ABSTRACT
BACKGROUND: Clinical and molecular diagnosis of inherited cardiac conditions is key to find at-risk subjects and avoid preventable deaths. This study aimed to identify genetic variants in a sample of Colombian patients diagnosed with inherited cardiac conditions. METHODS: Next-generation sequencing (Illumina platform) using a 231 gene panel was performed in blood samples of 25 unrelated patients with age disease onset between 9 and 55 years. RESULTS: Genetic testing yield was 52%. Two novel likely pathogenic/ pathogenic variants were found: a DSP nonsense variant in a patient with arrhythmogenic cardiomyopathy and a KCNE1 frameshift variant in two patients with long QT syndrome. Younger individuals (<18 years) had the highest genetic testing yield (66.6%) compared to 50% and 20% in young adults and patients over 40 years, respectively. All subjects affected with long QT syndrome with a severe event while exercising had a positive genetic test. They also had four times more loss of consciousness events and, resuscitated sudden cardiac arrest was more representative. CONCLUSION: This study is the first one undertaken in Colombia to evaluate inherited cardiac conditions. It highlights the need to perform mutational analysis to provide adequate genetic counseling and to be able to identify patients at risk of severe events.
Subject(s)
Death, Sudden, Cardiac , Long QT Syndrome , Young Adult , Humans , Child , Adolescent , Adult , Middle Aged , Colombia , Long QT Syndrome/genetics , Long QT Syndrome/diagnosis , Genetic Testing , Genetic CounselingABSTRACT
Chagas cardiomyopathy is a parasitic infection caused by Trypanosoma cruzi. Structural and functional abnormalities are the result of direct myocardial damage by the parasite, immunological reactions, dysautonomia, and microvascular alterations. Chronic Chagas cardiomyopathy (CCC) is the most serious and important manifestation of the disease, affecting up to 30% of patients in the chronic phase. It results in heart failure, arrhythmias, thromboembolism, and sudden cardiac death. As in other cardiomyopathies, scar-related reentry frequently results in ventricular tachycardia (VT). The scars typically are located in the inferior and lateral aspects of the left ventricle close to the mitral annulus extending from endocardium to epicardium. The scars may be more prominent in the epicardium than in the endocardium, so epicardial mapping and ablation frequently are required. Identification of late potentials during sinus rhythm and mid-diastolic potentials during hemodynamically tolerated VT are the main targets for ablation. High-density mapping during sinus rhythm can identify late isochronal regions that are then targeted for ablation. Preablation cardiac magnetic resonance imaging with late enhancement can identify potentials areas of arrhythmogenesis. Therapeutic alternatives for VT management include antiarrhythmic drugs and modulation of the cardiac autonomic nervous system.
ABSTRACT
La flutamida es un antiandrógeno no esteroideo, utilizado como terapia a largo plazo para el cáncer de próstata. Entre los efectos secundarios se incluye toxicidad hepática, la cual es muy rara vez reportada. Se presenta el caso de un adulto de 71 años con cáncer de próstata que desarrolla episodio de hepatitis colestásica durante tratamiento con flutamida. Luego de suspender la flutamida el paciente recupera progresivamente su función hepática, pero presenta recurrencia más severa al reiniciar la droga.No se justifica el reinicio del tratamiento luego de un primer episodio de hepatitis tóxica y es necesario tener en cuenta la toxicidad hepática del fármaco, cuando se decide indicarlo como tratamiento.
Flutamide is a nonsteroidal antiandrogen, used like therapy a long term for the prostate cancer. Between the indirects effects the hepatic toxicity is included, which is very rarely reported. The case of an adult of 71 years old with prostate cancer appears that develops episode of cholestatic hepatitis during treatment with flutamide. After to suspend flutamide the patient it recovers progressively his hepatic function, but he presented a recurrence more severely upon reintroduction of the drug.The resumption of the treatment after a first episode of toxic hepatitis is not justified and is necessary to consider the hepatic toxicity of the drug, when it is decided to indicate it like treatment.
