Smoking Cessation and Incident Atrial Fibrillation in a Longitudinal Cohort.

BACKGROUND: Although smoking heightens the risk of AF, it remains unknown if that risk is amenable to modification after smoking cessation. OBJECTIVES: This study sought to evaluate the association between smoking cessation and atrial fibrillation (AF) risk in a large longitudinal cohort. METHODS: After excluding those with prevalent AF and no history of smoking at baseline, we evaluated 146,772 UK Biobank participants with serial smoking assessments. We compared AF risk between former smokers at baseline and those who quit smoking during the study to current smokers. Incident AF was ascertained from outpatient and inpatient encounters and identified using International Classification of Diseases codes. Cox models were used to compare the risk of incident AF among current and former smokers as well as those who quit smoking during the study while controlling for age, sex, race, body mass index, education, cardiovascular comorbidities, alcohol use, and pack-years. RESULTS: Among the 146,772 participants (48.3% female; age: 57.3 ± 7.9 years), 37,377 (25.5%) currently smoked; 105,429 (72.0%) were former smokers; and 3,966 (2.7%) quit smoking during the study. Over a mean 12.7 ± 2.0 years of follow-up, 11,214 (7.6%) participants developed AF. Compared to current smokers, the adjusted risk of AF was 13% lower in former smokers (HR: 0.87; 95% CI: 0.83-0.91) and 18% lower in those who quit smoking during the study (HR: 0.82; 95% CI: 0.70-0.95). CONCLUSIONS: Compared to those who continue to smoke, smoking cessation was associated with a lower risk of AF.

Primary Atriopathy in Mitral Valve Prolapse: Echocardiographic Evidence and Clinical Implications.

BACKGROUND: Prominent multi-scallop systolic leaflet displacement toward the left atrium (atrialization) is typically observed in bileaflet mitral valve prolapse (MVP) with mitral annular disjunction. We hypothesized that mitral leaflet atrialization is associated with an underlying left atrial (LA) myopathy characterized by progressive structural and functional abnormalities, irrespective of mitral regurgitation (MR) severity. METHODS: We identified 334 consecutive patients with MVP, no prior atrial fibrillation, and comprehensive clinical and echocardiographic data. LA function was assessed by LA reservoir strain, LA function index, and LA emptying fraction. We also classified the stage of LA remodeling based on LA enlargement and LA reservoir strain (stage 1: no remodeling; stage 2: mild remodeling; stage 3: moderate remodeling; and stage 4: severe remodeling). The primary end point was the composite risk of sudden arrhythmic death, heart failure hospitalization, or the new onset of atrial fibrillation. RESULTS: Bileaflet MVP with no or mild MR had a lower LA reservoir strain (P=0.04) and LA function index (P<0.001) compared with other MVP subtypes. In multivariable linear regression adjusted for cardiovascular risk factors and MR ≥moderate, bileaflet MVP remained significantly associated with lower LA function parameters (all P<0.05). There was a significant increase in the risk of events as the LA reservoir strain and LA remodeling stage increased (P<0.001). In multivariable analysis, stage 4 of LA remodeling remained significantly associated with a higher risk of events compared with stage 1 (hazard ratio, 6.09 [95% CI, 1.69-21.9]; P=0.006). CONCLUSIONS: In a large MVP registry, bileaflet involvement is associated with reduced LA function regardless of MR severity, suggesting a primary atriopathy in this MVP subtype. Abnormal LA function, particularly when assessed through a multiparametric approach, is linked to a higher risk of cardiovascular events and may improve risk stratification in MVP, even in those without significant MR.

Mitral Annular Disjunction: An Under-Recognized Entity in Pediatrics.

Mitral annular disjunction (MAD) is a rare and under-recognized entity in the pediatric population. We present 2 cases of MAD in previously healthy pediatric patients and highlight clinical scenarios where MAD should be suspected.

Interstitial Fibrosis and Arrhythmic Mitral Valve Prolapse: Unravelling Sex-Based Differences.

