Effect of preoperative inspiratory muscle training on right ventricular systolic function in patients after heart valve replacement surgery

Effect of preoperative inspiratory muscle training on right ventricular systolic function in patients after heart valve replacement surgery Hari Hendriarti Satoto1*, Aditya Paramitha2, Sri Hastuti Barata2, Sugiri1, Suhartono3, Sri Wahyudati2, Sefri Noventi Sofia1 Background: The reduction of right ventricular function after heart valve surgery was associated with mortality and morbidity after cardiac surgery, prolonged ICU length of stay, and higher hospital cost. Inspiratory muscle training can be considered for improving right ventricular systolic function by optimizing afterload dan cardiac contractility. The study aims to determine the effect of inspiratory muscle training on right ventricular systolic function in patients after heart valve surgery. Methods: Patients undergoing heart valve surgery were randomized into a conventional preoperative rehabilitation group and conventional preoperative rehabilitation added high-intensity inspiratory muscle training at least 14 days before surgery. Echocardiography examination was performed before rehabilitation and after cardiac surgery. Results: There were 24 subjects consist of 12 control group and 12 intervention group. By using independent t-test or Mann Whitney test, we found significant differences on right ventricular function between intervention and control group, by using RV free wall strain (17.7 + 3.0% and 14.4 + 4.0%; p=0.033), RV FAC (43.2 + 4.9% and 35.1 + 8.8%; p=0.006), and TAPSE (12.7 + 3.4 mm and 9.9 + 2.7 mm; p=0.039). ICU length of stay in the intervention group was significantly shorter than the control group (3.2 + 0.8 and 4.2 + 1.3 days; p=0.044). Conclusion: Patients underwent conventional preoperative rehabilitation added inspiratory muscle training had better right ventricular systolic function than patients in control group.


INTRODUCTION
Valvular heart disease is one of heart failure etiology and caused high morbidity and mortality. Due to heart failure symptoms, patients were needed to undergo surgery. 1,2 One of the common problems after heart valve surgery is reducing the right ventricular function associated with the increasing risk of mortality and morbidity after cardiac surgery and increasing hospital cost. [3][4][5] The right ventricular function can be determined by preload, afterload, and contractility of the right ventricle. The right ventricle's structure was sensitive to sudden afterload changes. Some theories explained the reduction of right ventricle contractility during heart surgery such as pericardiotomy, inflammations due to cardiopulmonary bypass usage, mechanical ventilator usage, and pulmonary dysfunction after cardiac surgery. 4,6, 7 One of the new preoperative cardiac rehabilitation program concepts in heart surgery is maintaining good exercise capacity using aerobic and inspiratory muscle training programs. 8 Patients with heart failure commonly have inspiratory muscle weakness associated with complications and exercise capacity reduction after cardiac surgery. In heart failure patients, inspiratory muscle weakness was associated calcium regulation changes, calpain activation, and increasing inflammatory mediators. 9-11 These problems may have a role in reducing myocardial contractility. 12, 13 Inspiratory muscle training has been used as preoperative and cardiac rehabilitation program in patients with heart failure. 8,14-16 This study aimed to establish the role of inspiratory muscle training in patients' right ventricular function after heart valve surgery.

Patient Population
We randomized 30 stable heart failure patients (NYHA I -II), aged 18 -60 years old in Kariadi General Hospital, scheduled for elective heart valve surgery into control and intervention groups. This study was conducted in August 2019 until November 2019. Patients with comorbidities such as coronary heart disease, congenital heart disease, chronic pulmonary obstructive disease were excluded in this study. Patients with cardiopulmonary bypass time > 150 minutes, history of septic shock after surgery, and exercise discontinuation for more than three days were dropped out. The local ethics committee approved the study protocol.
the difference between right ventricle end-diastolic area and end-systolic area divided by end-diastolic area multiplied by one hundred. RV FAC < 35% indicates RV systolic dysfunction. TAPSE was measured by aligning an M-mode cursor parallel with the RV free wall as it meets the tricuspid annulus from the RV apical four-chamber view. TAPSE < 17 mm indicates RV systolic dysfunction. 4,19,20 Echocardiography examinations were performed before patients underwent preoperative cardiac rehabilitation and were discharged from the hospital.
Pulmonary hypertension probability was assessed using echocardiography measurement by sPAP (systolic pulmonary arterial pressure) assessment and supportive echocardiography signs. 21 Tricuspid regurgitation severity was evaluated by measuring the tricuspid regurgitation's vena contracta jet width in apical four-chamber view. 22 Other rhythm besides sinus rhythm on electrocardiogram were considered as arrhythmia.

Statistical analysis
Baseline characteristics data were analyzed using descriptive statistics. The normality of data was tested using the Saphiro-Wilk test. Numerical values were expressed as mean + standard deviation (normally distributed data) or median and interquartile range (non-normally distributed data) and compared using independent t-test or Mann-Whitney test, as appropriate. The p-value threshold was set at 0.05. Statistical analyses were performed with IBM SPSS statistic version 23.

