Long-term outcomes of severe rheumatic mitral stenosis after undergoing percutaneous mitral commissurotomy and mitral valve replacement: A 10-year experience

Introduction: Percutaneous mitral commissurotomy (PTMC) and mitral valve replacement (MVR) are treatments of choice for severe rheumatic mitral stenosis (MS). Data regarding the long-term outcomes of patients who underwent PTMC and MVR are limited. Methods: A retrospective cohort study was conducted to evaluate the long-term outcomes of patients with severe rheumatic MS who underwent PTMC or MVR between 2010 to 2020. The primary outcome comprised of all-cause death, stroke or systemic embolism, heart failure hospitalization and re-intervention. Cox regression was used to investigate predictors of the primary outcome. Results: 264 patients were included in analysis, 164 patients (62.1%) in PTMC group and 100 patients in MVR group (37.9%). The majority were females (80.7%) and had atrial fibrillation (68.6%). The mean age was 49.52 (SD: 13.03) years old. MVR group had more age and AF, higher Wilkins’ score with smaller MVA. Primary outcome occurred significantly higher in PTMC group (37.2% vs 22%, P=0.002), as well as, re-intervention (18.3% vs 0%, P<0.001). However, all-cause mortality, stroke or systemic embolism and heart failure hospitalization were not significantly different. In multivariate Cox regression analysis, PTMC (HR 1.94; 95%CI 1.14, 3.32; P=0.015), older age (HR 1.03; 95%CI 1.01, 1.06; P=0.009) and SPAP > 50 mmHg (HR 2.99; 95%CI 1.01, 8.84; P=0.047) were the only predictors of primary outcome. Conclusion: Primary outcome occurred in PTMC group more than MVR group which was driven by re-intervention. However, all-cause mortality, stroke or systemic embolism and heart failure hospitalization were not significantly different.


Introduction
Rheumatic heart disease (RHD) is one of the most common acquired valvular heart diseases. 1 RHD has declined dramatically worldwide, though in low-to middle-income countries, RHD is an important cause of death and disability. The prevalence of RHD ranged from

Procedures
The treatment strategy, including the prosthetic valve types (bioprosthesis or mechanical valve) and the need for concomitant tricuspid valve annuloplasty (TVA) in case of MVR, was decided by the heart team which consisted of cardiothoracic surgeons, cardiologists, echocardiographic specialists and anesthesiologists.
PTMC was performed with the Inoue commissurotomy technique using Inoue single balloon (Toray Industries, Inc., NY, United State) and transesophageal guided atrial septostomy and commissurotomy. 11 A balloon diameter and catheter size were chosen according to the patient height. Echocardiography, as well as left and right cardiac catheterization, were performed at baseline and after PTMC. Important parameters namely MVA, mean pressure gradient (PG) across MV, Wilkins' score, mitral regurgitation (MR) grading and pulmonary artery pressure were recorded.

Outcomes
The primary outcome was composite of all-cause death, stroke or systemic embolism, heart failure hospitalization and re-intervention rate. Secondary outcomes were allcause death, stroke or systemic embolism, heart failure hospitalization, re-intervention rate, PTMC success rate, periprocedural complications, valvular infection and serious bleeding (The Bleeding Academic Research Consortium (BARC) definition type 3 or more). 12 PTMC success rate was defined as MVA after procedure > 1.5 cm 2 or more than twice of the preprocedural value and no worsening of MR more than grade 2+). 13

Statistical analysis
Categorical variables were presented as frequency and percentage and analyzed using a Chi-square test or Fisher's exact test as appropriate. Continuous variables are presented as the mean with standard deviation (SD) or median with interquartile range (IQR) and analyzed using a t-test or Mann-Whitney test as appropriate. The periprocedural complications were not analyzed due to the different complications found between both groups. Univariate and multivariate Cox regression, adjusted for covariates with a p-value from the univariable model was less than 0.15, were performed to find the hazard ratio (HR). The Kaplan-Meier curve with log-rank tests was used for survival analysis. All analyses required a value of p < 0.05 for statistical significance. All statistical analyses were performed using SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, USA) and STATA/SE version 14.1 (StataCorp., Texas, USA).

