Inspiratory Muscle Weakness and Dyspnea in Chronic Heart Failure1- 3

COlM MCPARlAND, 4 BHARATH KRISHNAN,5 YIMEI WANG, 6 and CHARLES G. GAllAGHER7

Introduction

Dyspnea is a common, disabling symptom in patients with heart failure (1, 2), yet the underlying mechanisms remain unknown (1,3). The commonly held view that dyspnea in heart failure patients is a consequence of raised left atrial pressure may be correct for acute heart failure (1). Dyspnea in chronic heart failure, however, does not appear to be due to ~ changes in intrapulmonary vascular pressures (1, 2, 4-8), and many heart failure patients receivingmedical therapy remain symptomatic in the absence of evidence of fluid retention (9). Furthermore, exertional dyspnea in chronic heart failure cannot be attributed to alteration in arterial blood gas tensions (2, 6-8, 10),and it correlates poorly with the severity of chronic heart failure as determined by clinical evaluation, indices of left ventricular performance and aerobic capacity, or duration of survival (6, 7, 9). The respiratory muscles form a vital skeletal muscle pump, which may fail if the respiratory muscle energy demand exceeds the available energy supply (11). Respiratory muscle strength plays an important role in determining the respiratory muscle energy demand. Reduced respiratory muscle strength results in a greater fraction of the maximum pressure developed by the respiratory muscles being required to breathe (11). When the fraction of the maximum inspiratory pressure utilized during breathing increases, patients with respiratory disease and normal individuals experience increases in dyspnea intensity (12-14). Therefore, reduced inspiratory muscle strength may contribute to dyspnea, as well as predisposing to respiratory pump failure. Inspiratory muscle weaknessis an important factor in determining the magnitude of dyspnea in patients with chronic obstructive pulmonary disease (14-16), and in some of these patients the dyspnea is reduced by inspiratory muscle training (17). Failure of the respiratory pump has been demonstrated in dogs during acute failure of the other "vital pump," the

SUMMARY Dyspnea is a common, disabling symptom In chronic heart failure, yet the underlying mechanisms remain unknown. The respiratory muscle pump Is composed of skeletal muscles whose strength directly Influences the pump's performance. Respiratory muscle weakness Is Important In the dyspnea experienced by some patients with pulmonary disease; however,the role of the respiratory muscle pump In the dyspnea of chronic heart failure has not previously been examined. To assess respiratory muscle strength and Its relation to dyspnea during dally activity, we measured maximum Inspiratory and expiratory mouth pressures as Indices of respiratory muscle strength and the baseline dyspnea Index In nine stable, chronic cardiac pump failure patients who had no evidence of primary lung disease, and In nine age- and sex-matched healthy control subjects. The chronic heart failure patients, when compared with their matched control subjects, had reduced Inspiratory and expiratory muscle strength, and both Inspiratory and expiratory muscle strength were significantly correlated with dyspnea during dally activity (r 2 = 0.80, P = 0.001 and r 2 = 0.45, P = 0.05, respectively). Inspiratory muscle strength accounted for all of the variance In dyspnea that was correlated with respiratory muscle strength when the relative contributions of Inspiratory and expiratory muscle strength were examined. There was no correlation between lung volumes or spirometry and dyspnea In the heart failure patients. These findings Indicate that patients with stable chronic heart failure have Inspiratory and expiratory muscle weakness and further suggest that the respiratory muscle pump significantly contributes to the dyspnea during the activities of dally living. AM REV RESPIR DIS 1992; 146:467-472

cardiac pump (18). However, the role of the respiratory muscle pump in the dyspnea of chronic cardiac pump failure has not previously been examined. The goal of this study was therefore to examine the relationship between respiratory muscle strength and dyspnea in patients with stable, chronic heart failure. Methods A total of nine stable outpatients with chronic heart failure (CHF) and nine matched normal subjects were studied (table 1).

