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Generalised muscle weakness in young adults with congenital heart disease
  1. Matthias Greutmann1,
  2. Thao Lan Le2,
  3. Daniel Tobler1,
  4. Patric Biaggi1,
  5. Erwin N Oechslin1,
  6. Candice K Silversides1,
  7. John T Granton2
  1. 1Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, University Health Network, Division of Cardiology, University of Toronto, Toronto, Canada
  2. 2Division of Respirology, Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
  1. Correspondence to Dr Matthias Greutmann, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; matthias.greutmann{at}


Background In patients with heart failure from acquired cardiomyopathy, respiratory and skeletal muscle weakness is common and is an independent predictor for adverse events. Despite a different underlying pathology, many young adults with congenital heart disease (CHD) develop a syndrome comparable to heart failure from acquired cardiomyopathy and may be at risk for a similar skeletal muscle weakness.

Objectives To assess respiratory and skeletal muscle strength in adults with complex CHD.

Methods Respiratory and skeletal muscle function was assessed in 51 adults; 41 with complex CHD (16 tetralogy of Fallot, 11 univentricular anatomy with Fontan operation and 14 with subaortic right ventricles) and 10 controls. Maximal inspiratory (MIPs) and expiratory (MEPs) pressures, handgrip strength, lung volumes and aerobic capacity (peak VO2) were measured.

Results In patients with CHD (age 34±13 years), average% predicted MIPs, MEPs and handgrip strength were lower than in controls (77±27% vs 106±28%, 85±32% vs 116±41% and 72±15% vs 93±14%, respectively, p≤0.01). There was no significant difference in muscle weakness between CHD subgroups. In 39% of patients with CHD, the handgrip strength, and in 22%, respiratory muscle strength was <70% predicted. These patients had a significantly lower peak VO2 (50±12% vs 64±14% predicted, p=0.008).

Conclusion Respiratory and skeletal muscle weakness is common in young adults with complex CHD and similar to that found in older adults with advanced heart failure from acquired heart disease.

  • Congenital heart disease
  • respiratory muscle function
  • skeletal muscle function
  • exercise testing
  • heart failure
  • tetralogy
  • transposition of the great arteries
  • exercise testing
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Owing to advances in cardiac surgery and cardiology care, most children born with congenital heart defects are now surviving into adulthood and there are currently more adults with congenital heart disease (CHD) than children. Despite these advances, many young adults with CHD are at risk for premature death, with heart failure being one of the leading causes of death.

Exercise capacity has, in multiple studies, been shown to be an important determinant of survival.1 In patients with CHD, studies have suggested that exercise limitations are secondary to the cardiac defects,2 factors related to cardiac surgery, chronotropic incompetence3 and underlying lung disease.1 2 However, these variables alone often do not fully explain the exercise limitations found in this young population. Improving our understanding of the factors responsible for exercise limitations and perhaps, in the future, modifying these variables, may help to improve quality of life and survival.

Patients with heart failure from acquired cardiomyopathy (ischaemic or dilated) often have a generalised myopathy.4 The cause of this myopathy is not well understood and is thought to be multifactorial.4–6 The myopathy can involve the peripheral skeletal muscles and the respiratory muscles,7 8 particularly the diaphragm, and can have an impact on aerobic capacity9–11 and on respiratory response to exercise.12 Furthermore, decreased respiratory muscle strength is associated with poor outcomes13 14 and is a target for specific treatment with respiratory muscle training to improve functional capacity and quality of life.15–17

Although the primary cardiac defect in patients with CHD is not a myopathic process but rather a structural one, many patients with CHD develop a syndrome comparable to heart failure from acquired cardiomyopathy.18 It is not known, however, if and to what extent patients with complex CHD also exhibit skeletal and respiratory muscle dysfunction.

The aims of this study were therefore (1) to define the prevalence and severity of respiratory and skeletal muscle dysfunction in young adults with common forms of complex CHD that are typically associated with ventricular dysfunction and (2) to determine the association between muscle weakness and lung volumes or aerobic capacity during cardiopulmonary exercise testing.

