Background:Patients with mitral valve prolapse (MVP) are at risk of ventricular arrhythmias (VAs), ranging from premature ventricular complexes (PVCs) to life-threatening VAs. The association between PVC burden and heart rate in patients with MVP is not known. We aimed to identify the association between PVC burden and heart rate in patients with MVP. Methods:In this this cross-sectional ambispective case control study we included MVP patients with available Holter monitorings. We defined PVC profiles as fast-heart-rate-dependent-PVC (F-HR-PVC) in case of positive correlation with heart rate, slow-heart-rate-dependent-PVC (S-HR-PVC) in case of negative correlation, and independent-heart-rate-PVC (I-HR-PVC) when no correlation was found. For comparison, we included a control group of age- and sex-matched patients with idiopathic PVCs. Results:We included 70 patients with MVP (48 years [interquartile range 35-58], 79% female) and 70 age- and sex-matched patients with idiopathic PVCs. A total of 153 Holter monitorings from patients with MVP were analysed and compared to 70 Holter monitorings from patients with idiopathic PVCs. In the MVP group, we found F-HR-PVC in 44 (63%) patients, I-HR-PVC in 24 (34%) and S-HR-PVC in 2 (3%). MVP patients had more frequently F-HR-PVC and less frequently S-HR-PVC than the control group (p < 0.05 for both). MVP patients with F-HR-PVC had higher rate of NSVTs (incidence rate ratio 2.9 [95% confidence interval 1.1-7.8], p = 0.03) compared to I-HR-PVC. Conclusion:Fast-heart-rate-dependent-PVC was the most common PVC profile in MVP patients, and slow-heart-rate-dependent-PVC was rare. These findings suggest a catecholamine-sensitive mechanism acting as trigger for ventricular arrhythmias in MVP patients.

Mitral valve (MV) assessment is key to diagnosing valvular disease and to addressing its serious downstream complications. Cardiac magnetic resonance (CMR) has become an essential diagnostic tool in MV disease, offering detailed views of the valve structure and function, and overcoming the limitations of other imaging modalities. Automated detection of the MV leaflets in CMR could enable rapid and precise assessments that enhance diagnostic accuracy. To address this gap, we introduce DeepValve, the first deep learning (DL) pipeline for MV detection using CMR. Within DeepValve, we tested three valve detection models: a keypoint-regression model (UNET-REG), a segmentation model (UNET-SEG) and a hybrid model based on keypoint detection (DSNT-REG). We also propose metrics for evaluating the quality of MV detection, including Procrustes-based metrics (UNET-REG, DSNT-REG) and customized Dice-based metrics (UNET-SEG). We developed and tested our models on a clinical dataset comprising 120 CMR images from patients with confirmed MV disease (mitral valve prolapse and mitral annular disjunction). Our results show that DSNT-REG delivered the best regression performance, accurately locating landmark locations. UNET-SEG achieved satisfactory Dice and customized Dice scores, also accurately predicting valve location and topology. Overall, our work represents a critical first step towards automated MV assessment using DL in CMR and paving the way for improved clinical assessment in MV disease.

Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are structural abnormalities associated with life-threatening ventricular arrhythmias, known as arrhythmic mitral valve syndrome (AMVS). Clinically, MAD and MVP have been observed to often coincide with left ventricular (LV) remodeling, hypothesized to be linked to arrhythmogenesis. However, the complex geometric variations of the LV in MAD/MVP remain poorly understood, and traditional clinical metrics often do not fully capture nor quantify these. In this study, we use statistical shape modeling to quantify LV geometrical variation in MAD/MVP and investigate its association with arrhythmia. Using cardiac magnetic resonance (CMR) imaging data, we derived three-dimensional (3D) shape features to comprehensively quantify LV morphological variation in a clinical cohort. Our analysis found an LV shape mode significantly associated with arrhythmic events, aligning with the clinically-suggested role for MAD/MVP-induced LV structural remodeling in AMVS-related arrhythmogenesis. These findings suggest that 3D LV geometry shape analysis may provide novel biomarkers for arrhythmic risk, paving the way for improved risk stratification in patients with AMVS.