CHFGroup Patients wereconsidered eligible for the study if they had stable heart failure due to a cardiomyopathy for at least 3 months. Heart failure was defined as symptomatic left ventricular dysfunction, with left ventricular ejection fraction < 0.45 (19).The patients studied had left ventricular systolic dysfunction documented by two-dimensional echocardiography or radionuclide ventriculography and the clinical features of heart failure for 23 months on average (range 6 to 48 months); the mean resting left ventricular ejection fraction was 0.26 (range 0.16 to 0.40). All were ambulatory outpatients who had not been hospitalized for at least 1 month before testing. Patients were excluded if they had primary pulmonary, neurologic, or myopathic disease or if they had surgery within the previ-

ous 3 months or a viral illnesswithin the previous month. Six patients were male, and three were female. Heart failure was secondary to coronary artery disease in five patients and due to idiopathic dilated cardiomyopathy in the remaining four patients. Eight patients were taking diuretics and angiotensin-converting enzyme (ACE) inhibitors. Three patients weretaking digoxin, two patients were taking isosorbide dinitrate, and one patient was taking a calcium channel antagonist (diltiazem), in addition to ACE inhibitors and diuretics. One patient was tak(Received in original form June 24, 1991 and in revised form December 9, 1991) 1 From the Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. :z Supported by an operating grant from the Heart and Stroke Foundation of Canada. 3 Correspondence and requests for reprints should be addressed to Dr. Charles G. Gallagher, 5th Floor, Ellis Hall, Royal University Hospital, University of Saskatchewan, Saskatoon, Saskatchewan S7N OXO, Canada. .. Supported by a fellowship from the Saskatchewan Health Research Board. S Supported by a fellowship from the Saskatchewan Lung Association. 6 Supported by a fellowship from the John Moorehead Foundation. 7 Supported by a Saskatchewan Lung Association Scholarship.

467

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MCPARLAND, KRISHNAN, WANG, AND GALLAGHER

TABLE 1

ing isosorbide dinitrate and diltiazem only. Medication was not altered during the month preceding the test. None of the patients were housebound; sixtook daily walks outside their homes.

Normal Subjects Control subjects were studied using the same technique as for the CHF patients and were matched for variables known to affect respiratory muscle strength (15, 20). Possible control subjects were excluded if they had any evidence of pulmonary or cardiac disease, neuromyopathic disease, recent surgery,or viral illness or if they were receiving medication whose known side effects included possible myopathic or electrolyte abnormalities. The control subj ects in this study were part of a larger control group studied over a time period similar to that for the CHF patients, and matching wasdone by an investigator who was unaware of the subjects' test performance. After matching for sex, control subjects were matched for age (± 4 yr). All the control subjects were active and took daily walks outside their homes, but none was an athlete. The study was approved by the Medical Ethics Committee, University of Saskatchewan, and all subjects gave written informed consent. Assessment of Dyspnea Dyspnea experienced during ordinary daily activities was assessed in all subjects using the baseline dyspnea index (01) described by Mahler and colleagues (21). This index consistsof three sections:the magnitude of the task producing dyspnea, the magnitude of the effort required to produce dyspnea, and the functional impairment occurring as a consequence of dyspnea. Each of the three sections is scored on a five-point scale from 0 to 4 based on set criteria, and the DI is the total for all three sections. Thus the DI can range from oto 12 in whole numbers, and the most dyspneic have the lowest score. This index is reproducible, correlates with other clinical scales of dyspnea in patients with cardiac or respiratory disease (16,21,22), and also correlates with 6- and 12-min walk tests (21, 22). The dyspnea rating wasperformed before lung volume, spirometry, or respiratory muscle strength measurement. Lung Volumes and Spirometry Absolute lung volumes were measured using a constant-volume, variable-pressure body plethysmograph (Cardiopulmonary Instruments Corp., Houston, TX). FEV 1 and FVC were measured, using standard techniques (23), by a heated pneumotachographtransducer-demodulator-integrator system. The predicted normal values used for lung volume and spirometry were those of Goldman and Becklake (24) and those of Morris and coworkers (25), respectively. Respiratory Muscle Strength Mouth pressure during maximum static inspiratory efforts (PImax) at FRC and RV was

CLINICAL AND ANTHROPOMETRIC DATA CHF Patients

Subject 1 2 3 4 5 6 7 8 9

Etiology

NYHA Class

CAD CAD CAD CAD CAD IDCM IDCM IDCM IDCM

II II II IV III IV

Sex M M M M

F

111

M M

II II

F

Mean SEM

F

Control Subjects Age (yr)

Height (em)

Weight (kg)

