Identifying Mitral Valve Prolapse at Risk for Ventricular Arrhythmias and Myocardial Fibrosis from 12-lead Electrocardiograms using Deep Learning

Background: Mitral valve prolapse (MVP) is a common valvulopathy, with a subset of MVP patients developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) represents a marker of arrhythmic risk that is associated with myocardial fibrosis and increased mortality in MVP. We hypothesize that an ECG-based machine-learning model can identify MVP with ComVE and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging. Methods: A deep convolutional neural network (CNN) was trained to detect ComVE using 6,916 12-lead ECGs from 569 MVP patients evaluated at the University of California San Francisco (UCSF) between 2012 and 2020. A separate CNN was also trained to detect late gadolinium enhancement (LGE) using 87 ECGs from MVP patients with contrast CMR. Results: The prevalence of ComVE was 160/569 or 28% (20 patients or 3% had cardiac arrest or sudden cardiac death). The area under the curve (AUC) of the CNN to detect ComVE was 0.81 (95% CI, 0.78-0.84). AUC remained high even after excluding patients with moderate-severe mitral regurgitation (MR) [0.80 (95% CI, 0.77-0.83)], or with bileaflet MVP [0.81 (95% CI, 0.76-0.85)]. The top ECG segments able to discriminate ComVE vs no ComVE were related to ventricular depolarization and repolarization (early-mid ST and QRS fromV1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 21 (24%) of 87 patients with available CMR. The AUC for detection of LGE was 0.75 (95% CI, 0.68-0.82). Conclusions: Standard 12-lead ECGs analyzed with machine learning can detect MVP at risk for ventricular arrhythmias and fibrosis and can identify novel ECG correlates of arrhythmic risk regardless of leaflet involvement or mitral regurgitation severity. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.

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Predictors of sudden cardiac arrest in adolescents with mitral valve prolapse: an analysis of the nationwide inpatient sample

European Heart Journal ◽

10.1093/ehjci/ehaa946.2007 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B Narasimhan ◽

L Wu ◽

C.H Lucas ◽

K Bhatia ◽

A Shah ◽

...

Keyword(s):

Cardiac Arrest ◽

Family History ◽

Sudden Cardiac Death ◽

Mitral Valve ◽

Mitral Regurgitation ◽

Mitral Valve Prolapse ◽

Cardiac Death ◽

Sudden Cardiac Arrest ◽

Adolescent Patients ◽

History Of

Abstract Background Mitral valve prolapse (MVP) is the most commonly encountered valvular pathology seen in 2–3% of the general population. Though traditionally regarded as a benign pathology, recent literature suggests that sudden cardiac death is significantly more common in these patients with estimates of 0.2–0.4%/year. The exact underlying mechanism of these higher rates of SCD remain poorly understood. In this study, we aim to identify predictors of sudden cardiac arrest (SCA) in an adolescent population. Methods We conducted a retrospective study using the AHRQ-HCUP National Inpatient Sample 2016-2017 for the years 2016-17. All patients (≤18 years) admitted with Mitral valve prolapse were identified using ICD-10 codes and further sub stratified based on presence or absence of sudden cardiac arrest (SCA). Baseline characteristics were obtained and multivariate regression analysis was utilized to identify potential predictors of SCA. Independent risk factors for in-hospital mortality were identified using a proportional hazards model. Complications were defined as per the Agency for Health Care Research and Quality guideline. Results We screened a total of 71,473,874 admissions in the NIS database to identify a total of 1,372 adolescent patients admitted with MVP in the years 2016–17. These patients were then sub-categorized based on presence or absence of SCA during the hospitalization. Our findings revealed that patients with SCA were generally slightly older (15y vs 13y, p=0.036, OR-1.1, p=0.007) and more likely female (83.3% vs 13%, p=0.227, OR – 3.55, p=0.57)). Interestingly, patients in the SCA cohort were noted to have almost 4 fold higher rates of Mitral regurgitation (66.6% vs 18.35%, p=0.008, OR-8.89, p=0.005) as well as family history of SCD (16.7% vs 4.1%, p=0.145, OR-4.65, p=0.14). Conclusions Presence of Mitral regurgitation and a family history of sudden cardiac death are associated with significantly higher rates of SCA in adolescent patients with mitral valve prolapse. Predictors of SCA in Adolescent MVP Funding Acknowledgement Type of funding source: None

