The Association Between Late Gadolinium Enhancement by Cardiac Magnetic Resonance and Ventricular Arrhythmia in Patients With Mitral Valve Prolapse: A Systematic Review and Meta-Analysis.

INTRODUCTION: Malignant ventricular arrhythmia (VA) and sudden cardiac death (SCD) have been reported in patients with mitral valve prolapse (MVP); however, effective risk stratification methods are still lacking. Myocardial fibrosis is thought to play an important role in the development of VA; however, observational studies have produced contradictory findings regarding the relationship between VA and late gadolinium enhancement (LGE) in MVP patients. The aim of this meta-analysis and systematic review of observational studies was to investigate the association between left ventricular LGE and VA in patients with MVP. METHODS: We searched the PubMed, Embase, and Web of Science databases from 1993 to 2023 to identify case-control, cross-sectional, and cohort studies that compared the incidence of VA in patients with MVP who had left ventricular LGE and those without left ventricular LGE. RESULTS: A total of 1464 subjects with MVP from 12 observational studies met the eligibility criteria. Among them, VA episodes were reported in 221 individuals (15.1%). Meta-analysis demonstrated that the presence of left ventricular LGE was significantly associated with an increased risk of VA (pooled risk ratio 2.96, 95% CI: 2.26-3.88, p for heterogeneity = 0.07, I2 = 40%). However, a meta-regression analysis of the prevalence of mitral regurgitation (MR) showed that the severity of MR did not significantly affect the association between the occurrence of LGE and VA (p = 0.079). CONCLUSION: The detection of LGE could be helpful for stratifying the risk of VA in patients with MVP.

Mitral valve prolapse: arrhythmic risk during pregnancy and postpartum.

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.

Species designation of streptococci causing infective endocarditis in patients with mitral valve prolapse.

OBJECTIVES: Viridans group streptococci (VGS) have been previously linked to infective endocarditis (IE) in patients with mitral valve prolapse (MVP). The species identification of VGS is now available in clinical laboratories; however, it has not been examined in MVP IE. Therefore, we detailed the clinical profile, species designations, and antibiotic susceptibility of VGS isolates from patients with MVP IE. METHODS: We retrospectively queried all adults with MVP and a definite or possible IE diagnosis seen at medical centers of the Mayo Clinic Enterprise from January 2009 to December 2021. Data, including clinical characteristics, comorbidities, microbiology, and outcomes, were extracted from electronic health records. VGS isolates from patients with MVP and IE were subclassified into mutans, salivarius, anginosus, sanguinis, and mitis groups. RESULTS: A total of 38 patients with MVP with IE due to streptococcal species were included. Overall, median age was 62.4 years and 32% of patients were females. The most prevalent comorbidities were diabetes mellitus (26%), hypertension (21%), heart failure (16%), and malignancy (16%). A total of (37%) patients presented with an embolic event at the time of their IE diagnosis, 27 (66%) required valve surgery, and no patient died within the hospital stay. The Streptococcus mitis group was the predominant (n = 17, 45%) species designation; S. anginosus and S. sanguinis were identified in three (8%) each; S. mutans in two (5%); and S. salivarius in one (3%). Non-VGS streptococcal pathogens included S. agalactiae in three patients (8%), S. equi in two (5%), and S. dysgalactiae and S. bovis in one each (3%). VGS were identified in five (13%) patients, but species designation was not done. No penicillin resistance was identified among the isolates. CONCLUSION: The S. mitis group was the predominant species in our investigation. Continued evaluation of VGS species should be considered to profile the IE risk based on species identification.

Negative impact of high-performance flights on aviators with mitral valve prolapse.

