Randomized and comparative study between two intra-hospital exercise programs for heart transplant patients

Objective: To compare the effects of two physical therapy exercise in-hospital programs in pulmonary function and functional capacity of patients in the postoperative period of heart transplantation. Methods: Twenty-two heart transplanted patients were randomized to the control group (CG, n=11) and training group (TG, n=11). The control group conducted the exercise program adopted as routine in the institution and the training group has had a protocol consisting of 10 stages, with incremental exercises: breathing exercises, resistance training, stretching and walking. The programs began on the first day after extubation and stretched until hospital discharge. Assessed pulmonary function, distance walked in six minutes walk test (6MWT) and peripheral muscle strength by one repetition maximum test (1RM). Results: Similar behavior was observed between the two groups treated, with statistically significant increases between the first and second test of the following variables: FVC (59% in CG and 35.2% in TG); MIP (8.6% in CG and 53.5% in TG), MEP (28.8% in CG and 40.7% in TG) and 6MWT (44.5% in CG and 31.4% in TG). There was an increase of peripheral strength by 1RM test, over time, to the muscle groups of the elbow flexors, shoulder flexors, hip abductors and knee flexors. Conclusion: Heart transplant patients benefit from exercise programs in hospital, regardless of the program type applied. A new training proposal did not result in superiority compared to routine programme applied. Exercise protocols provided improves in ventilatory variables and functional capacity of this population. Descriptors: Heart transplantation. Rehabilitation. Physical therapy modalities. Resumo Objetivo: Comparar os efeitos de dois programas fisioterapêuticos de exercícios intra-hospitalares na função pulmonar e na capacidade funcional de pacientes no período pós-operatório de transplante cardíaco. Métodos: Vinte e dois transplantados de coração foram randomizados em Grupo Controle (GC, n=11) e Grupo de Treinamento (GT, n=11). O GC realizou o programa de exercícios adotado como rotina na instituição e o GT realizou protocolo


INTRODUCTION
Heart failure (HF) is a clinical syndrome being the final common pathway of heart disease caused by structural or functional abnormalities, acquired or inherited, leading to worsening of filling capacity and ventricular ejection.The heart becomes unable to maintain the tissues demands resulting in symptoms such as fatigue, dyspnea and intolerance to physical exertion [1,2].
In advanced stages of HF (functional classes III and IV), heart transplantation (HT) becomes a treatment able to restore hemodynamic function, improve quality of life and survival.It is recommended for patients whose symptoms do not respond to drug therapy or other surgical procedures [3].
Since the first human HT performed in South Africa by Christiaan Barnard in 1967, HT has improved since its initial experimental stage to devote these days as a treatment of choice for patients with end-stage HF, especially after the development of immunosuppressive therapy [4].Actually, the survival of patients submitted to HT is 80%, 70% and 60% in one, five and 10 years, respectively [3].
Most individuals waiting for a HT have prolonged hospital stay due to prolonged inotropic support or mechanical circulatory support [5].Even after surgery, these individuals show changes in hemodynamic performance due to central alterations, such as autonomic denervation graft, endothelial dysfunction, diastolic dysfunction and accelerated coronary atherosclerosis and poor adaptation of the peripheral   1).These patients did not perform exercise programs in the preoperative period.
(MIP) and maximal expiratory pressure (MEP) was obtained by manovacuometry (Marshall Town ® model).The patient was positioned sitting with a nose clip to allow only oral breathing during the test.A maximal inspiratory effort from residual volume (RV) was requested through a mouthpiece connected to a manometer.We considered the largest deflection obtained in the apparatus for the MIP value.Similarly, the expiratory effort was requested from the total lung capacity (TLC) to obtain the MEP value.The measurements were repeated for at least three times for each parameter, accepting less than 10% difference betwen the measures.The highest value was considered, since this has not been the last measure [9].The values are expressed in cmH 2 O and percentage of predicted values, according to Neder [10].The FVC was measured by ventilometry (Mark Wright Spirometer 8 ® model).FVC was obtained in liters (L) through a maximum inspiration followed by expiration until the maximum RV.The measurement was performed three times, accepting a difference less than 10% betwen the measures, considering the highest value obtained, since it was not the last one.All tests were performed on the first day after extubation (1 st test) and on the day before hospital discharge (2 nd test).
The functional capacity (FC) was assessed using the Six Minute Walk Test (6MWT) performed according to the Guidelines of the American Thoracic Society [11], with the distance measured in meters and percentage of predicted values and calculated according to the equation proposed by Enright & Sherrill [12].The first 6MWT was performed as soon as the patients had conditions for ambulation, which occurred at the end of the first week after extubation.The second test was performed on the day before discharge.
The dynamics of peripheral muscle strength was assessed by the One Repetition Maximum Test (1RM), following the protocol adapted to the Guidelines of the American College of Sports Medicine [13].Muscle groups responsible for elbow flexion, shoulder flexion, shoulder abduction, elbow extension, knee extension, hip abduction and knee flexion were tested.The first 1RM test was performed at the end of the first week after extubation and the second, on the day before discharge.Once defined the maximum load reached in the first test, we applied a load for resistance training of 50% 1RM set for each muscle group.