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1045 T1-mapping and CMR feature tracking in mitral valve prolapse

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.637 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

M Guglielmo ◽

L Fusini ◽

G Muscogiuri ◽

A Baggiano ◽

A Loffreno ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Mitral Valve ◽

Mitral Regurgitation ◽

Mitral Valve Prolapse ◽

Cardiac Death ◽

Feature Tracking ◽

T1 Mapping ◽

Remote Myocardium ◽

Severe Mitral Regurgitation ◽

T1 Map

Abstract BACKGROUND Several studies suggest that mitral valve prolapse (MVP) can be related to sudden cardiac death, owing to sustained ventricular arrhythmias (VAs). In patients with sudden cardiac death and complex VAs, a high percentage of either left ventricle (LV) papillary muscle fibrosis or inferobasal fibrosis has been described using cardiac magnetic resonance (CMR) with late gadolinium enhancement technique (LGE). However, LGE presents several technical limitations and requires contrast agent administration. Thanks to T1 mapping (T1-map) and feature tracking (FT) techniques, CMR may identify myocardial fibrosis and deformation abnormalities respectively. We sought to demonstrate that, in patients with MVP, T1 map can accurately identify the presence of myocardial fibrosis which, being related to myocardial stiffness, is associated to abnormal deformation indexes at CMR FT strain evaluation. METHODS Consecutive patientswith indication to mitral valve surgery for severe mitral regurgitation due to mitral valve prolapse were prospectively enrolled. CMR including Modified Look-Locker (MOLLI) sequences for T1 mapping was performed in each patient. In addition, CMR FT analysis of steady state free precession (SSFP) cine images was performed to obtain 2D global and segmental circumferential and radial strains. RESULTS 70 consecutive patients (age: 59 ± 12) were successfully evaluated with CMR. T1 native values were significantly higher in the basal and mid LV inferolateral wall compared to the remote myocardium (1074 ± 67 vs 1046 ± 40 msec, p< 0.001). Moreover, the average radial and circumferential strains of the basal and mid LV inferolateral were significantly reduced compared to those of the remote myocardium (21.1 ± 10.4 and -12.8 ± 5.6 vs 31.6 ± 9.1 and -17.3 ± 3.6 respectively, p < 0.001). CONCLUSIONS In patients with MVP and severe mitral regurgitation native T1 values of the LV inferolateral are higher as compared to remote myocardium and associated with reduced circumferential and radial strains. T1 mapping and CMR FT strain may be used as tools for the early identification of tissue changes in the LV inferolateral myocardial segment. Further studies are needed to evaluate if these changes are able to predict LGE development and are associated with higher risk for VAs

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Abstract 16798: Evidence of Abnormal T1 Mapping in Arrhythmic Mitral Valve Prolapse Without Significant Mitral Regurgitation

Circulation ◽

10.1161/circ.142.suppl_3.16798 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Brian B Agbor-Etang ◽

Lisa J Lim ◽

Karen G Ordovas ◽

Francesca N Delling

Keyword(s):

