Citations

Abstract Background Arrhythmogenic mitral valve prolapse (AMVP) is increasingly recognized as a cause of sustained ventricular arrhythmias (VA) and sudden cardiac death. Although prior studies have identified clinical and imaging risk markers in AMVP, it remains unclear whether the arrhythmogenic phenotype differs between women and men. Purpose To investigate sex-specific differences in clinical profiles, structural substrates, and arrhythmia presentations in patients with AMVP who experienced sustained VA. Methods We conducted a sex-based sub-analysis of a multicenter cohort (35 centers from 15 countries) of patients with AMVP and sustained VA. Participants were grouped by sex and by initial arrhythmia type (sustained monomorphic ventricular tachycardia [SMVT] vs ventricular fibrillation [VF]). Data collected included clinical history, ECG findings, echocardiographic measurements, and cardiac MRI (CMR) markers, such as late gadolinium enhancement (LGE) patterns and mitral annular disjunction (MAD). These factors were compared across groups. Results The study comprised 129 women (57%) and 96 men (43%). Women were diagnosed at younger ages (39±16 years vs. 49±16 years, p<0.03) and had more frequently a family history of MVP (22% vs 10%, p=0.027). MAD was significantly more common in women (66% vs 48%, p=0.015) while LGE was more frequently observed in men than women (N=39 (72%) vs N=41 (53%), p=0.028), with no significant regional patterns (myocardial and/or papillary muscle). ECG T-wave inversion (p=0.627), PVC burden (p>0.03) and arrhythmia types were similar in men and women. However, stress was a more often commonly recognized as the initiating trigger for VA in men than in women (38% [N=24] vs. 18% [N=18], p<0.05). The overwhelming majority of VA were initiated by PVCs in both sexes with no differences in the initiating mechanisms. Conclusion In patients with AMVP presenting with sustained VA, the arrhythmic phenotype and initiating mechanisms are similar between sexes, although stress was a significantly stronger trigger for VA in men. Women more often exhibited MAD, whereas LGE was more frequent in men. These findings suggest that structural and tissue-based markers, rather than sex alone, contribute to the development of malignant arrhythmias in AMVP.

Background Mitral valve prolapse (MVP) can be associated with ventricular arrhythmias (VA), but little is known about the relationship between VA and exercise in these patients. The aim of this study was to assess the occurrence and severity of VA during exercise tests in patients with MVP, and to explore the association between VA during exercise and the occurrence of arrhythmic events during follow-up. Methods In this multicentre study, 375 patients with MVP (58 (48–69) years, 53% male) who underwent a clinically indicated exercise test were included. Severity of VA during exercise was defined as: (1) no VA, (2) minor VA (premature ventricular contractions ≥5% or non-sustained ventricular tachycardia (nsVT) <120 beats per minute) and (3) major VA (nsVTs ≥120 beats per minute). Results During exercise test, 242 (65%) patients showed no VA, 88 (24%) minor VA and 45 (12%) major VA. Patients with minor and major VAs showed more often bileaflet prolapse and mitral annular disjunction (MAD) than patients with no VA (p<0.001). Over a median follow-up of 101 months (IQR 58–138 months), 35 patients (9%) developed a severe arrhythmic event, defined as sustained VA or ventricular fibrillation, implantation of an implantable cardioverter-defibrillator and VA ablation. At the Kaplan-Meier curve analysis, patients with major VA showed the worst arrhythmic event-free survival (log-rank p<0.001). On multivariable analysis, left ventricular end-systolic diameter, MAD and VA severity during exercise were independently associated with this outcome. Conclusions In patients with MVP, the occurrence of VA during exercise is associated with more advanced mitral valve abnormalities, including MAD, and with higher rates of severe arrhythmic events during follow-up. Performing an exercise test, combined with the clinical and echocardiographic assessments, may therefore offer important complementary information useful for patient management.

Abstract Background and Aims Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. Methods This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. Results The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8–16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23–5.76). Conclusions The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Abstract Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an arrhythmic form (AMVP) and its link to sudden cardiac death. Furthermore, the presence, frequency, and significance of the anatomic functional feature called mitral annular disjunction (MAD) have remained widely disputed. Recent case series and cohorts have shattered the concept that MVP is most generally benign and have emphasized the various phenotypes associated with clinically significant ventricular arrhythmias, including AMVP. The definition, evaluation, follow-up, and management of AMVP represent the focus of the present review, strengthened by recent coherent studies defining an arrhythmic MVP phenotypic that would affect a small subset of patients with MVP at concentrated high risk. The role of MAD in this context is of particular importance, and this review highlights the characteristics of AMVP phenotypes and MAD, their clinical, multimodality imaging, and rhythmic evaluation. These seminal facts lead to proposing a risk stratification clinical pathway with consideration of medical, rhythmologic, and surgical management and have been objects of recent expert consensus statements and of proposals for new research directions.

