The aim of this study is to assess the early clinical, hemodynamic, and echocardiographic changes after elective isolated mitral valve replacement or concomitant mitral valve replacement and aortic valve replacement in patients with PH. The study included patients with baseline systolic pulmonary artery pressure (PAPs) of at least 35 mmHg measured by echo who underwent elective MVR and/or aortic valve replacement (AVR).
Journal of military pharmaco-medicine no2-2018 EVALUATION THE CRITICAL CARE PERIOD RESULTS AFTER ISOLATED MITRAL VALVE REPLACEMENT OR SIMULTANEOUS MITRAL AND AORTIC VALVE SURGERY IN PATIENTS WITH PULMONARY HYPERTENSION Kieu Van Khuong*; Pham Thi Hong Thi**; Nguyen Quoc Kinh*** SUMMARY Objectives: To assess the early outcome after elective isolated or concomitant mitral valve replacement (MVR) in patients with pulmonary hypertension (PH) Subjects and methods: The study included patients with baseline systolic pulmonary artery pressure (PAPs) of at least 35 mmHg measured by echo who underwent elective MVR and/or aortic valve replacement (AVR) The systemic and pulmonary hemodynamic changes, arterial and mixed venous blood gas parameters were reported at various time points before and after operation Preoperative and postoperative transthoracic echocardiography was performed Results: Sixty seven patients (15 males and 52 females), arithmetic mean age was 45.51 ± 10.74 years (min - max: 20 - 68) were included in the study The operative mortality rate was 4.5% The receiver operating characteristic curves identified PAPs as a good predictor of operative mortality Postoperatively, there was a significant reduction in left atrial diameter (LAd) The arithmetic mean PAPs and pulmonary artery occlusion pressure (PAOP) decreased significantly after cardiopulmonary bypass (CPB) and persisted throughout the study period Central venous pressure (CVP) decreased after CPB time and remained so to PAC removing time point, postoperatively A decrease in SvO2 was significant after operation Conclusion: Proper perioperative care and anesthetic techniques resulted in the improvement of LAd, PAPs, PAOP, with acceptable operative mortality in patients with PH who was performed elective isolated MVR or simultaneous mitral and AVR * Keywords: Pulmonary hypertension; Aortic valve replacement; Mitral valve replacement INTRODUCTION All around the world, rheumatic heart disease remains a major health problem, although its prevalence in the developed countries is much reduced Involvement of the mitral valve and aortic valve results in stenosis and/or regurgitation heart valve diseases Where surgery is indicated, MVR is usually necessary [1] The development of pulmonary arterial hypertension (PAH) has been considered a risk factor for poor outcomes in patients undergoing MVR and/or AVR [2] However, * 103 Military Hospital ** Vietnam National Heart Institute *** Vietduc Hospital Corresponding author: Kieu Van Khuong (icudoctor103@gmail.com) Date received: 10/12/2017 Date accepted: 22/01/2018 154 Journal of military pharmaco-medicine no2-2018 there is no consensus on the outcome of patients with PAH after MVR in the literature; some studies have shown that severe PAH is associated with poorer outcome and higher mortality rate [3], whereas others not agree that severe PAH implies a higher risk during corrective surgery [4, 5, 6, 7] This study was designed to: Assess the early clinical, hemodynamic, and echocardiographic changes after elective isolated MVR or concomitant MVR and AVR in patients with PH SUBJECTS AND METHODS Subjects Between April, 2017 and November, 2017, 67 consecutive adult patients with a baseline PAPs of at least 35 mmHg (as measured by preinduction transthoracic echocardiography) who had performed mitral and/or simultaneous AVR at Heart Center of Hue Center