Late Gadolinium Enhancement ◽

Mitral Valve ◽

Mitral Regurgitation ◽

Myocardial Fibrosis ◽

Mitral Valve Prolapse ◽

Ventricular Arrhythmias ◽

T1 Mapping ◽

Diffuse Myocardial Fibrosis ◽

Diffuse Fibrosis ◽

Gadolinium Enhancement

Background: Prior cardiac magnetic resonance (CMR) studies have reported abnormal T1 mapping, reflective of diffuse myocardial fibrosis, in patients with mitral valve prolapse (MVP) and ventricular arrhythmias. However, T1 mapping was derived from conventional Look-Locker sequences and/or obtained in selected MVP patients with severe mitral regurgitation (MR) and a clinical indication for CMR. Hypothesis: We hypothesize that extracellular volume (ECV) fraction, a marker of diffuse fibrosis derived from research-based, MOLLI T1 mapping sequences, is increased in MVP subjects with ventricular arrhythmias, even in the absence of significant MR. Methods: We performed CMRs in 10 consecutive, randomly selected MVP patients identified through our echocardiographic database, age/gender matched to 10 controls free of significant cardiac disease. All 10 MVPs underwent ambulatory EKG monitoring. CMR images were acquired using a GE 3.0T Discovery MR750w scanner. Global ECV fraction was calculated using pre- and 10 minutes post-contrast T1 times after administration of 0.1 mmol/kg of gadobutrol (Gadavist). Late gadolinium enhancement (LGE) was also obtained. MR fraction was quantified by velocity encoded CMR. Mild MR was defined as MR fraction < 16%. Results: MVP patients had significantly higher ECV fraction compared to controls (mean ECV (%) 32 ± 4 vs 20 ± 6, p = 0.0002), with 5/10 demonstrating non-sustained VT on ambulatory EKG monitoring. The majority (9/10 or 90%) of MVPs had mild or no MR (MR fraction < 16%), and 1/10 or 10% had moderate MR (MR fraction 18%). Only one individual in the MVP group had late gadolinium enhancement (LGE) in the papillary muscles. Conclusion: MVP with ventricular arrhythmias is associated with increased global ECV reflective of diffuse myocardial fibrosis, even in the absence of significant MR or LGE. Our preliminary findings highlight for the first time a primary interstitial derangement in MVP. Larger studies are needed to understand the mechanisms and prognostic significance of primary diffuse fibrosis in MVP.

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Electrocardiographic and echocardiographic abnormalities associated with mitral valve prolapse in patients with Marfan syndrome

European Heart Journal ◽

10.1093/ehjci/ehaa946.1886 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Lasne ◽

O Milleron ◽

G Delorme ◽

F Arnoult ◽

N Hanna ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Mitral Valve ◽

Marfan Syndrome ◽

Mitral Valve Prolapse ◽

Cardiac Death ◽

Ventricular Arrhythmias ◽

Qtc Interval ◽

Interval Prolongation ◽

High Prevalence ◽

Qtc Interval Prolongation

Abstract Introduction Marfan syndrome (MFS) is responsible for cardiovascular disorders such as aortic aneurism and mitral valve prolapse (MVP). A malignant MVP phenotype combining clinical, electrical and morphological features has been described in symptomatic patients who have experienced sudden cardiac death or complex ventricular arrhythmias. We have taken advantage of the high prevalence of MVP in MFS patient to study the clinical, electrical and echocardiographic abnormalities associated with MVP. Purpose The aim of this study is to describe the clinical, electrical and morphological cardiac abnormalities associated with MVP in a cohort of MFS patients with FBN1 mutations with a high prevalence of MVP and who did not suffer from severe ventricular arrhythmias. Methods All consecutive patients coming to the National Reference Center for Marfan syndrome were evaluated prospectively i.e. clinical examination, 12-lead electrocardiogram, standard transthoracic echocardiography study and molecular genetic screening. Results 352 consecutive patients were included from April 2015 to October 2016 [250 FBN1 mutation carriers (MFS) and 102 healthy relatives (HR)]. None of the patients had a history of sudden cardiac death or complex ventricular arrhythmia. MFS vs HR: MFS patients were younger (33 vs 41yo p<0.001) and 2/3 were women in both groups. In the MFS group, abnormal T waves repolarization in lateral leads were more common [172 MFS (70.2%) vs. 87 HR (86.14%) p<0,0012], as was MVP [38.37% vs 1.96%; p<0,0001], and diastolic hypertrophy of the basal segment of the inferolateral wall (thickness >11mm) [22.31% vs. 9.18%; p<0.0001]. In MFS, MVP affected either one valve (21.22%), or both (17.14%), and was not associated with electric abnormalities. However, diastolic basal inferolateral wall hypertrophy was associated with mitral valve prolapse (p<0,0001), QTc interval prolongation (p<0.0229), abnormal T waves repolarization in the inferior leads (p=0.004), and higher aortic Z-Score (p=0.274). Conclusion In MFS patients, the prevalence of MVP is high and no significant association between MVP and electrical abnormalities was found. In contrast, basal inferolateral wall hypertrophy is associated with MVP and repolarization disorders in inferior leads and QTc interval prolongation, i.e, electrocardiographic abnormalities described in malignant MVP. QTc and basal inferolateral hypertrophy Funding Acknowledgement Type of funding source: None