Abstract Background The SARS-CoV-2 pandemic led to worldwide initiation of vaccination campaigns. The new mRNA vaccines were unexpectedly associated with vaccine-associated myocarditis (VAM). The incidence and severity of VAM has not been validated in a nation-wide and well-defined population. From December 2020 onwards the mRNA vaccines Comirnaty and Spikevax have been in widespread use in Norway. The National Patient Register (NPR) includes all hospital contacts with corresponding diagnostic codes (ICD-10), and all vaccinations are registered in the Norwegian Immunization Register (SYSVAK). Purpose We aimed to identify and validate all cases of suspected COVID-19 VAM in Norway during the national vaccination campaign between 2020-22. Methods We identified all cases of myocarditis acquired within 90 days of a COVID-19 vaccination through linkage of diagnostic codes for myocarditis in NPR and vaccination data in SYSVAK. Cases were included from December 2020 through April 2022. We assessed medical records, cardiac imaging, and biochemistry to retrospectively validate all myocarditis cases. The Brighton Criteria (international criteria for myocarditis diagnosis following immunization with defining levels of diagnostic certainty) were used to confirm the VAM diagnosis. Results From December 2020 to April 2022, 4 114 750 unique subjects (2 036 792 men and 2 077 958 women, median age first dose 47 years) above 16 years of age, received 10 915 098 unique doses of COVID-19 vaccines (8 651 703[79%] Comirnaty and 2 263 395[21%] Spikevax). Of 277 cases of myocarditis identified in NPR<90 days after receiving a COVID-19 vaccine, 176(64%) were validated as VAM (78 definite, 90 probable, and 8 possible VAM). Among the patients with VAM, 137(78%) were men with median age 30(IQR 24-47) years, and 39(22%) were women with median age 54(IQR 32-65) years. There were 4 cases of VAM per 100 000 vaccinated subjects: 7 per 100 000 men and 2 per 100 000 women. Sixty-three percent of VAM occurred after the second mRNA vaccine dose. There were 3.3 cases of VAM per 100 000 unique doses of Spikevax compared to 1.1 per 100 000 unique doses of Comirnaty. The most common time interval from vaccination to VAM was 3 days and occurred in 30 patients (17.3% of VAM, 93% men), and 34% of VAM (90% men) occurred during the first 5 days from vaccination(Figure). Median duration of hospital stay was 4(IQR 3-5) days, with only 7(4%) patients needing intensive care and 1 myocarditis related patient death during hospitalization. Conclusions In this unique nationwide study including all COVID-19 vaccinated subjects in Norway from 2020-22 we found 4 cases of VAM per 100 000 vaccinated subjects. The majority of VAM occurred in young men. Interestingly, women presented later than men with VAM and most frequently at middle to older age. The occurrence of this unexpected serious adverse event underscores the importance of large studies in broad populations in future vaccine programs.

BackgroundThe electrophysiological mechanism connecting mitral valve prolapse (MVP), premature ventricular complexes and life-threatening ventricular arrhythmia is unknown. A common hypothesis is that stretch activated channels (SACs) play a significant role. SACs can trigger depolarizations or shorten repolarization times in response to myocardial stretch. Through these mechanisms, pathological traction of the papillary muscle (PM), as has been observed in patients with MVP, may induce irregular electrical activity and result in reentrant arrhythmia.MethodsBased on a patient with MVP and mitral annulus disjunction, we modeled the effect of excessive PM traction in a detailed medical image-derived ventricular model by activating SACs in the PM insertion region. By systematically varying the onset of SAC activation following sinus pacing, we identified vulnerability windows for reentry with 1 ms resolution. We explored how reentry was affected by the SAC reversal potential (ESAC) and the size of the region with simulated stretch (SAC region). Finally, the effect of global or focal fibrosis, modeled as reduction in tissue conductivity or mesh splitting (fibrotic microstructure), was investigated.ResultsIn models with healthy tissue or fibrosis modeled solely as CV slowing, we observed two vulnerable periods of reentry: For ESAC of −10 and −30 mV, SAC activated during the T-wave could cause depolarization of the SAC region which lead to reentry. For ESAC of −40 and −70 mV, SAC activated during the QRS complex could result in early repolarization of the SAC region and subsequent reentry. In models with fibrotic microstructure in the SAC region, we observed micro-reentries and a larger variability in which times of SAC activation triggered reentry. In these models, 86% of reentries were triggered during the QRS complex or T-wave. We only observed reentry for sufficiently large SAC regions (>= 8 mm radius in models with healthy tissue).ConclusionStretch of the PM insertion region following sinus activation may initiate ventricular reentry in patients with MVP, with or without fibrosis. Depending on the SAC reversal potential and timing of stretch, reentry may be triggered by ectopy due to SAC-induced depolarizations or by early repolarization within the SAC region.

