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ORIGINAL ARTICLE
Year : 2021  |  Volume : 6  |  Issue : 2  |  Page : 102-108

Anatomical analysis and prognostic assessment of degenerative mitral regurgitation based on a large echocardiography database: Implications for transcatheter edge-to-edge and chordal repair


Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China

Date of Submission05-May-2021
Date of Acceptance09-Jun-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Jun-Bo Ge
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2470-7511.320322

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  Abstract 


Background and Objectives: The anatomical characteristics of patients with mitral valve prolapse (MVP) and mitral regurgitation (MR) have rarely been investigated demographically to determine the applicability of transcatheter intervention. Therefore, the study objective was to analyze potential candidates and their prognosis. Predictors determining the prognosis were also investigated. Methods: Patients diagnosed with MVP and MR severity of ≥2+ were screened from our echocardiography database from 2010 to 2012. All clinical and echocardiogram information was retrieved from electronic medical records. The endpoint was all-cause mortality analyzed by a proportional hazards model. Results: A total of 1268 patients (mean age 57.50 ± 14.88 years, 47.16% female) with MVP and MR severity of ≥ 2+ were included. Isolated P2 (n = 239, 18.85%) appeared as the most common site of leaflet prolapse. The incidence of MR jet solely from middle scallop (A2 and/or P2) was 31.07% (n = 394). If a nonsignificant jet from other locations was also accepted, the incidence of MR jet derived from mainly the middle scallop (A2 and/or P2) was 52.10% (n = 659). For MVP patients with MR R + 3, the conservative therapy group had higher mortality than the early surgery group (31.45% vs. 5.25%, P < 0.001) after 4.5 ± 1.0 years of follow-up, multiple analysis showed that surgical treatment (hazard ratio [HR]: 0.202, P < 0.001), systolic pulmonary artery pressure of o60 mmHg (HR: 6.816, P < 0.001), age of ≥ 60 years (HR: 3.838, P < 0.001), and pericardial effusion (HR: 1.915, P = 0.003) were independent predictors of all-cause mortality. Conclusions: In patients with MVP, one-fifth leaflet prolapse located solely in P2 and one-half of MR jet derived from the middle scallop were anatomically eligible for transcatheter chordal repair and edge-to-edge repair therapy, respectively. Initial conservative therapy, pericardial effusion, pulmonary hypertension, and advanced age were independent predictors of a higher mortality rate in MVP patients with MR severity of ≥ 3+.

Keywords: MitraClip; Mitral prolapse; Prevalence; Prognosis


How to cite this article:
Jin QC, Pan WZ, Chen SS, Zhang L, Zhou DX, Ge JB. Anatomical analysis and prognostic assessment of degenerative mitral regurgitation based on a large echocardiography database: Implications for transcatheter edge-to-edge and chordal repair. Cardiol Plus 2021;6:102-8

How to cite this URL:
Jin QC, Pan WZ, Chen SS, Zhang L, Zhou DX, Ge JB. Anatomical analysis and prognostic assessment of degenerative mitral regurgitation based on a large echocardiography database: Implications for transcatheter edge-to-edge and chordal repair. Cardiol Plus [serial online] 2021 [cited 2021 Jul 30];6:102-8. Available from: https://www.cardiologyplus.org/text.asp?2021/6/2/102/320322

Authors Qin.Chun Jin and Wen.Zhi Pan contributed equally to the work.





  Introduction Top


Mitral valve prolapse (MVP) is characterized as the dislodgment of a prolapsing segment into the left atrium (LA) during ventricular systole, typically accompanied with ruptured chordae and/or anomalous papillary muscles.[1] Its prevalence ranges from 2% to 3% in the general population.[2] Progressively worsening leaflet prolapse can contribute to severe comorbidities or deteriorating cardiac function. Surgery, the current standard therapeutic method, has a high morbidity and mortality rate.[3]

The MitraClip (Abbott Laboratories, Abbott Park, IL, USA) system is representative of edge-to-edge leaflet plication and has emerged as an effective alternative to open surgical intervention in prohibitive patients.[4],[5] The localization of prolapsing segments is fundamental for transcatheter procedures and clinical outcomes.[2] The central part of the leaflets is anatomically free of chordal insertion; hence, A2 and/or P2 is universally acknowledged as an ideal location for clip anchorization.[6] The 2017 ACC Expert Consensus demonstrated the use of the MitraClip in primary MVP patients with moderate-to-severe mitral regurgitation (MR). For transcatheter chordal repair techniques such as neochord, isolated P2 was the most suitable anatomical indication.[7],[8] However, very few articles have discussed the anatomical prerequisite or the constitution of the prolapsing segment at epidemiological levels. To the best of our knowledge, no study has investigated the constitution of prolapsing segments in patients with MR. A specific analysis will enable the determination of the optimal population.

