samples without any concern for the possible lactate differences from these sources. Eight normal subjects underwent two exercise tests on a bicycle ergometer. The protocol consisted of 3 min of rest, 3 min of 0 work load, and a 20 W/min ramp (1 W/3 s) until exhaustion. Simultaneous arterial and venous blood samples were drawn during the second test. Noninvasive gas response data were measured using a computerized breath-by-breath stress test system. Threshold phenomenon of the lactate accumulation was not found. The arterial lactate levels increased continuously after the start of the exercise ramp. The rise in venous lactate lagged behind the rise of the arterial lactate by about 1.5 min, and therefore venous lactate was not considered suitable for AT detection. Four independent exercise physiologists determined AT from the gas response data. The reviewer variability (avg range 16%) of AT for a given subject was representative of AT values reported for untrained and trained individuals (40-70% maximum O2 consumption). We concluded that 1) AT is not detectable using invasive methods (arterial and venous lactates); and 2) the noninvasive gas response determination has such a large range of reviewer variability that it is unsuitable for clinical use.