Abstract Background A subset of patients with mitral valve prolapse (MVP) are at risk of life-threatening ventricular arrhythmias (VAs), and a high burden of premature ventricular contractions (PVCs) is associated with increased mortality in patients with MVP. Previous studies indicate that PVC burden could either increase with increasing heart rate (HR), decrease with increasing HR, or with no relationship to HR. The association between PVC burden and HR in MVP is not known, nor if there is an association with VAs. Purpose We aimed to explore the relationship between PVC burden and HR in patients with MVP. Furthermore, we aimed to explore whether the different PVC profiles were associated with severe VA. Methods In this cross-sectional ambispective outcome study, we included patients with MVP and available Holter monitorings with >100 PVCs per 24-hours seen at our tertiary centre. The Holter monitoring with the highest PVC burden was used in case of multiple recordings. We investigated the relationship between hourly PVC burden and hourly mean HR by univariable mixed linear regression. We defined PVC profiles as (1) fast-HR-dependent-PVC (F-HR-PVC) when there was a significant positive correlation, (2) slow-HR-dependent-PVC (S-HR-PVC) when there was a significant negative correlation, and (3) independent-HR-PVC (I-HR-PVC) when no correlation between PVC and HR was found. The significance was set to 0.05. Severe VA was defined as sustained ventricular tachycardia, non-sustained ventricular tachycardia with haemodynamic instability, ventricular fibrillation, aborted cardiac arrest, or appropriate shock by a primary preventive implantable cardioverterefibrillator. Severe VA was recorded from retrospective medical history, prospective ICD interrogation or monitoring with implantable loop recorder. Results We included 75 patients with >100 PVCs at Holter monitoring (median age 48 years [IQR 35-58], 58% female). The median PVC burden was 1.9% per 24-hours (IQR 0.4-7.2). We found F-HR-PVC in 49 patients (65%), S-HR-PVC in 1 (1%), and I-HR-PVC in 25 (33%). Twelve (16%) patients had severe VA and these had higher PVC burden compared to those without severe VA (7.3% per 24-hours [IQR 4.2-10.4] vs 1.1% per 24-hours [IQR 0.3-5.3], p=0.004). The median PVC burden was 1.5% (IQR 0.3-8.0) for F-HR-PVC, 5.7% for S-HR-PVC and 1.5% (IQR 0.3-8.0) for I-HR-PVC. We found no association between different PVC profiles and the presence of severe VA (F-HR-PVC 65% vs 67%, S-HR-PVC 2% vs 0%, I-HR-PVC 33% vs 33%, p>0.05 for all groups). Conclusion Fast-HR-dependent-PVC was most common in MVP patients, and slow-HR-dependent-PVC were rare. A higher PVC burden was associated with severe VA. However, different PVC profiles did not infer higher risk of severe VA in our study. Further studies are needed to explore whether distinct PVC profiles can predict severe VA in larger patient populations.

Aims Arrhythmic mitral valve syndrome is linked to life-threatening ventricular arrhythmias. The incidence, morphology and methods for risk stratification are not well known. This prospective study aimed to describe the incidence and the morphology of ventricular arrhythmia and propose risk stratification in patients with arrhythmic mitral valve syndrome. Methods Arrhythmic mitral valve syndrome patients were monitored for ventricular tachyarrhythmias by implantable loop recorders (ILR) and secondary preventive implantable cardioverter-defibrillators (ICD). Severe ventricular arrhythmias included ventricular fibrillation, appropriate or aborted ICD therapy, sustained ventricular tachycardia and non-sustained ventricular tachycardia with symptoms of hemodynamic instability. Results During 3.1 years of follow-up, severe ventricular arrhythmia was recorded in seven (12%) of 60 patients implanted with ILR [first event incidence rate 4% per person-year, 95% confidence interval (CI) 2-9] and in four (20%) of 20 patients with ICD (re-event incidence rate 8% per person-year, 95% CI 3-21). In the ILR group, severe ventricular arrhythmia was associated with frequent premature ventricular complexes, more non-sustained ventricular tachycardias, greater left ventricular diameter and greater posterolateral mitral annular disjunction distance (all P < 0.02). Conclusions The yearly incidence of ventricular arrhythmia was high in arrhythmic mitral valve syndrome patients without previous severe arrhythmias using continuous heart rhythm monitoring. The incidence was even higher in patients with secondary preventive ICD. Frequent premature ventricular complexes, non-sustained ventricular tachycardias, greater left ventricular diameter and greater posterolateral mitral annular disjunction distance were predictors of first severe arrhythmic event.