Exercise Programs
CG performed the exercise program adopted as routine in the institution, composed by series of 10 repetitions of the following exercises: (a) diaphragmatic breathing exercises, inspiration in 3 times associated with upper limbs elevation in flexion and in abduction to 90°, (b) general exercises like bending their knees to hip height, lower limbs abduction to 45°, plantar flexion and dorsiflexion (c) orientation for ambulation without preestablished target distance.The session was conducted once a day, five times a week, under a physiotherapist supervision.

Fig. 1 -Flowchart of studied patients
Patients were admitted to the Surgical Intensive Care Unit in the immediate PP, in intubation and mechanical ventilation (Hamilton-Switzerland, Galileo ® model), on controled mandatory ventilation mode (CMV), with a tidal volume of 8 ml/kg, respiratory rate of 12 breaths/min; fraction of inspired oxygen of 60% and positive end-expiratory pressure (PEEP) of 5 cmH 2 O, as Unit routine [8].
The study began on the day after extubation, which followed institutional protocol [8].Bedridden patients or patients using vasoactive drugs initiated protocol in phases 1 and 2 and continued to phase 3 only when they were hemodynamically stable, with or without vasoactive drugs.
After the withdrawal of ventilatory support, patients were randomized to CG or TG.This randomization process was performed by sealed opaque envelopes.An independent individual generated a sequence of random numbers, putting up one by one in sealed envelopes.Patients were randomly and consecutively allocated in one of the study groups by the withdrawal of one envelope for each patient.
Pulmonary function was evalueted in terms of respiratory muscle strength and forced vital capacity (FVC).Respiratory muscle strength, expressed by maximal inspiratory pressure TG performed exercise program consisted in 10 phases of increasing complexity, including breathing exercises, active, resistance and aerobic exercises and stretching, as shown in Figure 2. The phases were established in order to promote incremental effort; progression to a new phase depended on the patient's clinical response and ability to perform the proposed activities at each phase without compensation and independently; progression was also based on the perception effort assessed by the modified Borg scale [14] which consists in a score of 0 to 10 grades, using descriptive terms.Patients were instructed to maintain a score of 4 (somewhat severe) to 6 (severe).When the score reached 7 (very severe) the patient was oriented to regress one phase of the protocol.The progression phases were suspended or had regression when it was necessary to remain at rest, for medical request, or when the patient was unable to carry out the activities by side effects of immunosuppressive therapy.During the exercise sessions, heart rate (HR), blood pressure (BP) and peripheral oxygen saturation (SpO 2 ) from the TG patients were monitored at the beginning, during the activity, at the end of the sessions and 5 minutes after the sessions, in order to evaluate the safety of the proposed protocol.
The statistical analysis used to compare the groups consisted on Student t test for normally distributed data which are presented as mean and standard deviation, or its corresponding Mann-Whitney, presented as median and interquartile ranges.To test the homogeneity between the proportions we used the chi-square test or Fisher's exact test.The variables were subjected to analysis of variance for repeated measures ANOVA and when the normality assumption was rejected we used the Friedman test [15].The level of statistical significance was 5%.

RESULTS
The general anthropometric characteristics and left ventricular ejection fraction (LVEF) values had no statistically significant difference between the groups, as shown in Table 1.There was a prevalence of 63.64% males in the population studied, with an equal proportion in both groups.
Chagas cardiomyopathy was the etiology of HF in 28% of patients in the CG and 55% in TG; idiopathic dilated cardiomyopathy in 45% of CG and 18% in TG; ischemic cardiomyopathy in 9% in both groups and other causes 9% in both groups.
Mechanical ventilation time was 11.83 hours (7.85 -21.17) in CG and 8.33 hours (4.93 -10.94) in TG, with no statistically significant difference between groups (P=0.094).The length of hospital stay in the postoperative period was 34 days (26 -48) in CG and 32 days (21 -46) in TG (P=0.768).The application period of the protocols was 26 ± 12 sessions in CG and 18 ± 6 sessions in TG, with no statistically significant difference between groups (P=0.074).
When comparing the responses against exercise programs applied, we had a statistically significant increase in MIP, MEP and FVC variables in both groups, as shown in Table 2.The same was observed in the 6MWT (Table 3) and in 1RM test for the movements of elbow flexion, shoulder flexion, hip abduction and knee flexion (Table 4).Although the TG values were higher than those of the CG, they did not reach statistical significance.The mean MIP, expressed as percentage of predicted values , in CG was 53% and 57% in the first and second tests respectively and in TG was 50% and 73%, respectively.There was no statistically significant difference between groups (P=0.616),but over time, the patients showed significant gains (P=0.009)(Figure 3).
6MWT mean values were 272m in the first test and 393m in the second test for CG, and 322m and 423m, respectively, in TG.The performance of the groups was similar (P=0.430), with significant improvement in the second test (P=0.001)(Figure 4).   4.

