Skeletal muscles show changes in cellular structure, depletion of phosphocreatine, alterations in oxidative capacity, and loss of muscle mass with atrophy of oxidative fibers in patients with chronic heart failure (CHF)(3,6,14,23). Changes in blood flow owing to increased vasoconstriction and impaired ability of arterial dilation have also been reported (12,34). These abnormalities result in impaired exercise capacity but have been shown to be partially reversible by exercise training(3,10,26,29). Since muscle strength has also been demonstrated to be an independent predictor of exercise capacity(31), both aerobic and strength exercises are required, using high exercise stimuli applied to peripheral muscles.
Until now, detailed standardized guidelines for exercise training in patients with CHF have not been established; however, some recommendations have been suggested (5,11,30). Exercise training methods applied in previous studies(3,10,26,29) were based on recommendations for fitness training (1) or on experience from rehabilitation of coronary patients (5,25), arbitrarily modified for CHF patients. Aerobic exercise was applied by continuous training method exclusively.
In this study, a new method of interval exercise training was applied over 3 wk of exercise training in patients with severe CHF. Results of cycle ergometer training were analyzed with respect to: 1) determination of exercise intensity from a specific steep ramp test; 2) readjustment of intensity according to the steep ramp test during the course of the training period; 3) detection of changes in cardiopulmonary and metabolic parameters, along with plasma catecholamines, and to rate of perceived exertion and dyspnea; 4) comparison of the training work rate with the usually applied intensity guidelines for aerobic exercises using continuous methods (75% peak˙VO2; ventilatory threshold).
Training benefit was documented through repeat ramp cycle ergometer testing for exercise capacity.
METHODS
The study protocol, approved by the State Medical Ethics Committee, was a random order crossover trial consisting of 3 wk of supervised exercise training and 3 wk of activity restriction (22). During these periods the patients were hospitalized. Prior to participating, all patients gave informed, written consent.
Patients. Eighteen males (aged 52 ± 2 yr, body mass index 24.7 ± 0.7) with stable CHF as a result of dilated cardiomyopathy(N = 9) and coronary heart disease (N = 9) were assessed. Half the patients were on a heart transplantation waiting list. Disease had been documented for 35 months on average (range 8 to 52). Eight patients were in NYHA class II and ten in class III. At rest, ejection fraction was 21± 1% and cardiac index was 2.2 ± 0.2 l·m2·min-1. Baseline aerobic capacity was 12.2± 0.7 ml·kg-1·min-1 (40 ± 2% of predicted maximum ˙VO2). Lung function was borderline normal, but typical for CHF patients (% of predicted (mean ± SEM): forced vital capacity (85 ± 4%); forced expiratory volume, 1 s (80 ± 4%) and peak expiratory flow (89 ± 9%)). All patients had normal hemoglobin values (> 15 g·dl-1). The patients, randomly assigned into groups with training first or activity restriction first, did not differ significantly in anthropometric data, number of candidates on transplant waiting list, central hemodynamics, peak ˙VO2, and pulmonary function. No patient currently had myocardial or peripheral ischemia, and all were in sinus rhythm without significant dysrhythmia. Long-term medication, which was not changed during study period, included ACE-inhibitors (Captopril 2-3 × 25 mg·d-1) and diuretics (Furosemide 2 × 40-80 mg·d-1) in 16 patients, digitalis (Digitoxin 1 × 0.1 mg·d-1 or Digoxin 1 × 0.2 mg·d-1)(N = 14), nitrates (ISDN 2 × 20 mg·d-1)(N = 13), betablockers (Metoprolol between 3 × 25 and 3× 50 mg·d-1) (N = 7), and phenprocoumon (1× 1.5-3 mg maintenance dose) (N = 15).
Exercise testing and training program. The training period lasted 3 wk. Patients remained on medication during the exercise training procedure. Before each session, patients were weighed, auscultated, and assessed for well-being. Exercise training and testing were performed between 9 and 11 a.m.
Before and at the end of the training period, an ordinary ramp cycle ergometry (3 min. unloaded pedaling, work rate increments of 12.5 W·min-1) was performed up to muscular fatigue and/or severe dyspnea. Submaximum intensity levels of 75% peak ˙VO2 and ventilatory threshold (see Measurements) were determined.
Cycle ergometer training (Corival 400, Mijnhard, Nederlands) was carried out 5 times weekly for 15 min each. An interval method was used with work phases of 30 s and recovery phases of 60 s. Exercise intensity for work phases was derived from a steep ramp test on a cycle ergometer (3 min unloaded pedaling, work rate increments of 25 W every 10 s), which was stopped when patients could not maintain 60 rpm. From the maximum work rate achieved, called “maximum short time exercise capacity” (MSEC), 50% was chosen as the intensity for work phases in interval training(Fig. 1). During the first three work phases of training, work rate was successively increased to reach the final rate in the fourth work phase (see Fig. 1). Based on the measured oxygen uptake above resting values, the energy cost during work phases in the third training week was approximately 130 kJ per session (calculated by indirect calometry). During recovery phases patients pedaled at 15 W. The steep ramp test was repeated at the beginning of each training week to adjust exercise intensity for the following week.
In addition, 3 times weekly for 10 min each, walking training on a treadmill was performed using an interval method. Sixty seconds of work phases(mean speed 2.4 mph, range 1.75-3.25 mph during the last week of training, adjusted according to each patient's maximum heart rate tolerated during cycle interval training) was alternated with 60 s of active recovery phases (mean speed 0.9 mph). The energy cost for walking during work phases in the last training week was approximately 90 kJ per session.
Training sessions were supervised by continuous monitoring of heart rate and rhythm (1-lead ECG), ratings of leg fatigue and dyspnea, and for other possible complaints such as vertigo or chest pain. Blood pressure was measured before beginning, every 4th min during bicycle training, and 2 min after exercise by cuff method.
Measurements. During the ordinary ramp cycle test, the final steep ramp test, and the last interval training session in the third training week, cardiopulmonary exercise measurements were obtained (Oxycon Sigma, Mijnhard, Netherlands). Before each test, the system was calibrated by gases of known reference values, and volume by a 3-1 syringe.
As for cardiopulmonary variables: oxygen uptake (˙VO2; ml·min-1), carbon dioxide production (˙VCO2; ml·min-1), and ventilation (˙VE; l·min-1) were measured breath by breath. From these values, the respiratory exchange ratio (˙VCO2/˙VO2), ventilatory equivalent for O2 (˙VE/˙VO2), and CO2(˙VE/˙VCO2) were calculated. In duplicate measurements of peak ˙VO2 in patients with severe CHF, the error of SD (and variation coefficient) was 46 ml (4.1%) (20).
Ventilatory threshold was determinable by V-slope method (˙VCO2 vs ˙VO2) in 17 patients, and by respiratory exchange ratio in one patient (32); the value used for analysis was that with the best agreement between two independent observers. If there was no consensus, a third independent observer made the decision (for methods see(19)).
Heart rate was recorded continuously by a 12-lead ECG, and blood pressure by plethysmomanometry (Finapres, Madison, WI). Rate-pressure product was calculated. From 20 μl capillary blood (ear lobe), lactate was determined enzymatic-amperometrically (ESAT, Eppendorf, Germany) at rest and every exercise and recovery minute during steep ramp tests and ordinary ramp test, as well as at the end of every work and recovery phase during the last interval training (see Fig. 1).
From 150 μl capillary blood, plasma norepinephrine and epinephrine levels were determined radioenzymatically according to DaPrada et al.(4). Measurements were performed every 2 exercise minutes during the ordinary ramp test, and during the last interval training sessions at rest and at the 5th, 10th, and 15th exercise minutes, and at the 3rd and 6th recovery minutes. During the same time periods that blood samples were taken for catecholamine determination, ratings of leg fatigue and dyspnea were assessed using a Borg Scale (2).