AbstractAimsCardiac disease progression prior to first ventricular arrhythmia (VA) in LMNA genotype–positive patients is not described.Methods and resultsWe performed a primary prevention cohort study, including consecutive LMNA genotype–positive patients from our centre. Patients underwent repeated clinical, electrocardiographic, and echocardiographic examinations. Electrocardiographic and echocardiographic disease progression as a predictor of first-time VA was evaluated by generalized estimation equation analyses. Threshold values at transition to an arrhythmic phenotype were assessed by threshold regression analyses. We included 94 LMNA genotype–positive patients without previous VA (age 38 ± 15 years, 32% probands, 53% females). Nineteen (20%) patients experienced VA during 4.6 (interquartile range 2.1–7.3) years follow up, at mean age 50 ± 11 years. We analysed 536 echocardiographic and 261 electrocardiogram examinations. Individual patient disease progression was associated with VA [left ventricular ejection fraction (LVEF) odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2–1.6 per 5% reduction, left ventricular end-diastolic volume index (LVEDVi) OR 1.2 (95% CI 1.1–1.3) per 5 mL/m2 increase, PR interval OR 1.2 (95% CI 1.1–1.4) per 10 ms increase]. Threshold values for transition to an arrhythmic phenotype were LVEF 44%, LVEDVi 77 mL/m2, and PR interval 280 ms.ConclusionsIncidence of first-time VA was 20% during 4.6 years follow up in LMNA genotype–positive patients. Individual patient disease progression by ECG and echocardiography were strong predictors of VA, indicating that disease progression rate may have additional value to absolute measurements when considering primary preventive ICD. Threshold values of LVEF <44%, LVEDVi >77 mL/m2, and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype.

Mitral annular disjunction (MAD) is characterized by an abnormal insertion of the posterior mitral leaflet on the atrial wall. Despite its often subtle presentation, the presence of MAD can be a warning sign of future ventricular tachycardia (VT) and sudden cardiac death (SCD), as recent studies have shown association among MAD-related imaging metrics and VT/SCA. Nevertheless, the precise mechanisms leading to VT/SCD in patients with MAD are poorly understood. A comprehensive 3D shape analysis of the left ventricles (LV) of patients with MAD may provide further insight and help to elucidate mechanisms. Towards this end, we created a patient-specific 3D LV geometry modelling pipeline for patients with MAD, to enable future morphological studies based on cardiac short axis magnetic resonance imaging (MRI). We applied our pipeline to derive personalized 3D LV geometries in a cohort of 69 patients with MAD originating from Oslo University Hospital. To demonstrate the utility of our pipeline, we perform a statistical comparison of the dominant modes of shape variation of our patient cohort with records of prior arrhythmia.

Aims We aimed to study the progression of cardiac dysfunction in patients with lamin A/C mutations and explore markers of adverse cardiac outcome. Methods and results We followed consecutive lamin A/C genotype-positive patients divided into tertiles according to age. Patients underwent repeated clinical examinations, electrocardiograms (ECGs), and echocardiograms. We followed left ventricular (LV) and right ventricular (RV) size and function, and the severity atrioventricular-valve regurgitations. Outcome was death, LVAD implant, or cardiac transplantation. We included 101 patients [age 44 (29-54) years, 39% probands, 50% female]. We analysed 576 echocardiograms and 258 ECGs during a follow-up of 4.9 (interquartile range 2.5-8.2) years. The PR-interval increased at young age from 204 +/- 73 to 212 +/- 69 ms (P < 0.001), LV ejection fraction (LVEF) declined from middle age from 50 +/- 12% to 47 +/- 13% (P < 0.001), while LV volumes remained unchanged. RV function and tricuspid regurgitation worsened from middle age with accelerating rates. Progression of RV dysfunction [odds ratio (OR) 1.3, 95% confidence interval (CI) (1.03-1.65), P = 0.03] and tricuspid regurgitation [OR 4.9, 95% CI (1.64-14.9), P = 0.004] were associated with outcome when adjusted for age, sex, comorbidities, LVEF, and New York Heart Association functional class. Conclusion In patients with lamin A/C genotype, electrical disease started at young age. From middle age, LV function deteriorated progressively, while LV size remained unchanged. Worsening of RV function and tricuspid regurgitation accelerated in older age and were associated with outcome. Our systematic map on cardiac deterioration may help optimal monitoring and prognostication in lamin A/C disease.

