Tomás Ripoll-Vera1, Consuelo Pérez Luengo2, Juan Carlos Borondo Alcázar3, Ana Belén García Ruiz2, Nieves Sánchez Del Valle2, Bernardino Barceló Martín4, Juan Luis Poncela García2, Gloria Gutiérrez Buitrago2, Concepción Dasi Martínez3, Juan Carlos Canós Villena3, Susana Moyano Corvillo3, Raquel Esgueva Pallarés3, Juan Ramón Sancho Sancho5, Gemma Guitart Pinedo6, Elena Hernández Marín7, Estela García García7, Albert Vingut López7, Jorge Álvarez Rubio8, Nancy Govea Callizo9, Yolanda Gómez Pérez8, Catalina Melià Mesquida8, Damián Heine9, Jordi Rosell Andreo9, Lorenzo Socías Crespí10. 1. Servicio de Cardiología, Hospital Universitario Son Llàtzer, Palma de Mallorca, Islas Baleares, Spain; Instituto de Investigación Sanitaria de Baleares (IdISBa), Palma de Mallorca, Islas Baleares, Spain. Electronic address: tripoll@hsll.es. 2. Instituto de Medicina Legal de las Islas Baleares, Palma de Mallorca, Islas Baleares, Spain. 3. Servicio de Histopatología, Instituto Nacional de Toxicología y Ciencias Forenses, Barcelona, Spain. 4. Instituto de Investigación Sanitaria de Baleares (IdISBa), Palma de Mallorca, Islas Baleares, Spain; Servicio de Análisis Clínicos y Toxicología, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain. 5. Instituto de Medicina Legal Islas Baleares, Ibiza, Islas Baleares, Spain. 6. Instituto de Medicina Legal Islas Baleares, Menorca, Islas Baleares, Spain. 7. Servicio de Química, Instituto Nacional de Toxicología y Ciencias Forenses, Barcelona, Spain. 8. Servicio de Cardiología, Hospital Universitario Son Llàtzer, Palma de Mallorca, Islas Baleares, Spain; Instituto de Investigación Sanitaria de Baleares (IdISBa), Palma de Mallorca, Islas Baleares, Spain. 9. Instituto de Investigación Sanitaria de Baleares (IdISBa), Palma de Mallorca, Islas Baleares, Spain; Sección de Genética, Unidad de Diagnóstico Molecular y Genética Clínica, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain. 10. Instituto de Investigación Sanitaria de Baleares (IdISBa), Palma de Mallorca, Islas Baleares, Spain; Servicio de Medicina Intensiva, Hospital Universitario Son Llàtzer, Palma de Mallorca, Islas Baleares, Spain.
Abstract
INTRODUCTION AND OBJECTIVES: Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of "molecular autopsy" may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. METHODS: We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. RESULTS: We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. CONCLUSIONS: Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications.
INTRODUCTION AND OBJECTIVES: Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of "molecular autopsy" may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. METHODS: We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. RESULTS: We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. CONCLUSIONS: Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications.