Mitral valve prolapse syndrome as cause of sudden death in young adults

doi:10.1016/j.forsciint.2006.10.011

Forensic Science International

Volume 171, Issues 2–3, 13 September 2007, Pages 127-130

https://doi.org/10.1016/j.forsciint.2006.10.011 Get rights and content

Abstract

Mitral valve prolapse syndrome (MVPS) is a relatively common disorder of the mitral valve and most cases take a benign clinical course. Only a subset of patients develop severe clinical symptoms such as arrhythmia, insufficiency of the mitral valve or infective endocarditis. As a consequence, sudden death might occur in these patients, thought to be caused by an arrhythmogenic event. By presenting six cases of sudden unexpected death in young female adults, we point at clinical and pathological data from the literature, which are of interest from the viewpoint of legal medicine. The incidence of MVPS in autopsy series has been reported to be about 4–5%, while clinical data hint at an incidence of about 2.5%. The presented cases suggest that even clinically benign cases of MVPS in young adults might result in sudden unexpected death. Such cases are not included in hospital based studies on the topic. This might lead to an underestimation of the fatal risk associated with the disease, even if sudden death might be a rare event in MVPS.

Introduction

From a forensic viewpoint, cases of sudden death in young adults may be attributed to lethal manifestations of pre-existing diseases. In this context especially cardiac malformations or diseases might be considered [1], like right ventricular dysplasia [2], coronary arteritis [3] or myocarditis [4].

Rarely, mitral valve prolapse syndrome (MVPS; Systolic-click-syndrome, Barlow-syndrome, Floppy-valve-syndrome, Flail-leaflet-syndrome, myxomytous transformation of the mitral valve) might result in sudden cardiac death. In some of these cases, MVPS can be reliably diagnosed at autopsy and by histological examination of the valve leaflets due to a characteristic morphology. Presenting characteristic cases of sudden death due to MVPS, we point at the clinical and morphologic characteristics and point out aspects concerning sudden death and legal medicine.

Section snippets

Case 1

An 18-year-old girl suddenly collapsed in a bus without expressing any complaints to her accompanying friend. Resuscitation was unsuccessful.

At the age of 5 months, a congenital defect of the ventricular septum was diagnosed, which showed spontaneous closure. Later the onset of a systolic heart murmur accompanied by a midsystolic click with punctum maximum above the apex was observed. ECG revealed no pathologic conditions, while echocardiography showed a systolic ballooning of the mitral valve

Autopsy findings

Autopsy revealed pathoanatomical signs of MVPS in all cases (Fig. 1):

Increase in area, expansion and ballooning of at least one mitral valve leaflet and swollen aspect of the valve margin. Elongation and thickening of the chordae. In some cases fibrous endocardial plaque in close vicinity to the mitral valve.

Histology

In all cases, characteristic histomorphological features of MVPS were seen at examination (Fig. 2):

Loss of fibrous tissue in the central valve fibrosa, replacement by acid mucopolysaccharide.

Toxicology

Toxicological analyses (including ethanol) were negative in all cases.

Discussion

MVPS represents the most common cardiac valvular disorder. Clinical studies have detected a prevalence of 2.4–6% [5], [6], [7], [8]. Basis of the disorder is an expansion, thickening and ballooning of one or both leaflets of the mitral valve with following systolic displacement into the left atrium. Mitral regurgitation might occur. The diagnosis of MVPS can easily be established by echocardiography. At clinical examination, a systolic heart murmur can be heard, not necessarily accompanied by a

Conclusion

In three out of the six presented cases, the deceased had no medical history concerning cardiac symptoms (Table 1), while in only one case with diagnosed MVPS clinical symptoms (arrhythmias) were present. This points at the fact, that even clinically benign cases of MVPS in young adults might result in sudden unexpected death. In none of the cases medical help or help from accompanying persons had been asked for, further suggesting sudden arrhythmic events to be the cause of death, that can

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Cited by (31)