BACKGROUND: While it appears not to affect healthy aviators' hearts, there are scarce data regarding the impact of high-performance flights on aviators with mitral valve prolapse (MVP). METHODS: A retrospective, comparative cohort study of military aviators with MVP. Subjects were categorized to either high-performance (jet fighter) or low-performance (transport and helicopter) aviators. The primary outcomes were the rates of mitral interventions and of adverse cardiovascular events since being an aircrew candidate and up to the end of flying career. Additional outcomes were echocardiographic measurements and the cumulative proportion of mitral valve interventions over time. RESULTS: Of 33 male aviators with MVP, 18 were high-performance aviators. On average, follow-up started at age 18.5 years and lasted 27.8 ±â€¯10.1 years. Baseline characteristics were similar between the study groups. Aviators of high-performance aircraft had increased rates of mitral valve surgery (33 % vs. 0, p = 0.021), MVP-related complications (39 % vs. 6.7 %, p = 0.046), and a higher incidence of mitral valve repair over time (p = 0.02). High-performance flight was associated with increased intraventricular septum thickness (IVS, 9.7 mm vs 8.9 mm, p = 0.015) and IVS index (p = 0.026) at the last echocardiographic assessment. High-performance aviators tended to develop worsening severity of mitral regurgitation. CONCLUSIONS: High-performance flight may be associated with an increased risk for valvular deterioration and need for mitral surgery in aviators with MVP.

Mitral Annular Disjunction Assessed Using CMR Imaging: Insights From the UK Biobank Population Study.

BACKGROUND: Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias and sudden death, its prevalence in the general population is not known. OBJECTIVES: The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort. METHODS: The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall. RESULTS: From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse was more frequent in subjects with disjunction (odds ratio [OR]: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01). CONCLUSIONS: This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding.

Genetic background of mitral valve prolapse.

Mitral valve prolapse (MVP) has a prevalence of 2-3% among the population. It involves a heterogeneous group of patients with different expressions and according to the phenotype can be further divided into fibroelastic deficiency, which is mainly considered as a degeneration due to aging, and myxomatous disease, frequently associated with familiar clusters. Thus, MVP can be present in syndromic, when part of a well-defined syndrome, and non-syndromic forms. The latter occurs more often. To the second belong both familiar and isolated or sporadic forms. On one hand, among familial forms, although X-linked transmission related to FLNA gene was initially identified, further studies reported also autosomal dominant mode involving MVPP genes, including DCHS1. On the other hand, genome-wide association studies (GWAS), among unrelated patients, allowed the identification of new MVP-associated genes, such as LMCD1, GLIS, and TNS1. Moreover, single nucleotide polymorphisms (SNPs) on metalloproteinase genes have been related to MVP. Interestingly some genes such as DCHS1 and DZIP1 have been reported to be involved in both familiar and isolated forms. The present review aims to illustrate the updated genetic background of MVP.

Myxomatous mitral valve disease in Miniature Schnauzers and Yorkshire Terriers: 134 cases (2007-2016).

OBJECTIVE: To characterize features of myxomatous mitral valve disease (MMVD) in Miniature Schnauzers and Yorkshire Terriers. ANIMALS: 69 Miniature Schnauzers and 65 Yorkshire Terriers, each with MMVD. PROCEDURES: Medical record data for each dog were collected; the study period was January 2007 through December 2016. If available, radiographic data were evaluated, and a vertebral heart scale score was assigned for each dog. Statistical analysis was performed with Student t and Fisher exact tests. RESULTS: Compared with Yorkshire Terriers, the prevalence of MMVD was significantly higher in Miniature Schnauzers and affected dogs were significantly younger at the time of diagnosis. Miniature Schnauzers were significantly more likely to have mitral valve prolapse and syncope, compared with Yorkshire Terriers. Yorkshire Terriers were significantly more likely to have coughing and have had previous or current treatment with cardiac medications, compared with Miniature Schnauzers. There was no statistical difference between breeds with regard to abnormally high vertebral heart scale scores or radiographic evidence of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE: With regard to MMVD, features of the disease among Miniature Schnauzers and Yorkshire Terriers were similar, but there were also a few discernable differences between these 2 breeds and from historical findings for dogs with MMVD of other breeds. Clinical signs at the time of diagnosis differed between the 2 breeds, which may have reflected concurrent breed-specific conditions (sick sinus syndrome or airway disease [eg, tracheal collapse]). Future work should include prospective studies to provide additional information regarding the natural progression of MMVD in these dog breeds.

[Mitral valve prolapse: beyond mitral regurgitation, the arrhythmic risk]. / Prolapsus mitral : une étiologie méconnue d'arythmie ventriculaire et de mort subite.

