Acute Kidney Injury after Cardiac Surgery: Prediction, Prevention, and Management.

Acute kidney injury (AKI) is a common complication in cardiac surgery patients, with a reported incidence of 20 to 30%. The development of AKI is associated with worse short- and long-term mortality, and longer hospital length of stay. The pathogenesis of cardiac surgery-associated AKI is poorly understood but likely involves an interplay between preoperative comorbidities and perioperative stressors. AKI is commonly diagnosed by using increases in serum creatinine or decreased urine output and staged using a standardized definition such as the Kidney Disease Improving Global Outcomes classification. Novel biomarkers under investigation may provide earlier detection and better prediction of AKI, enabling mitigating therapies early in the perioperative period. Recent clinical trials of cardiac surgery patients have demonstrated the benefit of goal-directed oxygen delivery, avoidance of hyperthermic perfusion and specific fluid and medication strategies. This review article highlights both advances and limitations regarding the prevention, prediction, and treatment of cardiac surgery-associated AKI.

Meeting Report: First Cardiovascular Outcomes Research in Perioperative Medicine Conference.

The first Cardiovascular Outcomes Research in Perioperative Medicine (COR-PM) conference took place on May 13, 2022, in Palm Springs, CA, and online. Here, we: (1) summarize the background, objective, and aims of the COR-PM meeting; (2) describe the conduct of the meeting; and (3) outline future directions for scientific meetings aimed at fostering high-quality clinical research in the broader perioperative medicine community.

Preoperative Thoracic CT Findings Associated With Postoperative Mechanical Ventilation in Patients Undergoing Major Abdominal or Pelvic Surgery: A Matched Case-Control Study.

BACKGROUND. Postoperative prolonged mechanical ventilation is associated with increased morbidity and mortality. Reliable predictors of the need for postoperative mechanical ventilation after abdominal or pelvic surgeries are lacking. OBJECTIVE. The purpose of this study was to explore associations between preoperative thoracic CT findings and the need for postoperative mechanical ventilation after major abdominal or pelvic surgeries. METHODS. This retrospective case-control study included patients who underwent abdominal or pelvic surgeries during the period from January 1, 2014, through December 31, 2018, and had undergone preoperative thoracic CT. Case patients were patients who required postoperative mechanical ventilation. Control patients and case patients were matched at a 3:1 ratio on the basis of age, sex, body mass index, chronic obstructive pulmonary disease, smoking status, and surgery type. Two radiologists (readers 1 and 2) reviewed the CT images. Findings were compared between groups. RESULTS. The study included 165 patients (70 women, 95 men; mean age, 67.0 ± 9.7 [SD] years; 42 case patients and 123 matched control patients). Bronchial wall thickening and pericardial effusion were more frequent in case patients than control patients for reader 2 (10% vs 2%, p = .03; 17% vs 5%, p = .01) but not for reader 1. Pulmonary artery diameter (mean ± SD) was greater in case patients than control patients for reader 2 (2.9 ± 0.5 cm vs 2.8 ± 0.5 cm, p = .045) but not reader 1. Right lung height was lower in case patients than control patients for reader 1 (18.4 ± 2.9 cm vs 19.9 ± 2.7 cm, p = .01) and reader 2 (18.3 ± 2.9 cm vs 19.8 ± 2.7 cm, p = .01). Left lung height was lower in case patients than control patients for reader 1 (19.5 ± 3.1 cm vs 21.1 ± 2.6 cm, p = .01) and reader 2 (19.6 ± 2.4 cm vs 20.9 ± 2.6 cm, p = .01). Anteroposterior (AP) chest diameter was greater for case patients than control patients for reader 1 (14.0 ± 2.3 cm vs 12.9 ± 3.7 cm, p = .02) and reader 2 (14.2 ± 2.2 cm vs 13.2 ± 3.6 cm, p = .04). In a multivariable regression model using pooled reader data, bronchial wall thickening exhibited an odds ratio (OR) of 4.6 (95% CI, 1.3-16.5; p = .02); pericardial effusion, an OR of 5.1 (95% CI, 1.7-15.5; p = .004); pulmonary artery diameter, an OR of 1.4 per 1-cm increase (95% CI, 0.7-3.0; p = .32); mean lung height, an OR of 0.8 per 1-cm increase (95% CI, 0.7-1.001; p = .05); and AP chest diameter, an OR of 1.2 per 1-cm increase (95% CI, 1.013-1.4; p = .03). CONCLUSION. CT features are associated with the need for postoperative mechanical ventilation after abdominal or pelvic surgery. CLINICAL IMPACT. Many patients undergo thoracic CT before abdominal or pelvic surgery; the CT findings may complement preoperative clinical risk factors.