SUbject

Sex

rt 60 50 77 70 67 55 61 64

185 179 164 171 151 175 179 168 161

98 87 80 71 71 88 101 66 86

1 2 3 4 5 6 7 8 9

M M M M

65 3

170 4

83 4

= chronic heart failure; = New York Heart Association

Definition of abbreviations: CHF myopathy; NYHA

= coronary

CAD

measured as an index of inspiratory muscle strength. Expiratory muscle strength was assessed by mouth pressure measured during maximum static expiratory efforts (PEmax) at FRC and TLC. Pressure was measured by a pressure transducer-demodulator system (ValidyneCorp., Northridge, CAl, which was calibrated using a manometer before each test (±300 em H 2 0 ), and recorded using an amplifier and chart recorder (Gould, BallainvilHers, France). All measurements were made with the subject seated, wearing a nose clip, and with visual feedback on an oscilloscope (Tektronix, Beaverton, OR). A scuba type of mouthpiece was used, with a small leak incorporated into the airway during all static maneuvers and light pressure applied to the cheeks during expiratory maneuvers to minimize the contribution of facial muscles (26). Subjects were specifically instructed not to use the facial muscles during static maneuvers, and this was closely watched for by the observers. .After demonstration of the technique required and several practice maneuvers, each subject performed serial maximal maneuvers with visual feedback and consistent verbal encouragement. Maneuvers were repeated until at least two readings sustained for 2 to 3 s and with a variation of less than 10070 at each lung volume were obtained (mean variation 4070). Several minutes of rest was given between each maximal attempt. The highest val-

F M M F F

artery disease; IDCM

Age (yr)

Height (em)

Weight (kg)

76 64 51 76 71 64 59 60 61

179 182 186 172 158 174 179 171 152

89 97 91 83 64 75 81 70 54

65 3

173 4

78 5

= idiopathic

dilated cardio-

ue achieved was used in the analysis. Inspiratory pressures are negative with respect to atmospheric pressure and are recorded with a negative sign.

Statistics Results are expressed as mean (SE). Differences between the CHF patients and matched control subjects were analyzed using the paired t test (27). The relation between dyspnea and respiratory muscle strength or pulmonary function variables in each group were examined using multiple linear regression analysis (28). A p value < 0.05 was considered significant. Results

The anthropometric data for the CHF patients and control subjects matched for sex and age (±4 yr) are listed in table 1. There was no significant difference between the CHF patients and matched control subjects in height or body weight. Lung volume and spirometric values for the two groups are listed in table 2. All subjects had spirometry and lung volumes within the normal range (24, 25). The CHF patients had lower lung volume and spirometric values than control subjects, but this difference was not significant.

TABLE 2 PULMONARY FUNCTION DATA CHF Patients Mean (SE) TlC, l VC,l RV, l FRC,l FEV" l/min %FEV,/FVC

5.57 (0.38) 3.51 (0.28) 2.06 (0.17) 3.29 (0.29) 2.49 (0.22) 74 (2)

0/0

of Predicted 93 93 93 97 87 98

Control Subjects Mean (SE)

0/0 of Predicted

6.54 (0.59) 4.09 (0.40) 2.46 (0.29) 3.81 (0.39) 2.78 (0.28) 73 (1)

103 102 105 107 93 98

Definition of abbreviations: CHF = chronic heart failure; TLC =- total lung capacity; VC =- vital capacity; RV • residual volume; FRC II: functional residual capacity; FEV1 iii forced expired vol~me in 1 s; FVC :a forced vital capacity.

RESPIRATORY MUSCLES AND DYSPNEA IN CHRONIC HEART FAIWRE

Respiratory Muscle Strength Respiratory muscle strength values for the CHF patients are listed in table 3, and the comparison between the respiratory muscle strength of the CHF patients and matched control subjects is shown in figure 1. The CHF patients had a significant reduction in inspiratory muscle strength; eight of the nine CHF patients

469

recorded lower PI max values than the matched control subjects at RV (mean reduction 26 ern H 20, p < 0.025), and six of the nine CHF patients recorded lower PImax values than the control subjects at FRC (mean reduction 18em H 20, p = 0.05). The CHF patients also had a significant reduction in expiratory muscle strength; seven of the nine CHF pa-

tients recorded lower PEmax values than the matched control subjects at TLC (mean reduction 40 em H 20, p < 0.0125). Expiratory muscle strength measured at FRC was also reduced in the CHF patients (mean reduction 17 em H 20), but this difference did not reach statistical significance (p < 0.10).