Abstract Background Arrhythmic mitral valve syndrome is linked to life-threatening ventricular arrhythmias, but the incidence and methods for risk stratification of ventricular arrhythmias are not well known. Purpose In this prospective study, we aimed to describe the incidence of ventricular arrhythmias by use of continuous rhythm monitoring and propose risk stratification in patients with arrhythmic mitral valve syndrome. Methods We included consecutive patients with arrhythmic mitral valve prolapse, defined as mitral valve prolapse and/or mitral annulus disjunction (MAD) with arrhythmic symptoms or documented complex premature ventricular complexes (PVC). We implanted loop recorders (ILR) in patients with arrhythmic mitral valve syndrome with no previous severe ventricular arrhythmias and all were followed by remote monitoring. We monitored for non-sustained ventricular tachycardias (NSVT) and severe ventricular arrhythmia, defined as aborted cardiac arrest, sustained ventricular tachycardia and NSVT with syncope/presyncope. At baseline, patients underwent echocardiography, 24-hour Holter monitoring, stress ECG and cardiac magnetic resonance imaging. Results We included 60 patients (73% female, 49 years [interquartile range [IQR] 37–60]). At baseline, median PVC burden was 232 per 24-hours (IQR 33–1329), and 8 (13%) patients had NSVT by Holter monitoring or stress ECG. During 3.0±0.5 years of follow-up, severe ventricular arrhythmia occurred in 7 (12%) patients (1 aborted cardiac arrest, 6 NSVT with syncope/pre-syncope). Annual incidence rate of severe events was 4% per person-year (95% confidence interval [CI] 2–9)). Predictors of severe ventricular arrhythmia were frequent PVCs (6683 PVCs per 24h [IQR 612–10861] vs. 154 PVCs per 24h [IQR 25–562], p=0.01), more NSVTs by ILR (4 NSVTs [IQR 2–7] vs. 0 NSVTs [0–1], p<0.001), greater left ventricular diameter (57±6 mm vs. 51±6 mm, p=0.01) and greater posterolateral MAD distance (9 mm [IQR 8–12] vs. 4 mm [IQR 0–6], p=0.02). Adjustment for age and sex did not change significant risk markers (all p<0.02). During follow-up 102 NSVTs were recorded in 24 (40%) patients. In multivariate Poisson regression adjusting for age, mitral regurgitation grade and bileaflet prolapse, predictors of high NSVT burden were frequent PVCs (incidence rate ratio [IRR] 1.14 [95% CI 1.04–1.27], p=0.01), PVCs from inferior left ventricle (IRR 5.19 [95% CI 2.80–9.63], p<0.001) and late gadolinium enhancement (IRR 3.16 [95% CI 1.68–5.97], p<0.001). Conclusion Yearly incidence of first severe ventricular arrhythmia was 4% in patients with arrhythmic mitral valve syndrome, emphasizing the high risk of life-threatening events in these patients. Frequent PVCs, NSVTs, greater left ventricular diameter and greater posterolateral MAD distance were predictors of first severe ventricular arrhythmia and should be used in risk stratification. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by a public grant from the Norwegian Research Council (#288438 and #309762), Precision Health Center for optimized cardiac care (ProCardio).

