Inspiratory muscle training in patients with chronic heart failure awaiting cardiac transplantation: results of a pilot clinical trial.

Inspiratory muscle training (IMT) benefits patients with pulmonary disease by increasing their ventilatory muscle strength and endurance and by decreasing their dyspnea, need for medications, emergency department visits, and number of hospitalizations.[1-7] Individuals with chronic heart failure (HF) have been found to have poor ventilatory muscle strength and endurance.[8-10] Poor ventilatory muscle strength has also been found to be correlated to the occurrence of dyspnea during daily activity.[8,10] Only one recent study[11] has evaluated IMT in patients with chronic HF. Eight patients with a mean ([+ or -] SD) New York Heart Association (NYHA) classification of 2.8 [+ or -] 1.0 performed an elaborate ventilatory muscle training program (via isocapnic hyperpnea, pressure-gauge strength training, breathing calisthenics, abdominal strengthening exercises, and a Threshold inspiratory muscle trainer(*)) three to seven times a week for 12 weeks and improved their ventilatory muscle strength and endurance as well as their submaximal and maximal exercise capacities.(11)

Improvement in ventilatory muscle strength and symptoms may decrease the medical and functional dependence, impairment, and possibly even costs associated with chronic HF.[8-12] Increased ventilatory muscle strength may also enhance early postoperative recovery in patients undergoing cardiac transplantation or thoracic surgery.[7,13,14] Because of these potential effects from IMT and the need for rapid improvement in ventilatory muscle strength prior to cardiac transplantation or thoracic surgery, the effects of a short-term standard IMT program (via targeted inspiratory muscle training alone) on ventilatory muscle strength and dyspnea in patients with chronic HF awaiting cardiac transplantation were investigated.

Method

Subjects

The study subjects were 14 patients (12 men and 2 women) with chronic HF (HF of [greater than or equal to] 1 year) for an average of 4 years who were randomly selected from patients admitted to Massachusetts General Hospital for precardiac transplantation evaluation. The subjects had a mean age of 52 years (SD=8.5, range=32-64). The mean left ventricular ejection fraction for these subjects was 23% [+ or -] 13% (normal=60%-80%), and the mean NYHA classification was 3.6 [+ or -] 0.6 (patients in class 1 have no limitation in ordinary physical activity, whereas patients in class 4 are unable to perform physical activity without discomfort). Twelve of the subjects were hospitalized during the IMT period while awaiting or undergoing evaluation for cardiac transplantation.

The etiology of chronic HF included idiopathic dilated cardiomyopathy (n=7), ischemic cardiomyopathy (n=6), and restrictive cardiomyopathy (n=1). All subjects underwent pulmonary function testing, and none had severe pulmonary disease (as defined by both a forced expiratory volume in 1 second [[FEV.sub.1]] and a forced vital capacity [FVC] of less than 50% of the predicted value, as suggested by the American Thoracic Society[15]), which may limit the effectiveness of IMT. The mean [FEV.sub.1], was 2.52 [+ or -] 0.78 L, and the mean FVC was 3.23 [+ or -] 1.05 L (67% [+ or -] 16% of the predicted values). Informed consent was obtained prior to participation in the study. The patient characteristics are listed in Table 1.

Patient No.   Disease   Gender   Age(y)   Height(cm)    Weight(kg)
 1            IDCM      M        32      173             84.0
 2            Isch CM   M        48      178             71.0
 3            IDCM      M        64      180             98.6
 4            Isch CM   M        51      185            106.8
 5            RCM       M        49      175             83.2
 6            Isch CM   M        62      168             81.8
 7            Isch CM   M        52      175             76.4
 8            Isch CM   M        51      175             81.8
 9            IDCM      M        40      175             68.2
10            Isch CM   M        54      185             85.4
11            IDCM      M        57      180             84.5
12            IDCM      M        61      175             78.2
13            IDCM      F        56      160             63.6
14            IDCM      F        49      160             52.3
X
SD                      52[+ or -]8.5  175[+ or -]8  80[+ or -]14