Respiratory Muscle Strength-Dyspnea Relation TABLE 3 DYSPNEA, RESPIRATORY MUSCLE STRENGTH, AND LUNG VOLUMES IN CHF PATIENTS

Subject

1 2 3 4 5 6 7 8 9 Mean SE

Plmax FRC (em H2O)

Plmax RV (em H2O)

PEmax FRC (em H2O)

PEmax TLC (em H2O)

TLC (L)

VC (L)

6 8 7 2 6 4 6 6 4

-80 -99 -108 -43 -99 -64 -73 -75 -75

-95 -125 -109 -51 -100 -56 -74 -87 -75

125 168 140 100 128 53 105 90 113

120 180 175 110 148 61 163 113 130

6.38 5.96 4.48 6.39 7.60 4.80 4.21 4.61 5.71

4.65 3.60 3.30 3.87 4.90 3.00 2.55 2.50 3.25

5 0.6

-80 7

-86 8

114 11

133 13

5.57 0.38

3.51 0.28

DI

Definition of abbreviations: CHF = chronic heart failure; DI = dyspnea index; Plmax FRC = maximum inspiratory mouth pressure at FRC; PImax RV = maximum inspiratory mouth pressure at RV; PEmax FRC, maximum expiratory mouth pressure at FRC; PEmax TLC, maximum expiratory mouth pressure at TLC.

Plmax FRC (cmH 2O)

250

-150

CHF

200

••

., •

-100 -50

a

PEmax FRC (cmH 2O)

150 100



a

-50

..

CHF

a

a

CONTROL

250

-150

CHF

• • ,

• • •

-50

a

,

200 150



CHF 100

0 -50

-100 -150

CONTROL

50 100 150 200 250

PEmax TLC (cmH 2O)

• •• •

,





50

a



CONTROL

Plmax RV (cmH 2O)

-100

• •

50

-100 -150





a

50 100 150 200 250

CONTROL

Fig. 1. Relation between matched control subjects and chronic heart failure (CHF) patients for inspiratory and expiratory muscle strength. P1maxFRC, maximal.inspiratory mouth pressure at FRC; P1maxRV, maximal inspiratory mouth pressure at RV; PEmaxFRC, maximal expiratory mouth pressure at FRC; PErnaxTLC, maximal expiratory mouth pressure at TLC; diagonal lines are the lines of identity.

The relation between dyspnea during ordinary daily activities (as represented by the DI) and inspiratory muscle strength (PI max measured at FRC) and expiratory muscle strength (PEmax measured at FRC) in the CHF patients is shown in figure 2. Inspiratory and expiratory muscle strength were significantly correlated with dyspnea during ordinary daily activity (r = 0.89, p = 0.001 and r = 0.67, p = 0.05, respectively). Similar correlations with dyspnea were observed for inspiratory and expiratory muscle strength measured at RV and TLC, respectively (table 4). The relative contributions of inspiratory and expiratory muscle strength to dyspnea in the CHF patients were examined by multiple linear regression with stepwise analysis of variance using PI max measured at FRC and PEmax measured at FRC. Inspiratory muscle strength accounted for all of the variance in dyspnea that could be attributed to its linear regression on respiratory muscle strength. Expiratory muscle strength did not significantly improve the correlation when inspiratory muscle strength was accounted for. There was no correlation between dyspnea during daily activity and any of the other respiratory variables measured in the CHF patients (table 4). All control subjects were asymptomatic and scored 12, the maximum value available, on the DI. Thus there was no correlation between dyspnea and respiratory muscle strength or the other respiratory function variables in the control group. Respiratory muscle strength was normalized by expressing it as a fraction of the matched control value, and its correlation with DI was assessed. Normalized PI max (measured at FRC) was significantly correlated with dyspnea during ordinary daily activity (r' = 0.73, p = 0.004); there was no correlation between normalized PE max (measured at FRC) and dyspnea (r 2 = 0.03, p = 0.64). Patients with the greatest reduction in inspiratory muscle strength (the lowest normalized fraction) were the most dyspneic.

470

MCPARLAND, KRISHNAN, WANG, AND GALLAGHER

Dyspnea Index (01) 12

Plmax r Rc

PEmax r Rc 10





8

• ••

6

• r

=



0.89

-150

-100

• •



4





2

-50

0





50

100

r

= 0.67

150

200

Pressure (em H20) 01

=

-0.08Plmax FRC -

01 = O.04PEmax FRC + 1.2

1.1

P = 0.001

P

= 0.05

Fig. 2. Relation between inspiratory and expiratory muscle strength and dyspnea during daily activities in the chronic heart failure (CHF) patients. PlmaxFRC, maximal inspiratory mouth pressure at FRC. PEmaxFRC, maximal expiratory mouth pressure at FRC.

