Fast tracking in cardiac surgery: is it safe?

BACKGROUND: While fast track clinical pathways have been demonstrated to reduce resource utilization in patients undergoing cardiac surgery, it remains unclear as to whether they adversely affect post-operative outcomes. The purpose of this study was to determine the impact of fast tracking on post-operative outcomes following cardiac surgery. METHODS: In a retrospective study, all patients undergoing first-time, on-pump, non-emergent coronary artery bypass grafting, valve, or coronary artery bypass grafting + valve at a single centre between 2010 and 2017 were included. Patients were considered to have been fast tracked if they were extubated and transferred from intensive care to a step-down unit on the same day as their procedure. The risk-adjusted effect of fast tracking on a 30-day composite of all-cause mortality, stroke, renal failure, infection, atrial fibrillation, and readmission to hospital was determined. Furthermore, propensity score matching was used to match fasting track patients in a 1-to-1 manner with their nearest "neighbor" in the control group and subsequently compared in terms of 30-day post-operative outcomes. RESULTS: 3252 patients formed the final study population (fast track: n = 245; control: n = 3007). Patients who were fast tracked experienced reduced time to initial extubation (4.3 vs. 5.6 h, p < 0.0001) and lower median initial intensive care unit length of stay (7.8 vs. 20.4 h, p < 0.0001). Fast tracked patients experienced lower 30-day rates of the composite outcome (42.4% vs. 51.5%, p = 0.008). However, following propensity score matching, fast tracked patients experienced similar 30-day rates of the composite outcome as the control group (42.4% vs. 44.5%, p = 0.72). After risk adjustment using multivariable regression modeling, fast tracking was predictive of an improved 30-day composite outcome (OR 0.75, 95% CI 0.57-0.98, p = 0.03). CONCLUSION: Fast track clinical pathways was associated with reduced intensive care unit, overall length of stay and similar 30-day post-operative outcomes. These results suggest that fast tracking appropriate patients may reduce resource utilization, while maintaining patient safety.

Adverse Outcomes in Obese Cardiac Surgery Patients Correlates With Altered Branched-Chain Amino Acid Catabolism in Adipose Tissue and Heart.

Background: Predicting relapses of post-operative complications in obese patients who undergo cardiac surgery is significantly complicated by persistent metabolic maladaptation associated with obesity. Despite studies supporting the linkages of increased systemic branched-chain amino acids (BCAAs) driving the pathogenesis of obesity, metabolome wide studies have either supported or challenged association of circulating BCAAs with cardiovascular diseases (CVDs). Objective: We interrogated whether BCAA catabolic changes precipitated by obesity in the heart and adipose tissue can be reliable prognosticators of adverse outcomes following cardiac surgery. Our study specifically clarified the correlation between BCAA catabolizing enzymes, cellular BCAAs and branched-chain keto acids (BCKAs) with the severity of cardiometabolic outcomes in obese patients pre and post cardiac surgery. Methods: Male and female patients of ages between 44 and 75 were stratified across different body mass index (BMI) (non-obese = 17, pre-obese = 19, obese class I = 14, class II = 17, class III = 12) and blood, atrial appendage (AA), and subcutaneous adipose tissue (SAT) collected during cardiac surgery. Plasma and intracellular BCAAs and BC ketoacids (BCKAs), tissue mRNA and protein expression and activity of BCAA catabolizing enzymes were assessed and correlated with clinical parameters. Results: Intramyocellular, but not systemic, BCAAs increased with BMI in cardiac surgery patients. In SAT, from class III obese patients, mRNA and protein expression of BCAA catabolic enzymes and BCKA dehydrogenase (BCKDH) enzyme activity was decreased. Within AA, a concomitant increase in mRNA levels of BCAA metabolizing enzymes was observed, independent of changes in BCKDH protein expression or activity. BMI, indices of tissue dysfunction and duration of hospital stay following surgery correlated with BCAA metabolizing enzyme expression and metabolite levels in AA and SAT. Conclusion: This study proposes that in a setting of obesity, dysregulated BCAA catabolism could be an effective surrogate to determine cardiac surgery outcomes and plausibly predict premature re-hospitalization.

Serum GDF15, a Promising Biomarker in Obese Patients Undergoing Heart Surgery.