DISCUSSION
Exercise programs are important for HT patients and should be started as early as possible to restore their FC after the surgical procedure, but also to recover part of the muscle Rev Bras Cir Cardiovasc 2013;28(3):338-46 Kawauchi TS, et al. -Randomized and comparative study between two intrahospital exercise programs for heart transplant patients dysfunction due to the long period of deconditioning in the preoperative phase and to the effects of immunosuppressive therapy in skeletal muscle [16].
Our study evaluated the effects of exercise programs immediately after HT still in hospital phase.The literature is rich in studies that evaluate the effectiveness of programs in post discharge phases (II and III).However, studies addressing phase I are scarce, probably due to the diversity in patient outcomes.Protocols assistance are applied by different transplant centers, but there is little information on the impact of such assistance [17].In our institution, the exercise program is performed tailored to each patient.To compare this program with a new proposal that includes exercise progression based on the complexity execution and resistance exercises, was the aim of this study.
Two programs of therapeutic exercise have been applied to patients in the PP of heart transplantation.The CG performed exercises according to a protocol routinely practiced in the institution and TG performed a new exercise protocol based on incremental workloads.Our data show that the implementation of both protocols contributed to the improvement in lung function, in peripheral muscle strength and physical performance over time, with no differences between the protocols.
Lung function may change in heart transplant in the PP, as well as in other cardio-thoracic surgery [18].Ferreira et al. [19] observed a reduction in vital capacity 40%-50% compared to preoperative values for at least 10-14 days after cardiac surgery and abdominal surgery.It is believed that factors such as pain, abnormal respiratory mechanics due to the sternotomy and the deleterious effects of general anesthesia on pulmonary function, contributes to these findings.In HT, poor preoperative condition and the surgical procedure itself favor the reduced respiratory capacity and increased pulmonary secretions, which can be minimized through breathing exercises, bronchial hygiene and cough stimuli.
Coronel et al. [20], in a retrospective cohort study evaluated 21 patients undergoing HT.The authors observed a volume and lung capacity reduction and a respiratory muscle strength decrease on the first postoperative day compared to the preoperative period and recovery of these values on the 14 th postoperative day.The improvement of FVC, MIP and MEP between the first and 14 th postoperative day was 70.1%, 75.1% and 62.8%, respectively.
In our study, there was an improvement in ventilatory variables between the first and second tests but our medium datas are lower than those observed by Coronel et al. [20] (59% in the CG versus 35.2% in TG for FVC, 8.6% in CG versus 53.5% in TG for MIP and 28.8% in the CG versus 40.7% in TG for MEP).Our results corroborate the finding that changes in ventilatory function in patients undergoing HT are predictable, but these recover the expression of respiratory muscle strength and lung capacity within two weeks, besides improving FC, considering the association between the HT surgery and functional rehabilitation a good therapeutic strategy for the treatment of advanced HF patients.
In relation to the MIP, both groups were lower than 70% of predicted values at the beginning of the programs adopted in our study and only the TG reached average values above this threshold in the second test.According to Borges [21], respiratory muscle weakness, characterized by MIP less than 70% of predicted values, is one of the risk factors for the development of postoperative pulmonary complications in patients undergoing cardiac surgery.Thus, programs that contribute to the improvement of muscle strength are beneficial, regardless the association of specific inspiratory muscle training, thus minimizing the risk of complications.
The improvement of FC in our study, 44.5% in CG and 31.4% in TG, was more expressive than in the study of Coronel et al. [20], where FC improved only 11.2% between tests.We believe that this result is due to the stimulus given to the patient to walk in the PP in our institution, either randomly (CG) or standardized by the proposed protocol (TG), where at the final phase, phase 10, the patients walked at least 900m per day and went up and down a flight of stairs.In the PP of coronary artery bypass surgery, we have demonstrated that a moderate supervised walking program during hospitalization improves walking ability at hospital discharge [22].Thus, the inclusion of hiking seems an important feature in phase I cardiac rehabilitation programs for improvement in FC patients in the PP of cardiac surgery, as well as in HT surgery.
Although the early indication of exercise in the PP of HT is a consensus, there are few publications that describe the protocols implemented in this population in the hospital phase.According to the Brazilian Cardiology Guidelines for Heart Transplantation [23], general exercises should be started in the immediate postoperative period, increased gradually until the patient develops muscle strength and adequate endurance to restore a level of fitness.The ambulation should be started as soon as possible and after discharge, the supervised program should include stretching, aerobic and endurance exercises.The intensity of aerobic activity can be prescribed between the anaerobic threshold and respiratory compensation point obtained in the cardiopulmonary exercise test, or 60%-85% of maximum HR achieved in the testing effort.Increased intensity during the program should be done gradually, taking into account the HR, BP, Borg scale and rejection episodes.
Squires [24] recommend performing passive mobility exercises for upper limbs (UL) and lower limbs (LL), exercises to get up and sit in the chair and ambulation prescribed after extubation of the HT patient, which in general occurs within the first 24 hours after surgery.A walk or aerobic exercises on a stationary bicycle for 20 to 30 minutes can be tolerated using prescription based on the Borg scale between 11 and 13.Training for strength gain is indicated for the first six months after HT, when the authors recommend a maximum weight of 5 kg for bilateral UL exercises, to avoid complications with the Rev Bras Cir Cardiovasc 2013;28(3):338-46 Kawauchi TS, et al. -Randomized and comparative study between two intrahospital exercise programs for heart transplant patients surgical incision, as sternal instability.Our patients underwent resistance training with a maximum of 2 kg to 3 kg for UL and LL, considered safe within the exercise protocol proposed.The use of resistance exercises during exercise programs in the PP of HT is being increasingly used, since this method helps to minimize the deleterious effects of corticosteroids and immunosuppressants.It is common to skeletal muscle atrophy and weakness in addition to osteoporosis in recipients of organ transplantation as a side effect of this drug therapy.In this context, resistance exercise have osteogenic effect, since during its execution leads to bone deformation, generating cellular responses that determine the release of bone growth factors [16].
Braith et al. [25], in 2005, evaluated 15 HT patients who were randomized into CG, who performed a walking program (n=7), and a resistance training group (RTG), who performed walking and resistance exercise (n=8).Both programs began two months before surgery and lasted up to 6 months after HT.The exercise protocol consisted of a 5 minutes warm-up, followed by strengthening exercises for UL and LL at 50% 1RM, a series of 10 to 15 repetitions, twice a week.In biopsies of the right vastus lateralis, a significant increase in citrate synthase was observed, and 3 hydroxyacyl CoA dehydrogenase and lactate dehydrogenase activity in the RTG when compared to CG.The concentration of the type I myosin heavy chains increased 73% in the RTG, while decreased 28% in the CG.The type II myosin heavy chain increased 17% in the CG but decreased by 33% in the RTG, with P≤0.05.This was the first study to demonstrate that resistance training stimulates the change of type II muscle fiber, less oxidative, for the most fatigue-resistant, type I, in HT patients, demonstrating that resistance exercise in the post-transplant period is effective in increasing enzyme reserves and change the morphology of the muscle fiber, making the HT individual more capable to practice physical activity and to respond for the metabolic requirements necessary to perform the activities of daily living.
Therefore, there is a need to develop protocols with specific exercises for the HT population, which consider both the aerobic and resistance training.Encouraging the practice of physical activity and adopting a healthy lifestyle should be initiated with educational and preventive actions still in-hospital phase [23].Our study has the limitation, for a better power of analysis, of a small sample size.More studies are needed to evaluate exercise programs in the PP of HT, including pre-operative data and effects over time.

