Eivind Westrum Aabel

Background: The diagnostic role of signal‐averaged ECG (SAECG) in arrhythmogenic right ventricular cardiomyopathy (ARVC) has lately been questioned. We assessed the value of SAECG‐derived late ventricular potentials (LP) in ARVC diagnosis and its association with disease manifestations. Methods and Results: Patients with definite ARVC diagnosis or genotype‐positive family members who underwent SAECG were included in register‐based observational study (n=357, mean age 41 years, 47% female, 43% probands). LP and terminal activation duration (TAD) were defined by Task Force Criteria 2010. We assessed the association of TAD and LP with structural RV abnormalities and ventricular tachycardia (VT), defined as sustained VT, appropriate implantable cardioverter‐defibrillator shock, aborted cardiac arrest, or sudden cardiac death, at diagnosis. LP were documented in 210 patients (59%) and abnormal TAD in 66 patients (18%). Each of the SAECG parameters was significantly associated with definite ARVC diagnosis in receiver‐operator characteristics curve analysis with area under the curve between 0.67 and 0.74. Exclusion of SAECG from diagnostic workup led to reclassification of 37 patients (16%) from definite to borderline ARVC (13 probands, 9 of whom had prevalent VT). Ninety patients (25%) had history of VT. LP, but not TAD, were associated with VT (adjusted odds ratio [OR _adj ], 2.42 [95%CI, 1.07–5.48]). LP had lower specificity (72% versus 97%) but higher sensitivity (71% versus 25%) for association with RV structural abnormalities than TAD. Conclusions: In the Nordic ARVC cohort SAECG‐derived LP are associated with VT and structural RV abnormalities and were critical for ascertainment of ARVC diagnosis in 16% of patients with narrow QRS complexes, including 8% of all probands.

BACKGROUND: Patients with arrhythmogenic mitral valve prolapse syndrome are at increased risk for life-threatening ventricular arrhythmias, but studies have been limited by small sample sizes. We sought to assemble an international arrhythmogenic mitral valve prolapse syndrome registry to delineate the clinical, imaging, and treatment characteristics of patients with arrhythmogenic mitral valve prolapse syndrome who survived sudden cardiac arrest (SCA) or had sustained ventricular tachycardia (VT) or ventricular fibrillation. METHODS: In this descriptive registry, we characterized patients with arrhythmogenic mitral valve prolapse syndrome who survived SCA, sustained VT, or ventricular fibrillation. Deidentified data were abstracted locally and combined centrally. RESULTS: We included 148 patients who had SCA or VT/ventricular fibrillation. Patients had a mean age of 43.7±15.4 years; 68% were women, 73% had bileaflet prolapse, 65% had mitral annular disjunction, 67% had nonsustained VT, and 59% had inferolateral T-wave inversions. Syncope (n=54, 48%) and anterolateral T-wave inversion (n=26, 22%) were relatively common. Catheter ablation was performed in 50 (35%) patients for premature ventricular complexes and in 18 (17.7%) patients for VT. Sites of origin for arrhythmias were commonly in the papillary muscles, fascicles, mitral annulus, and inferior/inferolateral left ventricle. CONCLUSIONS: In this international descriptive registry of patients with arrhythmogenic mitral valve prolapse syndrome and SCA, patients were young, women, and had bileaflet mitral valve prolapse, mitral annular disjunction, inferolateral T-wave inversions, and nonsustained VT. A history of syncope and anterolateral T-wave inversions was relatively common in patients who survived SCA or sustained VT/ventricular fibrillation.

Keratoconus is a progressive eye disease that results in thinning of the cornea, leading to visual impairment. Mitral valve prolapse (MVP) is a common disorder affecting around 2–4% of the general population. Previous studies have found an overrepresentation of MVP in individuals with keratoconus, with a prevalence of 38–65%, suggesting a shared underlying mechanism. In this case-control study, patients with keratoconus were enrolled from a quality and research registry. They were examined by a 2D echocardiography to identify if they had MVP, billowing or normal mitral leaflets. Controls were matched from the population-based Trøndelag Health Study. Patients and controls underwent a detailed echocardiographic examination to detect abnormal mitral valves. We included 101 patients (age 33 [IQR 29–40], 75% male) with keratoconus and 101 matched individuals. MVP was found in 2 (2%), while billowing was found in 5 (5%) of keratoconus patients. No significant association was found between keratoconus and the prevalence of MVP or billowing compared to the control group. Moreover, no associations were found between severity of keratoconus with presence of MVP nor with billowing of the mitral valves. We could not confirm the previously reported association between keratoconus and MVP, suggesting that routine screening for MVP in keratoconus patients may not be warranted. However, we cannot rule out the possibility of an association in other gender, age and ethnic groups different than ours.