OBJECTIVES:This study aimed to assess whether patients with MAD also have disjunction of the tricuspid annulus. BACKGROUND:Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus. Whether the disjunction extends to the right side of the heart is not known. METHODS:In a cohort of patients with MAD, we assessed the presence of tricuspid annulus disjunction (TAD) with the use of cardiac magnetic resonance. We explored the associations between TAD and MAD characteristics and the relationship to ventricular arrhythmias (nonsustained/sustained ventricular tachycardias and aborted cardiac arrest). RESULTS:We included 84 patients (mean age: 48 ± 16 years; 63% female). We observed TAD in 42 (50%). Patients with TAD were older (age 52 ± 16 years vs. 43 ± 15 years; p = 0.02), had greater circumferential extent of MAD (164 ± 57° vs. 115 ± 58°; p = 0.002), greater maximum longitudinal MAD distance (9.4 ± 2.9 mm vs. 6.2 ± 2.8 mm; p < 0.001), and more frequent mitral valve prolapse (n = 39 [92%] vs. n = 24 [57%]; p < 0.001). Ventricular arrhythmias had occurred in 34 patients (41%), who were younger (age 39 ± 14 years vs. 54 ± 14 years; p < 0.001) and had lower prevalence of TAD (n = 22 [29%] vs. n = 12 [52%]; p = 0.03). TAD was not associated with ventricular arrhythmias when adjusted for age (odds ratio adjusted for age: 0.54; 95% confidence interval: 0.20 to 1.45; p = 0.22). CONCLUSIONS:We report for the first time the existence of right-sided annulus disjunction as a common finding in patients with MAD. TAD was associated with more severe left-sided annulus disjunction and mitral valve prolapse, but not with ventricular arrhythmias.

Abstract Background Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus, frequently found in patients with high-risk arrhythmogenic mitral valve prolapse syndrome. It is unknown whether the annulus disjunction extends to the right side of the heart as tricuspid annulus disjunction (TAD), and whether it is associated with right ventricular electrical instability. Purpose We aimed to explore the presence of TAD, and if extended annulus disjunction was associated with ventricular arrhythmias. Methods We included patients with previously described MAD assessed by cardiac magnetic resonance imaging (CMR) in an ambispective cohort study. MAD and TAD was defined as ≥1 mm separation between the respective atrial wall-valve leaflet junction and the top of the ventricular myocardium. TAD was assessed in the lateral and inferior right ventricular free wall by means of the 4-chamber and right ventricular 2-chamber views, respectively. MAD circumference was assessed by a CMR study protocol with six left ventricular long axis views separated by 30 degrees. Mitral valve prolapse was defined as ≥2 mm superior displacement of any part of the mitral leaflets beyond the mitral annulus. Ventricular arrhythmias were defined as aborted cardiac arrest or non-sustained/sustained ventricular tachycardias recorded by electrocardiogram (ECG), stress ECG or Holter monitoring. Results We included 92 patients with MAD (62% female, age 47±16 years, 71% mitral valve prolapse). TAD was found in 48 (52%) patients, both in the lateral (n=40, 83%) and inferior (n=30, 63%) right ventricular free wall. Patients with TAD were older (age 51±16 years vs. 43±14 years, p=0.01), had greater MAD circumference (168±56° vs. 117±62°, p=0.001) and greater MAD distance (9.2±2.9 mm vs. 6.4±2.8 mm, p<0.001). Additionally, patients with TAD had more frequently mitral valve prolapse (40 patients [85%] vs. 25 patients [57%], p=0.003), whereas similar frequency of bileaflet prolapse (17 patients [39%] vs. 10 patients [39%], p=0.99). Ventricular arrhythmias had occurred in 38 (41%) patients, who were younger (age 40±14 years vs. 52±15 years, p<0.001) and had less frequently TAD (14 patients [37%] vs. 34 patients [63%], p=0.01; univariate odds ratio 0.34 [0.15–0.81], p=0.02). However, TAD was not associated with ventricular arrhythmias when adjusted for age (multivariate odds ratio 0.46 [0.18–1.15], p=0.10). Conclusions TAD by CMR was highly prevalent in patients with MAD and was a marker of severe annulus disjunction and mitral valve prolapse. TAD was not associated with more ventricular arrhythmias. This novel marker warrants further research to explore the clinical implications of right-sided annulus disjunction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian Research Council