Activity restriction. Patients were allowed only to take walks outside hospital for 1 h daily and to climb no more than one flight of stairs per day.
Statistical analysis. Statistical analysis was performed by BMDP Statistical Software (Berkeley, CA) and by INSTAT program (GRAPHPAD Software, San Diego, CA). At first, the presence of a carryover effect was assessed by an ANOVA over two factors: time of measurement and study order. As there were no significant differences between the two groups because of the study order, the group variable was discarded in further analysis. The Studentt-test for paired samples was applied to compare peak˙VO2, measured at baseline and after training, two similar measurements during interval exercise training (between 6 and 15 min; work and recovery phases; interval exercise (15 min) and ordinary ramp test (75% peak˙VO2; VT), and between steep ramp test and ordinary ramp test. An ANOVA, followed by Bonferroni test for multiple comparisons, was applied for MSEC during 3 wk of training and for differences between exercise data during interval training sessions and conventional guideline intensities. Data are presented as mean ± SEM (x ± SEM). A P value of < 0.05 was considered significant.
RESULTS
Exercise training was well tolerated by all patients. No patient had to refrain from participation in exercise training because of acute deterioration in clinical status.
Ordinary ramp test. After 3 wk of training, peak ˙VO2 was increased from 12.2 ± 0.7 to 14.6 ± 0.7 ml·kg-1·min-1 (P < 0.001). Peak respiratory exchange ratio was 1.06 and 1.08, respectively, and ratings of leg fatigue or dyspnea > 17 (“severe”) on a Borg scale(2).
Steep ramp test. Maximum work rate (MSEC; W) was increased significantly from the first to second week (P < 0.001) and the second to third week (P < 0.001) (144 ± 10 → 172± 10 → 200 ± 11 W). The mean test duration was 59 ± 2 s (first week), 68 ± 2 s (second week), and 79 ± 2 s (third week) (P < 0.001).
Steep and ordinary ramp test.Table 1 represents data from the steep ramp test of the third training week and from the ordinary ramp test performed at the end of the training period. Heart rate, blood pressure, ˙VO2, respiratory exchange ratio, and lactate were measured at rest, at maximum work rate, and in recovery minutes 0:30 to 4:00.
Interval cycle training. During interval cycle training, the intensity used during work phases was 50% of MSEC. As the MSEC increased, work rate (W) during work phases increased significantly from the first to the second week (P < 0.001) and from the second to the third week(P < 0.001) as follows: 72 ± 4 → 86 ± 6 → 100 ± 7 W. The same applied for work rate per kilogram body weight(W·kg-1): 0.95 ± 0.07 → 1.19 ± 0.08 → 1.31 ± 0.09 W·kg-1. The total amount of work (W per min) also increased from the first to second week (P < 0.001) and from the second to third week (P < 0.001): 457 ± 30 → 525± 27 → 584 ± 29 W·min-1. Nevertheless, heart rate and blood pressure as well as ratings of leg fatigue and dyspnea did not increase concomittantly (Fig. 2).
Table 2 presents the acute physical responses during interval cycle training at the end of the third training week.˙VO2, ˙VCO2, heart rate, systolic blood pressure,˙VE/˙VO2, and catecholamine levels did not increase significantly from the fourth work phase (6 min) to the last work phase (15 min) (for methods see Fig. 1), but lactate,˙VE/˙VCO2, and ratings of perceived exertion did(Table 2). Between work and recovery phases there was no significant difference for mean values of any mentioned variable.
Interval exercise intensity and conventional guideline intensities. Data measured during the last work phase of interval exercise(minute 15) were compared with the data measured at 75% of peak˙VO2 and ventilatory threshold as derived from ordinary ramp cycle ergometry (Table 3). At interval exercise, the work rate(W) was more than double the work rate at 75% of peak ˙VO2, while cardiac stress (rate-pressure product) was significantly lower. Metabolic stress, catecholamine levels, and ratings of perceived exertion did not differ between the two exercise conditions, but ventilatory efficiency did(Fig. 3).
