RESUMEN
This case report describes a patient in their 60s with atrial flutter ablation following admission to the hospital for heart failure exacerbation.
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Fibrilación Atrial , Aleteo Atrial , Ablación por Catéter , Fibrilación Atrial/cirugía , Electrocardiografía , HumanosRESUMEN
BACKGROUND: Patients with hemodynamically tolerated ventricular tachycardia (VT) and minimally reduced left ventricular ejection fraction (LVEF) remain a group that presents a prognostic and therapeutic dilemma. METHODS: We studied patients from our implanted cardioverter-defibrillator (ICD) database who received ICDs for hemodynamically tolerated VT and mildly reduced LVEF (36%-49%) at time of implant between May 2015 and December 2019. Time to appropriate ICD therapy was assessed. Clinical features associated with recurrent VT/ventricular fibrillation (VF) with ICD therapies were explored using binary logistic regression. RESULTS: Among 2037 ICDs placed between May 2015 and December 2019, 64 subjects met the inclusion criteria. The mean age of the study group was 68 ± 12 years, and 58 (90.6%) subjects were male. Average ejection fraction was 40% ± 4.4 (range 36%-49%). Twenty-two (34%) subjects received antitachycardia pacing (ATP) for VT at 229 ± 265 days after ICD placement. Fifteen (23%) subjects received appropriate ICD shocks 305 ± 321 days after implant. The rate of recurrent VT/VF among the 37 patients with ICD therapy was 195 ± 39 beats per minute (bpm). This was significantly more rapid than initial presenting VT rates before ICD placement (183 ± 27 bpm) (P = 0.048). Multivariate analysis showed no factors independently associated with recurrent VT/VF. CONCLUSIONS: Patients with mildly impaired LV function and hemodynamically tolerated VT receive appropriate ICD therapies over the 3 years following implant. This patient group warrants further investigation, as their recurrent VT/VF rates can be much more rapid, and 23% go on to receive appropriate ICD shocks.
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Desfibriladores Implantables , Taquicardia Ventricular , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas , Cardioversión Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico , Taquicardia Ventricular/etiología , Taquicardia Ventricular/terapia , Fibrilación Ventricular/terapia , Función Ventricular IzquierdaRESUMEN
OBJECTIVES: This study sought to identify minimum threshold values below which conduction over the atrioventricular (AV) node would be unexpected. BACKGROUND: Para-Hisian pacing is used to evaluate for the presence of a septal accessory pathway (AP); however, threshold values to differentiate nodal from AP conduction are unknown. METHODS: The authors performed high- and low-output para-Hisian pacing during sinus rhythm to capture the His and para-Hisian ventricular myocardium (H+V) and para-Hisian ventricular myocardium (V) alone, respectively. The change in stimulation (stim)-to-atrial electrogram interval after loss of His bundle capture in patients with (AP+) and without (AP-) a septal AP was evaluated. Stim-to-proximal coronary sinus (PCS) and stim-to-high right atrium (HRA) intervals were measured and within-patient differences (â³) for V and H+V capture were calculated. RESULTS: A total of 23 AP+ and 45 AP- patients were evaluated. The difference in stimulus to earliest atrial signal in the high right atrial catheter seen with the loss of His bundle capture (â³-stim-HRA) (21 ms; interquartile range [IQR]: 3 to 43 ms vs. 64 ms; IQR: 56 to 73 ms; p < 0.001) and difference in stimulus to earliest atrial signal in the proximal coronary sinus catheter seen with the loss of His Bundle capture (â³-stim-PCS) (11 ms; IQR: 0 to 30 ms vs. 61 ms; IQR: 52 to 72 ms; p < 0.001) were shorter in AP+ patients. The shortest â³-stim-PCS and â³-stim-HRA in AP- patients were 37 ms and 32 ms, respectively, whereas the longest corresponding intervals in AP+ patients were 51 ms and 75 ms, respectively. CONCLUSIONS: A â³-stim-PCS <37 ms or â³-stim-HRA <32 ms confirmed the presence of a septal AP, whereas a value >51 ms for â³-stim-PCS or >75 ms for â³-stim-HRA excluded it. Alternatively, the minimum â³-stim-PCS with loss of His capture compatible with AV nodal conduction in isolation was 37 ms, and a â³-stim-PCS >51 ms effectively ruled out the presence of a septal AP.
