Mitral Valve and Left Ventricular Features in Malignant Mitral Valve Prolapse
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Open access Valvular heart disease Open Heart: first published as 10.1136/openhrt-2018-000925 on 15 October 2018. Downloaded from Mitral valve and left ventricular features in malignant mitral valve prolapse Madalina Garbi,1 Patrizio Lancellotti,2,3 Mary N Sheppard4 To cite: Garbi M, Lancellotti P, ABSTRACT Key questions Sheppard MN. Mitral valve and Objective Mitral valve prolapse is a benign condition, left ventricular features in however with occasional reports of sudden cardiac death malignant mitral valve prolapse What is already known about this subject? . or out-of-hospital cardiac arrest in the absence of severe Open Heart 2018;5:e000925. ► Mitral valve prolapse is a benign condition, however mitral regurgitation or coronary artery disease, suggesting doi:10.1136/ with occasional reports of sudden cardiac death or the existence of a malignant form. The objective of openhrt-2018-000925 out-of-hospital cardiac arrest in the absence of se- our study was to contribute to the characterisation of vere mitral regurgitation or coronary artery disease, malignant mitral valve prolapse. suggesting the existence of a malignant form. Received 24 August 2018 Methods We performed a retrospective analysis of ► Sudden cardiac death is rare in mitral valve pro- Revised 4 September 2018 pathology findings in 68 consecutive cases of sudden lapse; however, the risk is twice as high as for the Accepted 26 September 2018 cardiac death with mitral valve prolapse as lone abnormal general population. finding, reported as cause of death. ► Characterisation of malignant mitral valve prolapse Results All mitral valve prolapse sudden death cases had is needed to underpin the selection of patients in mitral valve characteristics of Barlow disease, with extensive need of implantable cardioverter defibrillator for pri- bileaflet multisegmental prolapse and dilatation of the mary prevention. annulus. The majority of cases (80.9%) had microscopic left ventricular fibrosis with associated hypertrophy and What does this study add? degenerative features of the myocytes, and some cases ► Our study demonstrates association of mitral valve (10.9%) had right ventricular fibrosis as well. prolapse–related sudden cardiac death with Barlow Conclusions Malignant mitral valve prolapse is Barlow disease rather than fibroelastic deficiency or degen- disease. Sudden cardiac death in mitral valve prolapse is erative mitral valve disease in general. due to Barlow disease, which besides the typical mitral ► The association was independent of mitral regurgi- valve degeneration may comprise a distinct Barlow tation severity, however related with the existence of disease cardiomyopathy, as suggested by myocyte left ventricular interstitial fibrosis and degeneration degeneration and bi-ventricular involvement. of myocytes suggestive of a distinct cardiomyopathy. http://openheart.bmj.com/ How might this impact on clinical practice? ► While further evidence is needed to underpin the selection of patients in need of implantable car- INTRODUCTION dioverter defibrillator for primary prevention, our Mitral valve prolapse (MVP) is usually a results narrow down the spectrum of high-risk benign condition, however with sporadic characteristics to Barlow disease with associated © Author(s) (or their reports of sudden cardiac death (SCD) or cardiomyopathy. employer(s)) 2018. Re-use out-of-hospital cardiac arrest, often in the ► Additionally, our findings could guide further studies permitted under CC BY-NC. No 1–4 of myocardial fibrosis with cardiac magnetic reso- on October 2, 2021 by guest. Protected copyright. commercial re-use. See rights absence of significant mitral regurgitation, nance, combining T1-mapping and late gadolinium and permissions. Published suggesting the existence of a malignant by BMJ. form. MVP-related SCD has low incidence; enhancement for sudden death risk stratification in mitral valve prolapse. 1King's Health Partners, King’s however, the risk is twice as high as for the College Hospital NHS Foundation general population.5 The characterisation of Trust, London, UK a high-risk population in need of implantable 2Department of Cardiology, be an independent mortality risk factor in a cardioverter defibrillator (ICD) for primary GIGA Cardiovascular Sciences, community study of outcome of MVP.9 prevention is difficult because SCD can occur University of Liège Hospital, Our study aim was to contribute to the char- Liège, Belgium in cases with no previous clinical diagnosis. 