When work rate during work phases in interval training was related to that measured at ventilatory threshold, the work rate was also markedly higher (186± 12%; P < 0.001). The differences of all other variables mentioned above were similar to that observed at an intensity level of 75% peak ˙VO2.
DISCUSSION
Most patients had very low exercise capacity at baseline which did not allow endurance training work rates in excess of approximately 30 W. As the patients were already accustomed to these intensities from activities of daily living, any effects on peripheral musculature by training at this level probably would be slight. Attempting to compensate for lower intensities by longer duration of training is often limited by premature fatigue, and more frequent sessions might result in progression of CHF(33). These problems can be overcome if intense exercise stimuli are applied during short work periods in repeated sequence, the principle on which an interval exercise training method is based. Previously we have shown that different combinations of interval exercise relative to intensity and duration of work phases are applicable to and well tolerated by CHF patients (21). In rehabilitation after coronary bypass surgery, interval training has resulted in greater increase of aerobic capacity than continuous exercise training methods although the total amount of work performed was significantly lower (17).
With respect to frequency, duration of the training sessions, and calculated energy costs during work phases in interval walking and cycle training, the latter can be assumed to contribute more strongly to the improvement of peak ˙VO2.
Determination of the training work rate by a steep ramp test. A challenge for exercise prescription in patients with CHF is determining the appropriate exercise intensity. The rationale for developing a specific steep ramp test to determine interval training work rate was that not only endurance capacity but also dynamic muscle strength is required to perform intense work rates during interval training work phases. The steep ramp test enables one to determine maximum short time exercise capacity (MSEC) which partially reflects anaerobic capacity and leg muscle strength. A training intensity of 50% MSEC was derived empirically (Fig. 1), and we have previously shown that this intensity resulted in a marked increase of exercise capacity with only 3-4 wk of interval training (22,26).
Because of the rapid increase of work rate during the steep ramp test, the patients could perform MSEC of 200 W on average in the last training week. Although this was almost 2.5 times the maximum work rate from an ordinary ramp test, heart rate and blood pressure were relatively low and in the range of values of an ordinary ramp test (Table 1). ˙VO2 at maximum work rate during steep ramp test was approximately 33% of the˙VO2 expected for 200 W (18). Minimum test straining from a metabolic standpoint was indicated by maximum lactate concentration of approximately 2.40 mmol·l-1 (mean of all subjects) during the recovery period after steep ramp testing(Table 1). This result suggests that in the steep ramp test strength (ATP - phosphocreatine energy system) rather than aerobic system(H+/lactate system) is most likely of greater importance.
Readjustment of work rate for interval training. As a result of the weekly increased MSEC, work rate for interval training work phases was readjusted at the beginning of each training week. Notwithstanding, heart rate, blood pressure, and ratings of perceived exertion did not increase significantly during the training period (Fig. 2). This was probably because as fitness level improved and training work rate increased the relative exercise intensity remained unchanged. The fast adaptation of the patients to the training program suggests that, especially in the initial phase of a training period, exercise intensity should be readjusted according to the benefits achieved. In the most frequently quoted exercise training studies in patients with CHF(3,10,12,26,29), the principle of readjustment of work rates from repeated exercise testings was not considered although programs lasted 16 wk on average (range 4-24 wk).
Acute physical responses to interval exercise. During interval training sessions, ˙VO2, ˙VCO2, heart rate, and blood pressure stabilized at constant levels (Table 2) and at values which might be expected during continuous exercise training at a markedly lower exercise intensity level. The mean value of ˙VO2 was lower relative to work rate during work phases and higher relative to work rate during recovery phases. The ˙VCO2/˙VO2 ratio and lactate values (Table 2) indicate that overall, exercise was aerobic, and the low plasma catecholamine levels indicate that the withdrawal of vagal tone seems to be the primary factor for acute exercise adaptation (13,28). The significant increase of values for lactate concentration, leg fatigue, and dyspnea ratings, as well as of ˙VE/˙VCO2 during 15-min interval exercise(Table 2), indicate that, peripheral muscles were markedly stressed as intended while cardiac strain was in a stable and tolerable range of values.