Society of Cardiovascular Anesthesiologists Clinical Practice Update for Management of Acute Kidney Injury Associated With Cardiac Surgery.

Cardiac surgery-associated acute kidney injury (CS-AKI) is common and is associated with increased risk for postoperative morbidity and mortality. Our recent survey of the Society of Cardiovascular Anesthesiologists (SCA) membership showed 6 potentially renoprotective strategies for which clinicians would most value an evidence-based review (ie, intraoperative target blood pressure, choice of specific vasopressor agent, erythrocyte transfusion threshold, use of alpha-2 agonists, goal-directed oxygen delivery on cardiopulmonary bypass [CPB], and the "Kidney Disease Improving Global Outcomes [KDIGO] bundle of care"). Thus, the SCA's Continuing Practice Improvement Acute Kidney Injury Working Group aimed to provide a practice update for each of these strategies in cardiac surgical patients based on the evidence from randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane library databases were comprehensively searched for eligible studies from inception through February 2021, with search results updated in August 2021. A total of 15 RCTs investigating the effects of the above-mentioned strategies on CS-AKI were included for meta-analysis. For each strategy, the level of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Across the 6 potentially renoprotective strategies evaluated, current evidence for their use was rated as "moderate," "low," or "very low." Based on eligible RCTs, our analysis suggested using goal-directed oxygen delivery on CPB and the "KDIGO bundle of care" in high-risk patients to prevent CS-AKI (moderate level of GRADE evidence). Our results suggested considering the use of vasopressin in vasoplegic shock patients to reduce CS-AKI (low level of GRADE evidence). The decision to use a restrictive versus liberal strategy for perioperative red cell transfusion should not be based on concerns for renal protection (a moderate level of GRADE evidence). In addition, targeting a higher mean arterial pressure during CPB, perioperative use of dopamine, and use of dexmedetomidine did not reduce CS-AKI (a low or very low level of GRADE evidence). This review will help clinicians provide evidence-based care, targeting improved renal outcomes in adult patients undergoing cardiac surgery.

A Positive Cocaine Urine Toxicology Test and the Effect on Intraoperative Hemodynamics Under General Anesthesia.

BACKGROUND: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. METHODS: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. RESULTS: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (ß coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (ß coefficient = 0.2%, P < .001, CI, 4-3). CONCLUSIONS: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Packed red blood cell transfusion associates with acute kidney injury after transcatheter aortic valve replacement.