Hospital Patients with coronary artery disease or idiopathic PAP were excluded from the study Methods All preoperative assessments were carried out by two-dimensional transthoracic echocardiography A pulmonary artery catheter (PAC) was placed in the pulmonary artery to measure PAPs and PAOP General anesthesia was induced with fentanyl, - µg/kg All patients were operated on through a arithmetic mean sternotomy on CPB with moderate general hypothermia (28 - 30°C) We used two kinds of mechanical prosthesis: ATS valve and St Jude medical bileaflet mechanical prosthesis The hemodynamic and arterial blood gas parameters were reported at time points: T0: baseline or pre-induction; T1: post-intubation; T2: immediate postCPB; T3: at ICU; T4: hour post-ICU; T5: 24 hour post-ICU and Toff: before PAC removing and the hemodynamics had been stabilized postoperatively Hemodynamic parameters that were recorded included mean arterial pressure (MAP), PAPs, PAOP, and central venous pressure (CVP) All data were expressed as mean ± standard deviation, - max or number and percent as appropriate The preoperative and postoperative echocardiographic parameters, and the hemodynamic and arterial blood gas parameters obtained at various time intervals were compared with the baseline values The receiver operating characteristic (ROC) curves were used to estimate the relationship between sensitivity (proportion of true positive cases) and 1-specificity (proportion of false-positive cases) of PAPs in the prediction of operative mortality A p-value of 0.05 or less was considered significant RESULTS Table 1: Patient’s characteristics Variables Result Min - max Age (year) 45.5 ± 10.7 20 - 68 Gender [m/f, (%)] 15/52 (22.4/77.6) Body surface area (m ) 1.44 ± 0.11 Body mass index (kg/m ) 19.8 ± 2.4 15.4 - 25.2 155 Journal of military pharmaco-medicine no2-2018 Weight (kg) 48.0 ± 6.5 33 - 67 Height (cm) 155.9 ± 7.0 142 - 170 NYHA II (n, %) 21 (31.3) NYHA III (n, %) 44 (65.7) NYHA IV (n, %) (3) Atrial fibrillation (n, %) 31 (46.3) Cardiothoracic ratio > 50% (n, %) 40 (59.7) The study group was mainly female (77.6%) at arithmetic mean age of 45.51 ± 10.74 years The patients were classified as follows: 21 patients (31.3%) in NYHA II class and 44 patients (65.7%) in NYHA III class and cases in NYHA class IV Table 2: Intraoperative and postoperative clinical outcome variables Variables Result Min Max CPB time (min), arithmetic mean 114.2 ± 57.7 54 - 466 ACC time (min), arithmetic mean 79.8 ± 36.8 31 - 185 Tricuspid repair [n (%)] 15 (22.4%) LAA exclusion [n (%)] 18 (26.9) Thromboembolic removing [n (%)] 11 (16.4) Time of ventilator (h) Mechanical assist by IABP [n (%)] Operative mortality [n (%)] 156 20.9 ± 31.7 (6%) (4.5%) (ACC: Aortic cross-clamp time; CPB: Cardiopulmonary bypass time; IABP: Intra-aortic balloon pump; ICU: Intensive care unit LAA: Left atrial appendage) The arithmetic mean CPB time was 114.18 ± 57.71 mins (range: 54 - 466) and the arithmetic mean aortic crossclamp time was 79.76 ± 36.78 mins (range: 31 - 185) Tricuspid repair was performed in 15 patients (22.39%) Table 3: Comparison of preoperative and postoperative echocardiographic variables Variables T0 T3 Toff Lad (mm) 51.03 ± b 8.19 42.13 ± b 2.30 43.67 ± b 2.88 LVEDD (mm) 48.28 ± b 8.31 45.92 ± b 5.59 45.45 ± b 5.19 LVESD (mm) 34.66 ± b 7.15 32.61 ± b 5.40 31.87 ± a 5.31 EF (%) 53.49 ± 8.02 53.28 ± 7.38 55.21 ± 8.22 (a: Significant difference < 0.0001; b: Significant difference < 0.05 Abbreviation: EF: Ejection fraction; Lad: Left atrium diameter; LVEDD: Left ventricular enddiastolic diameter; LVESD: Left ventricular end-systolic diameter; CTR: Cardiothoracic ratio) There was a significant difference between LAd, LVEDD, LVESD at points time of postoperation and when to remove PAC in comparision with baseline time results