                                         Duration of
Patient No.     NYHA(1-4)     LVEF(%)    CHF(y)
 1              4             20         1.0
 2              3             12         1.0
 3              3             54         4.0
 4              4             18         1.0
 5              4             48        10.0
 6              3             13         4.0
 7              2             18         2.0
 8              4             25         2.0
 9              4             10         3.0
10              3             20         3.0
11              4             26         5.0
12              4             17        10.0
13              4             23         9.0
14              4             12         1.0
X
SD       3.6[+ or -].6   23[+ or -] 13   4[+ or -]3

(a) NYHA = New York Heart Association classification LVEF = left ventricular ejection fraction CHF = congestive heart failure IDCM = idiopathic dilated cardiomyopathy Isch CM = ischemic cardiomyopathy RCM = restrictive cardiomyopathy

Medical therapy was optimized prior to IMT and included the use of digoxin, diuretics, and angiotensinconverting enzyme inhibitor agents by all subjects; intravenous dobutamine was administered to eight subjects. Ventilatory muscle testing and training were initiated after a plateau in clinical status had been achieved (identified by signs and symptoms of stable compensated HF and lack of improvement in, or ability to perform, further exercise conditioning). Criteria for the initiation of ventilatory muscle testing and training in eight of the subjects who underwent optimization of medical therapy using invasive hemodynamic monitoring included a goal cardiac index of greater than 2.2 L/min/[m.sup.2] and a pulmonary capillary wedge pressure of less than 18 mm Hg, which we have accepted as signs of optimal cardiac performance in this patient population.(16)

Measurements

Ventilatory muscle strength. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured (in centimeters of water) with a device consisting of a Magnehelic gauge([dagger]) and one-way valve that was constructed similarly to that described by Black and Hyatt.[17] The device has an accuracy of [+ or -] 0.5% and a resolution of 5 cm [H.sub.2 O]. A 0.5-cm hole was made at the base of the one-way valve to prevent the generation of mouth pressure during testing of ventilatory muscle strength.

All measurements were made in the manner described by Black and Hyatt,[17] with subjects in a seated position and the trunk at a 90-degree angle to the hips. Measurements of MIP were obtained after a maximal expiration (near residual volume), and measurements of MEP were obtained after a maximal inspiration (total lung capacity). A noseclip was worn during ventilatory muscle testing.

Measurements of MIP and MEP wire repeated until consistent measurements were obtained. These measurement resulted in three to six MIP and MEP determination separated by several minutes of rest between measurements. The highest attained MIP and MEP were used and were compared with normal age- and gender-specific MIP and MEP values that were predicted using regression equations developed by Black and Hyatt.[17] The MIP was measured first, followed by the MEP. Measurements of MIP and MEP were repeated each week so that the IMT prescription could be updated. Data for test-retest reliability assessment were collected twice on each of two separate consecutive days during the initial test period in the manner described, with a 4-hour rest period between daily trials. The MIP and MEP data obtained on the first day of testing were compared with the MIP and MEP data obtained on the second day of testing. Intraclass correlation coefficients (ICC[1,1]) were calculated to evaluate the reliability of the MIP and MEP measurements. Test-retest reliability of the MIP and MEP measurements was essentially identical within and between sessions (ICC=.98). An F test was used to test the null hypothesis that ICC=0. The level of significance was P [is less than] .05.

Inspiratory muscle training. Targeted IMT was performed with a Threshold inspiratory muscle trainer at 20% of MIP for 5 to 15 minutes, three times every day, for 8 weeks. Inspiratory muscle training was initiated only after a plateau in medical and exercise therapy (upright cycle ergometry for 10-20 minutes daily at an rating of perceived exertion of 2-3/10) had been achieved. All subjects were observed during the initial IMT session for adverse signs or symptoms and to verify proper IMT technique. The initial IMT session duration was limited to 5 minutes, three times per day. When subjects were free of overt anxiety, dyspnea, fatigue, and respiratory muscle discomfort, the IMT duration was progressed by 2 to 5 minutes until 15 minutes of IMT was achieved. Subjects were instructed to record all IMT sessions on a log sheet. Twice-weekly evaluations of the IMT technique and IMT log sheet were performed. Inspiratory muscle training prescriptions were progressed based on weekly measurements of MIP to maintain IMT at 20% of MIP. To avoid impaired inspiration due to a full stomach, subjects were instructed to perform IMT prior to meals or 1 hour after eating and to wear a noseclip during IMT sessions. All other exercise and functional/recreational activities were kept constant during the study period. Adherence with IMT was calculated as a ratio of the number of documented and observed IMT sessions to that prescribed.