TABLE 4 DYSPNEA CORRELATIONS IN CHF PATIENTS BY LINEAR REGRESSION ANALYSIS r2 TLC VC FEV 1

DI DI DI

Plmax

FRC RV

DI DI

PEmax

FRC TLC

DI DI

= -0.2TLC + 6.7 = 0.02VC + 5.4 = 0.7FEV1 + 3.8 = - 0.08Plmax - 1.1 = - 0.07Plmax - 0.6 = 0.04PEmax + 1.2 = 0.04PEmax + 0.8

p Value

0.03 0.00 0.06

0.66 0.99 0.53

0.80 0.84

0.001 0.0005

0.45 0.50

0.05 0.03

Definition of abbreviations: CHF = chronic heart failure; 01 = dyspnea index; Plmax = maximum inspiratory mouth pressure; PEmax = maximum expiratorymouth pressure.

Those patients with normal or near normal inspiratory muscle strength were less dyspneic than patients with inspiratory muscle weakness, but were more dyspneic than control subjects. Discussion

The findings of this study are that patients with stable chronic heart failure have reduced inspiratory and expiratory muscle strength and that the inspiratory muscle weakness in these patients shows a strong correlation with dyspnea experienced during daily activities. It is very unlikely that the reduced PImax and PEmax values recorded in the CHF patients represent submaximal or poor effort. None of the patients experienced dyspnea or other symptoms during the maneuvers. All control subjects

and patients were encouragedin a consistent manner during each static maneuver to make maximal effort, they had visual feedback of the effect of their efforts, and, further, they were encouraged to attempt to surpass their previous best effort. In addition, it has been shown that normal people and dyspneic patients with severechronic obstructive pulmonary disease (including some with reduced PImax) maximally activate the diaphragm during static inspiratory efforts (29, 30). The demonstration of a diaphragmatic myopathy in an animal model of chronic heart failure (31)also supports the view that the reduced PImax and PE max values observed in our patients with stable chronic heart failure indicate reduced respiratory muscle strength. The only report of respiratory muscle strength in human chronic heart failure, other than this

report, is that of Hammond and colleagues (32) reporting respiratory muscle weakness in patients with severe chronic heart failure. De Troyer and coworkers (33) described reduced inspiratory muscle strength in patients with mitral valve disease (with or without aortic valve disease), but it is unclear how many had chronic heart failure. "Heart disease" patients with normal respiratory muscle strength, relative to predicted normal values, were reported by Mahler and Wells (16), but the type of heart disease or the presence of heart failure was not reported. Because of the sigmoidal shape of the pressure-volume curve of the respiratory system, mild to modest decreases in inspiratory muscle strength may cause only minor changes in total lung capacity and vital capacity. In fact, no significant change in these volumes occurred with experimentally induced inspiratory muscle fatigue in humans (34). Therefore, the minor but not statistically significant reductions in these volumes in our CHF patients (compared with the control subjects) is consistent with the observed respiratory muscle weakness. Our study is the first to demonstrate a correlation between inspiratory muscle strength and dyspnea during ordinary daily activities in stable, ambulatory chronic heart failure patients without evidence of primary lung disease. The reduction in our CHF patients' respiratory muscle strength was, on average, moderate. However, the strong correlation between inspiratory muscle strength (either absolute or normalized) and dyspnea, although not necessarily proving causation, suggests that inspiratory muscle weakness may contribute significantly to the morbidity. We particularly wished to assess the magnitude of dyspnea experienced by chronic heart failure patients during ordinary daily activities, as this symptom reduces their quality of life and it may not be the same as that experienced during maximal exercise testing (4, 22). Dyspnea during daily activity, measured by the baseline dyspnea index, has previously been correlated with respiratory muscle strength in patients with primary lung disease (16). The mechanism of dyspnea in chronic heart failure is not well understood. Unlike dyspnea associated with acute heart failure (1), it does not appear to be related to changes in intrapulmonary vascular pressures (1, 2, 4-8); it is not due to hypoxemia, because arterial oxygenation is normal during exertion in CHF pa-

