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Impact of Heart Transplantation on the Recovery of Peripheral and Respiratory Muscle Mass and Strength in Patients With Chronic Heart Failure

Fernandes, Lenise C. B. C., Physio, PhD1; de Oliveira, Italo M., MD, PhD2; Fernandes, Paula Frassinetti C. B. C., MD, PhD3; de Souza Neto, João David, MD, PhD2; Farias, Maria do Socorro Q., Physio, MS2; de Freitas, Nilce A., Physio, MS4; Magalhães, Nasser C., MD3; Bacal, Fernando, MD, PhD1

doi: 10.1097/TXD.0000000000000837
Heart Transplantation

Background To assess the impact of heart transplantation (HT) on the recovery of peripheral and respiratory muscle mass and strength in patients with congestive heart failure.

Methods The study included 23 patients with an indication for HT (patients in the waiting list [WL] group). These patients were monitored for 1.5 to 3 years after HT; 8 died before 6 months of follow-up, 15 patients completed the early follow-up period of 6 months after HT (FU6m group), 4 died between 6 months and 3 years after HT, and 11 patients completed the late follow-up period 1.5 to 3 years after HT (FU1.5-3y group). Twenty-three healthy subjects were included in the control group. The study variables included inspiratory muscle strength, expressed as the maximum inspiratory pressure (MIP); expiratory muscle strength, expressed as the maximum expiratory pressure (MEP); peripheral muscle strength, expressed as bilateral handgrip strength (bHGS); and the cross-sectional area of the bilateral psoas major muscle (CSAbPm).

Results The results showed a reduction in the CSAbPm (1238.9 ± 312.3 mm2), a reduction in the bHGS (27.0 ± 5.7 kg/f), a reduction in the MIP (60.2 ± 29.8 cmH2O), and a reduction in the MEP (75.2 ± 33.4 cmH2O) in patients in the WL group compared with the healthy controls. In the time series comparison, for patients in the WL, FU6m, and FU1.5-3y groups, increases were found in the CSAbPm (1305.4 vs 1458.1 vs 1431.3 mm2, respectively), bHGS (27.3 vs 30.2 vs 34.7 kg/f, respectively), MIP (59.5 vs 85.5 vs 90.9 cmH2O, respectively), and MEP (79.5 vs 93.2 vs 101.8 cmH2O, respectively) (P < 0.00).

Conclusions Sarcopenia was observed in patients in the WL group. Patients recovered peripheral and respiratory muscle mass and strength at 3 years after HT.

1 Heart Institute University of São Paulo School of Medicine and Heart and Lung Messejana's Hospital, Fortaleza, CE, Brazil.

2 Heart and Lung Messejana's Hospital, Fortaleza, CE, Brazil.

3 State University of Ceará, Fortaleza, CE, Brazil.

4 Fortaleza General Hospital, Fortaleza, CE, Brazil.

Published online 1 October, 2018.

Received 15 July 2018. Revision requested 30 July 2018.

Accepted 28 August 2018.

This article is part of the postgraduate work by Lenise Castelo Branco Camurça Fernandes and was developed with the sponsorship of “Programa de Doutorado Interinstitucional Novas Fronteiras (DINTER NF) and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (Funcap)”, grant MD1-0053-00037.01.00/12, notice provided 02/2011.

The authors declare no conflicts of interest.

L.C.B.C.F. collected the data; conceived of the design of the study; conducted the analysis and interpretation of the data, drafted the article or critically revised it for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. I.M.dO. collected the data, conceived of the design of the study; conducted the analysis and interpretation of the data, critically revised the article for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. P.F.C.B.C.F. collected the data, conceived of the design of the study; conducted the analysis and interpretation of the data, critically revised the manuscript for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. J.D.dS.N. collected the data, conducted the analysis and interpretation of the data, critically revised the manuscript for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. M.dS.Q.F. collected the data, conducted the analysis and interpretation of the data, critically revised the article for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. N.A.dF. collected the data, conducted the analysis and interpretation of the data, critically revised the article for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. N.C.M. collected the data, conducted the analysis and interpretation of the data, critically revised the article for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. F.B. collected the data, conducted the analysis and interpretation of the data, critically revised the article for important intellectual content, provided final approval of the version of the article to be published, agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Correspondence: Lenise Castelo Branco Camurça Fernandes, Rua Silva Paulet, 2020, Apt 1401, Aldeota, Fortaleza, Brazil. (lenisefernandes@gmail.com).