Background Increased high‐sensitivity cardiac troponin T (hs‐cTnT) above the upper reference limit (URL) after noncardiac surgery identifies patients at risk for mortality. Prior studies have not analyzed hs‐cTnT as a continuous variable or probed age‐ and sex‐specific URLs. This study compared the prediction of 30‐day mortality using continuous postoperative hs‐cTnT levels to the use of the overall URL and age‐ and sex‐specific URLs. Methods and Results Patients (876) >40 years of age who underwent noncardiac surgery were included. Hs‐cTnT was measured on postoperative day 1. Cox proportional hazards models were used to compare associations between 30‐day mortality and using hs‐cTnT as a continuous variable, or above the overall or age‐ and sex‐specific URLs. Comparisons were performed by the area under the receiver operating characteristic curve analysis. Mortality was 4.2%. For each 1 ng/L increase in postoperative hs‐cTnT, there was a 0.3% increase in mortality ( P <0.001). Patients with postoperative hs‐cTnT >14 ng/L were 37% of the cohort, while those above age‐ and sex‐specific URLs were 25.3%. Both manifested higher mortality (hazard ratio [HR], 3.19; 95% CI, 1.20–8.49; P =0.020) and (HR, 2.76; P =0.009) than those with normal levels. The area under receiver operating characteristic curve was 0.89 using hs‐cTnT as a continuous variable, 0.87 for age‐ and sex‐specific URLs, and 0.86 for the overall URL. Conclusions Hs‐cTnT as a continuous variable was independently associated with 30‐day mortality and had the highest accuracy. Hs‐cTnT elevations using overall and/or age‐ and sex‐specific URLs were also associated with higher mortality.

Abstract Background Mitral-annulus-disjunction (MAD), often described in mitral-valve-prolapse (MVP) patients, remains incompletely defined and its clinical outcome consequences are unknown. Objectives To assess MAD prevalence, clinical and echocardiographic characteristics, and independent impact on outcome in patients with isolated-MVP. Methods A cohort of 595 (65±16 years, 278 female) consecutive patients with MVP and comprehensive clinical, rhythmic and Doppler-echocardiographic characterization, was identified. Primary-endpoint was overall-survival, or occurrence of ventricular-arrhythmia. To eliminate clinical differences, we matched MAD-patients 1:1 with no-MAD based on propensity score for overall survival analysis using a greedy 5-to-1 digit-matching algorithm. Results MAD was frequent, present in 186 (31%) of MVP-patients and independently associated to bileaflet-MVP, leaflet-redundancy, younger-age, female-sex, enlarged left-ventricle-endsystolic-diameter and higher left-ventricle-ejection-fraction (all P≤0.04). Outcome primary-endpoint of survival after MVP diagnosis in matched-cohort (10-year 95±1%) was not associated with MAD presence (10-year 93±2% for no-MAD and 97±1% for MAD, P=0.4). Mortality was comparable for MAD (univariate-hazard-ratio 0.64 [0.25–1.65], P=0.4 vs. no-MAD), even adjusted-comprehensively including for MVP-characteristics (adjusted-hazard-ratio 1.17 [0.39–3.50], P=0.8). However, 220 (51%) MVP-patients were diagnosed ventricular-arrhythmia (161 with ventricular-tachycardia only) and long-term, MAD was associated with lower arrhythmia- and ventricular-tachycardia- overall freedom (adjusted-hazard-ratio for MAD 2.35 [1.75–3.15], P&lt;0.0001 vs. no-MAD and 2.71 [1.93–3.82], P&lt;0.0001 respectively). Hence, 10-year freedom of significant ventricular-arrhythmia in overall-cohort was severely reduced with MAD (41±4% vs. 62±3% for no-MAD). Conclusion In this unique MVP cohort, with arrhythmia and MAD comprehensively-characterized, MAD presence was frequent and independently associated to bileaflet-MVP and leaflet-redundancy. Long-term, MAD compared to no-MAD is not independently associated with higher-mortality but to reduced arrhythmia-freedom occurrence. Survival overall and by V arrhythmia Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Foundation