Faculty Collaboration Database

Adrenergic receptor genotypes influence postoperative outcomes in infants in the Single-Ventricle Reconstruction Trial. J Thorac Cardiovasc Surg 2017 Nov;154(5):1703-1710.e3

Date

07/25/2017

Pubmed ID

28734628

Pubmed Central ID

PMC5647218

DOI

10.1016/j.jtcvs.2017.06.041

Scopus ID

2-s2.0-85024884367 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

OBJECTIVES: Adrenergic receptor (ADR) genotypes have been associated with adverse outcomes in heart failure. Our objective was to evaluate the association of ADR genotypes with post-Norwood outcomes in infants with hypoplastic left heart syndrome (HLHS).

METHODS: Infants with HLHS participating in the Pediatric Heart Network Single-Ventricle Reconstruction Trial underwent genotyping for 4 single-nucleotide polymorphisms in 3 ADR genes: ADRB1_231A/G, ADRB1_1165G/C, ADRB2_5318C/G, and ADRA2A_2790C/T. The association of genotype with freedom from serious adverse events (SAEs) (death, transplant, extracorporeal membrane oxygenation, cardiopulmonary resuscitation, acute shunt failure, unplanned reoperations, or necrotizing enterocolitis) during 14 months' follow-up was assessed with Cox regression and the association with post-Norwood complications was assessed with Poisson regression. Models were adjusted for clinical and surgical factors.

RESULTS: The study included 351 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 5.6 ± 3.6 days. A total of 152 patients had SAEs during 14-month follow-up including 84 deaths and 10 transplants. ADRA2A_2790CC genotype had lower SAE-free survival compared with CT/TT genotypes during follow-up (Log rank test, P = .02), and this association was independent of clinical and surgical risk factors (adjusted Cox regression, hazard ratio 1.54 [95% confidence interval 1.04, 2.30] P = .033). Post-Norwood complication rate did not differ by genotype.

CONCLUSIONS: Infants with HLHS harboring ADR genotypes that are associated with greater catecholamine release or sensitivity had lower event-free survival after staged palliation. Excess catecholamine activation may adversely affect cardiovascular adaptation after the Norwood procedure. Future studies should explore whether targeting adrenergic activation in those harboring risk genotypes can improve outcomes. (ClinicalTrials.gov number NCT00115934).

Author List

Ramroop R, Manase G, Lu D, Manase D, Chen S, Kim R, Lee T, Mahle WT, McHugh K, Mitchell M, Tristani-Firouzi M, Wechsler SB, Wilder NS, Zak V, Lafreniere-Roula M, Newburger JW, Gaynor JW, Russell MW, Mital S

Author

Michael Edward Mitchell MD Chief, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Female
Follow-Up Studies
Humans
Hypoplastic Left Heart Syndrome
Infant, Newborn
Male
Norwood Procedures
Polymorphism, Single Nucleotide
Postoperative Complications
Proportional Hazards Models
Receptors, Adrenergic, alpha-2
Receptors, Adrenergic, beta-1
Receptors, Adrenergic, beta-2