Mitral prolapse is a common condition, defined by the systolic bulging of at least one mitral leaflet into the left atrium, which is often accompanied by various degree of mitral insufficiency. While for most of the patients the prognosis is linked to the severity of the valve regurgitation and its repercussions on the left ventricle (dilation and/or dysfunction), a minority of patients present with severe ventricular arrhythmia and an increased risk of sudden cardiac death, irrespective of the severity of the mitral regurgitation. To describe this particular condition, the terms arrhythmic or malignant mitral valve prolapse have been coined. The aim of this article is to describe the clinical, electrocardiographic and morphologic characteristics, which have been associated with an increased risk of arrhythmia in patients with mitral prolapse.

Le prolapsus mitral est une pathologie fréquente, définie par le bombement en systole d'au moins un feuillet mitral dans l'oreillette gauche, qui s'accompagne fréquemment d'un degré variable d'insuffisance mitrale. Dans la majorité des cas, le pronostic est lié à la sévérité de l'insuffisance valvulaire et ses répercussions sur le ventricule gauche (dilatation et/ou dysfonction). Toutefois, dans certaines formes, le prolapsus mitral se manifeste par une susceptibilité aux arythmies ventriculaires et s'associe à un risque accru de mort subite, indépendamment de la présence ou de la sévérité de l'insuffisance valvulaire. On parle alors de syndrome du prolapsus mitral arythmique ou prolapsus mitral malin. Cet article décrit les caractéristiques cliniques, électrocardiographiques et morphologiques associées au risque arythmique chez les patients atteints d'un prolapsus mitral.

Mitral Annular Disjunction-A New Disease Spectrum.

Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus, which has been described by pathologists to be associated with mitral leaflet prolapse. Mitral annular disjunction is a common finding in patients with myxomatous mitral valve diseases. The prevalence of mitral annular disjunction should be checked routinely during presurgical imaging. Otherwise, mitral annular disjunction itself might be an arrhythmogenic entity, irrespective of the presence of mitral valve prolapse (MVP). Therefore, we should check echocardiography keeping in mind mitral annular disjunction. Further prospective studies are needed to address whether a causative mechanistic link exists between mitral annular disjunction and arrhythmic MVP.

Presentation and Outcome of Arrhythmic Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) is often considered benign but recent suggestion of an arrhythmic MVP (AMVP) form remains incompletely defined and uncertain. OBJECTIVES: This study determined ventricular arrhythmia prevalence, severity, phenotypical context, and independent impact on outcome in patients with MVP. METHODS: A cohort of 595 (age 65 ± 16 years; 278 women) consecutive patients with MVP and comprehensive clinical, arrhythmia (24-h Holter monitoring) and Doppler-echocardiographic characterization, was identified. Long-term outcomes were analyzed. RESULTS: Ventricular arrhythmia was frequent (43% with at least ventricular ectopy ≥5%), most often moderate (ventricular tachycardia [VT]; 120 to 179 beats/min) in 27%, and rarely severe (VT ≥180 beats/min) in 9%. Presence of ventricular arrhythmia was associated with male sex, bileaflet prolapse, marked leaflet redundancy, mitral annulus disjunction (MAD), a larger left atrium and left ventricular end-systolic diameter, and T-wave inversion/ST-segment depression (all p ≤ 0.001). Severe ventricular arrhythmia was independently associated with presence of MAD, leaflet redundancy, and T-wave inversion/ST-segment depression (all p < 0.0001) but not with mitral regurgitation severity or ejection fraction. Overall mortality after arrhythmia diagnosis (8 years; 13 ± 2%) was strongly associated with arrhythmia severity (8 years; 10 ± 2% for no/trivial, 15 ± 3% for mild and/or moderate, and 24 ± 7% for severe arrhythmia; p = 0.02). Excess mortality was substantial for severe arrhythmia (univariate hazard ratio [HR]: 2.70; 95% confidence interval [CI]: 1.27 to 5.77; p = 0.01 vs. no/trivial arrhythmia), even after it was comprehensively adjusted, including for MVP characteristics (adjusted HR: 2.94; 95% CI: 1.36 to 6.36; p = 0.006) and by time-dependent analysis (adjusted HR: 3.25; 95% CI: 1.56 to 6.78; p = 0.002). Severe arrhythmia was also associated with higher rates of mortality, defibrillator implantation, VT ablation (adjusted HR: 4.68; 95% CI: 2.45 to 8.92; p < 0.0001), particularly under medical management (adjusted HR: 5.80; 95% CI: 2.75 to 12.23; p < 0.0001), and weakly post-mitral surgery (adjusted HR: 3.69; 95% CI: 0.93 to 14.74; p = 0.06). CONCLUSIONS: In this large cohort of patients with MVP, ventricular arrhythmia by Holter monitoring was frequent but rarely severe. AMVP was independently associated with phenotype dominated by MAD, marked leaflet redundancy, and repolarization abnormalities. Long-term severe arrhythmia was independently associated with notable excess mortality and reduced event-free survival, particularly under medical management. Therefore, AMVP is a clinical entity strongly associated with outcome and warrants careful risk assessment and well-designed clinical trials.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Familial occurrence of mitral regurgitation in patients with mitral valve prolapse undergoing mitral valve surgery.