There is reason to believe that the intermittent nature of the interval training allows the left ventricle to accommodate to an enhanced venous return associated with the high muscle work rates. Foster et al.(7) demonstrated significant augmentation of the left ventricular ejection fraction (LVEF) with the abrupt termination of exercise. This corresponds to the augmentation of LVEF shown during workload reductions by Seaworth et al. (27). The results contrast with the acute deterioration of LVEF with the abrupt onset of heavy exercise(8). However, given the relative protection from deterioration of LVEF during acute loading provided by warm-up(8), we speculate that the incremental nature of the first bouts of interval exercise and relatively longer time at low work rates (60 s) versus high-intensity exercise (30 s) allows even ventricles with abnormal function to accommodate to heavy loads. Further studies examining LVEF responses during interval exercise appear to be needed. However, in our study no patient demonstrated ST segment depression or serious ventricular arrhythmias during testing or training, and clinical results clearly suggests that interval training does not worsen heart failure(22).
Comparison of interval intensity and usual intensity guidelines. The frequently reported training intensity for endurance exercise training in healthy subjects is 60% of maximum heart rate or 50% of heart rate reserve(1,25). In terms of ˙VO2, it is 50% of the maximum achieved (1,25). In addition, an intensity level determined by anaerobic threshold was recommended in healthy and coronary patients (9,16,24). In patients with CHF, the usual intensity prescribed for steady-state exercise training was at levels of 70-80% of peak ˙VO2(10,11,29,30). In our study, maximum interval work rate at the end of the training period was markedly higher compared with that work rate patients achieved at an intensity level of 75% peak ˙VO2, while metabolic stress, catecholamines, and rating of perceived exertion were of the same general magnitude(Fig. 3; Table 3). The same could be said when interval exercise data were related to ventilatory threshold(Table 3). It is remarkable to notice that much higher work rates with significantly lower cardiac stress were achieved during interval training than during ramp-like cycle ergometry at intensity levels of 75% peak ˙VO2 and ventilatory threshold (Fig. 3). If the aim of exercise training is to reverse peripheral maladaptations of hemodynamics, metabolism, and muscle mass, high exercise stimuli are necessary. According to these results, the usual guidelines understimate the muscular work rate patients with CHF can tolerate during interval exercise training. Thus, new more specific guidelines should be formulated.
Clinical implications. From this analysis, recommendations for interval exercise training procedure can be established as follows: work phases of 30 s and recovery phases of 60 s are shown to be practicable and well tolerated with respect to the chosen exercise intensity. These short bouts enable intense stimuli of 50% of MSEC to working muscles with minimal cardiac strain. Training work rate can be ascertained more appropriately by a steep ramp test than by an ordinary ramp test. Commonly prescribed submaximum exercise intensities of 75% peak ˙VO2 or ventilatory threshold underestimate the muscular work rate patients can tolerate during interval exercise. During the first month of a training period, especially in patients with a low initial exercise capacity, the training intensity should be readjusted weekly on the basis of repeated steep ramp tests.
Limitations of the study. This analysis of an interval cycle training program was based on a previous study assessing the effects of short-term exercise training and activity restriction on functional capacity(22). During the period of activity restriction in that study neither exercise training nor testing was performed. Thus, it remains unclear whether the high work rates, performed during the weekly repeated steep ramp tests, were a training stimulus in themselves for these extremely deconditioned patients. Also, with respect to establishing interval training for patients with severe CHF, the specific steep ramp test as a new testing technique has to undergo further study to elucidate the underlying adaptation mechanisms.
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