RESUMEN
BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Desfibriladores Implantables , Humanos , Desfibriladores Implantables/efectos adversos , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/epidemiología , Displasia Ventricular Derecha Arritmogénica/terapia , Estudios Retrospectivos , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/terapia , Arritmias Cardíacas/etiología , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología , Factores de Riesgo , América del Norte/epidemiología , Europa (Continente)/epidemiologíaRESUMEN
BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.
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Displasia Ventricular Derecha Arritmogénica , Prevención Primaria , Femenino , Humanos , Masculino , Arritmias Cardíacas/epidemiología , Displasia Ventricular Derecha Arritmogénica/epidemiología , Displasia Ventricular Derecha Arritmogénica/prevención & control , Muerte Súbita Cardíaca/epidemiología , Desfibriladores Implantables , Prevención Primaria/métodos , Medición de Riesgo/métodos , Factores de Riesgo , Volumen Sistólico , Taquicardia Ventricular/epidemiología , Función Ventricular Derecha , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly caused by desmosomal genetic variants, and clinical hallmarks include arrhythmias and systolic dysfunction. We aimed at studying the impact of the implicated gene(s) on the disease course. METHODS: The Nordic ARVC Registry holds data on a multinational cohort of ARVC families. The effects of genotype on electrocardiographic features, imaging findings and clinical events were analysed. RESULTS: We evaluated 419 patients (55% men), with a mean follow-up of 11.2±7.4 years. A pathogenic desmosomal variant was identified in 62% of the 230 families: PKP2 in 41%, DSG2 in 13%, DSP in 7% and DSC2 in 3%. Reduced left ventricular ejection fraction (LVEF) ≤45% on cardiac MRI was more frequent among patients with DSC2/DSG2/DSP than PKP2 ARVC (27% vs 4%, p<0.01). In contrast, in Cox regression modelling of patients with definite ARVC, we found a higher risk of arrhythmias among PKP2 than DSC2/DSG2/DSP carriers: HR 0.25 (0.10-0.68, p<0.01) for atrial fibrillation/flutter, HR 0.67 (0.44-1.0, p=0.06) for ventricular arrhythmias and HR 0.63 (0.42-0.95, p<0.05) for any arrhythmia. Gene-negative patients had an intermediate risk (16%) of LVEF ≤45% and a risk of the combined arrhythmic endpoint comparable with DSC2/DSG2/DSP carriers. Male sex was a risk factor for both arrhythmias and reduced LVEF across all genotype groups (p<0.01). CONCLUSION: In this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.
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Displasia Ventricular Derecha Arritmogénica , Insuficiencia Cardíaca , Arritmias Cardíacas/genética , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/genética , Desmosomas , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Placofilinas/genética , Volumen Sistólico/genética , Función Ventricular IzquierdaRESUMEN
AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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Displasia Ventricular Derecha Arritmogénica , Desfibriladores Implantables , Taquicardia Ventricular , Arritmias Cardíacas/etiología , Arritmias Cardíacas/terapia , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/terapia , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Femenino , Humanos , Lactante , Masculino , Factores de Riesgo , Taquicardia Ventricular/etiología , Taquicardia Ventricular/terapiaRESUMEN
AIMS: Treatment with implantable cardioverter-defibrillators (ICD) is a cornerstone for prevention of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at describing the complications associated with ICD treatment in a multinational cohort with long-term follow-up. METHODS AND RESULTS: The Nordic ARVC registry was established in 2010 and encompasses a large multinational cohort of ARVC patients, including their clinical characteristics, treatment, and events during follow-up. We included 299 patients (66% males, median age 41 years). During a median follow-up of 10.6 years, 124 (41%) patients experienced appropriate ICD shock therapy, 28 (9%) experienced inappropriate shocks, 82 (27%) had a complication requiring surgery (mainly lead-related, n = 75), and 99 (33%) patients experienced the combined endpoint of either an inappropriate shock or a surgical complication. The crude rate of first inappropriate shock was 3.4% during the first year after implantation but decreased after the first year and plateaued over time. Contrary, the risk of a complication requiring surgery was 5.5% the first year and remained high throughout the study period. The combined risk of any complication was 7.9% the first year. In multivariate cox regression, presence of atrial fibrillation/flutter was a risk factor for inappropriate shock (P < 0.05), whereas sex, age at implant, and device type were not (all P > 0.05). CONCLUSION: Forty-one percent of ARVC patients treated with ICD experienced potentially life-saving ICD therapy during long-term follow-up. A third of the patients experienced a complication during follow-up with lead-related complications constituting the vast majority.