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Characteristic Histopathological Findings and Cardiac Arrest Rhythm in Isolated Mitral Valve Prolapse and Sudden Cardiac Death

Journal of the American Heart Association ◽

10.1161/jaha.119.015587 ◽

2020 ◽

Vol 9 (7) ◽

Cited By ~ 1

Author(s):

Hui‐Chen Han ◽

Sarah A. Parsons ◽

Andrew W. Teh ◽

Prashanthan Sanders ◽

Christopher Neil ◽

...

Keyword(s):

Cardiac Arrest ◽

Sudden Cardiac Death ◽

Mitral Valve ◽

Mitral Valve Prolapse ◽

Cardiac Death ◽

Histopathological Findings

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Cardiac Imaging for Risk Assessment of Malignant Ventricular Arrhythmias in Patients With Mitral Valve Prolapse

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.574446 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bhupendar Tayal ◽

Francesca N. Delling ◽

Maan Malahfji ◽

Dipan J. Shah

Keyword(s):

Sudden Cardiac Death ◽

Mitral Valve ◽

Cardiac Imaging ◽

Mitral Valve Prolapse ◽

Cardiac Death ◽

Ventricular Arrhythmias ◽

Mechanical Dispersion ◽

Increased Risk ◽

Replacement Fibrosis ◽

Imaging Markers

Recent studies have described the occurrence of complex ventricular arrhythmias and sudden cardiac death among patients with mitral valve prolapse (MVP). The reported incidence rate of sudden cardiac death or ventricular tachycardia is about 1–1.5% among patients with MVP. Various imaging markers have been associated with this increased risk, including mitral annular disjunction, replacement fibrosis by late gadolinium enhancement, and mechanical dispersion. In this review, we briefly discuss how multimodality cardiac imaging can be applied to identify MVP patients with high risk of sudden cardiac death and complex ventricular arrhythmias.

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Mechanistic insights of the left ventricle structure and fibrosis in the arrhythmogenic mitral valve prolapse

Global Cardiology Science and Practice ◽

10.21542/gcsp.2018.4 ◽

2018 ◽

Vol 2018 (1) ◽

Cited By ~ 1

Author(s):

Leticia Fernández-Friera ◽

Rafael Salguero ◽

Luca Vannini ◽

Ana Fidalgo Argüelles ◽

Fernando Arribas ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Mitral Valve ◽

Mitral Valve Prolapse ◽

Cardiac Death ◽

Ventricular Arrhythmias ◽

Imaging Techniques ◽

Current Evidence ◽

Special Focus ◽

Benign Condition ◽

Life Threatening

Mitral valve prolapse (MVP) is a common and benign condition. However, some anatomic forms have been recently associated with life-threatening ventricular arrhythmias and sudden cardiac death. Imaging MVP holds the promise of individualized MVP risk assessment. Noninvasive imaging techniques available today are playing an increasingly important role in the diagnosis, prognosis and monitoring of MVP. In this article, we will review the current evidence on arrhythmogenic MVP, with special focus on the utility of echocardiography and CMR for identifying benign and ‘‘malignant’’ forms of MVP. The clinical relevance of this manuscript lies in the value of imaging technology to improve MVP risk prediction, including those arrhythmic-MVP cases with a higher risk of sudden cardiac death.

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