The study on clinical phenotypes of pulmonary hypertension due to left heart disease at pre-operation time in patients with isolated mitral valve replacement or double valve replacement

We aimed at describing the different hemodynamic phenotypes of patients with pulmonary hypertension due to left heart disease before mitral valve replacement and/or concomitant aortic valve replacement and characterizing the impact of pulmonary hemodynamics on RV function. Subjects and method: 67 patients with pulmonary hypertension related to left heart diseases who underwent elective mitral valve replacement and/or aortic valve replacement enrolled in this prospective study from April, 2017 to April, 2018 at Hue Heart Center. Results and conclusions: Prevalence of three subgroups of patients pulmonary hemodynamics: isolated post-capillary pulmonary hemodynamics (Ipc - pulmonary hypertension); combined post- and pre-capillary pulmonary hypertension (Cpc - pulmonary hypertension); intermediate pulmonary hemodynamics were 43.2%, 28.4% and 28.4%, respectively. Cpc pulmonary hemodynamics presented with slightly higher weight and body mass index than intermediate patients (p < 0.05).

Journal of military pharmaco-medicine n02-2019 THE STUDY ON CLINICAL PHENOTYPES OF PULMONARY HYPERTENSION DUE TO LEFT HEART DISEASE AT PRE-OPERATION TIME IN PATIENTS WITH ISOLATED MITRAL VALVE REPLACEMENT OR DOUBLE VALVE REPLACEMENT Kieu Van Khuong1; Pham Thi Hong Thi2 SUMMARY Objectives: We aimed at describing the different hemodynamic phenotypes of patients with pulmonary hypertension due to left heart disease before mitral valve replacement and/or concomitant aortic valve replacement and characterizing the impact of pulmonary hemodynamics on RV function Subjects and method: 67 patients with pulmonary hypertension related to left heart diseases who underwent elective mitral valve replacement and/or aortic valve replacement enrolled in this prospective study from April, 2017 to April, 2018 at Hue Heart Center Results and conclusions: Prevalence of three subgroups of patients pulmonary hemodynamics: isolated post-capillary pulmonary hemodynamics (Ipc - pulmonary hypertension); combined post- and pre-capillary pulmonary hypertension (Cpc - pulmonary hypertension); intermediate pulmonary hemodynamics were 43.2%, 28.4% and 28.4%, respectively Cpc pulmonary hemodynamics presented with slightly higher weight and body mass index than intermediate patients (p < 0.05) There was a significant difference in PAPs, PAPd, PAPm, TPG, DPG, PVR, SV, CI parameters across the three subgroups of pulmonary hypertension left heart disease TAPSE showed a significantly difference between groups, while the ratio between TAPSE and systolic pulmonary artery pressures progressively decreased from Ipc pulmonary hemodynamics to “intermediate” pulmonary hypertension - left heart diseases to Cpc pulmonary hypertension (p < 0.0001) * Keywords: Pulmonary hypertension due to left heart disease; Mitral valve replacement INTRODUCTION Pulmonary hypertension (PH) is the underlying physiological consequence of left heart disease (LHD) In PH, both pulmonary arterial occlusion pressure (PAOP) and pre-capillary components may affect the right ventricular (RV) after load These changes contributed to RV failure and patient prognosis This study aimed: To characterize the different preoperative hemodynamics between the different PH phenotypes and impact of pulmonary hemodynamics on RV function SUBJECTS AND METHODS Subjects 67 patients with isolated mitral valve replacement or double valve replacement from April, 2017 to April in 2018 in the Centre of Cardiology of Hue Central Hospital 103 Military Hospital Vietnam National Heart Hospital Corresponding author: Kieu Van Khuong (icudoctor103@gmail.com) Date received: 20/12/2018 Date accepted: 20/01/2019 249 Journal of military pharmaco-medicine n02-2019 * Exclusion criteria: Patients with coronary diseases, systolic