Symptoms. Dyspnea was evaluated using a modified Borg scale of 0 to 10.[18] Subjects documented the degree of dyspnea at rest and during submaximal exercise (cycle ergometry at 0-10 W for a mean of 15 minutes).

Data Analysis

Statistical analysis was performed with the SYSTAT statistical package [double dagger] and included the calculation of means, standard deviations, and Pearson product-moment correlations; linear regression analysis; repeated-measures analysis of variance (ANOVA), and Friedman's test with post hoc analysis using Dunnett's procedure and all comparisons with a control procedure. The repeated-measures ANOVA and Dunnett's procedure were performed on the baseline and week 2, 4, 6, and 8 MIP and MEP measurements and dyspnea scores at rest of the eight subjects who completed the 8-week study. Friedman's test and all comparisons with a control procedure were performed on the baseline and week 2, 4, 6, and 8 dyspnea scores during exercise of the same subjects. Univariate linear regression analysis of the data for these subjects was performed to evaluate the relationships between a variety of patient characteristics (age, height, weight, NYHA classification, left ventricular ejection fraction, duration of HF, and IMT adherence) and MIP and MEP before and after IMT, percentage of change in MIP and MEP after IMT, degree of dyspnea at rest and during submaximal exercise before and after IMT, and percentage of change in dyspnea at rest and during exercise after IMT.

Results

Ventilatory Muscle Training

All subjects tolerated IMT without major complaint, complication, or change in medical therapy. The majority of subjects complained of mild abdominal discomfort after initial IMT, and several subjects had slight alterations ([is less than] 10%) in body weight and diuretic and dobutamine dosages.

Thirteen of the 14 subjects completed 4 weeks of IMT (1 subject underwent cardiac transplantation during week 3). Two subjects underwent cardiac transplantation, 1 subject underwent coronary artery bypass surgery, and 1 subject required intra-aortic balloon pump placement during week 5 of IMT, which prevented further IMT or testing of ventilatory muscle strength. One subject expired from sudden death during week 5 of IMT. The 8 remaining subjects completed 8 weeks of IMT.

Adherence to IMT was 63% [+ or -] 24%, with the majority of subjects completing three sessions of IMT per day for a mean of 10 [+ or -] 3 minutes each session. Seven subjects performed 50% or less of the prescribed IMT. Five of the seven subjects with adherence of 50% or less were in the cohort of subjects who completed the full 8 weeks of IMT. Nonetheless, the adherence of the eight subjects who completed 8 weeks of IMT was not different from that of the 6 subjects who were unable to complete 8 weeks of IMT (60% [+ or -] 26% versus 66% [+ or -] 22%). The level of adherence for each subject was consistent during the IMT period. The mean intensity of IMT during the 8-Week study period increased from a baseline value of 7 [+ or -] 3 cm [H.sub.2 0] to 12 [+ or -] 4 cm [H.sub.2 O].

Ventilatory Muscle Strength

Both the MIP and MEP increased after IMT (Fig. 1). Mean MIP increased 24% after 2 weeks of IMT (51 [+ or -] 21) cm [H.sub.2 0] to 63 [+ or -] 23 cm [H.sub.2 O]; P= .0001) and an additional 8% by week 6 of IMT. The initial and final MIPS were 44% [+ or -] 15% and 55% [+ or -] 15%, respectively, of age- and gender-predicted MIP. Mean MEP increased 13% after 2 weeks of IMT (85 [+ or -] 22 cm [H.sub.2 O] to 96 [+ or -] 19 cm [H.sub.2 O]; P=.0001) and remained at a plateau throughout the remainder of IMT. The initial and final MEPs were 39% [+ or -] 8% and 44% [+ or -] 6%, respectively, of age- and gender-predicted MEP.