Patients and methods

Study participants

Consecutive adults attending our outpatient clinic at a large tertiary care centre were asked to participate. We included patients with repaired tetralogy of Fallot, Fontan palliation for single ventricle physiology or transposition complexes with systemic, subaortic right ventricles. Ten healthy volunteers were used as a control group. Baseline characteristics, including New York Heart Association (NYHA) functional class and ventricular function, as determined by echocardiography or cardiac MRI, were collected by chart review. Subaortic ventricular dysfunction was defined as a ventricular ejection fraction <50%. All chest x-ray findings were reviewed for evidence of diaphragmatic paresis. The study was approved by the hospital's ethics committee and all participants provided written informed consent.

Study procedures

Respiratory muscle strength and pulmonary function testing

In all participants (patients with CHD and healthy controls) measurements of maximal inspiratory (MIPs) and expiratory pressures (MEPs) were performed by experienced respiratory technicians, following recommendations of published guidelines.19 20

MIPs represent mainly diaphragmatic muscle strength and MEPs the strength of the auxiliary respiratory skeletal muscles.19 MIPs were measured after maximal expiration and MEPs after maximal inspiration. A flanged mouthpiece was used and participants were asked to seal the mouthpiece with their hands during the manoeuvre to measure MEPs in order to avoid air leak. Of three measurements with <10% variability, the highest measurement was used for analysis.19 20 Measurements were performed immediately before exercise testing and 10 min after termination of exercise. Measurements were normalised for age and gender and expressed as percentage predicted.21 The range of normal respiratory muscle strength is not well defined.22 A cut-off value of <70% predicted has been used as inclusion criteria for studies showing a benefit of selective respiratory muscle training and thus served as a cut-off point for abnormal respiratory muscle strength in this study.15 17 As a measure of respiratory muscle fatigue with exercise, a decrease in MIPs or MEPs of >20% of baseline values at 10 min after exercise was considered a significant decrease. This arbitrary percentage was chosen based on the estimated decrease of MIPs in normal controls.8 Patients with CHD underwent full pulmonary function testing, including spirometry and measurement of total lung capacity (TLC) by body plethysmography. Healthy volunteers underwent spirometry before exercise testing, measuring forced vital capacity (FVC) and forced expiratory volume during the first second of expiration (FEV1). In contrast to FEV1 and FVC, TLC is less influenced by respiratory muscle strength and was therefore used as a surrogate for the severity of pulmonary or extrapulmonary restrictive respiratory disease. All measurements were normalised for age, gender and height, following published guidelines.20

Peripheral skeletal muscle function testing

As a surrogate for peripheral skeletal muscle strength, handgrip strength of the dominant hand was measured using a Jamar dynamometer. Measurements were performed in sitting position with the shoulder adducted and neutrally rotated, the elbow flexed at 90° and the forearm and wrist in neutral position. The highest of three measurements with <10% variation was used for analysis. Measurements were normalised for age and gender and expressed as percentage predicted.23

Cardiopulmonary exercise testing

All participants underwent symptom-limited cardiopulmonary exercise testing on a cycle ergometer (Elema, Solna, Sweden), in accordance with published guidelines. Measurement of expired gas was analysed breath by breath. In addition to heart rate and blood pressure, the following parameters were recorded at rest, at ventilatory threshold (derived by the slope method) and at peak exercise by averaging five out of seven breath cycles: Oxygen uptake (VO2), carbon dioxide output (VCO2) and minute ventilation (VE). The ventilatory equivalent for carbon dioxide (in this study defined as VE divided by VCO2 at ventilatory threshold) and heart rate reserve (heart rate at peak exercise–heart rate at rest) have previously been found to be predictors of adverse events in patients with CHD and were thus calculated.1 3 24 The respiratory exchange ratio (VCO2 divided by VO2) at peak exercise was calculated in all participants. A value of >1.05 is a marker for exercise effort and maximal exercise. Where appropriate, measurements were normalised for age, gender and height and expressed as percentage of predicted.