RESULTS
Thirty patients joined the study. Two patients had septic shock and one patient was died after surgery in intervention group. Patients who refused surgery had septic shock, and died were considered dropped out in the control group. There were 12 patients left in both groups. No differences were found between control and intervention groups for age, sex, height, weight, vital signs, diagnosis, medical therapies, surgery, arrhythmia, six-minute walking distance, cardiopulmonary bypass time, aortic cross-clamp time, surgery duration, echocardiography measurement, right ventricular function measured using RV free wall strain, RV FAC, and TAPSE. Some patients had decreased right ventricular function before cardiac surgery but there was no statistical difference in decreased right ventricular function patients' numbers between intervention and control groups ( Table 1).

Definitions
Inspiratory muscle training was performed at home at least 14 days before heart valve surgery, twice a day (10 minutes each exercise), with 5 x 10 Repetition Maximum (RM) intensity. The resistance was increased on the 8 th day of training. Exercise will be halted when the patient's shows worsen clinical signs and heart failure symptoms such as dyspnea, palpitations, fatigue, or cyanotic. Homebased exercise was supervised daily using video call. Both groups received standard preoperative exercise programs such as aerobic training, breathing techniques, ankle pump exercise, and range of motion exercise. 15,17, 18 Right ventricular systolic function was measured by echocardiography using three methods: right ventricular free wall strain (RV free wall strain), right ventricular fractional area changes (RV FAC), and Tricuspid Annular Plane Systolic Excursion (TAPSE). All methods were analyzed using Philips Qlab Software. RV free wall strain was assessed by tracing the right ventricular base, mid, and apex on apical four-chamber view. RV free wall strain <-20% indicates abnormal right ventricular function. RV FAC percentage was measured using   Right ventricular function was determined by preload, afterload, and contractility. Preload states can be excluded from the confounding factor because there was no significant estimated right atrial pressure difference/eRAP (p=0.698) measured using echocardiography between two groups. No significant differences on TVr procedures between two groups that may cause preload changes (p=1,0). 20,25, 26 We hypothesized that afterload changes might be the cause of right ventricular function reduction, but we didn't find any significant difference between two groups afterload which measured using pulmonary vascular resistance/ PVR (p=0.23) and sPAP (p=0.95) by echocardiography; and no significant differences on postoperative pulmonary complications in both groups (p=0.665) that may increase right ventricle afterload due to prolonged mechanical ventilators and acute respiratory distress syndromes. Parati et al. stated that breathing exercise reduced sPAP significantly in patients with chronic heart failure. 16 In this study, we found no increasing afterload because PVR and sPAP were reduced after cardiac surgery in both groups. This also explained why the patients were in excellent clinical conditions despite reduced right ventricular function. 23 Right ventricle contractility may reduce after cardiopulmonary bypass which caused myocardial and systemic inflammations. Patients with heart failure with inspiratory muscle Weakness has role in increasing pro-inflammatory factors and raising calpain activities which known resulted in decreasing myocardial contractility. Patients in intervention group may have better inspiratory muscle strength than patients in the control group. Although we didn't measure respiratory muscle strength using micro RPM, there was significant load progression (13% load This also explains TAPSE reduction below normal cut-off value in both groups because TAPSE only represents longitudinal not global right ventricular function. 20, 23 We found lower RV free wall strain reduction in intervention and control group (12% vs. 30%). Singh et al. stated that RV free wall strain reduction >20% might cause clinical implications. 23 Other clinical implications as Shukla et al. stated, RV free wall strain < -16.2% is the cut-off that increases mortality risk in pulmonary hypertension with multiple etiologies (OR= 3.67; CI 95% 2.82 -4.77; p<0.001). 30 We found that mean RV free wall strain in intervention group was higher than the cut-off point (-17.7 + 3.0%) and the control group means were below cut off point (-14.4 + 4.0%). The ICU length of stay (LOS) was significantly shorter in patients in intervention vs control group (3.2 + 0.8 vs 4.2 + 1.3 days; p=0.044). Katsura et al. stated that inspiratory muscle training reducing hospital LOS (p=0.03). 15 Bootsma et al study showed that low RVEF (20 -30%) was associated the increasing risk for longer ICU LOS (OR 3.25; p<0.001). 3

STUDY LIMITATIONS
The authors didn't perform invasive hemodynamic measurements to get PVR and sPAP values. We didn't perform the inspiratory muscle strength using standard micro RPM and small sample size in our study. The inflammatory biomarkers weren't measured in this study, and they may have roles in myocardial contractility differences between two groups in this study.

CONCLUSION
Patients underwent conventional preoperative rehabilitation added inspiratory muscle training had better right ventricular systolic function than patients in control group.