BACKGROUND: Initial studies have suggested the familial clustering of mitral valve prolapse, but most of them were either community based among unselected individuals or applied non-specific diagnostic criteria. Therefore little is known about the familial distribution of mitral regurgitation in a referral-type population with a more severe mitral valve prolapse phenotype. The objective of this study was to evaluate the presence of familial mitral regurgitation in patients undergoing surgery for mitral valve prolapse, differentiating patients with Barlow's disease, Barlow forme fruste and fibro-elastic deficiency. METHODS: A total of 385 patients (62 ± 12 years, 63% men) who underwent surgery for mitral valve prolapse were contacted to assess cardiac family history systematically. Only the documented presence of mitral regurgitation was considered to define 'familial mitral regurgitation'. In the probands, the aetiology of mitral valve prolapse was defined by surgical observations. RESULTS: A total of 107 (28%) probands were classified as having Barlow's disease, 85 (22%) as Barlow forme fruste and 193 (50%) patients as fibro-elastic deficiency. In total, 51 patients (13%) reported a clear family history for mitral regurgitation; these patients were significantly younger, more often diagnosed with Barlow's disease and also reported more sudden death in their family as compared with 'sporadic mitral regurgitation'. In particular, 'familial mitral regurgitation' was reported in 28 patients with Barlow's disease (26%), 15 patients (8%) with fibro-elastic deficiency and eight (9%) with Barlow forme fruste (P < 0.001). CONCLUSIONS: In a large cohort of patients operated for mitral valve prolapse, the self-reported prevalence of familial mitral regurgitation was 26% in patients with Barlow's disease and still 8% in patients with fibro-elastic deficiency, highlighting the importance of familial anamnesis and echocardiographic screening in all mitral valve prolapse patients.

Myxomatous mitral valve disease in the miniature poodle: A retrospective study.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disease in the dog. The natural history of the disease is wide ranging and includes patients without clinical signs as well as those with significant clinical consequences from cardiac arrhythmias, pulmonary hypertension and/or congestive heart failure. The factors that determine which dogs remain asymptomatic and which develop clinical disease are not known. Disease characteristics could be breed or family related; some breeds of dogs, particularly the Cavalier King Charles spaniels, develop MMVD at an early age. The purpose of this study was to retrospectively characterize MMVD in the miniature poodle, a commonly affected breed in which MMVD has not been well characterized. Thirty-two miniature poodles met the inclusion criteria. Mean age was 11±three years. Clinical signs included exercise intolerance, syncope and coughing. Eighteen dogs were classified as ACVIM Stage B1, 12 as stage B2, and two as stage C. Mean vertebral heart scale (VHS) was 10.2 (±standard deviation of 0.9); 15 of 28 dogs had a VHS <10.3. One dog had radiographic evidence of congestive heart failure. Mean diastolic left ventricle dimension normalized to body weight was 1.6 (±0.4) and mean systolic was 0.8 (±0.3). Mitral valve prolapse was subjectively classified as mild or moderate in 19 dogs and severe in two. In the miniature poodles reported here, MMVD appears to be a fairly late onset disease and often is a mild phenotype.

Coexistent bicuspid aortic valve and mitral valve prolapse: epidemiology, phenotypic spectrum, and clinical implications.