but no significant difference in EF Journal of military pharmaco-medicine no2-2018 Table 4: Early hemodynamic parameter changes CVP (mmHg) 2.43 ± 0.77 a 7.55 ± 4.11 b 94.48 ± 12.41 a 49.15 ± 17.52 a 23.43 ± 9.84 T1 1.66 ± 0.42 a 7.08 ± 3.21 67.66 ± 10.22 a 29.91 ± 11.08 a 16.48 ± 7.54 T2 2.58 ± 0.61 a 8.49 ± 2.80 74.54 ± 14.22 a 32.45 ± 10.31 a 11.40 ± 4.16 T3 3.02 ± 0.80 a 6.21 ± 2.99 b 93.01 ± 13.34 33.13 ± 11.94 a 9.63 ± 5.91 a T4 2.65 ± 0.55 a 6.10 ± 2.79 b 74.00 ± 11.63 a 32.18 ± 11.89 a 9.91 ± 5.43 a Toff 3.00 ± 0.69 a 6.21 ± 3.20 b 79.16 ± 10.70 a 31.45 ±1 1.99 a 9.63 ± 5.06 a Time points CI (L/min/m ) T0 MAP (mmHg) PAPs (mmHg) PAOP (mmHg) a a a (a: Significant difference < 0.0001; b: Significant difference < 0.05 Abbreviation: CI: Cardiac output index; CVP: Central venous pressure; MAP: Mean arterial pressure; POAP: Pulmonary artery occlusion pressure; PAPs: Pulmonary systolic arterial pressure) There was a significant decrease in PAPs, PAOP after induction, CPB stop, and this change persisted throughout at removing PAC time point postoperatively CVP and MAP decreased, but it kept in normal range CI decreased after induction anesthesia (T1) and increased significantly at T2, T3, Toff time point Table 5: Arterial and mixed venous blood gas parameter changes Time points pH PaCO2 (mmHg) PaO2 (mmHg) SaO2 (%) SvO2 (%) T0 7.42 ± 0.03 38.24 ± 4.22 210.64 ± 96.08 99.19 ± 1.99 72.57 ± 9.34 T1 7.48 ± 0.06 a 32.48 ± 5.54 a 319.56 ± 80.85 a 99.94 ± 0.37 b 72.37 ± 8.10 T2 7.45 ± 0.07 b 31.53 ± 6.40 a 301.00 ± 82.54 a 99.85 ± 0.76 74.53 ± 8.78 T3 7.40 ± 0.07 b 34.84 ± 8.35 b 175.43 ± 62.35 b 99.05 ± 1.20 69.19 ± 10.55 T4 7.39 ± 0.07 b 36.29 ± 5.88 b 163.98 ± 36.34 b 99.14 ± 0.66 63.34 ± 12.43 a Toff 7.45 ± 0.07 b 39.46 ± 6.19 104.50 ± 36.74 a 96.86 ± 2.67 a 59.24 ± 11.17 a a (a: Significant difference < 0.0001, b: Significant difference < 0.05) There was a significant difference of blood gas parameters between baseline time point (T0 time point) with other time points, excepted PaCO2 (Toff time point), PaO2 (T2 time point), SaO2 (T2, T3, T4 time point) and SvO2 (T1, T2, T3 time point) 157 Journal of military pharmaco-medicine no2-2018 Sensitivity PAPs 100 80 60 40 20 Sensitivity: 66.7 Specificity: 85.9 Criterion : >65 40 80 100-Specificity Figure 1: The receiver operating characteristic curve of systolic pulmonary arterial hypertension as a predictor of operative mortality DISCUSSION There were 67 patients involved in the study, the lowest age was 20, the highest was 68, the mean was 45.51 ± 10.74 years This finding is consistent with recent studies in cardiac valve surgery in India and Vietnam The study by Nirmal Kumar et al [7] in severe PH patients soon after MVR had an arithmetic mean age of 32.1 years, lower than our result This difference was due to the fact that study only included patients with mitral valve disease with severe PH (PAPs > 50 mmHg) and this feature was more common in acute rheumatoid arthritis in India [10] Age in our study was similar to result of Gửkhan Lafỗ [4] and two other local authors: Vu Quynh Nga (44.2 ± 11.5 years), Doan Duc Hoang (46.69 ± 12.57 years) [1, 2] The patients were mainly in NYHA III with 46.3% rhythm dysfunction as atrial fibrillation (AF) and 59.7% of them increased cardiothoracic ratio over 50% Some intraoperative and postoperative results showed in table The arithmetic mean CPB time (114.2 ± 57.7 mins) and the arithmetic mean ACC time (79.7 ± 158 36.8 mins) was similar to Xiaochun Song’s study (CPB: 119.9 ± 37.4 mins and ACC: 82.5 ± 31.8 mins) [7] Our result was higher than Vu Thuc Phuong’s study (CPB time of group D, using dobutamin: 95.2 ± 35.1 mins; CPB time of group E, using epinephrine: 86.5 ± 24.1 mins ACC time of group D: 73.5 ± 32.4 mins; ACC time of group E 67.2 ± 20.8 mins) It may be due to their patient