arterial hypertension (systolic blood pressure was higher than 140 mmHg), primary pulmonary hypertension, chronic obstructive pulmonary disease (FEV1/FVC < 0.7), central nerve disorder, and reoperation Surgeries combine with repair congenital malformation, atrial heart septal defect, ventricular septal defect, patients refuse to join the study Contraindication of pulmonary artery catheter, infectious dermatitis, severe disorder of coagulant system Methods A descriptive case series study Examination and investigation: Biochemistry, blood count, coagulant function, ECG, chest X-ray, and transthoracic echocardiography were performed as routine before cardiac surgery In operating room, peripheral vein, catheter pulmonary artery follow internal carotid artery pathway before preinduction (measure base parameters) Pulmonary hypertension patients were divided into subgroups: Isolated postcapillary pulmonary hypertension (DPG < mmHg, PVR < 3WU), pre-post capillary mixed pulmonary hypertension (DPG ≥ or PRV > 3WU), intermediate pulmonary hypertension (DPG < or PVR ≤ 3) DPG: Diastolic pressure gradient (PAPdPAOP) PVR: Pulmonary venous resistance All pulmonary and system, direct or indirect hemodynamic parameters were collected through Swan - Ganz catheter and Phillip MP70 monitor Data were processed by SPSS 21.0 edition software RESULTS Table 1: Characteristics of patients in subgroups of PH Charecteristics General group (n = 67) Isolated PH (n = 29) Intermediate PH (n = 19) Mixed PH (n = 19) p Patients (n) 67 (100) 29 (43.2) 19 (28.4) 19 (28.4) > 0.05 Female (n) 52 (77.6) 23 (79.3) 15 (78.9) 14 (73.7) > 0.05 Age (years) 45.5 ± 10.7 43.0 ± 10.6 48.2 ± 10.6 46.7 ± 10,7 > 0.05 Height (cm) 156.0 ± 7.0 156.1 ± 7.0 154.7 ± 7.5 157.0 ± 6.8 > 0.05 Weight (kg) 48.0 ± 6.7 50.5 ± 6.3 45.0 ± 7.4 47.3 ± 5.2 0.017 BMI (kg/m2) 19.8 ± 2.4 20.7 ± 2.4 18.8 ± 2.5 19.2 ± 1.9 0.012 BSA (m2) 1.45 ± 0.11 1.48 ± 0.11 1.40 ± 0.13 1.44 ± 0.99 > 0.05 NYHA II (n, %) 21 (31.3) 11 (37.9) (15.8) (36.8) > 0.05 NYHA III, IV (n, %) 46 (68.7) 18 (62.1) 16 (84.2) 12 (63.2) > 0.05 AF (n, %) 31 (46.3) (13.8) 13 (68.4) 14 (73.7) > 0.05 (BMI: Body mass index; BSA: Body surface area; NYHA: New York Heart Association; AF: Atrial fibrillation) 250 Journal of military pharmaco-medicine n02-2019 BSA and BMI among subgroups of pulmonary hypertension was significantly different (p < 0.05) There were no meaningful differences in other characteristics, such as gender (female), age, height, severity of heart failure (NYHA score) and atrial fibrillation proportion Table 2: Hemodynamic characteristics of subgroups PH Isolated PH (n = 29) Intermediate PH (n = 19) Mixed PH (n = 19) p HR (beat/min) 91.0 ± 22.4 101.6 ± 32.0 100.4 ± 21.3 0.224 ABPs (mmHg) 135.6 ± 21.1 132.9 ± 11.9 127.1 ± 20.9 0.317 ABPd (mmHg) 70.9 ± 11.6 77.7 ± 8.9 75.1 ± 11.8 0.195 MAP (mmHg) 91.6 ± 13.6 97.0 ± 7.9 93.4 ± 14.3 0.585 PAPs (mmHg) 39.2 ± 9.9 53.3 ± 16.0 60.2 ± 20.2 < 0.0001 PAPd (mmHg) 22.7 ± 7.6 29.7 ± 8.7 36.1 ± 9.6 < 0.0001 PAPm (mmHg) 30.0 ± 8.0 38.9 ± 10.8 45.6 ± 13.3 < 0.0001 PAOP (mmHg) 21.3 ± 8.3 27 ± 9.6 23.1 ± 11.6 0.147 TPG (mmHg) 8.66 ± 2.07 11.95 ± 3.14 22.6 ± 7.5 < 0.0001 DPG (mmHg) 1.34 ± 2.83 2.74 ± 3.05 13.05 ± 6.97 < 0.0001 170.7 ± 42.9 338.5 ± 109.5 655.5 ± 287.0 < 0.0001 6.7 ± 3.4 8.1 ± 3.6 8.4 ± 5.4 0.295 CVP/PAOP 0.33 ± 0.17 0.30 ± 0.09 0.41 ± 0.26 0.425 SV (mL) 48.9 ± 2.9 33.0 ± 15.5 31.9 ± 13.2 < 0.0001 2.82 ± 0.64 2.16 ± 0.72 2.12 ± 0.77 < 0.0001 Parameter PVR (dynes sec cm-5/m ) CVP (mmHg) CI (L/min/m ) (HR: Heart rate; ABPs: Systolic artery blood pressure; ABPd: Diastolic artery blood pressure; MAP: Mean artery pressure; PAPs: Systolic pulmonary artery pressure; PAPd: Diastolic pulmonary artery pressure; PAPm: Mean pulmonary artery pressure; PAOP: Pulmonary artery occlusion pressure; TPG: Transpulmonary gradient; DPG: Diastole pressure gradient; PVR: Pulmonary venous resistance; CVP: Central venous pressure, CVP/PAOP; SV: Stroke