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.

This editorial refers to ‘Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?’, by L.M. Verheul et al., https://doi.org/10.1093/ehjci/jeae054.

Patients with mitral valve prolapse (MVP) have high risk of life-threatening ventricular arrhythmias (VAs). Data on the impact of exercise on arrhythmic risk in these patients are lacking. We explored whether lifetime exercise dose was associated with severe VA and with established risk factors in patients with MVP. Furthermore, we explored the circumstances at the VA event. In this retrospective cohort study, we included patients with MVP and assessed lifetime exercise dose as metabolic equivalents of task (MET) hours/week. Severe VA was defined as sustained ventricular tachycardia or fibrillation, aborted cardiac arrest, and appropriate shock by a primary preventive implantable cardioverter defibrillator. We included 136 MVP patients (48 years [interquartile range (IQR) 35–59], 61% female), and 17 (13%) had previous severe VA. The lifetime exercise dose did not differ in patients with and without severe VA (17 MET h/week [IQR 9–27] vs. 14 MET h/week [IQR 6–31], P = 0.34). Lifetime exercise dose > 9.6 MET h/week was a borderline significant marker for severe VA (OR 3.38, 95% CI 0.92–12.40, P = 0.07), while not when adjusted for age (OR 2.63, 95% CI 0.66–10.56, P = 0.17). Ventricular arrhythmia events occurred most frequently during wakeful rest (53%), followed by exercise (29%) and sleep (12%). We found no clear association between moderate lifetime exercise dose and severe VA in patients with MVP. We cannot exclude an upper threshold for safe levels of exercise. Further studies are needed to explore exercise and risk of severe VA.

Cardiac disease progression prior to first ventricular arrhythmia (VA) in LMNA genotype–positive patients is not described. We 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. Incidence 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 77 mL/m², and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype. In a primary prevention cohort of 94 LMNA genotype–positive patients without VA at baseline, VA incidence was as high as 20% after 4.6 years follow up. Individual patient disease progression by ECG and echocardiography was a strong predictor of subsequent VA, suggesting additional value to the previously described risk factors in current guidelines for primary preventive ICD implantation. Threshold values of LVEF 280 ms indicated transition to a more arrhythmogenic phenotype. ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; VA, ventricular arrhythmia.

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. 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. 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). 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. We included 80 patients with arrhythmic mitral valve syndrome followed for 3.1 years; 60 were implanted with a loop recorder (ILR) and 20 had prior implantable cardioverter defibrillator (ICD). Severe ventricular arrhythmia occurred in seven patients (12%) in the ILR-group and four (20%) in the ICD-group. Servier Medical Art. LV = left ventricle, MR = mitral regurgitation, MVP = mitral valve prolapse, NSVT = non-sustained ventricular tachycardia, PVC = premature ventricular complex, VT = ventricular tachycardia.

This study aimed to explore the incidence of severe cardiac events in paediatric arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and ARVC penetrance in paediatric relatives. Furthermore, the phenotype in childhood-onset ARVC was described. Consecutive ARVC paediatric patients and genotype positive relatives ≤18 years of age were followed with electrocardiographic, structural, and arrhythmic characteristics according to the 2010 revised Task Force Criteria. Penetrance of ARVC disease was defined as fulfilling definite ARVC criteria and severe cardiac events were defined as cardiac death, heart transplantation (HTx) or severe ventricular arrhythmias. Childhood-onset disease was defined as meeting definite ARVC criteria ≤12 years of age. Among 62 individuals [age 9.8 (5.0–14.0) years, 11 probands], 20 (32%) fulfilled definite ARVC diagnosis, of which 8 (40%) had childhood-onset disease. The incidence of severe cardiac events was 23% (n = 14) by last follow-up and half of them occurred in patients ≤12 years of age. Among the eight patients with childhood-onset disease, five had biventricular involvement needing HTx and three had severe arrhythmic events. Among the 51 relatives, 6% (n = 3) met definite ARVC criteria at time of genetic diagnosis, increasing to 18% (n = 9) at end of follow-up. In a paediatric ARVC cohort, there was a high incidence of severe cardiac events and half of them occurred in children ≤12 years of age. The ARVC penetrance in genotype positive paediatric relatives was 18%. These findings of a high-malignant phenotype in childhood-onset ARVC indicate a need for ARVC family screening at younger age than currently recommended. Highly malignant disease in childhood-onset arrhythmogenic right ventricular cardiomyopathy: study design and summary results. In a paediatric ARVC cohort, childhood-onset ARVC was found in 40% of all patients with a definite diagnosis. There was a 23% cumulative incidence of severecardiac events and half of them occurred in children ≤12 years of age. The ARVC penetrance in genotype positive paediatric relatives was 18%.