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Displasia Ventricular Derecha Arritmogénica , Desfibriladores Implantables , Adulto , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/terapia , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables/efectos adversos , Cardioversión Eléctrica/efectos adversos , Femenino , Humanos , Masculino , Sistema de Registros , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIMS: Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) have increased prevalence of atrial arrhythmias indicating atrial involvement in the disease. We aimed to assess the long-term evolution of P-wave indices as electrocardiographic (ECG) markers of atrial substrate during ARVC progression. METHODS AND RESULTS: We included 100 patients with a definite ARVC diagnosis according to 2010 Task Force criteria [34% females, median age 41 (inter-quartile range 30-55) years]. All available sinus rhythm ECGs (n = 1504) were extracted from the regional electronic ECG databases and automatically processed using Glasgow algorithm. P-wave duration, P-wave area, P-wave frontal axis, and prevalence of abnormal P terminal force in lead V1 (aPTF-V1) were assessed and compared at ARVC diagnosis, 10 years before and up to 15 years after diagnosis.Prior to ARVC diagnosis, none of the P-wave indices differed significantly from the data at ARVC diagnosis. After ascertainment of ARVC diagnosis, P-wave area in lead V1 decreased from -1 to -30 µV ms at 5 years (P = 0.002). P-wave area in lead V2 decreased from 82 µV ms at ARVC diagnosis to 42 µV ms 10 years after ARVC diagnosis (P = 0.006). The prevalence of aPTF-V1 increased from 5% at ARVC diagnosis to 18% by the 15th year of follow-up (P = 0.004). P-wave duration and frontal axis did not change during disease progression. CONCLUSION: Initial ARVC progression was associated with P-wave flattening in right precordial leads and in later disease stages an increased prevalence of aPTF-V1 was seen.
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Displasia Ventricular Derecha Arritmogénica , Adulto , Arritmias Cardíacas , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/epidemiología , Biomarcadores , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2). METHODS: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed. RESULTS: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731). CONCLUSION: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.
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Displasia Ventricular Derecha Arritmogénica , Placofilinas , Adulto , Displasia Ventricular Derecha Arritmogénica/genética , Femenino , Humanos , Masculino , Mutación , Fenotipo , Placofilinas/genéticaRESUMEN
AIMS: Women with arrhythmogenic right ventricular cardiomyopathy (ARVC) are at relatively lower risk of ventricular arrhythmias (VAs) than men, but the physical burden associated with pregnancy on VA risk remains insufficiently studied. We aimed to assess the risk of VA in relation to pregnancies in women with ARVC. METHODS AND RESULTS: We included 199 females with definite ARVC (n = 121) and mutation-positive family members without ascertained ARVC diagnosis (n = 78), of whom 120 had at least one childbirth. Ventricular arrhythmia-free survival after the latest childbirth was compared between women with one (n = 20), two (n = 67), and three or more (n = 37) childbirths. Cumulative probability of VA for each pregnancy (n = 261) was assessed from conception through 2 years after childbirth and compared between those pregnancies that occurred before (n = 191) or after (n = 19) ARVC diagnosis and in mutation-positive family members (n = 51). The nulliparous women had lower median age at ARVC diagnosis (38 vs. 42 years, P < 0.001) and first VA (22 vs. 41 years, P < 0.001). Ventricular arrhythmia-free survival after the latest childbirth was not related to the number of pregnancies. No pregnancy-related VA was reported among the family members. Women who gave birth after ARVC diagnosis had elevated risk of VA postpartum (hazard ratio 13.74, 95% confidence interval 2.9-63, P = 0.001), though only two events occurred during pregnancies. CONCLUSION: In women with ARVC, pregnancy was uneventful for the overwhelming majority and the number of prior completed pregnancies was not associated with VA risk. Pregnancy-related VA was primarily related to the phenotypical severity rather than pregnancy itself.