AIMS: Bicuspid aortic valve (BAV) and mitral valve prolapse (MVP) are common but the prevalence and significance of coexistent conditions are unknown. This study investigated the prevalence, phenotypic expression, and clinical significance of coexistent MVP-BAV. METHODS AND RESULTS: Retrospective comparison of MVP-BAV and MVP-tricuspid aortic valve (TAV) prevalence including de novo echocardiographic analysis of all MVP-BAV patients between 2005 and 2015 was performed. The community prevalence of MVP-BAV was 2.7% vs. 3.4% for MVP-TAV (P = 0.45). Posterior mitral leaflet (PML)-MVP was the most common phenotype in both BAV and TAV (P = 0.38), but anterior mitral leaflet (AML)-MVP was twice more prevalent in BAV (31% vs. 15%, P < 0.0001). Among 130 subjects with coexistent MVP-BAV (81% men, 51 ± 16 years old), 31 (24%) exhibited AML:PML length ratio ≥3:1, termed large-AML prolapse (LAP-BAV), who had predominant BAV regurgitation when compared with those with non-LAP-BAV (P ≤ 0.001). An extreme phenotype of LAP-BAV with giant-AML prolapse and diminutive PML (GAP-BAV) was identified in 18/130 (14%) subjects. Compared with posterior-MVP-BAV, GAP-BAV patients were younger (42 ± 15 vs. 64 ± 12 years, P < 0.0001), had larger aortic annulus (28 ± 3 vs. 26 ± 2 mm, P = 0.01), and 61% had ≥ moderate BAV regurgitation (vs. 16%, P = 0.0007). Mitral repair occurred in 37/130 (28%) subjects. After median follow-up 5.5 months (4-83), 4/5 (80%) GAP-BAV patients required redo surgery for recurrent mitral regurgitation vs. 2/31 (6%) for non-LAP-BAV (P = 0.001). CONCLUSION: The community prevalence of coexistent MVP-BAV is comparable to MVP-TAV and their most common phenotype is posterior-MVP. However, anterior-MVP is twice as prevalent in MVP-BAV. A large-AML phenotype (LAP-BAV) with predominant BAV regurgitation affects 24% of MVP-BAV patients. An extreme phenotype of anterior-MVP (GAP-BAV) affects 14% of BAV patients; characterized by exceptionally large AML, diminutive PML, high mitral and aortic regurgitation prevalence, and high mitral repair failure rate.

Prevalence and clinical phenotype of concomitant long QT syndrome and arrhythmogenic bileaflet mitral valve prolapse.

BACKGROUND: Mitral valve prolapse (MVP), including the recently described arrhythmogenic bileaflet MVP syndrome (ABiMVPS), is associated with repolarization abnormalities and may represent an underestimated cause of sudden cardiac death. The impact of concomitant MVP or ABiMVPS on long QT syndrome (LQTS) clinical severity is unknown. METHODS AND RESULTS: Retrospective review of 754 LQTS patients [445 females (58%) and mean QTc 471 ±â€¯41 ms] with available echocardiographic data was performed to identify LQTS patients with not only MVP, but also a pro-arrhythmic ABiMVPS phenotype defined as bileaflet MVP, inferolateral T-wave inversions, and frequent complex ventricular ectopy/arrhythmia. As expected, 18/754 (2%) LQTS patients had concomitant MVP. Of these, 5/18 (28%) LQTS patients with MVP satisfied ABiMVPS diagnostic criteria. No difference in symptomatology, degree of QT prolongation, or clinical management was observed between LQTS patients with and without MVP. In contrast, LQTS plus ABiMVPS resulted in a severe cardiac phenotype as illustrated by symptomatic status (LQTS-ABiMVPS; 5/5; 100%; vs LQTS: 279/736; 39%; p = .008), degree of baseline QTc prolongation (LQTS-ABiMVPS: 536 ±â€¯58 ms; vs LQTS: 470 ±â€¯40 ms; p = .009), and number of patients experiencing ≥1 on-therapy break-through cardiac event (LQTS-ABiMVPS: 4/5; 80%; vs LQTS: 48/736; 7%; p < .001]. Lastly, individuals with LQTS plus ABiMVPS were more likely to experience appropriate ICD therapies post-cardiac denervation (LQTS-ABiMVPS: 2/3; 67% vs LQTS: 4/49; 8%; p = .03]. CONCLUSIONS AND RELEVANCE: The co-existence of LQTS and ABiMVPS may lead to a rare, but malignant, clinical entity characterized by potentially life-threatening arrhythmias despite maximal LQTS therapy.