volume; CI: Cardiac index) There was a significant difference in PAPs, PADd, PAPm, TPG, DPG, PVR, SV and CI between subgroups of PH (p < 0.0001) 251 Journal of military pharmaco-medicine n02-2019 Table 3: Change in right ventricle function in subgroups of PH General (n = 67) Isolated PH (n = 29) Intermediate PH (n = 19) Mixed PH p RVSWI (g/m /beat) 10.5 ± 5.2 10.5 ± 4.9 9.6 ± 4.8 11.4 ± 6.3 0.599 TAPSE (mm) 19.5 ± 3.5 21.7 ± 2.9 18.3 ± 2.9 17.4 ± 2.9 < 0.001 TAPSE/PAPs (mm/mmHg) 0.45 ± 0.18 0.58 ± 0.14 0.38 ± 0.15 0.33 ± 0.16 < 0.001 (22.4) (0) (5.3) (21.1) < 0,05 Parameters TAPSE/PAPs ≤ 0.27 (mm/mmHg) (n, %) (TAPSE: Tricuspid annular plane systolic excursion; TAPSE/PAPs ratio; RVSWI: Right ventricular stroke work Index) TAPSE and TAPSE/PAPs decreased significantly in isolated post-capillary PH, intermediate PH and mixed PH subgroup, respectively (p < 0.001) DISCUSSION Characteristics of patients Table indicated that the characteristics of patients such as female, age, height, NYHA severity of heart failure and proportion of AF were not significantly different among subgroups of PH However, they were different in weight and BMI, highest in isolated post-capillary pulmonary hypertension (50.5 kg and 20.07 ± 2.4 kg/m2), followed by mixed pulmonary hypertension and the lowest one was subgroup intermediate PH (p < 0.05) The difference corresponded with the study by Caravita [1], but the subgroup which had got the highest weight and BMI was mixed postpre-capillary PH Because his study subjects were patients with left heart disease due to degenerated valve, old age with 64 ± 13 years old, proportion of NYHA III, IV heart failure was around 69% While our subjects were almost post-rheumatic fever valve disease with a long time history of disease 252 Hemodynamic of patients among subgroups of PH Post-capillary PH is a common complication of left heart disease However, a few number of patients have got PH which can not be explained with the increase of PAOP In these cases, the complex interactions among disorder of endothelial function, vasoconstriction and reformat pulmonary vessels can develop the precapillary factors in addition to post-capillary PH Recently, guidelines of PH of ESC/ERS proposes definition of hemodynamic in order to classify postcapillary PH based on DPG and PVR [1] In our study, when classifying PH hemodynamic, we had got the proportion of isolated post capillary PH, intermediate PH and mixed PH as 43.2%, 28.4%, and 28.4%, respectively For Dixon, the proportion of Mixed PH to preserve EF heart failure patients was 7.5% [2] This rate was lower than our study because only 75.4% of 293 patients had Journal of military pharmaco-medicine n02-2019 got PH due to various reasons Otherwise, the proportion of patients whose PVR increased in his study was 18% According to Naeije, the proportion of mixed PH due to left heart disease was from 12 to 13%, these had got severe PH with higher TPG, DPG and PVR Besides, the subgroup of mixed PH showed the significant responding with ventilation, a lower elasticity of pulmonary artery, reduction of right ventricle and predicted life expectancy compared to isolated PH In our study, value of hemodynamic parameters such as PAPs, PAPd, PAPm, TPG, DPG, and PVR, respectively increased from isolated PH and reached the highest value in mixed PH This difference was statistically significant with p < 0.0001 The parameter which access the efficiency of heart function such as stroke volume and cardiac index reduce respectively in isolated PH (SV: 48.9 ± 2.9 mL, CI 2.82 ± 0.64 L/min/m 2), intermediate PH (33.0 ±15.5 mL and 2.16 ± 0.72 L/min/m2), and mixed PH (31.9 ± 13.2 mL and 2.12 ± 0.77 L/min/m2) (p < 0.0001) (table 2) Our result was similar to Caravita’s study, in which PAPs, PAPd, PAPm, PAOP, PDG, and TPG increased gradually statistically from isolated PH, intermediate PH to mixed PH And SV reduced gradually from isolated PH (64 ± 20 