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Displasia Ventricular Derecha Arritmogénica , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiología , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/epidemiología , Displasia Ventricular Derecha Arritmogénica/genética , Femenino , Humanos , Masculino , Mutación , Embarazo , Modelos de Riesgos Proporcionales , Sistema de RegistrosRESUMEN
AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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Arritmias Cardíacas , Displasia Ventricular Derecha Arritmogénica , Modelos Estadísticos , Adulto , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/mortalidad , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/epidemiología , Displasia Ventricular Derecha Arritmogénica/mortalidad , Muerte Súbita Cardíaca/epidemiología , Desfibriladores Implantables , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries risk of sudden death. We hypothesize that the S-wave angle differentiates ARVD/C with otherwise normal electrocardiograms from controls. MATERIALS AND METHODS: All patients met Task Force 2010 definite ARVD/C criteria. ARVD/C patients without Task Force depolarization/repolarization criteria (-ECG) were compared to controls. Electrocardiogram measures of QRS duration, corrected QT interval, and measured angle between the upslope and downslope of the S-wave in V2, were assessed. RESULTS: Definite ARVD/C was present in 155 patients (42.7⯱â¯17.3â¯years, 68.4%male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.8⯱â¯17.6â¯years, 65.2%male). Only the S-wave angle differentiated -ECG ARVD/C patients from controls (<0.001) with AU the ROC curve of 0.77 (95%CI 0.53 to 0.71) and odds ratio of 28.3 (95%CI 6.4 to 125.5). CONCLUSION: ARVD/C may lead to development of subtle ECG abnormalities distinguishable using the S-wave angle prior to development of 2010 Taskforce ECG criteria.
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Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Electrocardiografía/métodos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Fenotipo , Medición de RiesgoRESUMEN
BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls. METHODS: Task Force 2010 definite ARVD/C criteria were met for all patients. Those who did not fulfill Task Force depolarization or repolarization criteria (-ECG) were compared with age and gender-matched control subjects. Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT interval (QTc), and a measured angle including the upslope and downslope of the S-wave (S-wave angle) were assessed. RESULTS: Definite ARVD/C was present in 155 patients by 2010 Task Force criteria (41.7 ± 17.6 years, 65.2% male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.7 ± 17.6 years, 65.2% male). All parameters tested except the QRSd and QTc significantly differentiated -ECG ARVD/C from control patients (p < 0.004 to p < 0.001). The RPD angle and RtRMS-QRS best differentiated the groups. Combined, the 2 novel criteria gave 81.8% sensitivity, 90.9% specificity and odds ratio of 45.0 (95% confidence interval 15.8 to 128.2). CONCLUSION: ARVD/C disease process may lead to development of subtle ECG abnormalities that can be distinguishable using right-sided VCG or measured angle markers better than the spatial QRS-T angle, the QRSd or QTc, in the absence of Taskforce ECG criteria.
