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GNAS gene variants affect ?-blocker-related survival after coronary artery bypass grafting.

ABSTRACT: Cardiac overexpression of the ?-adrenoreceptor (?AR)-coupled stimulatory G-protein subunit G?s enhances inotropic responses to adrenergic stimulation and improves survival in mice under ?AR blockade. The authors recently identified three common haplotypes in the GNAS gene encoding G?s, with the greatest G?s protein expression and signal transduction in haplotype *3 carriers and less in haplotype *2 and *1 carriers. The authors tested the hypothesis that these GNAS variants result in altered mortality in patients after coronary artery bypass graft surgery, particularly in those receiving ?AR blockade.This prospective analysis included 1,627 European ancestry patients undergoing primary coronary artery bypass graft surgery. Patients were genotyped for two GNAS haplotype tagging single-nucleotide polymorphisms defining three major haplotypes. Up to 5-yr all-cause mortality was estimated using a Cox proportional hazard model; hazard ratios and 95% CIs were calculated while adjusting for demographics, clinical covariates, and the new EuroSCORE II.Univariate analysis revealed haplotype-dependent 5-yr mortality rates (*1/*1: 18.9%, *2/*1: 13.7%, *2/*2: 9.3%, *3/*1: 10.6%, *3/*2: 9.1%, and *3/*3: 9.6%; P = 0.0006). After adjustment for other predictors of death, homozygote haplotype *1 carriers showed a doubled risk for death (hazard ratio, 2.2; 95% CI, 1.2 to 3.8; P = 0.006). Considering only patients receiving ?AR blockers (n = 1,267), the adjusted risk of death even tripled (hazard ratio, 3.0; 95% CI, 1.5 to 6.1; P = 0.002).GNAS haplotypes independently associate with an increased risk of death after primary coronary artery bypass graft surgery. These results are most pronounced in patients receiving ?AR blockers, strengthening the rationale for personalized treatment, to decrease medication side effects and improve outcomes.

SUBMITTER: Frey UH

PROVIDER: S-EPMC4070180 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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GNAS gene variants affect β-blocker-related survival after coronary artery bypass grafting.

Frey Ulrich H UH Muehlschlegel Jochen D JD Ochterbeck Christoph C Fox Amanda A AA Shernan Stanton K SK Collard Charles D CD Lichtner Peter P Peters Jürgen J Body Simon S

Anesthesiology 20140501 5

<h4>Background</h4>Cardiac overexpression of the β-adrenoreceptor (βAR)-coupled stimulatory G-protein subunit Gαs enhances inotropic responses to adrenergic stimulation and improves survival in mice under βAR blockade. The authors recently identified three common haplotypes in the GNAS gene encoding Gαs, with the greatest Gαs protein expression and signal transduction in haplotype *3 carriers and less in haplotype *2 and *1 carriers. The authors tested the hypothesis that these GNAS variants res ...[more]

PMID: 24755784

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Project description:Background Over 180 000 coronary artery bypass grafting (CABG) procedures are performed annually, accounting for $7 to $10 billion in episode expenditures. Assessing tradeoffs between spending and quality contributing to value during 90-day episodes has not been conducted but is essential for success in bundled reimbursement models. We, therefore, identified determinants of variability in hospital 90-day episode value for CABG. Methods Medicare and private payor admissions for isolated CABG from 2014 to 2016 were retrospectively linked to clinical registry data for 33 nonfederal hospitals in Michigan. Hospital composite risk-adjusted complication rates (≥1 National Quality Forum-endorsed, Society of Thoracic Surgeons measure: deep sternal wound infection, renal failure, prolonged ventilation >24 hours, stroke, re-exploration, and operative mortality) and 90-day risk-adjusted, price-standardized episode payments were used to categorize hospitals by value by defining the intersection between complications and spending. Results Among 2573 total patients, those at low- versus high-value hospitals had a higher percentage of prolonged length of stay >14 days (9.3% versus 2.4%, P=0.006), prolonged ventilation (17.6% versus 4.8%, P<0.001), and operative mortality (4.8% versus 0.6%, P=0.001). Mean total episode payments were $51 509 at low-compared with $45 526 at high-value hospitals (P<0.001), driven by higher readmission ($3675 versus $2177, P=0.005), professional ($7462 versus $6090, P<0.001), postacute care ($7315 versus $5947, P=0.031), and index hospitalization payments ($33 474 versus $30 800, P<0.001). Among patients not experiencing a complication or 30-day readmission (1923/2573, 74.7%), low-value hospitals had higher inpatient evaluation and management payments ($1405 versus $752, P<0.001) and higher utilization of inpatient rehabilitation (7% versus 2%, P<0.001), but lower utilization of home health (66% versus 73%, P=0.016) and emergency department services (13% versus 17%, P=0.034). Conclusions To succeed in emerging bundled reimbursement programs for CABG, hospitals and physicians should identify strategies to minimize complications while optimizing inpatient evaluation and management spending and use of inpatient rehabilitation, home health, and emergency department services.

Project description:ObjectiveThe Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival.MethodsWe used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty.ResultsIn-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; -0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [-3866 to 56,826]) and quality-adjusted life years showed no difference (-0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year.ConclusionsThe addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Project description:ObjectiveWe evaluated whether interhospital variation in mortality rates for coronary artery bypass grafting was driven by complications and failure to rescue.MethodsAn observational study was conducted among 83,747 patients undergoing isolated coronary artery bypass grafting between July 2011 and June 2017 across 90 hospitals. Failure to rescue was defined as operative mortality among patients developing complications. Complications included the Society of Thoracic Surgeons 5 major complications (stroke, surgical reexploration, deep sternal wound infection, renal failure, prolonged intubation) and a broader set of 19 overall complications. After creating terciles of hospital performance (based on observed:expected mortality), each tercile was compared on the basis of crude rates of (1) major and overall complications, (2) operative mortality, and (3) failure to rescue (among major and overall complications). The correlation between hospital observed and expected (to address confounding) failure to rescue rates was assessed.ResultsMedian Society of Thoracic Surgeons predicted mortality risk was similar across hospital observed:expected mortality terciles (P = .831). Mortality rates significantly increased across terciles (low tercile: 1.4%, high tercile: 2.8%). Although small in magnitude, rates of major (low tercile: 11.1%, high tercile: 12.2%) and overall (low tercile: 36.6%, high tercile: 35.3%) complications significantly differed across terciles. Nonetheless, failure to rescue rates increased substantially across terciles among patients with major (low tercile: 9.1%, high tercile: 14.3%) and overall (low tercile: 3.3%, high tercile: 6.8%) complications. Hospital observed and expected failure to rescue rates were positively correlated among patients with major (R2 = 0.14) and overall (R2 = 0.51) complications.ConclusionsThe reported interhospital variability in successful rescue after coronary artery bypass grafting supports the importance of identifying best practices at high-performing hospitals, including early recognition and management of complications.

Dataset Information

GNAS gene variants affect ?-blocker-related survival after coronary artery bypass grafting.

Publications

GNAS gene variants affect β-blocker-related survival after coronary artery bypass grafting.

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