Despite the efficacy and safety of contemporary surgical treatment, the percentage of MVP patients with severe MR who undergo surgical correction remains low. Time of operation remains a complex issue and has come into consideration for renewed scrutiny. A prognostic comparison of MVP patients undergoing early surgical treatment and conservative therapy can provide modern guidance toward management strategies. Therefore, the objective of this study was to analyze the location of prolapse in patients with MVP and MR, the prognosis of these patients, and factors affecting prognosis.


  Materials and Methods Top


Patient selection and study design

Our research was approved by Institutional Review Board of Zhongshan Hospital, Fudan University, Shanghai, China(2019-002R). Transthoracic echocardiography (TTE) images of preliminary outpatients at Zhongshan Hospital, Fudan University, China, between 2010 and 2012, were reviewed (n = 166414). We included patients who were first documented to have MVP (n = 2715). Their clinical and echocardiogram information was retrieved from electronic medical records. The exclusion criteria were defined as MR severity of <2+, previous valve surgery, mitral stenosis, concomitant aortic valve disease, and a history of coronary artery disease. Thus, 1268 patients were included in the analysis, of whom 941 had MR severity of ≥3+. The latter were divided into two groups: the early surgery group that underwent surgery within 6 months of diagnosis (n = 534) and the conservative therapy group that received initial medical management or careful follow-up for 6 months (n = 407). The patient screening flow chart/diagram is shown in [Figure 1]. After enrollment, annual telephone and/or outpatient follow-up was performed for patients with MR severity of ≥3+. Their current clinical condition and data on whether re-operational cardiovascular surgery was performed were updated. The primary end point of this research was all-cause mortality.
Figure 1: Flow chart of study cohort selection.
TTE: Transthoracic echocardiography, MVP: Mitral valve prolapse, MR: Mitral regurgitation


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Echocardiography

TTE was performed according to the ACC/AHA guidelines recommended at our center.[9] Left ventricular volume at the end of systole and diastole was assessed in the parasternal long axis view together with the anteroposterior diameter of the LA and left ventricular ejection fraction. Systolic pulmonary artery pressure (SPAP), interventricular septal end-diastolic diameter, and left ventricular posterior wall end-diastolic diameter were also recorded. Specific mitral valve assessment was also performed according to previous studies.[9],[10]

Prolapsing leaflet segments were differentiated in all views from standard windows, and the severity of MR was classified as 1+ to 4+.[11],[12]

Statistical analysis

Continuous data are presented as mean ± standard deviation and categorical data as percentage. Comparisons of baseline information between the surgery and conventional therapy groups were performed using Student's t-test, ANOVA (Kruskal–Wallis test) or the Chi-square test. Predictors for management strategy were determined by multivariable logistic regression analysis. The primary end point was defined as survival rate and analyzed using Cox proportional hazards models. A P < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS 20.0 version (IBM, Armonk, NY, USA).


  Results Top


The Electronic Medical Record System identified 2715 (1.63%) patients with MVP diagnosed during routine echocardiography. Among them, 1268 candidates diagnosed with first-visit MVP having an MR severity of ≥2+ (mean age: 57.50 ± 14.88 years, 47.16% female) were included. Their baseline characteristics are shown in [Table 1]. Frequent comorbidities included hypertension, coronary artery disease, diabetes mellitus, cardiomyopathy, congenital heart disease, and hyperthyroidism. Among the included population, 941 (74.21%) patients were identified to have an MR severity of ≥3+.
Table 1: Baseline Characteristics of the study population

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Distribution of prolapsing segment

Anterior leaflet prolapse was seen in 31.70% of the patients and posterior leaflet prolapse in 61.28%; further, 7.02% patients had bileaflet prolapse [Figure 2].
Figure 2: Distribution of prolapsing segments in patients with MVP and MR severity of ≥ 2+.