RESPIRATORY MUSCLES AND DYSPNEA IN CHRONIC HEART FAIWRE

tients (2, 6-8, 10); and it correlates poorly with assessments of CHF severity (6, 7, 9) or fluid retention (9). Recent studies in patients with respiratory disease and in normal individuals suggest that the magnitude of dyspnea experienced is at least partly determined by the perception of the outgoing central motor command to the muscles of inspiration (3, 12, 35), the inspiratory motor output (IMO). IMO is increased by increases in minute ventilation, by increases in respiratory system impedance, and by weakness of the respiratory muscles (35). Reduced inspiratory muscle strength necessitates a greater IMO intensity to produce a given increase in dynamic inspiratory muscle pressure and ventilation. In our stable CHF patients, although both inspiratory and expiratory muscle weakness was demonstrated, only inspiratory muscle strength was significantly correlated with dyspnea when the relative contributions ~ of each to the symptom were assessed. This is consistent with the postulated mechanism that dyspnea magnitude is determined by the intensity of IMO (12, 35) and therefore increased by inspiratory muscle weakness. Furthermore, chronic heart failure is associated with reduced lung compliance, which by increasing respiratory system impedance further aggravates the effect of reduced inspiratory muscle strength on IMO intensity (35). Thus, inspiratory muscle weakness may playa role in the dyspnea of CHF by contributing, as one of several factors, to increases in IMO intensity. Since some of our patients who had normal strength were more dyspneic than control subjects, factors other than inspiratory muscle weakness must contribute to dyspnea in CHF. However, the significant correlation between dyspnea and normalized inspiratory muscle strength in our CHF patients indicates that, although factors other than strength contribute to dyspnea, differences in strength are a major determinant of differences in dyspnea between CHF patients. It is conceivable that reduced inspiratory muscle strength could be part of a nonspecific, global respiratory impairment related to the severity of heart failure. If so, the correlation between dyspnea and inspiratory muscle strength may occur simply because dyspnea and the global respiratory impairment are both primarily related to heart failure severity. The lack of correlation between dyspnea and the other respiratory variables measured (tables 3 and 4) provides strong evidence against this hypothesis. Patients with primary lung disease who previously

demonstrated a correlation between dyspnea and respiratory muscle strength (16) also had significant correlations between dyspnea and spirometric values (FEV 1 and FVC) consistent with global respiratory involvement. Although chronic heart failure patients maintain arterial oxygenation (2, 6-8, 10) and carbon dioxide tension (6, 7) at or near normal levels during exercise, they require a disproportionately large increase in minute ventilation (6, 8, 36, 37), mainly due to increased dead space ventilation (6, 8, 36, 37). This increased demand for ventilation must be met by the respiratory muscles. Several studies in CHF patients have demonstrated a reduction in blood flow to exercising peripheral skeletal muscles (38), increased muscular anaerobic activity (38), and substrate utilization abnormalities (39). Alterations in skeletal muscle fiber type, size, and enzyme content have also been demonstrated in chronic heart failure (40, 41), and some of these patients have reduced peripheral skeletal muscle strength (40). It has been suggested that these skeletal muscle abnormalities may contribute to the other main symptom in chronic heart failure, fatigue (38). The respiratory muscles, which are also skeletal muscles, responding to the increased ventilatory demands may be operating under similar adverse conditions. Thus the mechanisms underlying the two main symptoms of chronic heart failure, dyspnea and fatigue, may be interrelated (39). What are the possible mechanisms underlying inspiratory muscle weakness in stable CHF patients? Whatever the cause, it is not unique to inspiratory muscles because expiratory muscle strength was also reduced. It may be part of a generalized skeletal myopathy: as mentioned previously, recent studies have documented limb muscle weakness and myopathic changes in chronic heart failure (40, 41). Inspiratory muscle weakness may be due to impaired respiratory muscle blood flow, analogous to the impaired limb muscle perfusion that occurs in this condition (38, 39). Malnutrition (42) and electrolyte depletion, especially potassium and magnesium deficiency (43), may complicate chronic heart failure or its therapy and adversely affect respiratory muscle performance (44-46). The body weights of our CHF patients and control subjects were not significantly different, but body weight has limited usefulness as the sole indicator of nutritional status in edematous states. A skeletal myopathy, respiratory or global, may result in part from de conditioning secondary