Baseline characteristics
Two hundred and sixty-four patients were included in the analysis, 164 patients (62.1%) in the PTMC group and 100 patients in the MVR group (37.9%) ( Figure 1). The   Table 1).
From the Kaplan-Meier curve, MV intervention with PTMC had a significant higher rate of primary outcome (log-rank 4.67; p = 0.031) and re-intervention rate (logrank 23.12; p < 0.001) than MVR but not for the all-cause mortality (log-rank 0.21; p = 0.649) (Figure 2A-C).

Discussion
Unlike most of the previous studies which studied on PTMC or MVR alone, this study evaluated long-term outcomes of patients with clinically significant severe rheumatic MS who underwent MV intervention either PTMC or MVR within 10 years period. We found that the primary composite outcome comprised of all-cause death, stroke or systemic embolism, heart failure hospitalization and re-intervention was significantly higher in the PTMC group (37.2% vs 22%, p = 0.002). The higher primary outcome in the PTMC group was driven by the incidence of re-intervention (18.3% vs 0%, p < 0.001). However, allcause death, stroke or systemic embolism and heart failure hospitalization were not significantly different between the two groups. Previous studies reported a wide range of long-term outcomes depending on patient characteristics in each study. All-cause mortality was reported ranging from 0.6 -14% after PTMC and 6 -25% after MVR. 6,7,9,[14][15][16] In this study, all-cause mortality was 17.1% after PTMC and 15% after MVR, supporting the results of the previous studies. In addition, stroke and systemic embolism rate (4 -5%) was similar to the previous reports (2 -4%). 14,16 Regarding survival analyses, we found that MV intervention with PTMC (HR 1.94; 95% CI 1.14, 3.32; p = 0.015), older age (HR 1.03; 95% CI 1.01, 1.06; p = 0.009) and SPAP > 50 mmHg as an indication for MV intervention (HR 2.99; 95% CI 1.01, 8.84; p = 0.047) increased risk of primary outcome.
After PTMC, the mean MVA was increased by 0.58 cm 2 which was less than the previous report (0.84 cm 2 ) and the success rate was lower (67.1% vs 80-95%). 17,18 However, preprocedural MVA in current study was smaller than the previous report by 0.15 cm 2 . Besides, there was a significant proportion (68.3%) of patients with Wilkins' score ≥ 8 in this study, while excluded by previous studies. To our knowledge, MVA before intervention and Wilkins' score were important predictors of PTMC results. 19 Defined by postprocedural MVA > 1.5 cm 2 , many patients were classified as unsuccessful PTMC because MVA was not exceeding 1.5 cm 2 , although, their symptoms and MVA improved. Supported by the re-intervention rate in the current study was similar to other reports (18.3% vs 12 -40%) and PTMC could delay further intervention by a median of 40.0 (IQR: 10.0, 77.5) months even in patients with Wilkins' score ≥ 8, hence, unsuccessful PTMC by echocardiographic criteria might not be a good representative of clinical outcomes. 14,15,20 When compared to PTMC, the MVR group had more age and AF, higher Wilkins' score with smaller MVA indicated more disease severity and chronicity. The median length of hospital stay in the MVR group was 8-day longer than the PTMC group supported the result of the previous study. 20 Periprocedural complications including death were higher in the MVR group, however, long-term outcomes were not different.
Due to a high proportion of patients with Wilkins' score ≥ 8, this study showed evidence that PTMC could be considered and performed successfully in this patient group, especially when MVR was inappropriate or not preferred. Nevertheless, a prospective study should be further investigated to confirm the result.
This study had several limitations. First, this was a retrospective study, therefore outcomes were prone to review bias and subject to confounding from other factors. Second, there was no cardiac catheterization data in the MVR group, hence we could not compare PAP after intervention between groups. Third, this study was conducted in a tertiary referral center where interventionists and surgeons were experienced, thus limiting its generalizability especially in patients with Wilkins' score ≥ 8 and very small MVA < 1.0 cm 2 .

Conclusion
Primary composite outcome occurred in PTMC group more than MVR group which was driven by reintervention. PTMC group had a higher re-intervention rate, though, it could postpone further invasive procedure by 40 months. Moreover, PTMC could be performed successfully in patients with Wilkins' score ≥ 8 and might be considered particularly when a patient was not suitable for MVR. All-cause mortality, stroke or systemic embolism, heart failure hospitalization, valvular infection and serious bleeding were not significantly different between two groups.

Ethical approval
This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of Chulalongkorn University approved this study (IRB no.672/63).