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Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Electrocardiografía/métodos , Internacionalidad , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: Diagnostics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) are complex, and based on the 2010 Task Force document including different diagnostic modalities. However, recommendations for clinical management and follow-up of patients with ARVC and their relatives are sparse. This paper aims to give a practical overview of management strategies, risk stratification, and selection of appropriate therapies for patients with ARVC and their family members. DESIGN: This paper summarizes follow-up and treatment strategies in ARVC patients in the Nordic countries. The author group represents cardiologists who are actively involved in the Nordic ARVC Registry which was established in 2009, and contains prospectively collected clinical data from more than 590 ARVC patients from Denmark, Norway, Sweden, and Finland. RESULTS: Different approaches of management and follow-up are required in patients with definite ARVC and in genetic-mutation-positive family members. Furthermore, ARVC patients with and without implantable cardioverter defibrillators (ICDs) require different follow-up strategies. CONCLUSION: Careful follow-up is required in patients with ARVC diagnosis to evaluate the need of anti-arrhythmic therapy and ICD implantation. Mutation-positive family members should be followed regularly for detection of early disease and risk stratification of ventricular arrhythmias.
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Displasia Ventricular Derecha Arritmogénica/terapia , Fármacos Cardiovasculares/uso terapéutico , Ablación por Catéter , Muerte Súbita Cardíaca/prevención & control , Cardioversión Eléctrica , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/genética , Displasia Ventricular Derecha Arritmogénica/mortalidad , Fármacos Cardiovasculares/efectos adversos , Ablación por Catéter/efectos adversos , Muerte Súbita Cardíaca/etiología , Desfibriladores Implantables , Cardioversión Eléctrica/efectos adversos , Cardioversión Eléctrica/instrumentación , Cardioversión Eléctrica/métodos , Predisposición Genética a la Enfermedad , Humanos , Linaje , Fenotipo , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Países Escandinavos y Nórdicos/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long-term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias. METHODS AND RESULTS: Three hundred fifty-three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12-lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10 years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1-14] years. Reductions of QRS voltage, R- and T-wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102 ms (P<0.001), terminal activation duration (V1) from 47 to 52 ms (P<0.001), and QTc from 419 to 432 ms (P<0.001). T-wave inversions in leads V3 to V6 and aVF at first ECG were associated with ventricular arrhythmias (adjusted hazard ratio [HRadj][V3], 2.03 [95% CI, 1.23-3.34] and HRadj[aVF], 1.87 [95% CI, 1.13-3.08]). CONCLUSIONS: Depolarization and repolarization parameters evolved over time in patients with arrhythmogenic right ventricular cardiomyopathy, supporting the progressive nature of arrhythmogenic right ventricular cardiomyopathy. Electrocardiographic abnormalities may be detected before diagnosis and might, although not fulfilling the 2010 Task Force Criteria, be markers of early disease. T-wave inversion in leads V3 or aVF before diagnosis was associated with ventricular arrhythmias during follow-up.
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Displasia Ventricular Derecha Arritmogénica , Electrocardiografía , Humanos , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Displasia Ventricular Derecha Arritmogénica/complicaciones , Masculino , Estudios Retrospectivos , Femenino , Adulto , Persona de Mediana Edad , Factores de Tiempo , Factores de Riesgo , Progresión de la Enfermedad , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/etiología , Potenciales de Acción , Valor Predictivo de las PruebasRESUMEN
Background: Sudden cardiac death (SCD) is a global public health issue, accounting for 10-20% of deaths in industrialized countries. Identification of modifiable risk factors may reduce SCD incidence. Methods: This umbrella review systematically evaluates published meta-analyses of observational and randomized controlled trials (RCT) for the association of modifiable risk and protective factors of SCD. Results: Fifty-five meta-analyses were included in the final analysis, of which 31 analyzed observational studies and 24 analyzed RCTs. Five associations of meta-analyses of observational studies presented convincing evidence, including three risk factors [diabetes mellitus (DM), smoking, and early repolarization pattern (ERP)] and two protective factors [implanted cardiac defibrillator (ICD) and physical activity]. Meta-analyses of RCTs identified five protective factors with a high level of evidence: ICDs, mineralocorticoid receptor antagonist (MRA), beta-blockers, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with HF. On the contrary, other established, significant protective agents [i.e., amiodarone and statins along with angiotensin-converting enzyme (ACE) inhibitors in heart failure (HF)], did not show credibility. Likewise, risk factors as left ventricular ejection fraction in HF, and left ventricular hypertrophy, non-sustain ventricular tachycardia, history of syncope or aborted SCD in pediatric patients with hypertrophic cardiomyopathy, presented weak or no evidence. Conclusions: Lifestyle risk factors (physical activity, smoking), comorbidities like DM, and electrocardiographic features like ERP constitute modifiable risk factors of SCD. Alternatively, the use of MRA, beta-blockers, SGLT-2 inhibitors, and ICD in patients with HF are credible protective factors. Further investigation targeted in specific populations will be important for reducing the burden of SCD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216363, PROSPERO CRD42020216363.