BACKGROUND: Acute kidney injury after cardiac surgery significantly associates with morbidity and mortality. Despite not requiring cardiopulmonary bypass, transcatheter aortic valve replacement patients have an incidence of post-procedural acute kidney injury similar to patients who undergo open surgical aortic valve replacement. Packed red blood cell transfusion has been associated with morbidity and mortality after cardiac surgery. We hypothesized that packed red blood cell transfusion independently associates with acute kidney injury after transcatheter aortic valve replacement, after accounting for other risk factors. METHODS: This is a single-center retrospective cohort study of 116 patients undergoing transcatheter aortic valve replacement. Post-transcatheter aortic valve replacement acute kidney injury was defined by Kidney Disease: Improving Global Outcomes serum creatinine-based criteria. Univariate comparisons between patients with and without post-transcatheter aortic valve replacement acute kidney injury were made for clinical characteristics. Multivariable logistic regression was used to assess independent association of packed red blood cell transfusion with post-transcatheter aortic valve replacement acute kidney injury (adjusting for pre-procedural renal function and other important clinical parameters). RESULTS: Acute kidney injury occurred in 20 (17.2%) subjects. Total number of packed red blood cells transfused independently associated with post-procedure acute kidney injury (OR = 1.67 per unit, 95% CI 1.13-2.47, P = 0.01) after adjusting for pre-procedure estimated glomerular filtration rate (OR = 0.97 per ml/min/1.73m2, 95% CI 0.94-1.00, P = 0.05), nadir hemoglobin (OR = 0.88 per g/dL increase, CI 0.61-1.27, P = 0.50), and post-procedure maximum number of concurrent inotropes and vasopressors (OR = 2.09 per inotrope or vasopressor, 95% CI 1.19-3.67, P = 0.01). CONCLUSION: Packed red blood cell transfusion, along with post-procedure use of inotropes and vasopressors, independently associate with acute kidney injury after transcatheter aortic valve replacement. Further studies are needed to elucidate the pathobiology underlying these associations.

Atherosclerosis on CT Angiogram Predicts Acute Kidney Injury After Transcatheter Aortic Valve Replacement.

OBJECTIVE: The purpose of this study is to determine the association of vascular calcification and renal artery stenosis on CT angiogram (CTA) obtained before transcatheter aortic valve replacement (TAVR) with postprocedure acute kidney injury (AKI). MATERIALS AND METHODS: In this single-center retrospective cohort study, 106 pre-TAVR CTAs were evaluated by two independent blinded readers. Renal artery stenosis was visually graded as less than 50% or greater than or equal to 50% luminal narrowing. Calcification of the aorta and iliac arteries was scored from 0 (no calcification) to 3 (severe calcification) and was summed to develop a calcification score. Univariate comparisons between patients who did and did not develop AKI were made for radiologic measurements. Multivariable logistic regression was used to assess association of renal artery stenosis and atherosclerotic calcification with post-TAVR AKI. RESULTS: Post-TAVR AKI occurred in 20 of 106 patients. Subjects with bilateral main renal artery stenosis greater than or equal to 50% had significantly greater odds (odds ratio, 4.84; 95% CI, 1.41-16.54; p = 0.01) of developing post-TAVR AKI than did subjects with unilateral or no stenosis greater than or equal to 50% in the main renal arteries. Subjects who developed post-TAVR AKI had significantly higher aortic and iliac arterial calcification scores compared with subjects who did not develop post-TAVR AKI (mean ± SD, 21.4 ± 5.6 vs 17.9 ± 6.7; p = 0.04). CONCLUSION: AKI as a complication of TAVR is more likely to develop in patients with bilateral renal artery stenosis greater than or equal to 50% or severe atherosclerotic calcification of the aorta and iliac arteries.

A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury.

RATIONALE: Acute kidney injury is a common and severe complication of critical illness and cardiac surgery. Despite significant attempts at developing treatments, therapeutic advances to attenuate acute kidney injury and expedite recovery have largely failed. OBJECTIVES: Identifying genetic loci associated with increased risk of acute kidney injury may reveal novel pathways for therapeutic development. METHODS: We conducted an exploratory genome-wide association study to identify single-nucleotide polymorphisms associated with genetic susceptibility to in-hospital acute kidney injury. MEASUREMENTS AND MAIN RESULTS: We genotyped 609,508 single-nucleotide polymorphisms and performed genotype imputation in 760 acute kidney injury cases and 669 controls. We then evaluated polymorphisms that showed the strongest association with acute kidney injury in a replication patient population containing 206 cases with 1,406 controls. We observed an association between acute kidney injury and four single-nucleotide polymorphisms at two independent loci on metaanalysis of discovery and replication populations. These include rs62341639 (metaanalysis P = 2.48 × 10-7; odds ratio [OR], 0.64; 95% confidence interval [CI], 0.55-0.76) and rs62341657 (P = 3.26 × 10-7; OR, 0.65; 95% CI, 0.55-0.76) on chromosome 4 near APOL1-regulator IRF2, and rs9617814 (metaanalysis P = 3.81 × 10-6; OR, 0.70; 95% CI, 0.60-0.81) and rs10854554 (P = 6.53 × 10-7; OR, 0.67; 95% CI, 0.57-0.79) on chromosome 22 near acute kidney injury-related gene TBX1. CONCLUSIONS: Our findings reveal two genetic loci that are associated with acute kidney injury. Additional studies should be conducted to functionally evaluate these loci and to identify other common genetic variants contributing to acute kidney injury.

Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery.

Heme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; ≥27 GT repeats), and defined AKI as an increase in serum creatinine ≥0.3 mg/dl within 48 hours or ≥50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.

Using next-generation RNA sequencing to examine ischemic changes induced by cold blood cardioplegia on the human left ventricular myocardium transcriptome.

BACKGROUND: The exact mechanisms that underlie the pathological processes of myocardial ischemia in humans are unclear. Cardiopulmonary bypass with cardioplegic arrest allows the authors to examine the whole transcriptional profile of human left ventricular myocardium at baseline and after exposure to cold cardioplegia-induced ischemia as a human ischemia model. METHODS: The authors obtained biopsies from 45 patients undergoing aortic valve replacement surgery at baseline and after an average of 79 min of cold cardioplegic arrest. Samples were RNA sequenced and analyzed with the Partek Genomics Suite (Partek Inc., St. Louis, MO) for differential expression. Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA) and Biobase ExPlain (Biobase GmbH, Wolfenbuettel, Germany) systems were used for functional and pathway analyses. RESULTS: Of the 4,098 genes with a mean expression value greater than 5, 90% were down-regulated and 9.1% were up-regulated. Of those, 1,241 were significantly differentially expressed. Gene ontology analysis revealed significant down-regulation in immune inflammatory response and complement activation categories and highly consistent was the down-regulation of intelectin 1, proteoglycan, and secretory leukocyte peptidase inhibitor. Up-regulated genes of interest were FBJ murine osteosarcoma viral oncogene homolog and the hemoglobin genes hemoglobin α1 (HBA1) and hemoglobin ß. In addition, analysis of transcription factor-binding sites revealed interesting targets in factors regulating reactive oxygen species production, apoptosis, immunity, cytokine production, and inflammatory response. CONCLUSIONS: The authors have shown that the human left ventricle exhibits significant changes in gene expression in response to cold cardioplegia-induced ischemia during cardiopulmonary bypass, which provides great insight into the pathophysiology of ventricular ischemia, and thus, may help guide efforts to reduce myocardial damage during surgery.

Genetic Variants Associated With Atrial Fibrillation and PR Interval Following Cardiac Surgery.

OBJECTIVE: The authors hypothesized that genetic association between atrial fibrillation (AF)-associated and PR-associated genetic loci was biologically mediated through slower conduction velocities for some or all of these loci. DESIGN: Prospectively collected cohort study. SETTING: Single tertiary care university hospital. PARTICIPANTS: A total of 1227 Caucasian patients who underwent coronary artery bypass grafting (CABG). INTERVENTIONS: A total of 677 single nucleotide polymorphisms previously associated with ambulatory AF or PR interval were tested for association with postoperative atrial fibrillation (poAF) and preoperative PR interval, maximum PR interval, maximum change in PR interval, and maximum change in PR interval from preoperative PR interval. MEASUREMENTS AND MAIN RESULTS: The incidence of new-onset poAF was 31%. All of the PR interval variables were longer in the poAF cohort. Two variants on 1q21 and 12 on 4q25 were associated with poAF after adjustment for false discovery rate (FDR), but no variants were associated with PR interval variables after adjustment for FDR. Several variants were associated with both poAF and PR interval variables at p<0.05, but none of them remained significant after adjusting for FDR. CONCLUSION: It was found that patients with poAF have significantly longer PR interval. Genetic variants in both the 1q21 and 4q25 regions associate with poAF after CABG surgery, but the authors were unable to find association between these variants and PR interval after adjusting for FDR.

