Common genetic variants improve risk stratification after the atrial switch operation for transposition of the great arteries
International Journal of Cardiology, vol. 371, pp. 153–159
Abstract
Background Clinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical course remains. We studied whether common genetic variants are associated with outcome and add value to a clinical risk score in TGA-AtrSO patients. Methods and results This multicenter study followed 133 TGA-AtrSO patients (aged 28 [IQR 24–35] years) for 13 (IQR 9–16) years and examined the association of genome-wide single-nucleotide polymorphisms (SNPs) with a composite endpoint of symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one genome-wide significant ( p < 1 × 10 −8 ) locus and 18 suggestive loci (p < 1 × 10 −5 ). A genetic risk score constructed on the basis of independent SNPs with p < 1 × 10 −5 was associated with outcome after correction for the clinical risk score (HR = 1.26/point increase [95%CI 1.17–1.35]). Risk stratification improved with a combined risk score (clinical score + genetic score) compared to the clinical score alone ( p = 2 × 10 −16 , C-statistic 0.95 vs 0.85). In 51 patients with a clinical intermediate (5–20%) 5-year risk of events, the combined score reclassified 32 patients to low (<5%) and 5 to high (>20%) risk. Stratified by the combined score, observed 5-year event-free survival was 100%, 79% and 31% for low, intermediate, and high-risk patients, respectively. Conclusions Common genetic variants may explain some variation in the clinical course in TGA-AtrSO and improve risk stratification over clinical factors alone, especially in patients at intermediate clinical risk. These findings support the hypothesis that including genetic variants in risk assessment may be beneficial.
Authors 13
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Odilia I. Woudstra corresponding
Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Heart Center; Department of Clinical Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: o.i.woudstra@amsterdamumc.nl
Department of Clinical Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Heart Center
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Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Heart Center; Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Heart Center
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Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Heart Center; Department of Clinical Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Department of Clinical Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Heart Center
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University Medical Center Utrecht
Affiliation as printed
Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
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University Medical Center Utrecht · St. Antonius Ziekenhuis
Affiliation as printed
Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands
Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands
Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
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Monique R.M. Jongbloed Aachen Department of Anatomy and Embryology Department of Cardiology, Leiden University Medical Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; Department of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands
Department of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands
Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Cardiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands
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University Medical Center Groningen
Affiliation as printed
Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands
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Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Heart Center; Department of Clinical Cardiology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands
Department of Clinical Cardiology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands
Heart Center
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Department of Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Department of Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
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Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Heart Center; Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Heart Center
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Amsterdam University Medical Centers · Amsterdam Cardiovascular Sciences · University of Amsterdam
Affiliation as printed
Heart Center; Department of Clinical Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Department of Clinical Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Heart Center
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
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