RESUMEN
Revision of the Task Force diagnostic criteria (TFC) for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), in 2010, has increased the sensitivity for the diagnosis of early and familial forms of the disease. Epsilon wave (EW) is a major diagnostic criterion in the context of ARVC/D, however, it remains unquantifiable and therefore, may leave room for substantial subjective interpretation, thus, explaining the existing high inter-observer variability in the assessment of EW. EW, when present, coexists with other disease characteristics, which are sufficient for ARVC/D diagnosis, making EW generally not required for ARVC/D diagnosis. Nevertheless, EW remains an important part of the electrocardiographic phenotype of ARVC/D that may be useful in planning diagnostic work-up, which needs to be recognized.
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Displasia Ventricular Derecha Arritmogénica/diagnóstico , Electrocardiografía/métodos , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Femenino , Humanos , MasculinoRESUMEN
Background: Atrial arrhythmias are present in up to 20% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Catheter ablation (CA) is an effective treatment for atrial arrhythmias in the general population. Data regarding CA for atrial arrhythmias in ARVC are scarce. Objective: To assess the safety and efficacy of CA for atrial arrhythmias in patients with ARVC. Methods: In this international collaborative effort, all patients with a definite diagnosis of ARVC undergoing CA for atrial fibrillation (AF), focal atrial tachycardia (AT), or cavotricuspid isthmus (CTI)-dependent atrial flutter (AFl) were extracted from twelve ARVC registries. Demographic, periprocedural, and long-term arrhythmic outcome data were collected. Results: Thirty-seven patients were enrolled in the study (age 50.2 ± 16.6 years, male 84%, CHA2DS2VASc 1 (1,2), HAS-BLED 0 (0-2)). The arrhythmia leading to CA was AF in 23 (62%), focal left AT in 5 (14%), and CTI-dependent AFl in 9 (24%). Acute procedural success was achieved in all procedures but one (n = 1 focal left AT; 97% acute success). The median follow-up period was 27 (13-67) months, and 96%, 74%, and 61% of patients undergoing AF ablation were free from any atrial arrhythmia recurrence after a single procedure at 6 months, 12 months, and last follow-up, respectively. After focal AT ablation, freedom from atrial arrhythmia recurrence was 80%, 80%, and 60% at 6 months, 12 months, and last follow-up, respectively. All patients undergoing CTI ablation were free from atrial arrhythmia recurrences at 6 months, with 89% single-procedural arrhythmic freedom at last follow-up. One major complication (2.7%; PV stenosis requiring PV stenting) occurred. Conclusions: CA is safe and effective in managing atrial arrhythmias in patients with ARVC, with success rates comparable to the general population.
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OBJECTIVE: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). METHODS: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. RESULTS: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. CONCLUSION: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control.