mL), mixed PH (58 ± 21 mL), intermediate PH (54 ± 14 mL) [1] Therefore, pulmonary and systemic hemodynamic in subgroup mixed PH is usually worse than isolated PH The study by Palazzini performed on 276 patients also demonstrates that the patients with isolated PH have got better prognosis than the other subgroups (increase of PVR and DPG only) Impact of RV function in subgroups of PH Post-capillary PH is a frequent pathophysiological complication of left heart disease In PH patients, both PAOP and pre-capillary PH affect afterload of RV These changes lead to RV dysfunction and a worse prognosis RV dysfunction, include reduction of RV systolic function and RV overload, for example: reduction of RV leads to the increase of afterload Characteristics of impact of hemodynamic on RV function in this study were shown in table We used TAPSE index and ratio TAPSE/PAPs, RVSWI, CVP/PAOP as the alternative hemodynamic index to assess the disorder of RV function According to Gerges M et al, in their prospective cohort study with 664 systolic heart failure patients and 339 diastolic heart failure cases, who were assessed pulmonary hemodynamic with intra-cardiac catheter, there were 12% mixed PH and the ratio TAPSE/PAPs can predict mixed PH Younger age (p = 0.004), valvular heart disease (p = 0.046) and echo-derived tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio predicted mixed PH in DHF (p = 0.016) Right ventricular-pulmonary vascular coupling was worse in mixed PH than in those with isolated PH [5] CONCLUSION The average age was 46.7 ± 10.7 in isolated mitral valve replacement or simultaneous aortic and mitral valve 253 Journal of military pharmaco-medicine n02-2019 replacement patients, proportion of isolated PH, intermediate PH and mixed PH were 43.2%, 28.4%, 28.4%, respectively BMI and weight of subgroups was significantly different (p < 0.05) PAPs, PAPd, PAPm, TPG, DPG, and PVR got the highest value in subgroup mixed PH, followed by intermediate PH and lowest in isolated PH patients (p < 0.001) Mixed TAP subgroup has got lowest TAPSE (17.4 ± 2.9 mm), and lower TAPSE/PAPs ratio (0.33 ± 0.16d mm/mmHg) with p < 0.001 REFERENCES Caravita S, Faini A, Carolino D'Araujo S et al Clinical phenotypes and outcomes of pulmonary hypertension due to left heart disease: Role of the pre-capillary component PLoS One 2018, 13 (6), pp.1-16 Dixon D.D, Trivedi A, Shah S.J Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved 254 ejection fraction Heart Fail Rev 2016, 21 (3), pp.285-297 Naeije R, Gerges M, Vachiery J.L et al Hemodynamic phenotyping of pulmonary hypertension in left heart failure Circ Heart Fail 2017, 10 (9), pp.1-10 Palazzini M, Dardi F, Manes A et al Pulmonary hypertension due to left heart disease: Analysis of survival according to the haemodynamic classification of the 2015 ESC/ERS Guidelines and insights for future changes Eur J Heart Fail 2018, 20 (2), pp.248-255 Mario Gerges, Christian Gerges, AnnaMaria Pistritto et al Pulmonary hypertension in heart failure: Epidemiology, right ventricular function and survival The American Thoracic Society, 2015, pp.1-50 Drazner M.H, Velez-Martinez M Ayers C.R et al Relationship of right-to left-sided ventricular filling pressures in advanced heart failure: Insights from the ESCAPE trial Circ Heart Fail 2013, (2), pp.264-270  ... pharmaco-medicine n02-2019 got PH due to various reasons Otherwise, the proportion of patients whose PVR increased in his study was 18% According to Naeije, the proportion of mixed PH due to left heart disease. .. number of patients have got PH which can not be explained with the increase of PAOP In these cases, the complex interactions among disorder of endothelial function, vasoconstriction and reformat pulmonary. .. defect, patients refuse to join the study Contraindication of pulmonary artery catheter, infectious dermatitis, severe disorder of coagulant system Methods A descriptive case series study Examination