CONCLUSION
Results showed that HT patients had benefits with the implementation of exercise programs in-hospital period, regardless of the type of the program implemented.A new training proposal resulted in no superiority over the routine program.Exercise protocols improved ventilatory variables and the FC of this population.
only individuals who signed an informed consent form, according to Resolution 196/96.Patients who underwent orthotopic HT at the Heart Institute, from February 2009 to November 2011, aged over 13 years participated in this study.During this period, 26 individuals who initially filled the criteria for hemodynamic stability and absence of acute or chronic lung disease, neurological and orthopedic complications hindering the realization of the proposed protocols were included.Four individuals were excluded from the program: an individual due to secondary symptomatic hypertension to cyclosporine therapy, two for neurological complications and one due to death related to acute rejection from the graft.Therefore, 22 subjects completed the study, 11 patients in the control group (CG), which performed the conventional physiotherapy program, and 11 in the training group (TG), which performed a new exercise program (Figure

Fig. 4 -
Fig. 4 -Distance in the Six Minute Walk Test before and after the training programs Fig. 3 -Values of maximal inspiratory pressure expressed as percentage of predicted values

Table 1 .
Anthropometric data and left ventricular ejection fraction

Table 2 .
Lung function variables before and after the implementation of training programs * P<0.05 when compared with the value obtained in 1 st intra-group test

Table 3 .
Functional capacity variables before and after the implementation of the training programs

Table 4 .
Test of 1RM values before and after implementation of the training programs * P<0.05 when compared with the value obtained in the 1 st intra-group test