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The specific demographic distribution of prolapsing leaflet subgroups is shown in [Figure 2]. The subgroup of anatomic scallops showed that isolated P2 (n = 239, 18.85%) appeared as the most common site of leaflet prolapse and the percentage of A2 was 10.17% (n = 129). The MR jet derived solely from middle scallops (A2 and/or P2) was 31.07% (N = 394). If a nonsignificant jet from other locations was also included, the MR jet derived from mainly middle scallops (A2 and/or P2) was 52.10% (n = 659).

Predictors for early surgical therapy

Among the 941 MVP patients with MR severity of ≥3+, 534 patients underwent early surgical management (85% mitral valve repair) within 6 months of diagnosis (early surgery group), whereas 407 patients were managed conservatively (conservative therapy group). During follow-up, 46 patients (11.3%) who underwent initial conservative therapy required surgery (73% mitral valve repair). A comparison of characteristics between the early surgery and conservative therapy groups is shown in [Table 2]. At baseline, elderly MVP patients were found less likely to undergo surgical management once diagnosed with MR severity of ≥3+ (P = 0.000). The early surgery group had larger left ventricular end-diastolic diameter and left ventricular end-systolic diameter, more prevalent tricuspid regurgitation, atrial fibrillation, severe MR, and pericardial effusion and were younger (all P < 0.05) than the conservative therapy group. Multivariable logistic regression analysis with a forward selection procedure showed that age (odds ratio [OR]: 0.971; P < 0.001; 95% confidence interval [CI]: 0.962–0.981) and severity of MR (OR: 1.679; P < 0.001; 95% CI: 1.275–2.210) were independent predictors of surgical management within 6 months of initial diagnosis.
Table 2: Comparison of characteristics between the early surgery and conservative therapy groups

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Clinical outcomes and its predictors

Early outcomes within 6 months of diagnosis showed that only four patients died overall. Among them, three patients were from the early surgery and one from the conservative therapy group, suggesting a nonsignificant difference in short-term prognosis between both groups (P > 0.05). After a mean follow-up of 4.5 ± 1.0 years, 120 patients (13.13%) were missed. Overall, all-cause mortality rate was 16.58%. Twenty-eight (5.25%) patients in the early surgery group and 128 (31.45%) patients in the conservative therapy group died during follow-up (P < 0.001). Regarding the therapy strategy on mortality, Kaplan-Meier survival analysis revealed a significant effect of surgical management at 5-year follow-up (OR: 4.774; 95% CI: 4.724–4.824; P < 0.001) [Figure 3]. We studied the association among initial individual condition, therapeutic differences, and mortality using a Cox proportional hazards model. Unadjusted and adjusted Cox proportional hazards model for all-cause mortality over 5 years are listed in [Table 3]. After multivariable adjustments, pericardial effusion (hazard ratio [HR]: 1.915, 95% CI [1.252–2.929], P = 0.003), surgical therapy (HR: 0.202, 95% CI [0.132–0.307], P < 0.001), SPAP of ≥60 mmHg (HR: 6.816, 95% CI [4.674–9.940], P < 0.001), and age of ≥60 years (HR: 3.838, 95% CI [2.300–6.406], P < 0.001) remained independent predictors of overall mortality.
Table 3: Unadjusted and adjusted Cox proportional hazards models for all-cause mortality

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Figure 3: Kaplan-Meier survival curve of all-cause mortality between the early surgery and conservative therapy groups.

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  Discussion Top


This large-scale single-center observational study in a Chinese population is the first, to the best of our knowledge, to investigate specific demographic localization of prolapsing leaflets in MVP patients and to further assess potential candidates for MitraClip therapy with regard to anatomical prerequisites. We found that more than half of the incidence of MR jet was mainly from the middle scallop (A2 and/or P2), which were standardized indications for MitraClip therapy. Isolated P2 was the most common single prolapsed scallop, accounting for approximately 20% of the patients. After 4.5±1.0 years of follow-up, multiple analysis showed that initial conservative therapy, pericardial effusion, SPAP of ≥60 mmHg, and age of ≥60 years were independent predictors of all-cause mortality.