Plasma corin decreases after coronary artery bypass graft surgery and is associated with postoperative heart failure: a pilot study.

OBJECTIVE: Corin is a natriuretic peptide-converting enzyme that cleaves precursor pro-B-type natriuretic peptide to active B-type natriuretic peptide (BNP) (diuretic, natriuretic, and vasodilatory properties). Increased plasma BNP is a known diagnostic and prognostic heart failure (HF) biomarker in ambulatory and surgical patients. Recent studies indicate that plasma corin is decreased significantly in chronic HF patients, yet perioperative plasma corin concentrations have not been assessed in cardiac surgical patients. The objectives of this study were to determine the effect of coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) on plasma corin concentrations and to assess the association between change in perioperative plasma corin concentration and long-term postoperative HF hospitalization or death. It was hypothesized that plasma corin concentrations decrease significantly from preoperative baseline during postoperative days 1 to 4 and that hospitalization or death from HF during the 5 years after surgery is associated with higher relative difference (preoperative baseline to postoperative nadir) in plasma corin concentrations. DESIGN: Prospective observational pilot study. SETTING: Two institutions: Brigham and Women's Hospital, Boston, Massachusetts and the Texas Heart Institute, St. Luke's Hospital, Houston, Texas. PARTICIPANTS: 99 patients of European ancestry who underwent isolated primary CABG surgery with CPB. INTERVENTIONS: Nonemergency isolated primary CABG surgery with CPB. MEASUREMENTS AND MAIN RESULTS: Plasma corin concentration was assessed preoperatively and at 4 postoperative time points (postoperative days 1-4). HF hospitalization or HF death events during the 5 years after surgery were identified by review of hospital and death records. Postoperative plasma corin concentrations were significantly lower than preoperative baseline concentrations (p<0.0001). Perioperative corin concentrations were significantly higher in males than in females (p<0.0001). Fifteen patients experienced long-term postoperative HF events. Patients who experienced HF hospitalization or HF death during study follow-up had significantly higher relative difference in plasma corin concentration (preoperative baseline to postoperative nadir) than patients who did not experience HF events during study follow-up (p=0.03). CONCLUSIONS: Plasma corin concentrations decrease significantly from preoperative concentrations after CABG surgery. HF hospitalization or HF death during the 5 years after CABG surgery with CPB is associated with larger relative decrease in plasma corin concentration from preoperative baseline. Further investigation is warranted to determine the role of corin in postoperative HF biology.

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

BACKGROUND: Cardiac overexpression of the ß-adrenoreceptor (ßAR)-coupled stimulatory G-protein subunit Gαs enhances inotropic responses to adrenergic stimulation and improves survival in mice under ßAR 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 result in altered mortality in patients after coronary artery bypass graft surgery, particularly in those receiving ßAR blockade. METHODS: 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. RESULTS: 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 ßAR 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). CONCLUSIONS: 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 ßAR blockers, strengthening the rationale for personalized treatment, to decrease medication side effects and improve outcomes.

Increased perioperative b-type natriuretic peptide associates with heart failure hospitalization or heart failure death after coronary artery bypass graft surgery.