Statistical analysis

Statistical analysis was performed using SPSS V.17.0 (SPSS Inc). Mean, SD, median and range were determined for continuous variables, when appropriate; frequencies were determined for nominal variables. For comparison between groups, Student t test, Mann–Whitney, χ2 or Fisher's exact tests were used as appropriate. Pearson correlation was used to determine correlations between measures of respiratory muscle function, static and dynamic lung volumes, measurements of cardiopulmonary exercise testing and systemic ventricular ejection fraction. A p value <0.05 (two-sided) was considered to be significant.



Baseline characteristics of patients with CHD and the control group of healthy volunteers are given in table 1. Of 41 participants with CHD, 16 had repaired tetralogy of Fallot, 11 had single ventricle physiology with Fontan operations and 14 had transposition complexes with subaortic right ventricles (seven with congenitally corrected transposition of the great arteries and seven with transposition of the great arteries palliated with an atrial switch operation). There were no differences in age, gender or body mass index between the control group and the CHD group. There was no statistically significant difference in self-reported physical activity between the CHD and the control groups. Almost half of the patients with CHD reported not to perform regular physical activity in their day-to-day life. Three patients with Fontan palliation had mildly decreased oxygen saturation at rest (87%, 88% and 89%) but none of them had progressive desaturation during exercise testing.

Table 1

Baseline characteristics

Comparison of baseline characteristics between CHD subgroups showed that there were no significant differences in age (p=0.21) or gender (p=0.09). Systemic ventricular dysfunction was common (19% in patients with tetralogy of Fallot, 73% in Fontan patients and 93% in patients with subaortic right ventricles). Patients with Fontan palliation and subaortic right ventricles had significantly lower mean systemic ventricular ejection fraction than patients with repaired tetralogy of Fallot (42±12%, 41±11% and 55±10%, respectively). The majority (88%) of patients with repaired tetralogy of Fallot had documented subpulmonic ventricular dysfunction (mean right ventricular ejection fraction 41±3% on cardiac MRI).

Cardiopulmonary exercise testing and lung function testing

Results of cardiopulmonary exercise testing and lung function testing are given in table 2. All measures of exercise capacity, except the respiratory exchange ratio, were significantly lower in patients with CHD than in controls. Patients with CHD also had significantly lower dynamic lung volumes than normal subjects.

Table 2

Cardiopulmonary exercise testing and lung function testing

On comparison of CHD subgroups, patients with Fontan palliation and subaortic right ventricles had significantly lower peak VO2 (% predicted) than patients with repaired tetralogy of Fallot (51±12%, 59±10% and 70±15%, respectively; p=0.002 for comparison between groups). There were no significant differences between any of the parameters from lung function testing between CHD subgroups.

Respiratory muscle function and peripheral skeletal muscle function

On average, patients with CHD had significantly lower inspiratory and expiratory muscle strength, as well as handgrip strength than the control group (figure 1). Details of respiratory and skeletal muscle function testing are given in table 3. The prevalence and extent of skeletal and respiratory muscle weakness was not significantly different between CHD subgroups. Patients with global respiratory muscle weakness (MIPs and MEPs <70%) or global muscle weakness (MIPs, MEPs and handgrip strength <70%) showed no significant differences in baseline characteristics or ventricular function compared with those without.

Figure 1

Respiratory and skeletal muscle strength in patients with congenital heart disease and normal controls. Differences between maximal inspiratory pressures (MIPs), maximal expiratory pressures (MEPs) and handgrip strength between normal controls (white bars) and patients with congenital heart disease (grey bars) are depicted.

