Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials

Arthur M. Feldman; Lilin She; Dennis M. McNamara; Douglas L. Mann; Michael R. Bristow; Alan S. Maisel; Daniel R. Wagner; Bert Andersson; Luigi Chiariello; Christopher S. Hayward; Paul Hendry; John D. Parker; Normand Racine; Craig H. Selzman; Michele Senni; Janina Stepinska; Marian Zembala; Jean Rouleau; Eric J. Velazquez; Kerry L. Lee

doi:10.1159/000368221

Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials

Arthur M. Feldman, Lilin She, Dennis M. McNamara, Douglas L. Mann, Michael R. Bristow, Alan S. Maisel, Daniel R. Wagner, Bert Andersson, Luigi Chiariello, Christopher S. Hayward, Paul Hendry, John D. Parker, Normand Racine, Craig H. Selzman, Michele Senni, Janina Stepinska, Marian Zembala, Jean Rouleau, Eric J. Velazquez, Kerry L. Lee

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Objectives and Background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the β₂-adrenergic receptor gene (β₂-AR Gln27Glu) and in the A₁-adenosine receptor gene (A₁-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.

Original language	English
Pages (from-to)	69-81
Number of pages	13
Journal	Cardiology (Switzerland)
Volume	130
Issue number	2
DOIs	https://doi.org/10.1159/000368221
State	Published - Feb 24 2015

Keywords

Coronary artery disease
Genotype
Heart failure

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Feldman, A. M., She, L., McNamara, D. M., Mann, D. L., Bristow, M. R., Maisel, A. S., Wagner, D. R., Andersson, B., Chiariello, L., Hayward, C. S., Hendry, P., Parker, J. D., Racine, N., Selzman, C. H., Senni, M., Stepinska, J., Zembala, M., Rouleau, J., Velazquez, E. J., & Lee, K. L. (2015). Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Cardiology (Switzerland), 130(2), 69-81. https://doi.org/10.1159/000368221

@article{25985081590f4c8291e9f1ad234bce68,

title = "Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials",

abstract = "Objectives and Background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the β2-adrenergic receptor gene (β2-AR Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.",

keywords = "Coronary artery disease, Genotype, Heart failure",

author = "Feldman, {Arthur M.} and Lilin She and McNamara, {Dennis M.} and Mann, {Douglas L.} and Bristow, {Michael R.} and Maisel, {Alan S.} and Wagner, {Daniel R.} and Bert Andersson and Luigi Chiariello and Hayward, {Christopher S.} and Paul Hendry and Parker, {John D.} and Normand Racine and Selzman, {Craig H.} and Michele Senni and Janina Stepinska and Marian Zembala and Jean Rouleau and Velazquez, {Eric J.} and Lee, {Kerry L.}",

note = "Publisher Copyright: {\textcopyright} 2015 S. Karger AG, Basel.",

year = "2015",

month = feb,

day = "24",

doi = "10.1159/000368221",

language = "English",

volume = "130",

pages = "69--81",

journal = "Cardiology (Switzerland)",

issn = "0008-6312",

number = "2",

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Feldman, AM, She, L, McNamara, DM, Mann, DL, Bristow, MR, Maisel, AS, Wagner, DR, Andersson, B, Chiariello, L, Hayward, CS, Hendry, P, Parker, JD, Racine, N, Selzman, CH, Senni, M, Stepinska, J, Zembala, M, Rouleau, J, Velazquez, EJ & Lee, KL 2015, 'Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials', Cardiology (Switzerland), vol. 130, no. 2, pp. 69-81. https://doi.org/10.1159/000368221

Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. / Feldman, Arthur M.; She, Lilin; McNamara, Dennis M. et al.
In: Cardiology (Switzerland), Vol. 130, No. 2, 24.02.2015, p. 69-81.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction

T2 - Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials

AU - Feldman, Arthur M.

AU - She, Lilin

AU - McNamara, Dennis M.

AU - Mann, Douglas L.

AU - Bristow, Michael R.

AU - Maisel, Alan S.

AU - Wagner, Daniel R.

AU - Andersson, Bert

AU - Chiariello, Luigi

AU - Hayward, Christopher S.

AU - Hendry, Paul

AU - Parker, John D.

AU - Racine, Normand

AU - Selzman, Craig H.

AU - Senni, Michele

AU - Stepinska, Janina

AU - Zembala, Marian

AU - Rouleau, Jean

AU - Velazquez, Eric J.

AU - Lee, Kerry L.

PY - 2015/2/24

Y1 - 2015/2/24

N2 - Objectives and Background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the β2-adrenergic receptor gene (β2-AR Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.

AB - Objectives and Background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the β2-adrenergic receptor gene (β2-AR Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.

KW - Coronary artery disease

KW - Genotype

KW - Heart failure

UR - http://www.scopus.com/inward/record.url?scp=84921342173&partnerID=8YFLogxK

U2 - 10.1159/000368221

DO - 10.1159/000368221

M3 - Article

C2 - 25592552

AN - SCOPUS:84921342173

SN - 0008-6312

VL - 130

SP - 69

EP - 81

JO - Cardiology (Switzerland)

JF - Cardiology (Switzerland)

IS - 2

ER -

Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: Results of the genetic substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials

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Keywords

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