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Heart transplantation (HT) is considered the best therapeutic modality for patients in the most advanced stage of heart failure (HF). After HT, significant improvements in the symptoms, hemodynamics, heart function, and sympathetic neural activity are observed.1 However, skeletal muscle abnormalities have been suggested to remain for months after HT and may contribute to the impaired exercise capacity observed in these patients.1

The loss of muscle mass in patients with HF (also known as sarcopenia, muscular atrophy, or myopenia) is a poorly investigated comorbidity. The first study2 to evaluate the clinical prevalence and impact of muscle mass loss in patients with stable HF was published in 2013 as part of a landmark study3 that investigated the presence of diabetes mellitus, cachexia, and obesity as factors that aggravated HF. The study showed the presence of muscle loss in 19.5% of the patients and concluded that muscle mass loss was a frequent comorbidity in HF.2

Cachexia is a serious complication that may be present in patients with chronic diseases. Similar to sarcopenia, cachexia presents a loss of muscular mass during the evolution of the disease. Cardiac cachexia is a serious complication that is associated with a poor prognosis, which increases the morbidity and mortality of patients.4

In view of these findings, the importance of the topic, and the lack of studies in this area, we assessed the impact of HT on the recovery of the peripheral and respiratory muscle mass and strength in HF patients.

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CASUISTIC AND METHODS

This study was an observational, prospective, cohort study with a control group (CG) that was performed at a teaching hospital specializing in heart and lung diseases in the state of Ceará, Brazil.

The Research Ethics Committee of Messejana's Heart and Lung Hospital approved the present investigation under number 823/11, and all subjects provided written informed consent.

Forty patients 18 years or older were selected during the period from August 2011 to March 2013. Patients on the waiting list (WL) for HT and healthy subjects without heart disease participated in the study. Fifteen of the patients on the WL for HT were excluded for the following reasons: motor sequelae in the upper and lower limbs, hemodynamic instability, clinical improvement, and refusal to participate. Therefore, 25 patients were eligible for the study. One subject died while on the WL for HT. Twenty-four subjects underwent the transplant surgery, although 1 subject did not complete the second assessment due to technical problems. Ultimately, a total of 23 patients were investigated before HT and followed-up for 3 years after surgery.

We examined the data of patients on the WL before transplantation (WL group), during the early follow-up period performed 6 months after HT (FU6m group), and during the late follow-up period conducted from 1.5 to 3 years after transplantation (FU1.5-3y group).

The CG comprised healthy subjects without heart disease who were matched for age, sex, weight, and height and were employees of the participating hospital. The participants in this group underwent an interview to obtain data concerning hypertension, diabetes, smoking habits, and use of medication, which was followed by the selection of subjects for inclusion in the CG (n = 23).

After HT, 8 patients died before reaching the 6-month follow-up, and 15 patients survived and completed the early follow-up period (FU6m group). Between 1.5 and 3 years after HT, 4 patients died, and 11 survived to complete the late follow-up period (FU1.5-3y group) (Figure 1).