Background: Interstitial fibrosis as quantified by cardiac magnetic resonance (CMR) has been demonstrated in arrhythmic mitral valve prolapse (MVP), a condition with known female predominance. However, prior studies included only MVP cases with significant mitral regurgitation (MR) or mitral annular disjunction (MAD). We sought to evaluate the association between interstitial fibrosis and complex ventricular ectopy (ComVE) in MVPs unselected for MAD or severe MR, and to investigate the contribution of sex to this association. Methods: We performed contrast CMR in consecutive individuals with MVP between 2020 and 2022. Extracellular volume fraction (ECV%), a surrogate marker for interstitial fibrosis, was quantified using T 1 mapping. Replacement fibrosis was assessed using late gadolinium enhancement (LGE). ComVE, defined as frequent premature ventricular contractions and/or non-sustained/sustained ventricular tachycardia (VT), was detected using ambulatory ECG monitoring. Results: We identified 59 MVP cases without severe MR (49% women, 80% with mild or less MR) and available ECV% measurement. Among these, 23 (39%) had ComVE, including a case of aborted ventricular fibrillation (VF) and one with sudden arrhythmic death, both females. Global ECV% was significantly greater in ComVE versus non-ComVE (31%[27-33] vs 27%[23-30], p=0.002). In MVP-ComVE, higher segmental ECV% was not limited to the inferolateral/inferior LV wall, but was also demonstrated in atypical segments including the anterior/anterolateral wall (p<0.05). The association between ComVE and ECV% was driven by female sex (32%[30-33] vs 28%[26-30], p=0.003 in females; 31%[25-33] vs 26%[23-30], p=0.22 in males). ECV% remained independently associated with an increased risk of ComVE, including VT/VF, after adjustment for cardiovascular risk factors, MAD, and LGE (p<0.01). Conclusion: In MVP without significant MR, interstitial fibrosis by CMR is associated with an increased risk of ComVE, suggesting a primary myopathic process. The stronger association between interstitial fibrosis and ComVE in females may explain why severe arrhythmic complications are more prevalent among women.

Cannabis use and incident atrial fibrillation in a longitudinal cohort.

BACKGROUND: Cannabis use is increasing worldwide. While prior studies have reported an association between cannabis use and a higher risk of atrial fibrillation (AF), most were cross-sectional and generally relied on diagnostic coding to identify cannabis users, which may not be representative of the typical recreational cannabis user. OBJECTIVE: The purpose of this study was to examine the association between recreational cannabis use and lifetime AF risk. METHODS: We evaluated the AF risk of participants of the UK Biobank cohort who completed the cannabis use lifestyle questionnaire. Cannabis exposure was categorized as "Occasional Use" for less than 100 times used, "Frequent Use" for more than 100 times used, and "Never" users. AF events were identified using International Classification of Diseases codes. Cox models were used to estimate the hazard ratios (HRs) between cannabis use and incident AF and were subsequently adjusted for age, sex, race, alcohol, coffee, smoking, education, and baseline cardiovascular comorbidities. RESULTS: A total of 150,554 participants (mean age 63.4 ± 7.7 years; 86,487 (57.4%) female; and 33,442 (22.2%) using cannabis at least once) were followed for a mean period of 6.1 ± 0.6 years. After multivariable adjustment, there were no statistically significant differences in incident AF among occasional users (HR 0.98; 95% confidence interval 0.89-1.08) nor frequent users (HR 1.03; 95% confidence interval 0.81-1.32) as compared with never users. CONCLUSION: In a large prospective cohort study, there was no evidence that cannabis use was associated with a higher risk of incident AF. An evaluation of cannabis ingestion methods and quantification was not possible using the current data set.

Left ventricular fibrosis in arrhythmic mitral valve prolapse: quantification and comparison of semi-automated techniques assessed by cardiac magnetic resonance.

PURPOSE: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols. METHODS: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard. RESULTS: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935). CONCLUSION: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient.

Identifying Mitral Valve Prolapse at Risk for Arrhythmias and Fibrosis From Electrocardiograms Using Deep Learning.

BACKGROUND: Mitral valve prolapse (MVP) is a common valvulopathy, with a subset developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) is a marker of arrhythmic risk associated with myocardial fibrosis and increased mortality in MVP. OBJECTIVES: The authors sought to evaluate whether electrocardiogram (ECG)-based machine learning can identify MVP at risk for ComVE, death 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 from the University of California-San Francisco between 2012 and 2020. A separate CNN was trained to detect late gadolinium enhancement (LGE) using 1,369 ECGs from 87 MVP patients with contrast CMR. RESULTS: The prevalence of ComVE was 28% (160/569). The area under the receiver operating characteristic curve (AUC) of the CNN to detect ComVE was 0.80 (95% CI: 0.77-0.83) and remained high after excluding patients with moderate-severe mitral regurgitation [0.80 (95% CI: 0.77-0.83)] or bileaflet MVP [0.81 (95% CI: 0.76-0.85)]. AUC to detect all-cause mortality was 0.82 (95% CI: 0.77-0.87). ECG segments relevant to ComVE prediction were related to ventricular depolarization/repolarization (early-mid ST-segment and QRS from V1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 24% patients with available CMR; AUC for detection of LGE was 0.75 (95% CI: 0.68-0.82). CONCLUSIONS: CNN-analyzed 12-lead ECGs can detect MVP at risk for ventricular arrhythmias, death and/or fibrosis and can identify novel ECG correlates of arrhythmic risk. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.

