ABSTRACT
Introducción y objetivos: La muerte súbita cardiaca (MSC) de origen no isquémico está causada predominantemente por miocardiopatías y canalopatías. La batería de test diagnósticos es amplia e incluye pruebas complejas. El objetivo de nuestro estudio es analizar la rentabilidad diagnóstica del estudio etiológico sistematizado de la MSC. Métodos: Se estudió a 56 familias con al menos 1 caso índice con MSC (reanimada o no). En los supervivientes se exploró con electrocardiograma, imagen cardiaca avanzada, ergometría, estudio familiar, estudio genético y, puntualmente, test farmacológicos. En los fallecidos se examinó la necropsia, así como la autopsia molecular con next generation sequencing (NGS), junto con estudio clínico familiar. Resultados: El diagnóstico se alcanzó en el 80,4% de los casos, sin diferencias entre supervivientes y fallecidos (p = 0,53). Entre los supervivientes, el diagnóstico de canalopatía fue más frecuente que entre los fallecidos (el 66,6 frente al 40%; p = 0,03). De los 30 sujetos fallecidos, en 7 la autopsia aportó un hallazgo concluyente. El diagnóstico de miocardiopatía tendía a asociarse con mayor tasa de eventos en la familia. El test genético con NGS se realizó en 42 de los casos; se obtuvo resultado positivo en 28 (66,6%), sin diferencias entre supervivientes y fallecidos (p = 0,21). Conclusiones: La probabilidad de alcanzar el diagnóstico en la MSC tras un protocolo exhaustivo es alta, con mayor prevalencia de canalopatías en los supervivientes y un aparente peor pronóstico en las miocardiopatías. El test genético mediante NGS muestra utilidad en casos de MSC e incrementa la rentabilidad respecto al estudio con Sanger (AU)
Introduction and objectives: Nonischemic sudden cardiac death (SCD) is predominantly caused by cardiomyopathies and channelopathies. There are many diagnostic tests, including some complex techniques. Our aim was to analyze the diagnostic yield of a systematic diagnostic protocol in a specialized unit. Methods: The study included 56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with electrocardiogram, advanced cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the postmortem findings, familial evaluation, and molecular autopsy with next-generation sequencing (NGS). Results: A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and nonsurvivors (P = .53). Cardiac channelopathies were more prevalent among survivors than nonsurvivors (66.6% vs 40%, P = .03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and nonsurvivors (P = .21). Conclusions: There is a strong likelihood of reaching a diagnosis in SCD after a rigorous protocol, with a more prevalent diagnosis of channelopathy among survivors and a worse familial prognosis in cardiomyopathies. Genetic testing with NGS is useful and its value is increasing with respect to the Sanger method (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Death, Sudden, Cardiac/etiology , Cardiomyopathies/diagnosis , Cardiomyopathies/genetics , Cardiomyopathies/mortality , Ventricular Fibrillation/diagnostic imaging , Retrospective Studies , Longitudinal Studies , Genetic Testing/methods , Algorithms , Electrocardiography/methods , Autopsy/methods , Epinephrine/analysisABSTRACT
INTRODUCTION AND OBJECTIVES: Nonischemic sudden cardiac death (SCD) is predominantly caused by cardiomyopathies and channelopathies. There are many diagnostic tests, including some complex techniques. Our aim was to analyze the diagnostic yield of a systematic diagnostic protocol in a specialized unit. METHODS: The study included 56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with electrocardiogram, advanced cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the postmortem findings, familial evaluation, and molecular autopsy with next-generation sequencing (NGS). RESULTS: A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and nonsurvivors (P=.53). Cardiac channelopathies were more prevalent among survivors than nonsurvivors (66.6% vs 40%, P=.03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and nonsurvivors (P=.21). CONCLUSIONS: There is a strong likelihood of reaching a diagnosis in SCD after a rigorous protocol, with a more prevalent diagnosis of channelopathy among survivors and a worse familial prognosis in cardiomyopathies. Genetic testing with NGS is useful and its value is increasing with respect to the Sanger method.
Subject(s)
Arrhythmias, Cardiac/diagnosis , Cardiomyopathies/diagnosis , Channelopathies/diagnosis , Death, Sudden, Cardiac/etiology , Family , Genetic Testing , Adolescent , Adult , Arrhythmias, Cardiac/complications , Arrhythmias, Cardiac/genetics , Arrhythmogenic Right Ventricular Dysplasia/complications , Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Arrhythmogenic Right Ventricular Dysplasia/genetics , Brugada Syndrome/complications , Brugada Syndrome/diagnosis , Brugada Syndrome/genetics , Cardiomyopathies/complications , Cardiomyopathies/genetics , Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/genetics , Channelopathies/complications , Channelopathies/genetics , Child , Electrocardiography , Exercise Test , Female , Genetic Predisposition to Disease , Heart Defects, Congenital/complications , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/genetics , High-Throughput Nucleotide Sequencing , Humans , Long QT Syndrome/complications , Long QT Syndrome/diagnosis , Long QT Syndrome/genetics , Male , Middle Aged , Phenotype , Retrospective Studies , Sequence Analysis, DNA , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/genetics , Young AdultABSTRACT
BACKGROUND: The HER2 655 A>G genetic variant has recently been associated with trastuzumab-induced cardiotoxicity in HER2 breast cancer patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients. METHODS: Our study population was composed of 78 HER2 breast cancer patients receiving trastuzumab. The HER2 655 A>G (rs1136201) genetic variant was genotyped using TaqMan allelic discrimination technology. Patients were classified on the basis of the occurrence of cardiotoxic events or the absence of cardiotoxic events during 1 year after the first infusion. RESULTS: The HER2 655 A>G polymorphism was significantly associated with cardiotoxicity: AG versus AA [P=0.012, odds ratio (OR)=5.12, 95% confidence interval (CI) 1.43-18.36], AG+GG versus AA (P=0.01, OR=5.72, 95% CI 1.50-21.76), AG versus AA+GG (P=0.005, OR=7.17, 95% CI 1.82-28.29). A meta-analysis combining these data with the results from previous studies confirmed this association. CONCLUSION: Our results support the role of the HER2 655 A>G polymorphism as a genetic marker of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.