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Inteligencia Artificial , COVID-19/diagnóstico , Electrocardiografía , Estudios de Casos y Controles , Humanos , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. METHODS: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. RESULTS: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. CONCLUSIONS: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
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Displasia Ventricular Derecha Arritmogénica/complicaciones , Muerte Súbita Cardíaca/epidemiología , Función Ventricular Derecha/fisiología , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Displasia Ventricular Derecha Arritmogénica/terapia , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Electrocardiografía , Estudios de Seguimiento , Salud Global , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Volumen SistólicoRESUMEN
Catheter ablation may reduce ventricular tachycardia (VT) burden in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, little is known about factors predicting need for ablation. Therefore, we sought to investigate predictors and use of VT ablation and to evaluate the postprocedural outcome in ARVC patients. We studied 435 patients from the Nordic ARVC registry including 220 probands with definite ARVC according to the 2010 task force criteria and 215 mutation-carrying relatives identified through cascade screening. Patients were followed until first-time VT ablation, death, heart transplantation, or January 1st 2018. Additionally, patients undergoing VT ablation were further followed from the time of ablation for recurrent ventricular arrhythmias. The cumulative use of VT ablation was 4% (95% confidence interval [CI] 3% to 6%) and 11% (95% CI 8% to 15%) after 1 and 10 years. All procedures were performed in probands in whom cumulative use was 8% (95% CI 5% to 12%) and 20% (95% CI 15% to 26%). In adjusted analyses among probands, only young age predicted ablation. In patients undergoing ablation, risk of recurrent arrhythmias was 59% (95% CI 44% to 71%) and 74% (95% CI 59% to 84%) 1 and 5 years after the procedure. Despite high recurrence rates, the burden of ventricular arrhythmias was reduced after ablation (pâ¯=â¯0.0042). Young age, use of several antiarrhythmic drugs and inducibility to VT after ablation were associated with an unfavorable outcome. In conclusion, twenty percent of ARVC probands developed a clinical indication for VT ablation within 10 years whereas mutation-carrying relatives were without such need. Although the burden of ventricular arrhythmias decreased after ablation, risk of recurrence was substantial.
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Antiarrítmicos/uso terapéutico , Displasia Ventricular Derecha Arritmogénica/terapia , Ablación por Catéter/estadística & datos numéricos , Desfibriladores Implantables , Taquicardia Ventricular/cirugía , Adulto , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/genética , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación , Recurrencia , Taquicardia Ventricular/etiología , Resultado del Tratamiento , Adulto JovenRESUMEN
Myocarditis most often affects otherwise healthy athletes and is one of the leading causes of sudden death in children and young adults. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder with increased risk for paroxysmal ventricular arrhythmias and sudden cardiac death. The clinical picture of myocarditis and ARVC may overlap during the early stages of cardiomyopathy, which may lead to misdiagnosis. In the literature, we found several cases that presented with episodes of myocarditis and ended up with a diagnosis of arrhythmogenic cardiomyopathy, mostly of the left predominant type. The aim of this case presentation is to shed light upon a possible link between myocarditis, a desmoplakin (DSP) gene variant, and ARVC by describing a case of male monozygotic twins who presented with symptoms and signs of myocarditis at 17 and 18 years of age, respectively. One of them also had a recurrent episode of myocarditis. The twins and their family were extensively examined including electrocardiograms (ECG), biochemistry, multimodal cardiac imaging, myocardial biopsy, genetic analysis, repeated cardiac magnetic resonance (CMR) and echocardiography over time. Both twins presented with chest pain, ECG with slight ST-T elevation, and increased troponin T levels. CMR demonstrated an affected left ventricle with comprehensive inflammatory, subepicardial changes consistent with myocarditis. The right ventricle did not appear to have any abnormalities. Genotype analysis revealed a nonsense heterozygous variant in the desmoplakin (DSP) gene [NM_004415.2:c.2521_2522del (p.Gln841Aspfs*9)] that is considered likely pathogenic and presumably ARVC related. There was no previous family history of heart disease. There might be a common pathophysiology of ARVC, associated with desmosomal dysfunction, and myocarditis. In our case, both twins have an affected left ventricle without any right ventricular involvement, and they are carriers of a novel DSP variant that is likely associated with ARVC. The extensive inflammation of the LV that was apparent in the CMR may or may not be the primary event of ARVC. Nevertheless, our data suggest that irrespective of a possible link here to ARVC, genetic testing for arrhythmogenic cardiomyopathy might be advisable for patients with recurrent myocarditis associated with a family history of myocarditis.