Stroke in mitral valve prolapse: risk factors and left atrial function in cryptogenic versus non-cryptogenic ischemic subtypes.

Background and purpose: Mitral valve prolapse (MVP) has been associated with an increased risk of ischemic stroke. Older age, thicker mitral leaflets, and significant mitral regurgitation (MR) leading to atrial fibrillation have been traditionally considered risk factors for ischemic stroke in MVP. However, specific risk factors for MVP-stroke subtypes are not well defined. The aim of this study is to evaluate clinical and echocardiographic parameters, including left atrial (LA) function, in MVP with cryptogenic (C) vs. non-cryptogenic (NC) stroke. Methods: In this case-control matched study, MVPs were identified in consecutive echocardiograms obtained after a stroke from January 2013 to December2016 at the University of California, San Francisco. MVP was defined as leaflet displacement ≥2 mm in the parasternal long-axis view at end-systole. Age/gender matched MVPs without stroke and healthy controls without MVP were also identified. We analyzed LA end-systolic/diastolic volume index, emptying fraction (LAEF), function index (LAFI), and global longitudinal strain in all MVPs and controls. We also measured left ventricular (LV) volume indexes, mass index, ejection fraction (EF), degree of MR and leaflet thickness. Results: We identified a total of 30 MVPs (age 70 ± 12, 50% females) with stroke (11 with C- and 19 with NC-stroke), 20 age/gender matched MVPs without a stroke and 16 controls. MVPs without stroke had lower BMI, less hypertension but more MR (≥moderate in 45% vs. 17%), more abnormal LA function (lower LAEF, LAFI) and larger LV volumes/mass (all p < 0.05) when compared to MVPs with stroke. Leaflet thickness was overall mild (<3 mm) and similar in the 2 groups. Within the MVP stroke group, NC-stroke had higher BMI, more hypertension and more atrial fibrillation compared to C-stroke. In the variables tested, patients with C-stroke did not differ from controls. Conclusions: MVP-related MR may be protective against stroke despite abnormal LA function. Risk of NC-stroke in MVP is related to common stroke risk factors rather than mitral valve leaflet thickness. The etiology of C-stroke in MVP warrants further studies.

Mechanical Dispersion Discriminates between Arrhythmic and Non-Arrhythmic Sudden Death: From the POST SCD Study.

Background: Global longitudinal strain (GLS) and mechanical dispersion (MD) by speckle-tracking echocardiography can predict sudden cardiac death (SCD) beyond left ventricular ejection fraction (LVEF) alone. However, prior studies have presumed cardiac cause from EMS records or death certificates rather than gold-standard autopsies. Objectives: We sought to investigate whether abnormal GLS and MD, reflective of underlying myocardial fibrosis, are associated with autopsy-defined sudden arrhythmic death (SAD) in a comprehensive postmortem study. Methods: We identified and autopsied all World Health Organization-defined (presumed) SCDs ages 18-90 via active surveillance of out of hospital deaths in the ongoing San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study to refine presumed SCDs to true cardiac causes. We retrieved all available pre-mortem echocardiograms and assessed LVEF, LV-GLS, and MD. The extent of LV myocardial fibrosis was assessed and quantified histologically. Results: Of 652 autopsied subjects, 65 (10%) had echocardiograms available for primary review, obtained at a mean 1.5 years before SCD. Of these, 37 (56%) were SADs and 29 (44%) were non-SADs; fibrosis was quantified in 38 (58%). SADs were predominantly male, but had similar age, race, baseline comorbidities, and LVEF compared to non-SADs (all p>0.05). SADs had significantly reduced LV-GLS (median: -11.4% versus -18.5%, p=0.008) and increased MD (median: 14.8 ms versus 9.4 ms, p=0.006) compared to non-SADs. MD was associated with total LV fibrosis by linear regression in SADs (r=0.58, p=0.002). Conclusion: In this countywide postmortem study of all sudden deaths, autopsy-confirmed arrhythmic deaths had significantly lower LV-GLS and increased MD than non-arrhythmic sudden deaths. Increased MD correlated with higher histologic levels of LV fibrosis in SADs. These findings suggest that increased MD, which is a surrogate for the extent of myocardial fibrosis, may improve risk stratification and specification for SAD beyond LVEF. PERSPECTIVES: Competency in medical knowledge: Mechanical dispersion derived from speckle tracking echocardiography provides better discrimination between autopsy-defined arrhythmic vs non-arrhythmic sudden death than LVEF or LV-GLS. Histological ventricular fibrosis correlates with increased mechanical dispersion in SAD.Translational outlook: Speckle tracking echocardiography parameters, in particular mechanical dispersion, may be considered as a non-invasive surrogate marker for myocardial fibrosis and risk stratification in SCD.

