Arrhythmic disorder mapped to chromosome 1q42–q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts
| Autor: | Kirsi Piippo, Pekka Keto, Heikki Swan, Päivi Heikkilä, Katariina Kainulainen, Lauri Toivonen, Juha Kere, Matti Viitasalo, Timo Paavonen, Kimmo Kontula |
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| Rok vydání: | 1999 |
| Předmět: |
Tachycardia
Male Potassium Channels Genetic Linkage Biopsy Chromosome Disorders 030204 cardiovascular system & hematology Ventricular tachycardia Coronary Angiography Electrocardiography 0302 clinical medicine Child 0303 health sciences Flecainide Reverse Transcriptase Polymerase Chain Reaction Hypertrophic cardiomyopathy Chromosome Mapping Middle Aged Magnetic Resonance Imaging 3. Good health Pedigree Survival Rate Chromosomes Human Pair 1 Echocardiography cardiovascular system Cardiology Cineangiography Female medicine.symptom Cardiology and Cardiovascular Medicine Anti-Arrhythmia Agents medicine.drug Adult medicine.medical_specialty Adolescent Long QT syndrome Catecholaminergic polymorphic ventricular tachycardia Sudden death Diagnosis Differential 03 medical and health sciences Potassium Channels Tandem Pore Domain Internal medicine medicine Humans cardiovascular diseases 030304 developmental biology Chromosome Aberrations business.industry Myocardium medicine.disease Myocardial Contraction Death Sudden Cardiac Bigeminy Exercise Test Tachycardia Ventricular RNA Lod Score business |
| Zdroj: | Journal of the American College of Cardiology. 34(7):2035-2042 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/s0735-1097(99)00461-1 |
| Popis: | OBJECTIVESThe purpose of this study was to provide clinical and anatomical characteristics as well as genetic background of a malignant arrhythmogenic disorder.BACKGROUNDAn inherited autosomally dominant cardiac syndrome causing stress-induced polymorphic ventricular tachycardia and syncope in the absence of structural myocardial changes was detected in two families.METHODSTwo unrelated families with six victims of sudden death and 51 living members were evaluated. Resting and exercise electrocardiograms (ECG), echocardiography, magnetic resonance imaging (MRI), cineangiography, microscopic examination of endomyocardial biopsies and a drug testing with a class IC antiarrhythmic agent flecainide were performed. A genetic linkage analysis was carried out to map the gene locus.RESULTSOf the 24 affected individuals, 10 had succumbed with six cases of sudden death, and 14 survivors showed evidence of disease. Exercise stress test induced ventricular bigeminy or polymorphic ventricular tachycardia in affected individuals. Three children initially examined before 10 years of age developed arrhythmias during a four-year follow-up. Resting ECGs were normal in affected subjects except a slight prolongation of the QT intervals adjusted for heart rate (QTc) (430 ± 18 vs. 409 ± 19 ms, affected vs. nonaffected, p < 0.01). Administration of flecainide did not induce ECG abnormalities encountered in familial idiopathic ventricular fibrillation. Ventricular volumes, contractility and wall measurements were normal by echocardiography, right ventricular cineangiography and MRI. Histopathological examination showed no fibrosis or fatty infiltration. The cumulative cardiac mortality by the age of 30 years was 31%. The disease locus was assigned to chromosome 1q42–q43, with a maximal pairwise lod score of 4.74 in the two families combined. Only one heterozygous carrier was clinically unaffected suggesting high disease penetrance in adulthood.CONCLUSIONSA distinct cardiac disorder linked to chromosome 1q42–q43 causes exercise-induced polymorphic ventricular tachycardia in structurally normal hearts and is highly malignant. Delayed clinical manifestation necessitates repeated exercise electrocardiography to assure diagnosis in young individuals of the families. |
| Databáze: | OpenAIRE |
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