Symptoms

Dyspnea scores at rest and during exercise decreased (29% and 28%, respectively) within 2 weeks after the initiation of IMT and remained at a plateau throughout the remainder of IMT (Fig. 1). Dyspnea scores at rest decreased from a mean of 2.0 [+ or -] 0.7 to 1.3 [+ or -] 0.05 P=.0001; a rating change from slight to very slight), and dyspnea scores during exercise decreased from a mean of 3.6 [+ or -] 0.5 to 2.6 [+ or -] 0.6 P=.003; a rating change from somewhat severe to moderate).

Correlation Analyses

Correlation analyses identified relationships between MIP after IMT and percentage of predicted FVC (r = .71, P=.04), dyspnea score at rest after IMT and FVC (r=-.77, P=.02) and total lung capacity (r=-.82, P=.01), baseline MEP and percentage of change in MEP after IMT (r=-.72, P=.04), and adherence to IMT and [FEV.sub.1] (r=.79, P=.02). There was no correlation between NYHA classification, left ventricular ejection fraction, duration of HF, or baseline measure of MIP and the percentage of change in MIP, MEP, or dyspnea score at rest or during exercise after IMT. Near-significant correlations, however, were found between baseline MIP and percentage of change in dyspnea scores at rest and during exercise (r=.67, P=.07 and r=.69, P=.06, respectively), level of adherence to IMT and MIP and MEP after IMT (r=.65, P=.08 and r=.68, P=.06, respectively), and measures of pulmonary function and MIP and MEP after IMT ([FEV.sub.1], and MIP: r=.68, P=.06 and [FEV.sub.1], and MEP: r=.69, P=.05) and level of adherence to IMT (FVC and adherence: r=.66, P=.07).

When the final measurements of all 14 subjects were included in the correlation analyses, correlations were observed between MIP and MEP after IMT and patient adherence to IMT (r=.78 and .77, respectively; P=.001), the percentage of change in MEP after IMT and patient age (r= -.64, P= .01), and the degree of dyspnea at rest and during exercise before and after IMT and pulmonary function. The correlations between dyspnea and pulmonary function of the 14 subjects prior to IMT and of the 8 subjects completing 8 weeks of IMT are shown in Table 2. Pearson Product-Moment Correlations Between Dyspnea and Pulmonary Function(a)

                                          Pearson r
Dyspnea Variable                          [FEV.sub.1] (%)   FVC (%)

Pre-IMT dyspnea at rest (N=14)            -.60               -.59
Pre-IMT dyspnea during exercise (N=14)    -.57               -.67
Post-IMT dyspnea at rest (n=8)              ...                ...

Dyspnea Variable                          FVC (L)    TLC (L)
Pre-IMT dyspnea at rest (N=14             ...        ...
Pre-IMT dyspnea during exercise (N=14)    ...        ...
Post-IMT dyspnea at rest (n=8)           -.77       -.82

Discussion

Comparison With Other Studies

The improvements observed in ventilatory muscle strength and dyspnea after 2 weeks of standard IMT in patients with advanced chronic HF are the major findings of this study. Only one previous study[11] has evaluated the effects of IMT on ventilatory muscle strength in a less compromised group of patients with HF. Improvements in ventilatory muscle strength, endurance, and both submaximal and maximal exercise capacity were observed after 12 weeks of intensive IMT in a small group of patients with HF.[11] The methods of ventilatory muscle training used in the study by Mancini et al[11] included isocapnic hyperpnea, maximal inspiratory and expiratory strength training via pressure gauges, targeted inspiratory muscle training (via the Threshold inspiratory muscle trainer), and breathing calisthenics, all of which required approximately 90 minutes and specialized equipment. The method of IMT used in our study was simpler, less costly, less cumbersome, and less time consuming and produced results similar to those using more extensive methods of ventilatory muscle training.

The absence of other studies of the effects of IMT on patients with HF surprises us because patients with chronic HF have been shown to have poor ventilatory muscle strength and endurance and because their primary complaint is dyspnea.[8-10,19] The early improvements in ventilatory muscle strength and dyspnea that we observed may be due to the debilitating effects of chronic end-stage HF (thus, eliciting early training effects)[20-24] or to the absence of a hyperinflated chests as seen in patients with obstructive lung disease.[25] Review of five studies of ventilatory muscle training in female subjects with no history of cardiopulmonary disease, patients who had undergone thoracic surgery, and patients with chronic obstructive lung disease, however, revealed similar improvements in ventilatory muscle strength after only 2 to 4 weeks of ventilatory muscle training (Fig. 2).[1-4,7] Our results, therefore, are in keeping with those of other published studies and further support the likelihood of early elicitation of training effects on ventilatory muscles in end-stage cardiopulmonary disease.

Patients with chronic HF have been observed to increase their peripheral skeletal muscle strength and endurance after only 4 to 8 weeks of aerobic exercise conditioning.[20-24] Aerobic exercise performed for greater than 4 to 8 weeks appears to produce no substantial improvement in cardiorespiratory fitness. The degree of improvement in cardiorespiratory fitness of patients with chronic HF was 21% [+ or -] 9%[20-24] after a mean of 1.7 [+ or -] 0.45 months of aerobic exercise conditioning compared with 25% [+ or -] 4% after a mean of 10.5 [+ or -] 6.0 months.[26-29] In view of these findings, patients with chronic HF appear to elicit an earlier, yet limited, training effect. Possible limitations in producing further training effects in patients with chronic HF include skeletal muscle myopathies[30,31]; cardiovascular abnormalities[32,33]; and, pertinent to our study, the ventilatory dysfunction of patients with chronic HF and pulmonary edema, which may limit further adaptations to exercise training.[34,35]

Role of Inspiratory Muscle Training

The contribution of continued aerobic exercise and medical therapy in improving ventilatory muscle strength and symptoms seems unlikely because IMT was initiated only after a plateau was observed in medical and exercise therapy, as determined by either invasive hemodynamic measurements or patient symptoms and exercise performance. Furthermore, the majority of these patients were hospitalized with limited ability to exercise. We believe, therefore, that IMT is responsible for the results we observed.

The early improvements and subsequent plateauing in ventilatory muscle strength and patient symptoms may be due to a learning effect. However, in addition to studies showing early improvement in ventilatory muscle strength,[1-4,7] the excellent reliability of repeated measurements of MIP and MEP and the reduction in dyspnea at rest and during exercise support the major contribution of IMT rather than a learning effect due to familiarization with the IMT technique. The contribution of IMT in improving ventilatory muscle strength and dyspnea is further supported by previous investigations[8-10,25] that demonstrated a relationship between dyspnea and poor ventilatory muscle strength. A greater intensity of IMT or level of adherence to IMT might have led to greater gains in ventilatory muscle strength beyond 2 weeks. The less than desirable level of adherence in this study was likely the result of time constraints due to medical testing and therapy and fatigue from advanced HF.

Clinical Implications

Although the majority of subjects who were unable to complete 8 weeks of IMT underwent anticipated procedures during week 5 of IMT, we have concerns because one subject required intra-aortic balloon pump placement and one subject died. These concerns are further supported by the observation that patients similar to ours in another study[11] who were performing aggressive IMT required an increase in diuretic therapy and two hospitalizations for angina approximately 1 month after the initiation of IMT (which were attributed to increased activity). Our subjects required no change in their medical therapy during less intense IMT. Whether IMT could have played any role in patient decompensation warrants further investigation.