FIGURE 1

FIGURE 1

Data were analyzed from the population, including the following categorical and continuous variables: age; sex; weight; height; HF causes; hypertension; diabetes; time on the WL; time of hospitalization after HT; measurement of inspiratory muscle strength, expressed as the maximum inspiratory pressure (MIP); expiratory muscle strength, expressed as the maximum expiratory pressure (MEP); dominant handgrip strength (dHGS); nondominant handgrip strength (ndHGS); cross-sectional area of the left psoas major muscle (CSAlPm); cross-sectional area of the right psoas major muscle (CSArPm); body mass index (BMI); and creatinine concentration. All variables were assessed in the WL group and reassessed in the same patients during follow-up after transplantation. One observer technician who specialized in radiology performed the cross-sectional area of the bilateral psoas major muscle (CSAbPm) measurements, and all other parameters were measured by a single observer (the author of this paper: LCBCF) to minimize measurement bias.

We used mass and muscle strength measurements in the present study as criteria for the diagnosis of sarcopenia according to the recommendations of the European Consensus on Sarcopenia.5

Notably, the patients in the study did not undergo any heart rehabilitation program after HT.

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Assessment of Handgrip Strength

Peripheral muscle strength was measured through handgrip strength (HGS) using the Jamar digital dynamometer (Sammons Preston, Mississauga, ON, Canada) according to the protocol of Moreira et al6

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Assessment of Respiratory Muscle Strength

Inspiratory muscle strength, expressed as MIP, and expiratory muscle strength, expressed as MEP, were measured using an analog CRK model manovacuometer. The patient was seated with the trunk straight to form a 90° angle with the thighs and feet supported on the ground.7 A nasal clamp was used during the measurements, and a nozzle was applied as an interface. The MIP was measured at functional residual capacity (ie, the patient performed normal expiration followed by maximum inspiration). The MEP was measured at total lung capacity (ie, the patient performed a maximum inspiration followed by a maximum expiration).7

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Assessment of Muscle Mass

Pelvic computed tomography (CT) was used to assess the muscle mass by quantifying the CSAbPm at the fourth lumbar vertebra level (L4).8 The CT scanner used was the Multi Slice BrightSpeed Elite 16 Channels General Electric.

The patient was positioned supine on the CT scanner table with semi-inflected knees to minimize the lordotic curvature.9-10 The point delineated to analyze the psoas major muscle measurement in all patients was the upper edge level of L4.8 The resulting area of the outlined regions (right and left) was calculated to determine the CSAbPm. Measurement are shown in mm2.

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Statistical Analysis

Data were analyzed using the Statistical Package for the Social Sciences software version 20.0.

In the univariate descriptive analysis, the frequency distribution test was used for categorical variables, and measurements of central tendency and dispersion were used for numerical variables.

Pearson's (r) correlation test was used to analyze the correlations between the muscle mass and the peripheral and respiratory muscle strength variables.

Generalized linear models (ANOVA) were used to analyze the muscle mass and strength variables at the 3 time points of the study (before HT and at 6 months and 1.5-3 years of follow-up). Differences were considered significant at P ≤ 0.05.

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RESULTS

We observed survival rates of 60.9% at 1 year after HT and 47.8% at the end of the study after a mean follow-up period of 2 years for the 23 patients included in this study (ie, 11 patients were alive with functioning heart grafts) (Figures 2A and B). The causes of death included 4 deaths due to septic shock, 4 deaths from heart arrest without a specific cause, 2 deaths due to sudden death, 1 death due to biventricular dysfunction, and 1 death due to acute HF. Patients in the group who died posttransplant had no baseline differences in any of the measures of muscle mass or strength compared to posttransplant survivors (Table 1).

FIGURE 2

FIGURE 2

TABLE 1

TABLE 1

A total of 87% of patients were male. Nonischemic cardiomyopathy was the most common HF etiology and was observed in 65.2% of the patients, followed by ischemic cardiomyopathy in 17.4% and chagasic cardiomyopathy in 17.4% of patients. Among all patients, 39.1% were categorized as functional class III, and 60.9% categorized as functional class IV. The left ventricle ejection fraction was 27.6 ± 6.9%. The mean time on the WL for HT was 50.2 ± 42.7 days. The median hospitalization time after HT was 26 (21-37) days, and the mechanical ventilation time was less than 1 (1-1) day. Before HT, only 1 patient was diabetic, and during early follow-up after HT, another patient developed transitory diabetes. However, during the late follow-up period, only 1 patient remained diabetic. Systemic hypertension was observed in 5 patients before transplantation, in 8 patients during early follow-up, and in 7 patients during late follow-up after HT. Table 2 shows the clinical and demographic characteristics of the study patients.