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Taquicardia por Reentrada en el Nodo Atrioventricular , Nodo Atrioventricular , Fascículo Atrioventricular , Estimulación Cardíaca Artificial , Técnicas Electrofisiológicas Cardíacas , HumanosRESUMEN
INTRODUCTION: Septal accessory pathway (AP) ablation can be challenging due to the complex anatomy of the septal region. The decision to access the left atrium (LA) is often made after failure of ablation from the right. We sought to establish whether the difference between ventriculo-atrial (VA) time during right ventricular (RV) apical pacing versus the VA during tachycardia would help establish the successful site for ablation of septal APs. METHODS: Intracardiac electrograms of patients with orthodromic reciprocating tachycardia (ORT) using a septal AP with successful catheter ablation were reviewed. The ∆VA was the difference between the VA interval during RV apical pacing and the VA interval during ORT. The difference in the VA interval during right ventricular entrainment and ORT (StimA-VA) was also measured. RESULTS: The median ∆VA time was significantly less in patients with a septal AP ablated on the right side compared with patients with a septal AP ablated on the left side (12 ± 19 vs. 56 ± 10 ms, p < .001). The StimA-VA was significantly different between the two groups (22 ± 14 vs. 53 ± 9 ms, p < .001). The ∆VA and StimA-VA were always ≤ 40 ms in patients with non-decremental septal APs ablated from the right side and always greater than 40 ms in those with septal APs ablated from the left. CONCLUSION: ΔVA and StimA-VA values identified with RV apical pacing in the setting of ORT involving a septal AP predict when left atrial access will be necessary for successful ablation.
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Fascículo Atrioventricular Accesorio , Ablación por Catéter , Taquicardia por Reentrada en el Nodo Atrioventricular , Fascículo Atrioventricular Accesorio/cirugía , Fascículo Atrioventricular , Ablación por Catéter/efectos adversos , Electrocardiografía , Sistema de Conducción Cardíaco/diagnóstico por imagen , Sistema de Conducción Cardíaco/cirugía , Humanos , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugíaRESUMEN
OBJECTIVES: The authors studied the response rates and relative sensitivity of the most common agents used in the sodium-channel blocker (SCB) challenge. BACKGROUND: A type 1 Brugada electrocardiographic pattern precipitated by an SCB challenge confers a diagnosis of Brugada syndrome. METHODS: Patients undergoing an SCB challenge were prospectively enrolled across Canada and the United Kingdom. Patients with no prior cardiac arrest and family histories of sudden cardiac death or Brugada syndrome were included. RESULTS: Four hundred twenty-five subjects underwent SCB challenge (ajmaline, n = 331 [78%]; procainamide, n = 94 [22%]), with a mean age of 39 ± 15 years (54% men). Baseline non-type 1 Brugada ST-segment elevation was present in 10%. A total of 154 patients (36%) underwent signal-averaged electrocardiography, with 41% having late potentials. Positive results were seen more often with ajmaline than procainamide infusion (26% vs. 4%, p < 0.001). On multivariate analysis, baseline non-type 1 Brugada ST-segment elevation (odds ratio [OR]: 6.92; 95% confidence interval [CI]: 3.15 to 15.2; p < 0.001) and ajmaline use (OR: 8.76; 95% CI: 2.62 to 29.2; p < 0.001) were independent predictors of positive results to SCB challenge. In the subgroup undergoing signal-averaged electrocardiography, non-type 1 Brugada ST-segment elevation (OR: 9.28; 95% CI: 2.22 to 38.8; p = 0.002), late potentials on signal-averaged electrocardiography (OR: 4.32; 95% CI: 1.50 to 12.5; p = 0.007), and ajmaline use (OR: 12.0; 95% CI: 2.45 to 59.1; p = 0.002) were strong predictors of SCB outcome. CONCLUSIONS: The outcome of SCB challenge was significantly affected by the drug used, with ajmaline more likely to provoke a type 1 Brugada electrocardiographic pattern compared with procainamide. Patients undergoing SCB challenge may have contrasting results depending on the drug used, with potential clinical, psychosocial, and socioeconomic implications.