471

to inactivity because of underlying chronic heart failure or prescribed restrictions in daily activity (35, 39-41). All the CHF patients studied in this report were ambulatory; none was completely inactive. It is possible that the reduced PIffiax in chronic heart failure is not due to weakness but that inspiratory muscle activation (during the PIffiax measurement) was submaximal because of monosynaptic inhibition by pulmonary C (unmyelinated) fibers, stimulated by increased lung water, that is, Paintal's "J reflex" (47). This possibility cannot be excluded, but the in vitro evidence of a diaphragm myopathy in rabbits with chronic heart failure (31) makes it unlikely. Even if this were the case, such inspiratory muscle inhibition should be as marked, if not more so, during "normal" inspiratory muscle activation (exercise, for example), so that the measured PI ffiax would still be a good assessment of the inspiratory muscle strength available for daily activities. An important clinical consequence of inspiratory muscle weakness in CHF patients, in addition to a probable significant contribution to the dyspnea, is a predisposition to respiratory pump failure, especially when the inspiratory muscle energy demands are increased further, as with acute pulmonary edema or respiratory infection (11). Specific inspiratory muscle training in patients with chronic obstructive pulmonary disease who have inspiratory muscle weakness can increase inspiratory muscle strength and reduce dyspnea (17). General physical training in patients with chronic heart failure secondary to coronary artery disease can improve fitness, increase exercise duration, and reduce patient-rated symptom scores, including breathlessness rating (48). In view of the inspiratory muscle weakness in stable, ambulatory chronic heart failure patients and its strong correlation with their dyspnea during ordinary daily activity as demonstrated in this study, inspiratory muscle training either alone or as part of general physical training may provide a means of reducing dyspnea in this clinical setting. This merits further investigation. In conclusion, this study demonstrates that inspiratory and expiratory muscle strength are impaired in ambulatory patients with stable chronic heart failure and that inspiratory muscle weakness is significantly correlated to the dyspnea during daily activities. Although this correlation is striking it does not prove causation, but it raises the possibility that inspiratory muscle weakness may signif-

472

MCPARLAND, KRISHNAN, WANG, AND GALLAGHER

icantly contribute to the morbidity. Further work is needed on the mechanisms of dyspnea in chronic heart failure to establish whether a causal role exists. In the interim, these patients should be evaluated for reversible factors that may impair respiratory muscle performance. Acknowledgment We thank Dr. Bibiana Cujec, Dr. James McMeekin, and Dr. Whit Firor for allowing us to study patien ts under their care and Mrs. Theresa Dufault for assistance in preparing the manuscript. References 1. Lipkin DP, Poole-Wilson PA. Symptoms limiting exercise in chronic heart failure. Br Med J 1986; 292:1030-1. 2. Weber KT, Szidon JP. Exertional dyspnea. In: Cardiopulmonary exercise testing. Physiologic principles and clinical applications. Weber KT, Janicki JS, eds. Philadelphia: W. B. Saunders, 1986; 290-301. 3. Cockcroft A, Guz A. Breathlessness. Postgrad Med J 1987; 63:637-41. 4. Gibbs JSR, Keegan J, Wright C, Fox KM, Poole-Wilson PA. Pulmonary artery pressure changes during exercise and daily activities in chronic heart failure. J Am ColI Cardiol1990; 15:52-61. 5. Lipkin DP, Canepa-Anson R, Stephens MR, Poole-Wilson PA. Factors determining symptoms in heart failure: comparison of fast and slow exercise tests. Br Heart J 1986; 55:439-45. 6. Sullivan MJ, Higginbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. Circulation 1988; 77:552-9. 7. Franciosa JA, Leddy CL, Wilen M, Schwartz DE. Relation between hemodynamic and ventilatory responses in determining exercise capacity in severe congestive heart failure. Am J Cardiol1984; 53:127-34. 8. Wilson JR, Ferraro N. Exercise intolerance in patients with chronic left heart failure: relation to oxygen transport and ventilatory abnormalities. Am J Cardiol 1983; 51:1358-63. 9. Packer M. How should we judge the efficacy of drug therapy in patients with chronic congestive heart failure? The insights of six blind men. J Am ColI Cardiol 1987; 9:433-8. 10. Rubin SA, Brown HV, Swan HJC. Arterial oxygenation and arterial oxygen transport in chronic myocardial failure at rest, during exercise and after hydralazine treatment. Circulation 1982; 66:143-8. 11. Macklem PT. Respiratory muscles: the vital pump. Chest 1980; 78:753-8.

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Inspiratory muscle weakness and dyspnea in chronic heart failure.

Dyspnea is a common, disabling symptom in chronic heart failure, yet the underlying mechanisms remain unknown. The respiratory muscle pump is composed...
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