TABLE 2

TABLE 2

Univariate analysis of the WL group compared to the CG showed that sarcopenia was present based on a decrease in the peripheral muscle mass and strength. The variables (CSAbPm, bilateral HGS [bHGS], MIP, and MEP) were similar between the CG and FU1.5-3y group, demonstrating recovery of sarcopenia at 3 years after HT (Table 3).

TABLE 3

TABLE 3

When the muscle mass and strength variables were compared over time (in the WL, FU6m, and FU1.5-3y groups) in the 11 surviving patients, we found an increase in muscle mass and peripheral and respiratory muscle strength during the 3 years of follow-up after transplantation (Tables 4 and 5).

TABLE 4

TABLE 4

TABLE 5

TABLE 5

In the multivariate analysis, MIP and bHGS differed significantly among the WL, FU6m, and FU1.5-3y groups.

The WL group exhibited a strong correlation between bHGS and MIP (P = 0.00 and r = 0.63) and between bHGS and MEP (P < 0.00 and r = 0.75). In the FU6m group, no correlation was found between the peripheral and respiratory muscle strength. In the FU1.5-3y group, a strong correlation was found between bHGS and MEP (P = 0.00 and r = 0.80) (Figure 3).

FIGURE 3

FIGURE 3

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DISCUSSION

In the present study, the univariate analysis revealed sarcopenia in the WL group. The sarcopenia levels had recovered in the FU6m and FU1.5-3y groups compared with those in the WL group (Table 3). These outcomes conflict with those of other studies1,11,12 that have observed intrinsic abnormalities in the skeletal muscle of patients before and after HT, thereby contributing to a lower exercise capacity after transplantation. At the end of the late follow-up (FU1.5-3y group), the heart transplant patients presented muscle mass and strength levels similar to those in the CG, confirming the recovery of muscle mass and strength in the study population (Table 3). A recent study on the fragility phenotype performed in patients after HT and after ventricular assist device implantation supports the findings of the present study.13

The results of the multivariate analysis between the WL group and CG showed a reduction of peripheral muscle strength (P = 0.01) but not in muscle mass (P = 0.06). We can infer some explanations for this finding, such as the patients' noncachectic profile, the use of lower doses of glucocorticoids, or the small sample size.

A rapid recovery of muscle mass and respiratory muscle strength occurred in the FU6m group, whereas peripheral muscle strength progressively recovered in the FU1.5-3y group (Table 5).

Braith et al14 demonstrated that lean mass was significantly decreased at 2, 5 and 8 months after transplantation in the CG members who did not participate in the training (this group was similar to our patients who did not undergo any training). These results were in contrast to our findings, which demonstrated that muscle mass increased by 11.7% in the early follow-up (FU6m) group after transplantation, even though our patients were taking a mean dosage of 15 mg/d of glucocorticoids (prednisone).

Our results might reflect the nutritional status of our patients, who presented with an average BMI of 25.1 kg/m2, which did not correspond to clinical malnutrition or cachexia but rather revealed an overweight status according to the World Health Organization. These data are in agreement with those of several congestive HF databases,15,16 indicating the so-called obesity paradox (ie, patients with congestive HF and a higher BMI may have a decreased risk of death and hospitalization compared to those with a “normal” BMI).

Mancini et al17 reported the presence of muscular atrophy in patients with HF. The authors demonstrated the incidence of severe muscle atrophy in 68% of patients with HF. They suggested that these anthropometric measurements of the arm could underestimate muscular atrophy due to the presence of substantial fat infiltration into the skeletal muscle detected by nuclear magnetic resonance.