Table 3

Respiratory muscle strength, skeletal muscle strength, aerobic capacity and lung volumes

Measures of inspiratory muscle weakness among patients with CHD were more pronounced than weakness of expiratory muscles (MIPs 76±27% predicted vs MEPs 84±32% predicted, p=0.03), and suggest that there was greater diaphragmatic weakness than weakness of the auxiliary respiratory skeletal muscles. At 10 min after exercise, there was no significant decrease in MIPs (76±27% predicted vs 76±29% predicted, p=0.89) but a trend towards decreased MEPs (80±32% predicted vs 84±32% predicted, p=0.055). At 10 min after exercise, a decrease of MIPs >20% from baseline was found in 3/41 patients (7%) and 1/10 controls (10%) (p=0.6) and a decrease in MEPs of >20% was found in 15 patients (37%) and 4 controls (40%) (p=0.6). In two patients (5%) MIPs and MEPs decreased by >20%. A decrease in MEPs of >20% after exercise was not different in patients who performed regular aerobic exercise (more than once a week) compared with those who did not (28% vs 46%, p=0.19).

In patients with CHD, inspiratory and expiratory muscle strength showed significant correlation (r=0.74, p<0.0001), and both parameters correlated with handgrip strength (r=0.57 and 0.51, respectively, p<0.0001 for both).

On review of chest x-ray findings only one patient (2%) was found to have evidence of right-sided diaphragmatic hemiparesis. MIP in this patient was 73% of predicted.

Correlation of skeletal and respiratory muscle strength with measures of exercise capacity

MIPs and MEPs but not handgrip strength correlated significantly with peak VO2 (r=0.33, p=0.03; r=0.38, p=0.01 and r=0.06, p=0.71, respectively). Patients with significantly decreased global respiratory muscle strength (MIPs and MEPs <70% predicted) had a significantly lower peak VO2 (50±12% vs 64±14% predicted, p=0.008) than those without.

Additionally, patients with decreased global respiratory muscle strength (MIPs and MEPs <70% predicted) had a significantly lower maximal voluntary minute ventilation than those without (84±13% predicted vs 96±11% predicted, p=0.01). Maximal minute ventilation at peak exercise showed moderate correlation with peak VO2 (r=0.624, p=0.001). These findings support an association between respiratory muscle function and exercise capacity.

Association of respiratory muscle strength with static and dynamic lung volumes

Within the group of patients with CHD, average dynamic lung volumes were significantly more reduced than TLC (FVC 81±12% predicted and FEV1 78±13% predicted vs TLC 88±12% predicted, p<0.0001 for both comparisons). As TLC is the main measure of restrictive lung disease, the extent to which dynamic lung volumes were reduced cannot be fully explained by restrictive lung physiology alone. There was a significant correlation between MIPs with dynamic lung volumes (FEV1: r=0.44, p=0.001; FVC: r=0.46, p=0.001) but none with TLC (r=0.101, p=0.54), further suggesting an impact of respiratory muscle function on dynamic lung volumes.


In this study we describe a generalised muscle weakness in young adults with CHD. We found that skeletal muscle dysfunction and respiratory muscle weakness were relatively common. Although the majority of patients with CHD were in NYHA functional class I, the degree of impairment of functional capacity and the degree of respiratory and skeletal muscle weakness were comparable to those of patients with advanced heart failure from acquired heart disease.14 Furthermore, patients with significant global respiratory muscle dysfunction had significantly lower aerobic capacity. Because exercise limitations have been shown to be strong determinants of survival in this population, targeted treatments to improve the muscle weakness could translate to improvements in exercise capacity and have an important impact on outcomes.14

Muscular deconditioning due to reduced physical activity may explain some of our findings. Self-reported frequency of physical exercise was, however, not different between the CHD and the control groups. While there was evidence of a generalised muscle weakness in patients with CHD, inspiratory muscle weakness was more pronounced than weakness of expiratory muscles. This is consistent with findings from studies in patients with heart failure from acquired heart disease and suggests that there may be specific diaphragmatic impairment in this group of patients.7 Why the diaphragm is more easily affected in heart failure is not well understood. The diaphragmatic musculature has a high content of type I (oxidative) muscle fibres. As a result, the diaphragm may be more susceptible to decreased blood flow in low cardiac output states. A study examining muscle biopsy specimens of diaphragmatic and skeletal muscles in patients with heart failure has found a variety of abnormalities within muscle fibres that were more prevalent in the diaphragmatic musculature.25 One may speculate that the structural composition and oxidative properties of the diaphragmatic musculature may be altered in a similar fashion as demonstrated in several studies for peripheral skeletal muscles.4–6 In this regard, respiratory muscle weakness may be common in patients with CHD because their functional impairment is usually longstanding and many went through periods of profound cyanosis at the beginning of their lives, before they had reparative surgery for their underlying cardiac defects.