Genetics of syndromic and non-syndromic mitral valve prolapse.

Mitral valve prolapse (MVP) is a common condition that affects 2%-3% of the general population. MVP is thought to include syndromic forms such as Marfan syndrome and non-syndromic MVP, which is the most frequent form. Myxomatous degeneration and fibroelastic deficiency (FED) are regarded as two different forms of non-syndromic MVP. While FED is still considered a degenerative disease associated with ageing, frequent familial clustering has been demonstrated for myxomatous MVP. Familial and genetic studies led to the recognition of reduced penetrance and large phenotypic variability, and to the identification of prodromal or atypical forms as a part of the complex spectrum of the disease. Whereas autosomal dominant mode is the common inheritance pattern, an X linked form of non-syndromic MVP was recognised initially, related to Filamin-A gene, encoding for a cytoskeleton protein involved in mechanotransduction. This identification allowed a comprehensive description of a new subtype of MVP with a unique association of leaflet prolapse and paradoxical restricted motion in diastole. In autosomal dominant forms, three loci have been mapped to chromosomes 16p11-p12, 11p15.4 and 13q31-32. Although deciphering the underlying genetic defects is still a work in progress, DCHS1 mutations have been identified (11p15.4) in typical myxomatous disease, highlighting new molecular pathways and pathophysiological mechanisms leading to the development of MVP. Finally, a large international genome-wide association study demonstrated the implication of frequent variants in MVP development and opened new directions for future research. Hence, this review focuses on phenotypic, genetic and pathophysiological aspects of MVP.

Demographics and Epidemiology of Sudden Deaths in Young Competitive Athletes: From the United States National Registry.

BACKGROUND: Sudden deaths in young competitive athletes are tragic events, with high public visibility. The importance of race and gender with respect to sport and the diagnosis and causes of sudden death in athletes has generated substantial interest. METHODS: The US National Registry of Sudden Death in Athletes, 1980-2011, was accessed to define the epidemiology and causes of sudden deaths in competitive athletes. A total of 2406 deaths were identified in young athletes aged 19 ± 6 years engaged in 29 diverse sports. RESULTS: Among the 842 athletes with autopsy-confirmed cardiovascular diagnoses, the incidence in males exceeded that in females by 6.5-fold (1:121; 691 vs 1:787,392 athlete-years; P ≤.001). Hypertrophic cardiomyopathy was the single most common cause of sudden death, occurring in 302 of 842 athletes (36%) and accounting for 39% of male sudden deaths, almost 4-fold more common than among females (11%; P ≤.001). More frequent among females were congenital coronary artery anomalies (33% vs 17% of males; P ≤.001), arrhythmogenic right ventricular cardiomyopathy (13% vs 4%; P = .002), and clinically diagnosed long QT syndrome (7% vs 1.5%; P ≤.002). The cardiovascular death rate among African Americans/other minorities exceeded whites by almost 5-fold (1:12,778 vs 1:60; 746 athlete-years; P <.001), and hypertrophic cardiomyopathy was more common among African Americans/other minorities (42%) than in whites (31%; P ≤.001). Male and female basketball players were 3-fold more likely to be African American/other minorities than white. CONCLUSIONS: Within this large forensic registry of competitive athletes, cardiovascular sudden deaths due to genetic and/or congenital heart diseases were uncommon in females and more common in African Americans/other minorities than in whites. Hypertrophic cardiomyopathy is an under-appreciated cause of sudden death in male minority athletes.

Is there any link between joint hypermobility and mitral valve prolapse in patients with fibromyalgia syndrome?