BACKGROUND: Heart failure (HF) is a leading cause of hospitalization and mortality. Plasma B-type natriuretic peptide (BNP) is an established diagnostic and prognostic ambulatory HF biomarker. We hypothesized that increased perioperative BNP independently associates with HF hospitalization or HF death up to 5 yr after coronary artery bypass graft surgery. METHODS: The authors conducted a two-institution, prospective, observational study of 1,025 subjects (mean age = 64 ± 10 yr SD) undergoing isolated primary coronary artery bypass graft surgery with cardiopulmonary bypass. Plasma BNP was measured preoperatively and on postoperative days 1-5. The study outcome was hospitalization or death from HF, with HF events confirmed by reviewing hospital and death records. Cox proportional hazards analyses were performed with multivariable adjustments for clinical risk factors. Preoperative and peak postoperative BNP were added to the multivariable clinical model in order to assess additional predictive benefit. RESULTS: One hundred five subjects experienced an HF event (median time to first event = 1.1 yr). Median follow-up for subjects who did not have an HF event = 4.2 yr. When individually added to the multivariable clinical model, higher preoperative and peak postoperative BNP concentrations each, independently associated with the HF outcome (log10 preoperative BNP hazard ratio = 1.93; 95% CI, 1.30-2.88; P = 0.001; log10 peak postoperative BNP hazard ratio = 3.38; 95% CI, 1.45-7.65; P = 0.003). CONCLUSIONS: Increased perioperative BNP concentrations independently associate with HF hospitalization or HF death during the 5 yr after primary coronary artery bypass graft surgery. Clinical trials may be warranted to assess whether medical management focused on reducing preoperative and longitudinal postoperative BNP concentrations associates with decreased HF after coronary artery bypass graft surgery.

Thoracic Interfascial Plane Blocks and Outcomes After Minithoracotomy for Valve Surgery.

Introduction. Thoracic interfascial plane blocks are increasingly used for pain management after minimally invasive thoracotomy for valve repair and replacement procedures. We hypothesized that the addition of these blocks to the intercostal nerve block injected by the surgeon would further reduce pain scores and opioid utilization. Methods. In this retrospective cohort study, 400 consecutive patients who underwent minimally invasive thoracotomy for mitral or aortic valve replacement and were extubated within 2 hours of surgery were enrolled. The maximum pain score and opioid utilization on the day of surgery and other outcome variables were compared between patients who received interfascial plane blocks and those who did not. Results.193 (48%) received at least one interfascial plane block while 207 (52%) received no interfascial plane block. Patients who received a thoracic interfascial plane block had a maximum VAS score on the day of surgery (mean 7.4 ± 2.5) after the block was administered which was significantly lower than patients in the control group who did not receive the block (mean 7.9 ± 2.2) (P = .02). Opioid consumption in the interfascial plane block group on the day of surgery was not significantly different from the control group. Conclusion. Compared to intercostal blocks alone, the addition of thoracic interfascial plane blocks was associated with a modest reduction in maximum VAS score on the day of surgery. However, no difference in opioid consumption was noted. Patients who received interfascial plane blocks also had decreased blood transfusion requirements and a shorter hospital length of stay.

Polymorphism in the protease-activated receptor-4 gene region associates with platelet activation and perioperative myocardial injury.

Protease-activated receptors (PAR)-1 and -4 are the principal receptors for thrombin-mediated platelet activation. Functional genetic variation has been described in the human PAR1 gene, but not in the PAR4 gene (F2RL3). We sought to identify variants in and around F2RL3 and to determine their association with perioperative myocardial injury (PMI) after coronary artery bypass graft surgery. We further explored possible mechanisms for F2RL3 single nucleotide polymorphism (SNP) associations with PMI including altered receptor expression and platelet activation. Twenty-three SNPs in the F2RL3 gene region were genotyped in two phases in 934 Caucasian subjects. Platelets from 43 subjects (23 major allele, 20 risk allele) homozygous for rs773857 (SNP with the strongest association with PMI) underwent flow cytometry to assess PAR4 receptor number and response to activation by a specific PAR4 activating peptide (AYPGKF) measured by von Willebrand factor (vWf) binding and P-selectin release and PAC-1 binding. We identified a novel association of SNP rs773857 with PMI (OR = 2.4, P = 0.004). rs773857 risk allele homozygotes have significantly increased platelet counts and platelets showed a significant increase in P-selectin release after activation (P = 0.004). We conclude that rs773857 risk allele homozygotes are associated with risk for increased platelet count and hyperactivity.