Despite the early plateau seen during IMT, increases in MIP and MEP have previously been shown to be associated with fewer postoperative complications after thoracic surgery.[7,13,14] Similarly, additional IMT may decrease the likelihood of postoperative complications by increasing ventilatory muscle endurance.[36,37]

Although the MIP and MEP were greater after a short-term program of IMT, the values were still much lower than normal. After IMT, the MIP and MEP were 55% [+ or -] 15% and 44% [+ or -] 6% of age- and gender-predicted values. Despite this degree of residual dysfunction, the overall 32% and 13% improvements in MIP and MEP, respectively, improved dyspnea at rest and with exercise. A similar improvement in dyspnea at rest was observed by Mancini et al.[11]

The correlations between dyspnea and pulmonary function that we observed is not surprising, but these correlations were not observed in subjects with less advanced HF (mean NYHA class=2.6 [+ or -] 0.8).[8] McParland et al[8] concluded that the lack of correlation between dyspnea and pulmonary function provides strong evidence against "global respiratory impairment" due to HF. Our results and the results of other researchers,[9,10,34,35] however, suggest that more advanced HF may produce a "global respiratory impairment," as seen in patients with primary lung disease.[38]

The results of our correlation analyses suggest that greater levels of pulmonary function were associated with greater improvements in ventilatory muscle strength and dyspnea after IMT. Initiating an IMT program early in the course of HF may delay any global respiratory impairment of advanced HF and increase the likelihood of improvement in ventilatory muscle strength and dyspnea.

Limitations

The limitations of this study include the absence of an untreated control group, the small sample size, the inclusion of only patients with severe heart failure, the inability of six patients to complete the full 8 weeks of IMT, the utilization of a relatively low-intensity IMT program, the absence of a standardized measure of quality of life or patient function, and the lack of measurement of ventilatory muscle endurance. Of these limitations, we believe that the small sample size and lack of a control group are the greatest threats to the external validity of this study.

The possible, but unlikely, contribution of continued aerobic exercise conditioning and medical therapy, as well as a learning effect in improving ventilatory muscle strength and patient symptoms, exists. The excellent results of reliability testing and the initiation of IMT only after optimization of medical and exercise therapy was achieved, however, decrease the likelihood of a learning effect or continued therapy contributing to improvements in ventilatory muscle strength and patient symptoms. A type II statistical error may have been responsible for the plateau in ventilatory muscle strength and dyspnea observed after week 4 of IMT when six of the subjects were unable to further participate in IMT because of either transplantation or unanticipated events. This plateau, however, may represent a physiologic limit to further improvement in ventilatory muscle strength because of impaired ventilatory muscle performance or pulmonary function from chronic HF. The utilization of a relatively low-intensity IMT program may also be responsible for the plateau in ventilatory muscle strength and patient symptoms that we observed.

Conclusion

Despite its limitations, our study demonstrates that a standard targeted IMT program can produce early improvements in ventilatory muscle strength and dyspnea at rest and during exercise in some patients with advanced HF. Greater levels of pulmonary function were associated with greater improvements in dyspnea and ventilatory muscle strength after IMT. These improvements may decrease the debilitating effects of chronic HF as well as the functional and medical dependence and impairment observed in patients with chronic HF. In view of the limitations of our study, the generalizability of the study results is limited. Future study of IMT in patients with HF should (1) include a control group and a broader spectrum of HF severity, (2) evaluate the effects of higher-intensity IMT and other modes of ventilatory muscle training, and (3) measure the effects of IMT on survival, quality of life, and patient function.

(*) Healthscan Products Inc, 908 Pompton Ave, Cedar Grove, NJ 07009.

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LP Cahalin, PT, CCS, is Physical Therapist, Heart Failure and Transplantation Service, Massachusetts General Hospital, and Clinical Associate Professor, Sargent College of Allied Health Profession, Boston University, Boston, Mass. Address all correspondence to Mr Cahalin at Physical Therapy Department, Sargent College of Allied Health Professions, Boston University, 635 Commonwealth Ave, Boston, MA 02215 (USA) ([e-mail]).

MJ Semigran, MD, is Physician, Heart Failure and Transplantation Service, Massachusetts General Hospital, and Assistant Professor of Medicine Harvard Medical School, Cambridge, Mass.

GW Dec, MD, is Medical Director, Heart Failure and Transplantation Service, and Acting Chief Cardiac Unit, Massachusetts General Hospital, and Associate Professor of Medicine, Harvard Medical School.

This study was approved by the Human Subject Review Committee of Massachusetts General Hospital.

This research was supported in part by a grant from the Ionta Fund and the Foundation for Physical Therapy Inc.