Abnormal Mechanics Relate to Myocardial Fibrosis and Ventricular Arrhythmias in Patients With Mitral Valve Prolapse.

BACKGROUND: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia. METHODS: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation). RESULTS: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis (P<0.001). An abnormal strain pattern with distinct peaks pre-end-systole and post-end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, P<0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis. CONCLUSIONS: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.

Research Opportunities in the Treatment of Mitral Valve Prolapse: JACC Expert Panel.

In light of the adverse prognosis related to severe mitral regurgitation, heart failure, or sudden cardiac death in a subset of patients with mitral valve prolapse (MVP), identifying those at higher risk is key. For the first time in decades, researchers have the means to rapidly advance discovery in the field of MVP thanks to state-of-the-art imaging techniques, novel omics methodologies, and the potential for large-scale collaborations using web-based platforms. The National Heart, Lung, and Blood Institute recently initiated a webinar-based workshop to identify contemporary research opportunities in the treatment of MVP. This report summarizes 3 specific areas in the treatment of MVP that were the focus of the workshop: 1) improving management of degenerative mitral regurgitation and associated left ventricular systolic dysfunction; 2) preventing sudden cardiac death in MVP; and 3) understanding the mechanisms and progression of MVP through genetic studies and small and large animal models, with the potential of developing medical therapies.

Valvular disease burden in the modern era of percutaneous and surgical interventions: the UK Biobank.

BACKGROUND: The burden of valvular heart disease (VHD) has increased significantly among ageing populations, yet remains poorly understood in the present-day context of percutaneous and surgical interventions. OBJECTIVE: To define the incidence, clinical correlates and associated mortality of VHD in the UK Biobank cohort. METHODS: We interrogated data collected in the UK Biobank between 1 January 2000 and 30 June 2020. VHD incidence was determined using International Classification of Disease-10 codes for aortic stenosis (AS), aortic regurgitation (AR), mitral stenosis, mitral regurgitation (MR) and mitral valve prolapse. We calculated HRs for incident VHD and all-cause mortality. Clinical correlates of VHD included demographics, coronary artery disease, heart failure and atrial fibrillation. Surgical and percutaneous interventions for mitral and aortic VHD were considered time-dependent variables. RESULTS: Among 486 187 participants, the incidence of any VHD was 16 per 10 000 person-years, with highest rates for MR (8.2), AS (7.2) and AR (5.0). Age, heart failure, coronary artery disease and atrial fibrillation were significantly associated with all types of VHD. In our adjusted model, aortic and mitral VHD had an increased risk of all-cause death compared with no VHD (HR 1.62, 95% CI 1.44 to 1.82, p<0.001 and HR 1.25, 95% CI 1.09 to 1.44, p=0.002 for aortic and mitral VHD, respectively). CONCLUSION: VHD continues to constitute a significant public health burden, with MR and AS being the most common. Age and cardiac comorbidities remain strong risk factors for VHD. In the modern era of percutaneous and surgical interventions, mortality associated with VHD remains high.

Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-ß signalling molecules and spectrin ß. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.

Sex Differences and Similarities in Valvular Heart Disease.

As populations age worldwide, the burden of valvular heart disease has grown exponentially, and so has the proportion of affected women. Although rheumatic valve disease is declining in high-income countries, degenerative age-related causes are rising. Calcific aortic stenosis and degenerative mitral regurgitation affect a significant proportion of elderly women, particularly those with comorbidities. Women with valvular heart disease have been underrepresented in many of the landmark studies which form the basis for guideline recommendations. As a consequence, surgical referrals in women have often been delayed, with worse postoperative outcomes compared with men. As described in this review, a more recent effort to include women in research studies and clinical trials has increased our knowledge about sex-based differences in epidemiology, pathophysiology, diagnostic criteria, treatment options, outcomes, and prognosis.

Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions.

Importance: The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated. Objective: To assess the association between consumption of common caffeinated products and the risk of arrhythmias. Design, Setting, and Participants: This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses. Exposures: Daily coffee intake and genetic polymorphisms that affect caffeine metabolism. Main Outcomes and Measures: Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes. Results: A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism-related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia. Conclusions and Relevance: In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.

Antemortem and Post-Mortem Characteristics of Lethal Mitral Valve Prolapse Among All Countywide Sudden Deaths.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Long-term outcomes of ablation for ventricular arrhythmias in mitral valve prolapse.

PURPOSE: Prior studies reporting efficacy of radiofrequency catheter ablation for complex ventricular ectopy in mitral valve prolapse (MVP) are limited by selective inclusion of bileaflet MVP, papillary muscle only ablation, or short-term follow-up. We sought to evaluate the long-term incidence of hemodynamically significant ventricular tachycardia (VT) or fibrillation (VF) in patients with MVP after initial ablation. METHODS: We studied consecutive patients with MVP undergoing ablation for complex ventricular ectopy between 2013 and 2017 at our institution. Of 580 patients with MVP, we included 15 (2.6%, 10 women; mean age 50 ± 14 years, 53% bileaflet) with complex ventricular ectopy treated with initial ablation. RESULTS: Over a median follow-up of 3406 (1875-6551) days or 9 years, 5 of 15 (33%) patients developed hemodynamically significant VT/VF after their initial ablation and underwent placement of an implantable cardioverter defibrillator (ICD). Three of 5 also underwent repeat ablations. Sustained VT was inducible prior to index ablation in all 5 who developed VT/VF, compared to none of the 10 patients who did not develop VT/VF after index ablation (p = 0.002). Complex ventricular ectopy at index ablation was multifocal in all 5 patients who underwent repeat intervention versus 4 of 10 patients (40%) who did not (p = 0.04). All 3 patients with subsequent VT/VF who underwent repeat ablation had a new clinically dominant focus of ventricular arrhythmia and 3 of the patients with ICD had appropriate VT/VF therapies. CONCLUSIONS: In the long term, a subset of MVP patients treated with ablation for ventricular arrhythmias, all with multifocal ectopy on initial EP study, develop hemodynamically significant VT/VF. Our findings suggest the progressive nature of ventricular arrhythmias in patients with MVP and multifocal ectopy.

Characteristics and Significance of Tricuspid Valve Prolapse in a Large Multidecade Echocardiographic Study.

BACKGROUND: Characteristics of tricuspid valve prolapse (TVP) on transthoracic echocardiography are not well defined. As tricuspid valve interventions are increasingly considered, information on the definition and clinical significance of TVP is needed. METHODS: At the authors' institution, between January 26, 2000, and September 20, 2018, 410 patients (0.3%) were determined to have suspected TVP. These transthoracic echocardiograms and those of 97 age- and sex-matched normal control subjects were reviewed. Interrater agreement on TVP by visual inspection was assessed in a blinded subset. Leaflet atrial displacement (AD) > 2 SDs above the mean in normal control subjects was used to identify an empiric definition of TVP Features of patients meeting this definition were evaluated. RESULTS: Three hundred twelve transthoracic echocardiograms with available and interpretable images (76.1%) were included. Interrater agreement on TVP diagnosis by visual inspection was moderate. Normal values of AD were up to 4 mm in the right ventricular inflow view and 2 mm in all other views. AD > 2 mm in the parasternal short-axis view had the best accuracy against suspected TVP to identify TVP. Those with TVP by this definition more frequently had 3 to 4+ tricuspid regurgitation (22.2% vs 3.1%; P < .001), mitral valve prolapse (MVP; 75.0% vs 3.1%; P < .001), and more clinically significant MVP (greater prevalence of 3 to 4+ mitral regurgitation). No difference in mortality was observed in those with isolated TVP versus TVP and MVP (log-rank P = .93). CONCLUSIONS: In the largest study of TVP to date, interrater agreement on TVP diagnosis by visual inspection was moderate. A cutoff of >2-mm AD in the parasternal short-axis view was optimal to define TVP. Those with TVP by this definition had more significant tricuspid regurgitation, larger right ventricles, and more clinically significant MVP. Overall, these results suggest an increased role for surveillance for TVP and the need for clear diagnostic criteria in updated guidelines.