Antemortem and Post-Mortem Characteristics of Lethal Mitral Valve Prolapse Among All Countywide Sudden Deaths
2021, JACC: Clinical Electrophysiology
The goal of this study was to investigate the characteristics of mitral valve prolapse (MVP) in a post-mortem study of consecutive sudden cardiac deaths (SCDs) in subjects up to 90 years of age.
Up to 2.3% of subjects with MVPs experience SCD, but by convention SCD is rarely confirmed by autopsy. In a post-mortem study of persons <40 years of age, 7% of SCDs were caused by MVP; bileaflet involvement, mitral annular disjunction (MAD), and replacement fibrosis were common.
In the San Francisco POST SCD (Postmortem Systematic Investigation of Sudden Cardiac Death) study, autopsies have been performed on >1,000 consecutive World Health Organization–defined (presumed) cases of SCD in subjects aged 18 to 90 years since 2011; a total of 603 were adjudicated. Autopsy-defined sudden arrhythmic death (SAD) required absence of nonarrhythmic cause; MVP diagnosis required leaflet billowing. One hundred antemortem echocardiograms were revised to identify additional MVPs missed on autopsy.
Among the 603 presumed SCDs, 339 (56%) were autopsy-defined SADs, with MVP identified in 7 (1%). Six additional MVPs were identified by review of echocardiograms, for a prevalence of at least 2% among 603 presumed SCDs and 4% among 339 SADs (vs. 264 non-SADs; p = 0.02). All 6 additional MVPs had monoleaflet rather than bileaflet involvement and mild mitral regurgitation, ruling out hemodynamic cause. Less than one-half had MAD with replacement fibrosis, but all had multisite interstitial fibrosis.
In a countywide post-mortem study of all adult cases of SCD, MVP prevalence was at least 4% of SADs, but one-half were missed on autopsy. Monoleaflet MVP was often underdiagnosed post-mortem. Compared with young cases of SCD, lethal MVP in older cases of SCD did not consistently have bileaflet anatomy, replacement fibrosis, or MAD.
Arrhythmic Mitral Valve Prolapse: JACC Review Topic of the Week
2018, Journal of the American College of Cardiology
Citation Excerpt :
However, of those “unexplained” cases, more than one-half were noted to have mitral valve prolapse at autopsy (11). This lack of classification may result in an underestimation of the true incidence of MVP-related SCD, especially when autopsy studies show that MVP remains one of the most common causes of death in otherwise healthy young patients where MVP is offered as a classification (4,12,13). A 21-year prospective clinical-pathological investigation in Italy (<35 years of age) found MVP to be the third most common cardiac condition associated with SCD with an incidence of 12%, with arrhythmogenic right ventricular dysplasia (24%) and atherosclerotic coronary artery disease (20%) being the only diagnoses that were more common (14).
There is an increasing awareness of the association between mitral valve prolapse and sudden cardiac death. There are several clinical risk factors associated with an increased risk of mitral valve prolapse–related sudden cardiac death, most of which can be evaluated with noninvasive diagnostic modalities. For example, characteristic changes on the electrocardiogram (T-wave inversions in the inferior leads), complex ventricular ectopy, a spiked configuration of the lateral annular velocities by echocardiography, and evidence of myocardial fibrosis by cardiac magnetic resonance imaging have all been implicated as markers of risk. Herein, the authors review the reported incidence of sudden death to mitral valve prolapse, the clinical profile of at-risk patients, and the basic components necessary to initiate and perpetuate ventricular arrhythmias (substrate and trigger) as well as potential interventions to consider for those at highest risk.
Mitral valve prolapse and sudden cardiac arrest in the community
2016, Heart Rhythm
Citation Excerpt :
Several studies indicate that a subset of patients may suffer adverse outcomes, with sudden cardiac arrest (SCA) potentially the most devastating of these. SCA has been described as one of the possible outcomes on follow-up in MVP,4,5 and several instances of SCA in young patients with MVP have been reported.6,7 In addition, the occurrence of ventricular arrhythmias on resting or ambulatory electrocardiograms is reported to be higher in patients with MVP,8,9 though some studies have challenged this finding.10
Mitral valve prolapse (MVP) is relatively common in the general population with recently reported prevalence of 1% and familial clustering (Framingham Heart Study). However, its association with ventricular arrhythmias and sudden cardiac arrest (SCA) remains controversial.