Background Arrhythmogenic cardiomyopathy (AC) is characterized by biventricular dysfunction, exercise intolerance, and high risk of ventricular tachyarrhythmias and sudden death. Predisposing factors for left ventricular (LV) disease manifestation and its prognostic implication in AC are poorly described. We aimed to assess the associations of exercise exposure and genotype with LV dysfunction in AC, and to explore the impact of LV disease progression on adverse arrhythmic outcome. Methods and Results We included 168 patients with AC (50% probands, 45% women, 40±16 years old) with 715 echocardiographic exams (4.1±1.7 exams/patient, follow‐up 7.6 [interquartile range (IQR), 5.4–10.9] years) and complete exercise and genetic data in a longitudinal study. LV function by global longitudinal strain was −18.8% [IQR, −19.2% to −18.3%] at presentation and was worse in patients with greater exercise exposure (global longitudinal strain worsening, 0.09% [IQR, 0.01%–0.17%] per 5 MET‐hours/week, P=0.02). LV function by global longitudinal strain worsened, with 0.08% [IQR, 0.05%–0.12%] per year; (P<0.001), and progression was most evident in patients with desmoplakin genotype (P for interaction <0.001). Deterioration of LV function predicted incident ventricular tachyarrhythmia (aborted cardiac arrest, sustained ventricular tachycardia, or implantable cardioverter defibrillator shock) (adjusted odds ratio, 1.1 [IQR, 1.0–1.3] per 1% worsening by global longitudinal strain; P=0.02, adjusted for time and previous arrhythmic events). Conclusions Greater exercise exposure was associated with worse LV function at first visit of patients with AC but did not significantly affect the rate of LV progression during follow‐up. Progression of LV dysfunction was most pronounced in patients with desmoplakin genotypes. Deterioration of LV function during follow‐up predicted subsequent ventricular tachyarrhythmia and should be considered in risk stratification.

Objective Displacement of the mitral valve, mitral annulus disjunction (MAD), is described as a possible aetiology of sudden cardiac death. Stress-induced fibrosis in the mitral valve apparatus has been suggested as the underlying mechanism. We aimed to explore the association between stretch-related and fibrosis-related biomarkers and ventricular arrhythmias in MAD. We hypothesised that soluble suppression of tumourigenicity-2 (sST2) and transforming growth factor-β1 (TGFβ1) are markers of ventricular arrhythmias in patients with MAD.Methods We included patients with ≥1 mm MAD on cardiac MRI. We assessed left ventricular ejection fraction (LVEF) and fibrosis by late gadolinium enhancement (LGE). The occurrence of ventricular arrhythmia, defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia, was retrospectively assessed. We assessed circulating sST2 and TGFβ1 levels.Results We included 72 patients with MAD, of which 22 (31%) had ventricular arrhythmias. Patients with ventricular arrhythmias had lower LVEF (60 % (±6) vs 63% (±6), p = 0.04), more frequently papillary muscle fibrosis (14 (64%) vs 10 (20%), p < 0.001) and higher sST2 levels (31.6 ± 10.1 ng/mL vs 25.3 ± 9.2 ng/mL, p = 0.01) compared with those without, while TGFβ1 levels did not differ (p = 0.29). Combining sST2 level, LVEF and papillary muscle fibrosis optimally detected individuals with arrhythmia (area under the curve 0.82, 95% CI 0.73 to 0.92) and improved the risk model (p < 0.05) compared with single parameters.Conclusion Circulating sST2 levels were higher in patients with MAD and ventricular arrhythmias compared with arrhythmia-free patients. Combining sST2, LVEF and LGE assessment improved risk stratification in patients with MAD.

Abstract Background Mitral annulus disjunction (MAD), a basal displacement of the mitral valve annulus, is described as a possible aetiology of sudden cardiac death. Stretch-induced fibrosis in the sub-valvular apparatus has been suggested as the substrate of arrhythmias. Purpose We hypothesized that the stretch related biomarker soluble Suppression of Tumorigenicity-2 (sST2) is a marker of ventricular arrhythmias in patients with MAD. Methods We included patients with ≥1 mm MAD on cardiac magnetic resonance imaging, and recorded left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) suggesting papillary muscle fibrosis. Circulating levels of sST2 were assessed by blood sampling. The occurrence of ventricular arrhythmias, defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia, was assessed retrospectively. Results We included 72 patients with MAD [55 (35–62) years old, 48 (67%) female], of which 22 (31%) had ventricular arrhythmias. Patients with ventricular arrhythmias had lower LVEF (60±6% vs. 63±6%, p=0.04), more prevalent papillary muscle fibrosis [14 (64%) vs. 10 (20%), p<0.001] and higher sST2 levels [31.6±10.1 ng/mL vs. 25.3±9.2 ng/mL, p=0.01] compared to those without. Combining sST2-level, LVEF and papillary muscle fibrosis optimally detected individuals with arrhythmias (area under the curve 0.82, 95% CI 0.73–0.92) and improved the risk model (p<0.05) compared to individual parameters (Figure right panel). Conclusion Circulating sST2 levels were higher in patients with MAD and ventricular arrhythmias compared to patients without arrhythmias. Combining sST2, LVEF and LGE may improve risk stratification in patients with MAD. Acknowledgement/Funding This work was supported by public grant [203489/030] from the Norwegian Research Council, Oslo, Norway. E. Scheirlynck received an ESC research grant