Respiratory muscle function, lung volumes and exercise capacity

We propose that respiratory muscle weakness is a contributor to reduced dynamic lung volumes (FEV1 and FVC). The findings contradict the general perception that reduced dynamic lung volumes in patients with CHD are mainly caused by pulmonary or extrapulmonary restriction (diagnosed by demonstration of reduced static lung volumes, mainly TLC).2 26 This may be important as, in contrast to restrictive lung disease or extrapulmonary restriction, respiratory muscle weakness is amenable to therapeutic intervention. Several studies have shown improved respiratory muscle strength with resistive respiratory muscle training. The improvement in respiratory muscle strength translated into decreased levels of dyspnoea for a given level of exercise and improved overall exercise capacity.15–17 27 28 Moreover, a recent study in patients with heart failure has demonstrated an incremental benefit of respiratory muscle training to standard exercise training in patients with heart failure and reduced respiratory muscle strength.17

Respiratory muscle strength as a potential prognostic marker

In acquired heart failure, respiratory muscle dysfunction is an independent marker for adverse outcomes.14 In this study, we show that patients with CHD, like patients with heart failure, have an increased prevalence of respiratory muscle dysfunction. As such, we are intrigued by the possibility of using measures of respiratory muscle strength as prognostic indicators and indicators for treatment in CHD populations.

In our choice of participants for this study, we focused on three groups of patients frequently encountered in the care of adults with CHD. The common characteristic of these patients is that the majority will require reintervention in adulthood (tetralogy of Fallot) or are at risk for premature death from circulatory failure (Fontan patients and patients with subaortic right ventricles). Timing for reintervention or transplantation is, however, difficult and thus refined prognostic markers may be of clinical value.

Implications for future research

The presence of respiratory muscle weakness in patients with CHD—most of whom are young—may have important implications for their management. Confirmation of the respiratory muscle weakness with alternative methods such as measurements of transdiaphragmatic pressures or measurement of diaphragmatic strength with non-volitional tests such as phrenic nerve stimulation would be important.29 It may also be of clinical importance to test prevalence and extent of reduced maximal sustainable ventilation in patients with CHD as this may be a more important measure of respiratory muscle function for day-to-day life.30 The prognostic relevance of respiratory and skeletal muscle dysfunction needs to be examined in a longitudinal study. The role of specific resistive respiratory muscle training in patients with CHD needs to be defined.


One of the main limitations is the relatively small sample size. However, despite the limited size of our cohort, we were able to identify a significant proportion of young adults with skeletal muscle dysfunction. The small sample size, however, may have limited our ability to detect differences between subgroups of CHD based on the underlying defect. Measurements of respiratory muscle strength, dynamic lung volumes and peak aerobic exercise capacity are effort dependent. By repeating at least three measurements with <10% variation, we tried to ensure that measurements of respiratory muscle strength and lung volumes were reproducible. In addition, the respiratory exchange ratio on exercise testing, a marker for maximal exercise effort, was not different between the CHD and the control group. This suggests that there were few or no differences in motivation and effort between the study groups. For future studies it may be worth including non-volitional tests of respiratory muscle strength.


Respiratory and skeletal muscle weakness is common in young adults with complex CHD and similar to that found in older adults with advanced heart failure from acquired heart disease. Reduced respiratory muscle strength may contribute to reduced dynamic lung volumes.


We thank the whole team from the pulmonary function laboratory at the Toronto General Hospital for their support with this study.


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  • See Editorial, p 1115

  • Linked articles 217141.

  • MG and TLL have contributed equally to the manuscript.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University Health Network, Toronto, Canada.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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