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Ajmalina/farmacología , Síndrome de Brugada/diagnóstico , Electrocardiografía/efectos de los fármacos , Procainamida/farmacología , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Adulto , Síndrome de Brugada/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
AIMS: Treatments for persistent atrial fibrillation (AF) offer limited efficacy. One potential strategy aims to return the right atrium (RA) to sinus rhythm (SR) by ablating interatrial connections (IAC) to isolate the atria, but there is limited clinical data to evaluate this ablation approach. We aimed to use simulation to evaluate and predict patient-specific suitability for ablation of IAC to treat AF. METHODS AND RESULTS: Persistent AF was simulated in 12 patient-specific geometries, incorporating electrophysiological heterogeneity and fibres, with IAC at Bachmann's bundle, the coronary sinus, and fossa ovalis. Simulations were performed to test the effect of left atrial (LA)-to-RA frequency gradient and fibrotic remodelling on IAC ablation efficacy. During AF, we simulated ablation of one, two, or all three IAC, with or without pulmonary vein isolation and determined if this altered or terminated the arrhythmia. For models without structural remodelling, ablating all IAC terminated RA arrhythmia in 83% of cases. Models with the LA-to-RA frequency gradient removed had an increased success rate (100% success). Ablation of IACs is less effective in cases with fibrotic remodelling (interstitial fibrosis 50% success rate; combination remodelling 67%). Mean number of phase singularities in the RA was higher pre-ablation for IAC failure (success 0.6 ± 0.8 vs. failure 3.2 ± 2.5, P < 0.001). CONCLUSION: This simulation study predicts that IAC ablation is effective in returning the RA to SR for many cases. Patient-specific modelling approaches have the potential to stratify patients prior to ablation by predicting if drivers are located in the LA or RA. We present a platform for predicting efficacy and informing patient selection for speculative treatments.
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Potenciales de Acción , Fibrilación Atrial/cirugía , Función del Atrio Izquierdo , Función del Atrio Derecho , Ablación por Catéter , Atrios Cardíacos/cirugía , Frecuencia Cardíaca , Modelos Cardiovasculares , Modelación Específica para el Paciente , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Remodelación Atrial , Ablación por Catéter/efectos adversos , Toma de Decisiones Clínicas , Fibrosis , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Magnética , Selección de Paciente , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Síndrome de Wolff-Parkinson-White , Lobos , Animales , Niño , Muerte Súbita Cardíaca , HumanosAsunto(s)
Cardiomiopatía Hipertrófica/complicaciones , Ablación por Catéter , Aneurisma Cardíaco/etiología , Hipertrofia Ventricular Izquierda/complicaciones , Taquicardia Ventricular/cirugía , Potenciales de Acción , Anciano , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Desfibriladores Implantables , Ecocardiografía Doppler , Cardioversión Eléctrica/instrumentación , Técnicas Electrofisiológicas Cardíacas , Femenino , Aneurisma Cardíaco/diagnóstico por imagen , Frecuencia Cardíaca , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiología , Resultado del TratamientoRESUMEN
INTRODUCTION: Radiofrequency (RF) ablation is effective for slow pathway ablation, but carries a risk of inadvertent AV block requiring permanent pacing. By comparison, cryoablation with a 4-mm distal electrode catheter has not been reported to cause permanent AV block but has been shown to be less effective than RF ablation. We sought to define the safety and efficacy of a 6-mm distal electrode cryoablation catheter for slow pathway ablation in patients with atrioventricular nodal reentry tachycardia (AVNRT). METHODS AND RESULTS: Twenty-six U.S. and eight Canadian centers participated in the study. Patients with supraventricular tachycardia (SVT) thought likely to be AVNRT were enrolled. If AVNRT was inducible and confirmed to be the clinical SVT, then the slow pathway was targeted with a cryoablation catheter using a standardized protocol of best practices. Acute success was defined as inducibility of no more than one echo beat after cryoablation. Primary efficacy was defined as acute success and the absence of documented recurrent AVNRT over 6 months of follow-up. Primary safety was a composite of serious procedure-related adverse events and/or device-related complications. Note that 397 subjects met enrollment criteria after the EP study and received cryoablation. Mean ablation procedure duration (including a waiting period) was 89 ± 40 minutes, and mean fluoroscopy time was 4.8 ± 5.9 minutes. Isoproterenol was administered before cryoablation in 53% and after the last lesion in 85% of cases. Acute procedural success was realized in 95% (378 of 397) of subjects. No subject received a permanent pacemaker due to AV block. The slow pathway could not be ablated in 19 subjects, including: 12 due to inefficacy, 2 due to transient AV block, and 5 due to both inefficacy and transient AV block. RF ablation was used in the same procedure in 11 of 19 failed subjects, and was ineffective in 3 subjects. Among the group with acute success, 10 subjects (2.7%) had documented recurrent AVNRT over the 6-month follow-up period, and all occurred within 3 months of the index cryoablation. Serious procedure-related adverse events occurred in 4 subjects (1.0%), including one each: tamponade, pulmonary embolism, femoral vein hemorrhage, and diagnostic EP catheter knotting. None of these serious adverse events were related to use of the cryoablation catheter. Overall, 93% of subjects had successful slow pathway ablation at 6 months with the study cryoablation catheter. CONCLUSIONS: Cryoablation for AVNRT using a focal 6-mm catheter was safe and effective. It resulted in a low risk of recurrence over 6 months of follow-up with no incidence of AV block requiring permanent pacing.