BACKGROUND Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral valve leaflet hinge point. MAD has been associated with mitral valve prolapse (MVP) and sudden cardiac death. OBJECTIVES The purpose of this study was to describe the clinical presentation, MAD morphology, association with MVP, and ventricular arrhythmias in patients with MAD. METHODS The authors clinically examined patients with MAD. By echocardiography, the authors assessed the presence of MVP and measured MAD distance in parasternal long axis. Using cardiac magnetic resonance (CMR), the authors assessed circumferential MAD in the annular plane, longitudinal MAD distance, and myocardial fibrosis. Aborted cardiac arrest and sustained ventricular tachycardia were defined as severe arrhythmic events. RESULTS The authors included 116 patients with MAD (age 49 perpendicular to 15 years; 60% female). Palpitations were the most common symptom (71%). Severe arrhythmic events occurred in 14 (12%) patients. Longitudinal MAD distance measured by CMR was 3.0 mm (interquartile range [IQR]: 0 to 7.0 mm) and circumferential MAD was 150 degrees (IQR: 90 degrees to 210 degrees). Patients with severe arrhythmic events were younger (age 37 +/- 13 years vs. 51 +/- 14 years; p = 0.001), had lower ejection fraction (51 +/- 5% vs. 57 +/- 7%; p = 0.002) and had more frequently papillary muscle fibrosis (4 [36%] vs. 6 [9%]; p = 0.03). MVP was evident in 90 (78%) patients and was not associated with ventricular arrhythmia. CONCLUSIONS Ventricular arrhythmias were frequent in patients with MAD. A total of 26 (22%) patients with MAD did not have MVP, and MVP was not associated with arrhythmic events, indicating MAD itself as an arrhythmogenic entity. MAD was detected around a large part of the mitral annulus circumference and was interspersed with normal tissue. (J Am Coll Cardiol 2018; 72: 1600-9) (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: We aimed to investigate if history of vigorous exercise was associated with changes in left ventricular morphology, left ventricular function and ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy genotype positive, phenotype negative (Genotype+LVH-) and in phenotype positive (HCM LVH+). Methods: In this cross sectional study we included 187 subjects (age 49 +/- 16 years, 89(48%) female, 121(65%) HCMLVH+ and 66 (35%) Genotype+LVH-) who answered a questionnaire on physical activity history. Exercise >= 6 metabolic equivalents was defined as vigorous. Subjects with a history of vigorous exercise = >= 4 h/week during >= 6 years were defined as athletes. All underwent echocardiography and Holter monitoring. VAs were defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia. Results: In both Genotype+LVH- and HCM LVH+, lifetime vigorous exercise correlated with larger left ventricular end-diastolic volume (rho 0.44 and 0.38 respectively, both p < 0.001). Lifetime vigorous exercise correlated with increased left ventricular mass in Genotype+LVH-(rho 0.28, p = 0.03), but not in HCM LVH+ (p=0.53). Left ventricular systolic function was similar between athletes and non-athletes in Genotype+LVH- and HCM LVH+. HCMLVH+ athletes had lower E/e' (p=0.03) and higher e' (p=0.02) compared to non-athletes, while this difference was not observed in Genotype+LVH-. Lifetime vigorous exercise was similar among HCM LVH+ with and without VAs (p=0.89). Conclusions: Increased lifetime vigorous exercise was associated with larger left ventricular volumes in hypertrophic cardiomyopathy, but correlated to left ventricular mass only in Genotype+LVH-. Vigorous exercise was associated with favorable diastolic function in HCM LVH+, and was not associated with VAs. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.