Schaufelberger et al1 demonstrated that intrinsic abnormalities in skeletal muscle found before HT remained 6 and 9 months after HT and might contribute to a lower exercise capacity and muscle strength in these patients, in contrast to our findings.

The mean values found for bHGS measurements in the CG patients of the present study are consistent with those from studies18,19 conducted in the Brazilian population that evaluated HGS values in normal subjects.

When comparing the 3 follow-up periods, our study showed that bHGS was significantly different (P < 0.00). bHGS increased by 10.5% during the early follow-up and by 5% during the late posttransplant period. These results are in contrast to those of studies1,20,21 that demonstrated impaired skeletal muscle function years after HT.

Some authors22,23 have identified muscle strength as a long-term cardiovascular risk factor and mortality index.24 A cohort study25 showed that decreased muscle strength was associated with increased all-cause mortality but that reduced muscle mass was not strongly associated with mortality.

The analysis of the respiratory muscle strength was showed a decrease in both MIP and MEP in the patients in the WL group. We found a significant difference compared to the CG. During the posttransplantation follow-up (especially in the FU6m group), the MIP increased by 43.5% compared with that in the WL group, which indicated significant early recovery after cardiac transplantation.

Coronel et al26 assessed patients before HT and reported mean MIP and MEP values of 88.85 ± 29.28 cmH2O and 122.7 ± 42.02 cmH2O, respectively. These values were higher than those determined in our study. This discrepancy may be attributable to the use of functional residual capacity because this measurement has the advantage of not being affected by the respiratory system elastic recoil.27

According to Meyer et al,28 patients with HF have a significant decrease in MIP, which is potentially a consequence of a reduced muscle mass. This reduction of the muscle mass might alter the capillary density and the activity of oxidative enzymes, which could be the main factor causing diaphragm atrophy.29 A decrease in MIP is associated with the worst prognosis in these patients.28

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Final Remarks

The results of this study revealed that patients with lower peripheral muscle strength before HT underwent a late recovery after HT.

The inclusion of a CG allowed us to compare rare data in the literature.

This study provided survival data through the Kaplan-Meier method, which permitted the analysis of patients with different follow-up periods.

This study has some limitations. For instance, studies of heart transplant patients and patients in the final stage of HF are difficult because these patients have high mortality rates. Therefore, the study had a small sample size (75% power) because it comprised surviving patients.

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CONCLUSIONS

The findings of this study revealed sarcopenia in patients before HT.

Three years after HT, the patients recovered peripheral and respiratory muscle mass and strength.