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Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Criocirugía/instrumentación , Sistema de Conducción Cardíaco/cirugía , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Taquicardia Supraventricular/cirugía , Potenciales de Acción , Adulto , Anciano , Bloqueo Atrioventricular/etiología , Bloqueo Atrioventricular/fisiopatología , Cateterismo Cardíaco/efectos adversos , Criocirugía/efectos adversos , Diseño de Equipo , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia por Reentrada en el Nodo Atrioventricular/fisiopatología , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear. METHODS AND RESULTS: The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians' discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6-9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1-9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%; P=0.04) but was associated with more variants of unknown significance (55% versus 5%; P<0.01). CONCLUSIONS: Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique Identifier: NCT00292032.
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Pruebas Genéticas , Paro Cardíaco/patología , Sistema de Registros , Adulto , Canales de Calcio Tipo L/genética , Cardiomiopatías/genética , Cardiomiopatías/patología , Canalopatías/genética , Canalopatías/patología , Vasos Coronarios/metabolismo , Electrocardiografía , Femenino , Paro Cardíaco/genética , Humanos , Masculino , Persona de Mediana Edad , Canal de Sodio Activado por Voltaje NAV1.5/genética , Oportunidad Relativa , Fenotipo , Canal Liberador de Calcio Receptor de Rianodina/genética , Sobrevivientes , Función Ventricular Izquierda/genéticaRESUMEN
The management of the asymptomatic pre-excited patient largely hinges on risk stratification and individual patient considerations and choice. A high threshold to treat patients may lead to a small overall risk of death while a low threshold clearly leads to increased invasive testing and ablation with associated cost and procedural risk. A firm recommendation to uniformly assess all by electrophysiology study or, alternatively, reassure all is inappropriate and unjustified by data as reflected in the recent guideline recommendations. The use of noninvasive and invasive parameters to identify the potentially at-risk individual with surveillance for symptoms in those comfortable with this approach or ablation for those choosing this alternative for individual reasons remains the cornerstone of best practice.
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American Heart Association , Cardiología/normas , Muerte Súbita Cardíaca/prevención & control , Guías de Práctica Clínica como Asunto/normas , Síndromes de Preexcitación/terapia , Adolescente , Adulto , Niño , Muerte Súbita Cardíaca/epidemiología , Femenino , Humanos , Masculino , Síndromes de Preexcitación/diagnóstico , Síndromes de Preexcitación/epidemiología , Medición de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Progression from paroxysmal to persistent atrial fibrillation (AF) has important clinical implications and is relevant to the management of patients with AF. OBJECTIVE: The purpose of this study was to define the long-term rate of progression from paroxysmal to persistent AF and the relevant clinical variables. METHODS: The Canadian Registry of Atrial Fibrillation enrolled patients after a first electrocardiographic diagnosis of paroxysmal AF. Associations between baseline characteristics and clinical outcomes were evaluated using a multivariable Cox proportional hazard model and a competing risk model accounting for death as a competing risk, where appropriate. RESULTS: We enrolled 755 patients (61.7% men) aged between 14 and 91 years (mean age 61.2 ± 14.2 years). The median follow-up was 6.35 years (interquartile range 2.93-10.04 years), with a rate of progression to persistent AF at 1, 5, and 10 years was 8.6%, 24.3%, and 36.3%, respectively. All-cause mortality was 30.3% at 10 years. Factors associated with AF progression were increasing age (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.23-1.60, for each 10-year increment), mitral regurgitation (HR 1.87; 95% CI 1.28-2.73), left atrial dilatation (HR 3.01; 95% CI 2.03-4.47), aortic stenosis (HR 2.40; 95% CI 1.05-5.48), and left ventricular hypertrophy (HR .47; 95% CI 1.04-2.08). Factors associated with a lower rate of progression were a faster heart rate during AF (HR 0.94; 95% CI 0.92-0.96 per 5-beat/min increment) and angina (HR 0.54; 95% CI 0.38-0.77). After accounting for death as a competing risk, left ventricular hypertrophy and aortic stenosis were no longer significant. CONCLUSION: Within 10 years of presenting with paroxysmal AF, >50% of patients will progress to persistent AF or be dead. Increasing age, mitral regurgitation, aortic stenosis, left ventricular hypertrophy, and left atrial dilatation were associated with progression to persistent AF.