groups were mainly replaced one valve surgery (> 60% in both groups) and no preoperative heart failure A comparison of preoperative and postoperative (T3 time point), removing PAC time point (Toff) echocardiographic variables is presented in table Postoperatively, there was a significant reduction in LAd, LVEDD, LVESD (p < 0.05) The increased left atrial (LA) pressure in mitral valve disease is passively transmitted to the pulmonary vasculature and can lead to an increase in pulmonary vascular resistance (PVR) Some other factors such as reactive pulmonary vasoconstriction and organic changes in pulmonary vasculature are also responsible for this increase in PVR [11] Following mitral valve surgery, LA loading can Journal of military pharmaco-medicine no2-2018 be adequately decompressed This decompression is very influential in the regression of PH [4] LA enlargement is a pathophysiological response to volume overload resulting from valvular diseases which is known as LA remodeling, and has been shown previously to be associated with cardioembolic events Following MVR, the LA may undergo reverse remodeling characterized by LA volume reduction LA size reduces with the return of normal sinus rhythm and a decrease in the gradient across the mitral valve Our results showed a significant decrease in PAPs and PAOP after CPB (T2 time point), and this change persisted to time point of PAC removing, postoperatively (table 4) These findings were in agreement with some other researchers who have reported hemodynamic changes in patients with rheumatic mitral valve disease at different intervals after MVR, with an immediate reduction in PAPs In the study by Kumar [9], the mean PAPs, PAOP, and pulmonary vascular resistance decreased significantly soon after CPB in patients with severe PH The mean PAPs approached near-normal values (26 ± mmHg) hours and 24 hours, postoperatively The study by Mubeen et al [12] showed that the mean PAPs decreased by 38% from a mean preoperative level of 59.8 to 37.1 mmHg immediately following MVR Although it continued to decrease over the next 24 hour, this further decrease was not statistically significant In a recent study by Bayat et al, PAP in patients with severe PAH showed no significant reduction immediately after MVR, but it decreased significantly below the range of severe PAP over the first 24 hours after operation The present study showed that MVR could be performed in patients with rheumatic valvular disease and severe PH with an acceptable operative mortality of 10% The study by Mubeen et al [12] showed that the operative mortality was 5.5% in patients with subsystemic PAP, with a mean of 58.1 mmHg and 28.5% in patients with a suprasystemic PAP of 83.2 mmHg The operative mortality rate in our study was 4.5% (table 2) The ROC curves (figure 1) identified PAPs as a good predictor of operative mortality (area under the ROC curve: 0.794; p < 0.05), and the value greater than 65 mmHg has the highest specificity (85.9%) and sensitivity (66.7%) for the risk of operative mortality in those patients Similarly, the recent study by Corciova et al identified PAPs value greater than 65 mmHg to have the highest specificity and sensitivity for the risk of perioperative death in mitral regurgitation patients (area under the ROC curve: 0.782; p < 0.001) SvO2 did not change at T1, T2 time point (table 5) but it decreased significantly after operation even when hemodynamic in stable (at Toff time point) SvO2 can be used to assess the adequacy of tissue perfusion and oxygenation When analyzing in conjunction with other hemodynamic parameters, following trends in the SvO2 does offer insight into cardiac performance and tissue oxygen delivery In the postoperative cardiac surgical patient, a fall in SvO2 generally reflects decreased oxygen delivery or