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REFERENCES

1. Schaufelberger M, Eriksson BO, Lönn L, et al. Skeletal muscle characteristics, muscle strength and thigh muscle area in patients before and after cardiac transplantation. Eur J Heart Fail. 2001;3:59–67.
2. Fulster S, Tacke M, Sandek A, et al. Muscle wasting in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Eur Heart J. 2013;34:512–519.
3. von Haehling S, Lainscak M, Doehner W, et al. Diabetes mellitus, cachexia and obesity in heart failure: rationale and design of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). J Cachexia Sarcopenia Muscle. 2010;1:187–194.
4. Zamboni M, Rossi AP, Corzato F, et al. Sarcopenia, Cachexia and Congestive Heart Failure in the Elderly. Endocr Metab Immune Disord Drug Targets. 2013;13:58–67.
5. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39:412–423.
6. Moreira D, Álvarez RRA, Gogoy JRd, et al. Abordagem sobre preensão palmar utilizando o dinamômetro JAMAR®: uma revisão de literatura. Rev Bras Ci e Mov. 2003;11:95–99.
7. Souza RB. Pressões respiratórias estáticas máximas. J Pneumol. 2002;28:S155–S165.
8. Englesbe MJ, Patel SP, He K, et al. Sarcopenia and Post-Liver Transplant Mortality. J Am Coll Surg. 2010;211:271–278.
9. Chaffin DB, Redfern MS, Erig M, et al. Lumbar muscle size and locations from CT scans of 96 women of age 40 to 63 years. Clin Biomech (Bristol, Avon). 1990;5:9–16.
10. Gatton ML, Pearcy MJ, Pettet GJ. Difficulties in estimating muscle forces from muscle cross-sectional area. An example using the psoas major muscle. Spine (Phila Pa 1976). 1999;24:1487–1493.
11. Marconi C, Marzorati M. Exercise after heart transplantation. Eur J Appl Physiol. 2003;90:250–259.
12. Myers J. Principles of exercise prescription for patients with chronic heart failure. Heart Fail Rev. 2008;13:61–68.
13. Jha SR, Hannu MK, Newton PJ, et al. Reversibility of frailty after bridge-to-transplant ventricular assist device implantation or heart transplantation. Transplant Direct. 2017;3:e167.
14. Braith RW, Welsch MA, Mills RM Jr, et al. Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients. Med Sci Sports Exerc. 1998;30:483–489.
15. Horwich TB, Fonarow GC, Hamilton MA, et al. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol. 2001;38:789–795.
16. Davos CH, Doehner W, Rauchhaus M, et al. Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity. J Card Fail. 2003;9:29–35.
17. Mancini DM, Walter G, Reichek N, et al. Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation. 1992;85:1364–1373.
18. Novaes RD, Miranda AS, Silva JO, et al. Equações de referência para a predição da força de preensão manual em brasileiros de meia idade e idosos. Fisioterapia e Pesquisa. 2009;16:217–222.
19. Caporrino FA, Faloppa F, Santos JBG, et al. Estudo populacional da força de preensão palmar com dinamômetro Jamar. Rev Bras Ortop. 1998;33:150–154.
20. Movassaghi S, Nasiri Toosi M, Bakhshandeh A, et al. Frequency of musculoskeletal complications among the patients receiving solid organ transplantation in a tertiary health-care center. Rheumatol Int. 2012;32:2363–2366.
21. Lampert E, Mettauer B, Hoppeler H, et al. Structure of skeletal muscle in heart transplant recipients. J Am Coll Cardiol. 1996;28:980–984.
22. Gale CR, Martyn CN, Cooper C, et al. Grip strength, body composition, and mortality. Int J Epidemiol. 2007;36:228–235.
23. Ruiz JR, Sui X, Lobelo F, et al. Association between muscular strength and mortality in men: prospective cohort study. BMJ. 2008;337:a439.
24. Lopez-Jaramillo P, Cohen DD, Gómez-Arbeláez D, et al. Association of handgrip strength to cardiovascular mortality in pre-diabetic and diabetic patients: a subanalysis of the ORIGIN trial. Int J Cardiol. 2014;174:458–461.
25. Newman AB, Kupelian V, Visser M, et al. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci. 2006;61:72–77.
26. Coronel CC, Bordignon S, Bueno AD, et al. Variáveis perioperatórias de função ventilatória e capacidade física em indivíduos submetidos a transplante cardíaco. Rev Bras de Cir Cardiovasc. 2010;25:190–196.
27. Rodrigues-Machado M. Bases da fisioterapia respiratória: terapia intensiva e reabilitação. Rio de Janeiro: Guanabara Koogan. 2008;9:111–124.
28. Meyer FJ, Zugck C, Haass M, et al. Inefficient ventilation and reduced respiratory muscle capacity in congestive heart failure. Basic Res Cardiol. 2000;95:333–342.
29. Forgiarini Junior LA, Rubleski A, Garcia D, et al. Avaliação da força muscular respiratória e da função pulmonar em pacientes com insuficiência cardíaca. Arq Bras Cardiol. 2007;89:36–41.
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