3 acterisation of malignant MVP by reviewing Anthea Hospital, Gruppo Villa A study of out-of-hospital cardiac arrest survi- the mitral valve and left ventricular pathology Maria Care and Research, Bari, vors found bileaflet involvement in malignant Italy 6 findings in MVP-related SCD. 4Cardiovascular Pathology Unit, MVP, and these patients had ICD-treated St Georges Hospital Medical ventricular fibrillation recurrences. School, London, UK Unexplained left ventricular systolic METHODS dysfunction, in the absence of severe mitral We performed a retrospective analysis Correspondence to regurgitation or coronary artery disease, is of pathology findings in 68 consecutive Dr Madalina Garbi; madalina. 7 8 garbi@ nhs. net reported occasionally and it was found to SCD cases with MVP reported as cause of Garbi M, et al. Open Heart 2018;5:e000925. doi:10.1136/openhrt-2018-000925 1 Open Heart Open Heart: first published as 10.1136/openhrt-2018-000925 on 15 October 2018. Downloaded from Figure 1 Barlow mitral valve with thickening and ballooning of the leaflets in between the chords and thickening and Figure 2 Ventricular fibrosis in Barlow disease. elongation of the chords. The existence of MVP without chordal rupture death. The pathology assessment of all cases had been prompted thorough assessment for myocardial fibrosis performed for diagnostic purposes, as part of a clinical in all cases; this is because, in the absence of chordal autopsy, with no preconceived research hypothesis, by rupture, based on pathology guidelines,10 MVP is a highly the same expert cardiovascular pathologist (MNS), at probable cause of the SCD only in the presence of asso- the Cardiovascular Pathology Reference Centre of the ciated myocardial fibrosis. Macroscopic analysis found St George’s Medical School in London. The assessment no evidence of ventricular wall fibrosis in any of the 68 had next-of-kin consent and followed cardiac pathology 10 11 cases. However, microscopic analysis found ventricular guidelines and the methodology described by MNS. fibrosis in the majority of cases (n=55, 80.9%), confined to the left ventricle in 49 cases (89.1%) and involving the RESULTS right ventricle as well in six cases (10.9%). The fibrosis Almost half of the SCD cases (48.5%) were younger than (figure 2) was focal, usually fine and interstitial within 35 years old, with a mean age of 38 years (SD±15). There the inner wall, involving particularly the inner suben- was marginal male predominance (51.7%). docardium, trabeculae and papillary muscles. In the http://openheart.bmj.com/ Clinical information was available in 50 cases (73.5%), left ventricle, within the inner third of the basal poste- revealing lack of symptoms (n=30) and documented mild rior wall, the fibrosis became confluent, with extensive only mitral regurgitation (n=20). Six cases had relevant replacement fibrosis extending into the trabeculae and family history, comprising MVP with female predomi- posteromedial papillary muscle. The fibrosis was never nance and SCD in three female relatives. epicardial or diffuse throughout the wall. Because MVP All 68 SCD cases had no evidence of coronary artery with associated fibrosis is a highly probable but not certain disease at autopsy. cause of SCD based on pathology guidelines, histological In all cases, the mitral valve had extensive bileaflet analysis of the myocardium was also performed. Associ- multisegmental prolapse and dilatation of the annulus. ated with the myocardial fibrosis, there was hypertrophy on October 2, 2021 by guest. Protected copyright. The leaflets had pronounced permanent displacement and degenerative features of the myocytes with focal cyto- into the left atrium (atrialisation) and thickening and plasmic vacuolation (figure 3) suggestive of existence ballooning in between the chords (figure 1). In all cases, of a cardiomyopathy. There was no myocyte disarray to there was severe tissue redundancy of the leaflets, with establish a diagnosis of hypertrophic cardiomyopathy, grade III prolapse.5 The chords were thickened and elon- and there was no associated fatty infiltration to establish gated, but there was no chordal rupture. In conclusion, a diagnosis of arrhythmogenic cardiomyopathy. All cases all cases had typical mitral valve characteristics of Barlow had posterior left ventricular wall and posterior papillary disease, suggesting SCD association with Barlow disease muscle involvement. Twelve cases had lateral and anterior specifically, rather than with fibroelastic deficiency and left ventricular wall involvement as well. Sixteen cases had rather than with degenerative mitral valve disease or MVP midwall interventricular septum fibrosis, which became in general. confluent with the basal posterior fibrosis. In the right There was no associated tricuspid valve prolapse; the ventricle, the fibrosis was usually subendocardial, with tricuspid valve was normal in all cases. fine interstitial pattern in the posterior wall extending In only 17 cases (25%), there was hypertrophy with into the basal posterior