increased oxygen extraction by tissues and is suggestive of a reduction in cardiac output However, other constantly changing factors that affect oxygen supply and demand may 159 Journal of military pharmaco-medicine no2-2018 also influence SvO2 and must be taken into consideration These include shivering, temperature, anemia, alteration in FiO2, and the efficiency of alveolar gas exchange A decresae in SvO2 at T3, T4 time point (patients in ventilation support) (table 5) can result from a decrease CO, low hemoglobin level or an increase in oxygen consumption SvO2 decreased at Toff may be relative with a decrease in FiO2 (in room air), fever or anemia It is very important to take care the patients in this stage because SvO2 reduction under threshold leads to the danger of organ dysfunction that is reason why they come back to intensive care unit ward CONCLUSION Isolated MVR or concomitant MVR and AVR was safe and effective even in patients with PH, with acceptable operative mortality and a significant improvement in left atrial diameter, pulmonary hemodynamics (PAPs, PAOP), but a decrease in mixed venous saturation early after operation The anesthetic technique and perioperative care can be useful in improving the outcome in such patients Lafci G, A.I Diken, H.S Gedik et al Alterations in pulmonary artery pressure following mitral valve replacement Turk Kardiyol Dern Ars 2012, 40 (3), pp.235-241 Svein Simonsen K.F Anders Andersen and Leif Efskind Hospital mortality after mitral valve replacement 1974 Parvathy U.T, R Rajan, A.G Faybushevich Reversal of abnormal cardiac parameters following mitral valve replacement for severe mitral stenosis in relation to pulmonary artery pressure: A retrospective study of noninvasive parameters - early and late pattern Interv Med Appl Sci 2016, (2), pp.49-59 Song X.C, Zhang X Chen et al An excellent result of surgical treatment in patients with severe pulmonary arterial hypertension following mitral valve disease J Cardiothorac Surg 2015, 10, p.70 Thunberg C.A, B.D Gaitan, A Grewal et al Pulmonary hypertension in patients undergoing cardiac surgery: pathophysiology, perioperative management and outcomes J Cardiothorac Vasc Anesth 2013, 27 (3), pp.551-572 REFERENCE Kumar N.P Sevta S, Satyarthy et al Early results of mitral valve replacement in severe pulmonary artery hypertension - An institutional prospective study World Journal of Cardiovascular Surgery 2013, (2), pp.63-69 Hoằng Đ.Đ Nghiên cứu vai trò số SvO2 hồi sức huyết động bệnh nhân phẫu thuật tim có nguy cao 2017 10 Padmavati S Present status of rheumatic fever and rheumatic heart disease in India Indian Heart J 1995, 47 (4), pp.395-398 Nga V.Q Nghiên cứu số thông số huyết động chức tim siêu âm Doppler bệnh nhân phẫu thuật thay van hai Sorin Bicarbon 2010 11 Ott B Valvular heart disease a companion to Braunwald's heart disease expert consult third edition 2009 Zakkar M, E Amirak, K.M Chan et al Rheumatic mitral valve disease: current surgical status Prog Cardiovasc Dis 2009, 51 (6), pp.478-481 160 12 Mohammad Mubeen, Amrendra K Singh, Surendra K Agarwal, Jeewan Pillai, Shalini Kapoor, Ashok K Srivastava Mitral valve replacement in severe pulmonary arterial hypertension 2008 ... 4) These findings were in agreement with some other researchers who have reported hemodynamic changes in patients with rheumatic mitral valve disease at different intervals after MVR, with an immediate... hypertension as a predictor of operative mortality DISCUSSION There were 67 patients involved in the study, the lowest age was 20, the highest was 68, the mean was 45.51 ± 10.74 years This finding... finding is consistent with recent studies in cardiac valve surgery in India and Vietnam The study by Nirmal Kumar et al [7] in severe PH patients soon after MVR had an arithmetic mean age of 32.1