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Fibrilación Atrial/diagnóstico , Electrocardiografía/métodos , Predicción , Sistema de Registros , Medición de Riesgo/métodos , Taquicardia Paroxística/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/epidemiología , Fibrilación Atrial/fisiopatología , Canadá/epidemiología , Causas de Muerte/tendencias , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Taquicardia Paroxística/epidemiología , Taquicardia Paroxística/fisiopatología , Adulto JovenRESUMEN
OBJECTIVES: This study sought to investigate for an underlying genetic etiology in cases of apparent idiopathic bundle branch re-entrant ventricular tachycardia (BBRVT). BACKGROUND: BBRVT is a life-threatening arrhythmia occurring secondary to macro-re-entry within the His-Purkinje system. Although classically associated with dilated cardiomyopathy, BBRVT may also occur in the setting of isolated, unexplained conduction system disease. METHODS: Cases of BBRVT with normal biventricular size and function were recruited from 6 North American centers. Enrollment required a clinically documented wide complex tachycardia and BBRVT proven during invasive electrophysiology study. Study participants were screened for mutations within genes associated with cardiac conduction system disease. Pathogenicity of identified mutations was evaluated using in silico phylogenetic and physicochemical analyses and in vitro biophysical studies. RESULTS: Among 6 cases of idiopathic BBRVT, each presented with hemodynamic compromise and 2 suffered cardiac arrests requiring resuscitation. Putative culprit mutations were identified in 3 of 6 cases, including 2 in SCN5A (Ala1905Gly [novel] and c.4719C>T [splice site mutation]) and 1 in LMNA (Leu327Val [novel]). Biophysical analysis of mutant Ala1905Gly Nav1.5 channels in tsA201 cells revealed significantly reduced peak current density and positive shifts in the voltage-dependence of activation, consistent with a loss-of-function. The SCN5A c.4719C>T splice site mutation has previously been reported as disease-causing in 3 cases of Brugada syndrome, whereas the novel LMNA Leu327Val mutation was associated with a classic laminopathy phenotype. Following catheter ablation, BBRVT was noninducible in all cases and none experienced a clinical recurrence during follow-up. CONCLUSIONS: Our investigation into apparent idiopathic BBRVT has identified the first genetic culprits for this life-threatening arrhythmia, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing in this condition. Our findings also highlight BBRVT as a novel genetic etiology of unexplained sudden cardiac death that can be cured with catheter ablation.
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Arritmias Cardíacas/complicaciones , Cardiomiopatía Dilatada/complicaciones , Muerte Súbita Cardíaca/prevención & control , Taquicardia Ventricular/genética , Adolescente , Adulto , Arritmias Cardíacas/fisiopatología , Síndrome de Brugada/genética , Cardiomiopatía Dilatada/fisiopatología , Ablación por Catéter/efectos adversos , Muerte Súbita Cardíaca/etiología , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas/métodos , Femenino , Humanos , Lamina Tipo A/genética , Masculino , Mutación/genética , Canal de Sodio Activado por Voltaje NAV1.5/genética , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/terapia , Adulto JovenRESUMEN
BACKGROUND: Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for cardiac abnormalities. METHODS AND RESULTS: Around 398 first-degree family members (186 UCA, 212 sudden unexplained death victims' relatives; mean age, 44±17 years) underwent extensive cardiac workup, including ECG, signal averaged ECG, exercise testing, cardiac imaging, Holter-monitoring, and selective provocative drug testing with epinephrine or procainamide. Genetic testing was performed when a mutation was identified in the UCA survivor or when the diagnostic workup revealed a phenotype suggestive of a specific inherited arrhythmia syndrome. The diagnostic strength was classified as definite, probable, or possible based on previously published definitions. Cardiac abnormalities were detected in 120 of 398 patients (30.2%) with 67 of 398 having a definite or probable diagnosis (17%), including Long-QT syndrome (13%), catecholaminergic polymorphic ventricular tachycardia (4%), arrhythmogenic right ventricular cardiomyopathy (4%), and Brugada syndrome (3%). The detection yield was similar for family members of UCA and sudden unexplained death victims (31% versus 27%; P=0.59). Genetic testing was performed more often in family members of UCA patients (29% versus 20%; P=0.03). Disease-causing mutations were identified in 20 of 398 relatives (5%). The most common pathogenic mutations were RyR2 (2%), SCN5A (1%), and KNCQ1 (0.8%). CONCLUSIONS: Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.