MVP is a common heritable disorder affecting approximately one in every forty individuals. The present study confirmed 2715 (1.63%) patients to have this valvular heart disease based on routine echocardiography, slightly lower than that reported in previous studies.[13],[14] A regurgitation jet originating from the A2 and/or P2 segments of the mitral valve is universally acknowledged as the site of optimal placement for MitraClip according to the EVEREST trial criteria.[11],[15],[16] Our data using real-world data showed that posterior leaflets are the most common prolapsing leaflet (61.28%) among MVP patients with MR severity of ≥2+. The central portion of each leaflet (A2, P2) is the most frequent scallops (52.10%). Considering the freedom of chordal insertion in the central portion of mitral valve leaflets, this finding provides indication for patient selection as well as the ideal site for MitraClip. Similarly, isolated P2 was the most suitable site for transcatheter chordal repair.[7] It was the most common single prolapsed scallop, accounting for approximately 20% scallops in our study.

Our study revealed two independent predictors of early treatment strategies in MVP patients. Patients recommended to undergo initial careful observation or medical therapy were older patients with more severe MR, in contrast with that observed in previous studies.[17],[18] Our study showed that early surgical treatment has no effect on short-term (6 months) mortality, whereas the comparison of long-term follow-up for 2 years showed significantly better survival benefits (overall all-cause mortality rate : 5.25% vs 31.45%). The advantage of early surgical treatment appears to be more obvious at the 5-year follow-up. Emil Hayek[19] reported that the 10-year mortality rate of asymptomatic MVP patients was 19% ± 2% and 5-year survival rate was estimated to be approximately 10%; moderate-to-severe MR emerged as the most frequent risk predictor. The present study accords with the natural history of MVP; thus, the absence of a significant difference in the short term between the two groups might be related to its benign chronic course.[19],[20],[21] Worse long-term outcomes in the conservative therapy group support the early surgery strategy for MVP patients with severe MR.

Further, patients with pericardial effusion, an age of >60 years, and SPAP of ≥60 mmHg were more likely to exhibit an unfavorable prognosis based on variable Cox regression analysis. Advanced age and preprocedural pericardial effusion both indicated vulnerable status and increased operative risk. In a large, multicenter study, Barbieri et al. showed that pulmonary hypertension doubled the mortality rate and incidence of heart failure.[22] Once pulmonary hypertension is confirmed, a negative prognosis would be expected regardless of whether surgical correction is performed.[22],[23] At present, percutaneous edge-to-edge mitral valve repair is considered an attractive option for degenerative MVP patients with prohibitively high surgical risks.[4],[24],[25] Therefore, further research on the short- and long-term prognosis of these patients after the MitraClip therapy is required.

Limitations

There are several limitations to this study. First, it is a single-center, observative investigation containing relatively large samples. However, detailed echocardiogram parameters, such as mitral annular diameter, effective regurgitant orifice area, personal laboratory data, and clinical manifestations at follow-up, were not evaluated due to limited reserved electronic information. Second, this was not a randomized study, and the baseline basis existed between the surgery and conservative therapy groups. Third, only all-cause mortality was analyzed in this study. Since there are emerging links between MVP (especially severe MR) and sudden cardiac death, the arrhythmic event of MVP determined by electrocardiography data should be collected and detailed causes of mortality in this research should be further illustrated. In addition, heart failure resulting from these adverse events should be considered.


  Conclusions Top


In patients with MVP, one-fifth leaflet prolapse is located solely in P2 and one-half of the MR jet is derived from the middle scallop. These are anatomically eligible indications for transcatheter chordal repair and edge-to-edge repair therapy, respectively. For patients with MVP and MR severity ≥+3, those who underwent conservative therapy had significantly higher 5-year mortality rate than those who underwent early surgery. Pericardial effusion, surgical therapy, SPAP of ≥60 mmHg, and age of ≥60 years were independent predictors of all-cause mortality in the whole population.

Financial support and sponsorship

This study is supported by the funds from the Science and Technology Commission of Shanghai Municipality (No. 18411950200).

Conflicts of interest

Jun-Bo Ge is an Editorial Board Member of Cardiology Plus. The article was subject to the journal's standard procedures, with peer review handled independently of the editorial board member and their research groups.



 
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