Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center

Christine Rootwelt-Norberg; Øyvind H Lie; Lars A Dejgaard; Monica Chivulescu; Ida S Leren; Thor Edvardsen; Kristina H Haugaa

doi:10.1016/j.ijcard.2018.12.066

Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center

Int J Cardiol. 2019 Mar 15:279:79-83. doi: 10.1016/j.ijcard.2018.12.066. Epub 2018 Dec 27.

Authors

Christine Rootwelt-Norberg¹, Øyvind H Lie², Lars A Dejgaard³, Monica Chivulescu⁴, Ida S Leren⁵, Thor Edvardsen⁶, Kristina H Haugaa⁷

Affiliations

¹ Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, 0424 Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway. Electronic address: christine.rootwelt@rr-research.no.
² Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, 0424 Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318 Oslo, Norway. Electronic address: oyvind.haugen.lie@rr-research.no.
³ Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, 0424 Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318 Oslo, Norway. Electronic address: lars.andreas.dejgaard@rr-research.no.
⁴ Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway.
⁵ Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, 0424 Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318 Oslo, Norway.
⁶ Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, 0424 Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318 Oslo, Norway. Electronic address: thor.edvardsen@medisin.uio.no.
⁷ Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, 0424 Oslo, Norway; Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Domus Medica 4 (DM4), PO Box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, PO Box 1171, Blindern, 0318 Oslo, Norway. Electronic address: kristina.haugaa@medisin.uio.no.

PMID: 30638987
DOI: 10.1016/j.ijcard.2018.12.066

Abstract

Background: Arrhythmogenic cardiomyopathy (AC) is an inheritable progressive heart disease with high risk of life-threatening ventricular arrhythmia (VA). We aimed to explore the prevalence of VA as presenting event in patients with AC over two decades, symptoms preceding VA and compare the clinical presentations and rate of AC-diagnosis over time.

Methods: We included consecutive AC-patients from our tertiary referral center. We recorded clinical history, VA (aborted cardiac arrest, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator therapy), cardiac symptoms preceding VA in AC, and compared the history of patients diagnosed before and after implementation of genetic testing.

Results: We included 179 consecutive AC-patients and mutation-positive family members (95 [53%] probands, 84 [45%] female, 49 ± 17 years), 33 (18%) diagnosed before and 146 (82%) after genetic testing became available. VA led to the AC-diagnosis in 46 (26%), and was less prevalent after implementation of genetic testing (17[52%] vs. 29[20%], p < 0.001), also when adjusted for proband status (Adjusted OR 2.7, 95% CI 1.1-6.7, p = 0.03). Yearly rate of AC-diagnosis increased after implementation of genetic testing in probands (2.7 ± 1.3 vs. 6.8 ± 4.3, p = 0.01) and family members (0.7 ± 1.1 vs. 7.7 ± 5.9, p = 0.002). Most patients with VA (92%) reported cardiac symptoms prior to event, and exercise-induced syncope was the strongest marker of subsequent VA (Adjusted OR 5.3, 95% CI 1.7-16.4, p = 0.004).

Conclusion: VA led to AC-diagnosis in 46% of probands and was preceded by cardiac symptoms in the majority of cases. Yearly rate of AC-diagnoses increased after the implementation of genetic testing and life-threatening presentation of AC-disease seemed to decrease.

Keywords: Arrhythmogenic cardiomyopathy; Cardiac arrest; Genetic screening; Symptoms; Ventricular arrhythmia.

Publication types

Comparative Study

MeSH terms

Adult
Aged
Arrhythmogenic Right Ventricular Dysplasia / diagnosis
Arrhythmogenic Right Ventricular Dysplasia / genetics*
Arrhythmogenic Right Ventricular Dysplasia / physiopathology
Cohort Studies
Cross-Sectional Studies
Female
Genetic Testing / methods
Genetic Testing / trends*
Genomics / methods
Genomics / trends*
Humans
Male
Middle Aged
Mutation / genetics
Retrospective Studies
Tertiary Care Centers / trends*
Time Factors
Ventricular Fibrillation / diagnosis
Ventricular Fibrillation / genetics*
Ventricular Fibrillation / physiopathology