The objective of the present study is to determine whether benign joint hypermobility syndrome (BJHS) modifies the risk of mitral valve prolapse (MVP) in patients with fibromyalgia (FM). Female patients fulfilling the 1990 American College of Rheumatology (ACR) diagnostic criteria for FM were included into the study. Joint hypermobility and BJHS were assessed using Beighton's scoring system and Brighton criteria, respectively. Echocardiograpic evaluation was performed in order to test the presence of MVP. Of the 75 female FM patients, 68.0 % (n = 51) and 20.0 % (n = 15) were diagnosed with BJHS and MVP, respectively. The frequencies of both MVP and BJHS seemed higher than the general population prevalence (p = 0.000 for both). The frequency of MVP was significantly higher in patients with BJHS than that in patients without BJHS (p = 0.028). In addition, BJHS was found to increase the risk of MVP approximately ninefold [odds ratio (OR) 8.7, 95 % confidence interval (CI) 1.1-70.7]. As a result, BJHS and MVP are both common in female patients with FM. Moreover, among the female patients with FM, those with BJHS are about nine times more prone to MVP than those without BJHS. Cardiologic assessment might be added to the routine follow-up strategies in FM patients with BJHS in order to exclude the cardiac pathologies, especially MVP.

P210Long- term outcome of primary mitral valve prolapse: results from a population of 250 patients referred to a tertiary cardiovascular center.

BACKGROUND: Outcome of Mitral Valve Prolapse (MVP) was controversial for long time. Many studies reported great differences in the incidence of cardiovascular events due, above all, to heterogeneous and small studied populations. Most of theme were also published to late '80 of the last century till early '00. PURPOSE: To make a contemporary survey on the incidence of cardiovascular events in a selected population of patients affected by primary MVP referred to a tertiary cardiovascular center for the medical and surgical care of valvular heart disease. METHODS: We reviewed our MVP database; patients with at least 2 cardiologic evaluations inclusive of echocardiographic examination and at least 6 months follow up were enrolled. A total of 250 patients (126 F) were selected. Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up time was 100 months (8,33 yrs). RESULTS: At the first medical and echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR), 104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP (94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%) and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior mitral annulus diameter was 37 mm. During the follow up 7 patients died of non-cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture occurred during the follow up in most cases concerning mitral chordae linked to posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an evolution of the clinical condition of 48 patients (19.2%) which developed Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at the initial evaluation). A total of 45 patients (18%) underwent mitral valve surgery. 40 needed in-hospital treatment in most cases due to the development of atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6 (2.4%). The overall cardiovascular event rate was 4,33/100 patients-year, significantly higher than reported in community based studies. CONCLUSIONS: The prognosis of a MVP population referred to a tertiary cardiovascular center is not benign. The most frequent complications are progression of MR and MV surgery. Sudden death is also more frequent than in general population. More studies are needed to identify what patients with MVP are at risk for it.

Mitral valve repair with loop technique via median sternotomy in 180 patients.

OBJECTIVES: Artificial chordal reconstruction technique uses several expanded polytetrafluoroethylene loops to achieve mitral valve repair. METHODS: We studied retrospectively 180 patients who underwent mitral valve repair using the loop technique via median sternotomy: 86 for posterior leaflet prolapse, 48 for anterior leaflet prolapse and 26 for bileaflet prolapse. RESULTS: Of the 180 patients, 138 required 1 loop set; 40 patients required 2 and 2 patients with Barlow's disease required 3. Loop sets contained two to nine loops ranging in length from 14 to 26 mm. Additional techniques required to ensure complete repair using the loop technique included commissural edge-to-edge suture in 78 patients, loop-in-loop technique for extension of the artificial loop in 18 and use of needle-side sutures in 18. Systolic anterior leaflet motion was observed in only 2 patients (1.1%). One patient with immune deficiency died of sepsis. Predischarge echocardiograms showed no or trace mitral regurgitation (MR) in 160 patients (89%), mild MR in 17 patients (9.4)% and mild-to-moderate MR in 3 patients (1.7%). Only 1 patient required redo operation due to recurrent MR freedom from MR greater than moderate was seen in 98.0 ± 1.4% of patients at 1 year, 91.5 ± 2.8% of patients at 3 years, and 91.5 ± 2.8% at 5 years postoperatively. No significant difference was seen in the rate of recurrence of MR among the sites of prolapsing leaflets. CONCLUSIONS: The loop technique via median sternotomy to treat posterior, anterior and, especially, bileaflet prolapse provided satisfactory mid-term outcomes.