The purpose of this study was to characterize the frequency and clinical profile of patients with MVP who suffer SCA in the community.
Patients with SCA cases were prospectively identified in the population-based Oregon Sudden Unexpected Death Study (population ~1 million). The presence of MVP was identified from echocardiograms recorded prior but unrelated to the SCA event. The detailed clinical profile of patients with SCA and MVP was compared with that of SCA patients without MVP to identify potential differences.
A total of 729 SCA patients were evaluated over a 12-year period (mean age 69.5 ± 14.8 years; 64.6% men). MVP was observed in 17 (2.3%) prior to the SCA event (95% confidence interval 1.2%–3.4%). Mitral regurgitation was present in 14 SCA patients with MVP (82.3%) and was moderate or severe in 10 (58.8%). Compared with SCA patients without MVP, SCA patients with MVP were younger (mean age 60.9 ± 16.4 years vs 69.7 ± 14.7 years; P = .02), with fewer risk factors (diabetes 5.9% vs 46.4%; P = .001; hypertension 41.2% vs 78.9%; P = .001) or known coronary disease (29.4% vs 65.6%; P < .001).
MVP was observed in a small proportion (2.3%) of SCA patients in the general population, suggesting a low risk overall. Since SCA patients with MVP were characterized by younger age and relatively low cardiovascular comorbidity, a focus on imaging for valve structure/insufficiency as well as genetics could aid future risk stratification approaches.
Malignant bileaflet mitral valve prolapse syndrome in patients with otherwise idiopathic out-of-hospital cardiac arrest
2013, Journal of the American College of Cardiology
The aim of this study was to investigate the prevalence of mitral valve prolapse (MVP) and its association with ventricular arrhythmias in a cohort with “unexplained” out-of-hospital cardiac arrest.
Ventricular arrhythmias are an important cause of sudden unexpected death in the young. The role of MVP in sudden unexpected death remains controversial.
Of 1,200 patients evaluated between July 2000 and December 2009 in the Mayo Clinic’s Long QT Syndrome/Genetic Heart Rhythm Clinic, all 24 (16 women, median age 33.5 years) with idiopathic out-of-hospital cardiac arrest (i.e., negative for ischemia, cardiomyopathy, and channelopathy) were reviewed.
All 24 patients had implantable cardioverter-defibrillators (ICDs). Out-of-hospital cardiac arrest was the sentinel event in 22 (92%). Bileaflet MVP was found in 10 (42%). Compared with patients with normal mitral valves, patients with bileaflet MVP: 1) were over-represented by women (9 of 10 [90%] vs. 7 of 14 [50%], p = 0.04); 2) had a higher prevalence of biphasic or inverted T waves (7 of 9 [77.8%] vs. 4 of 14 [29%], p = 0.04); and 3) on Holter interrogation had higher prevalence of ventricular bigeminy (9 of 9 [100%] vs. 1 of 10 [10%], p < 0.0001), ventricular tachycardia (7 of 9 [78%] vs. 1 of 10 [10%], p = 0.006), and premature ventricular contractions originating from the outflow tract alternating with the papillary muscle or fascicular region (7 of 9 [78%] vs. 2 of 10 [20%], p = 0.02). Over a median 1.8 years (range: 0.1 to 11.9 years) from ICD placement, 13 of 24 patients (54%) received appropriate ventricular fibrillation–terminating ICD shocks. Only bileaflet MVP was associated with ventricular fibrillation recurrences requiring ICD therapy on follow-up (logistic regression odds ratio: 7.2; 95% confidence interval: 1.1 to 48; p = 0.028).
The authors describe a “malignant” subset of patients with MVP who experienced life-threatening ventricular arrhythmias. This phenotype is characterized by bileaflet MVP, female sex, and frequent complex ventricular ectopic activity, including premature ventricular contractions of the outflow tract alternating with papillary muscle or fascicular origin.
Sudden cardiac death in the young: The bogeyman
2015, Cardiology in the Young
Arrhythmias in paediatric valvar disease
2014, Cardiology in the Young

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Mitral valve prolapse syndrome as cause of sudden death in young adults

Abstract

Introduction

Section snippets

Case 1

Autopsy findings

Histology

Toxicology

Discussion

Conclusion

Am. Heart J.

Am. Heart J.

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Am. J. Human Genet.

J. Am. Coll. Cardiol.

Hum. Pathol.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Legal Med.

Am. Heart J.

J. Clin. Forensic Med.

Cardiovascular causes of sudden death in young individuals including athletes

Cardiol. Rev.

Sudden unexpected death in young adult due to right ventricular dysplasia

J. Forensic Sci.

Coronary arteriitis diagnosed at autopsy: three case reports and review of the literature

Am. J. Forensic Med. Pathol.