In this cohort study, we retrospectively enrolled all eligible at-least moderate non-ischemic FMR patients, referred to Rajaie CMRC for medical treatment and/or CRT between 2003 and 2019 using the electronic database of Rajaei CMRC. The inclusion criteria were as follows: Patients over 18 years of age diagnosed with at least moderate non-ischemic FMR using coronary angiography or CT angiography, in whom the epicardial coronary arteries were normal or contained nonsignificant/mild lesions incapable of explaining MR severity. The exclusion criteria were as follows: 1. Primary MR 2. MR, secondary to ischemia or rheumatic heart disease. 3. Patients who lack complete echocardiographic examination in the first visit or follow-ups. An ultimate sample size of 200 patients met the inclusion criteria.
The variables recorded were NYHA class, echocardiographic parameters (LVEF, LVEDD, LVESD, LVVI, LA size, RV size, TAPSE, MR severity, TR severity, and sPAP), baseline characteristics (age, gender, BMI, and BSA), comorbidities like hypertension, medications prescribed (ACEi, ARB, beta-blocker, Nitrate, diuretic, Digoxin, and Hydralazine), CRT insertion. The endpoint outcomes were all-cause mortality, stroke, all-cause rehospitalization, and the need for heart transplantation.
MR severity, TR severity, LV dysfunction and LV remodeling parameters (LVEF, LVEDD and LVESD), and chamber volumes were extracted from patients’ records. MR severity criteria is summarized as: 1. Mild: VCW ≤ 0.3 cm, PISA radius absent or ≤ 0.3 cm, Normal LV and LA size, EROA < 0.2 cm, RVol < 30 ml, RF < 30%. 2. Moderate: intermediate values and EROA 0.20-0.39 cm, RVol 30-59 ml, RF 30-49%. 3. Severe: Flail leaflet, VCW ≥ 0.7 cm, PISA radius ≥ 1.0 cm, EROA ≥ 0.4 cm, RVol ≥ 60 ml, RF ≥ 50%. TR severity criteria is summarized as: 1. Mild: VCW ≤ 0.3 cm, PISA radius <0.3 cm, Normal RV and RA size, EROA < 0.2 cm2, RVol < 30 ml. 2. Moderate: intermediate values and VCW 0.3-0.69 cm, EROA 0.20-0.40 cm, RVol 30-44 ml. 3. Severe: Flail leaflet, VCW ≥ 0.7 cm, PISA radius > 0.9 cm, EROA > 0.4 cm2, RVol ≥ 45 ml .
All enrolled patients had been followed up after at least six months of the first visit, and the data were recorded in the database. The follow-up data were insufficient for certain patients, and those patients were contacted for a follow-up visit. In the follow-up visits, the symptoms of the patients, NYHA classification, follow-up echocardiographic examination, and medication dosage adjustment were recorded.
The normality of the data was evaluated using the Kolmogorov-Smirnov test. Continuous variables are indicated as mean (SD) or median (IQR), and the difference between subgroups was analyzed using t-test or Mann-Whitney U test for two subgroups and ANOVA or Kruskal-Wallis test for more than two subgroups. Wilcoxon signed-rank test was employed to compare the change in the continuous data of the first visit and the follow-up. Sankey diagrams were utilized to visualize the difference in the data from the first visit to the follow-up. Categorical data are expressed as percentages and are compared using the Chi-squared test. The endpoints were all-cause mortality, stroke, and the need for heart transplantation. Using multivariate modeling, a Cox proportional hazards analysis was employed to identify the survival predictors. The results were expressed as Hazard Ratio (HR) and 95% CI. The survival analysis was carried out using the Kaplan-Meier method, censoring patients at the time of the last follow-up, and survival and event-free survival based on the LVEF, MR severity, and NYHA classification were measured using the long-rank test. All data analysis was conducted by SPSS version 25 (SPSS, Inc, Chicago, IL), and the significance level was set to <0.05.
This study adheres to the Helsinki statement and is approved by the institutional ethics review board of the Rajaei CMCR. All patients’ data is kept confidential. Since this study is retrospective, the need for written consent was waived.