Background: Obesity is a risk factor that negatively impacts outcomes in patients undergoing heart surgery by mechanisms that are not well-defined nor predicated on BMI alone. This knowledge gap has fuelled a search for biomarkers associated with cardiovascular diseases that could provide clinical insight to surgeons. One such biomarker is growth differentiation factor15(GDF15), associated with inflammation, metabolism, and heart failure outcomes but not yet examined in the context of obesity and cardiac surgery outcomes. Methods: Patients undergoing open-heart surgery were consented and enrolled for blood and tissue (atria) sampling at the time of surgery. Biomarker analysis was carried out using ELISA and western blot/qPCR, respectively. Biomarker screening was classified by inflammation(NLR, GDF15, Galectin3, ST2, TNFR2), heart failure(HF)/remodeling(NT-proBNP) and metabolism(glycemia, lipid profile). Patients were categorized based on BMI: obese group (BMI ≥30.0) and non-obese group(BMI 20.0-29.9). Subsequent stratification of GDF15 high patients was conservatively set as being in the 75th percentile. Results: A total of 80 patients undergoing any open-heart surgical interventions were included in the study. Obese (mean BMI = 35.8, n = 38) and non-obese (mean BMI = 25.7, n = 42) groups had no significant differences in age, sex, or co-morbidities. Compared to other biomarkers, plasma GDF15 (mean 1,736 vs. 1,207 ng/l, p < 0.001) was significantly higher in obese patients compared to non-obese. Plasma GDF15 also displayed a significant linear correlation with BMI (R 2 = 0.097; p = 0.0049). Atria tissue was shown to be a significant source of GDF15 protein and tissue levels significantly correlated with plasma GDF15 (R 2 = 0.4, p = 0.0004). Obesity was not associated with early/late mortality at median follow-up >2years. However, patients with high GDF15 (>1,580 ng/l) had reduced survival (65%) compared to the remaining patients with lower GDF15 levels (95%) by Kaplan Meier Analysis (median >2 years; p = 0.007). Conclusions: Circulating GDF15 is a salient biomarker likely sourced from heart tissue that appears to predict higher risk obese patients for adverse outcomes. More importantly, elevated GDF15 accounted for more sensitive outcome association than BMI at 2 years post-cardiac surgery, suggesting it heralds links to pathogenicity and should be actively studied prospectively and dynamically in a post-operative follow-up. Trial number: NCT03248921.

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery.

BACKGROUND: The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome. METHODS: Voluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry. RESULTS: A total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16-). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio). CONCLUSION: Atrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management.

Impact of Obesity on Postoperative Outcomes following cardiac Surgery (The OPOS study): rationale and design of an investigator-initiated prospective study.

INTRODUCTION: Increasing levels of obesity worldwide have led to a rise in the prevalence of obesity-related complications including cardiovascular risk factors such as diabetes, hypertension and dyslipidaemia. Healthcare providers believe that overweight and obese cardiac surgery patients are more likely to experience adverse postoperative outcomes. The body mass index (BMI) is the primary measure of obesity in clinical practice, without accounting for a patient's level of cardiopulmonary fitness or muscle mass. The objective of this study is to determine whether fitness capacity of obese cardiac surgical patients and biomarkers, alone or in combination, will help identify patients at risk for adverse outcomes when undergoing cardiac surgery. METHODS AND ANALYSIS: Patients between the ages of 18 and 75 years undergoing elective cardiac surgery are consented to participate in this prospective observational study. Patients will be invited to participate in measures of obesity, functional capacity and exercise capacity assessments, quality of life questionnaires, and blood and tissue sampling for biomarker analysis. The endpoints evaluated are measures other than BMI that could be predictive of short-term and long-term postoperative outcomes. Clinical outcomes of interest are prolonged ventilation, hospital length of stay, renal failure and all-cause mortality. Biomarkers of interest will largely focus on metabolism (lipids, amino acids) and inflammation (adipokines, cytokines and chemokines). ETHICS AND DISSEMINATION: This study has been approved by the institutional review board at the Horizon Health Network. On completion of the study, the results shall be disseminated through conference presentations and publications in peer-reviewed journals. Additionally, the report shall also be diffused more broadly to the general public and the cardiovascular community. TRIAL REGISTRATION NUMBER: NCT03248921.

Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans.

BACKGROUND: Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. OBJECTIVES: This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. METHODS: LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients. RESULTS: LPA1-6 were expressed in myocardium and white adipose tissue from mice and humans, except for LPA3, which was undetectable in murine adipocytes and human adipose tissue. Obesity was associated with increased LPA4, LPA5 and/or LPA6 levels in mice ventricles and cardiomyocytes, HL-1 cells exposed to high palmitate, and human atrial tissue. LPA4 and LPA5 mRNA levels in human atrial tissue correlated with measures of obesity. LPA5 mRNA levels were increased in HFHS-fed mice and insulin resistant adipocytes, yet were reduced in adipose tissue from obese patients. LPA4, LPA5, and LPA6 mRNA levels in human adipose tissue were negatively associated with measures of obesity and cardiac surgery outcomes. This study suggests that obesity leads to marked changes in LPA receptor expression in the murine and human heart and white adipose tissue that may alter LPA receptor signaling during obesity.

Impact of Obesity on Intensive Care Unit Resource Utilization After Cardiac Operations.

BACKGROUND: Much has been published about the effect of obesity on adverse outcomes after cardiac operations, yet little is known regarding the effect of obesity on intensive care unit (ICU) resource utilization. This study examined the effect of obesity on ICU resource utilization after cardiac operations. METHODS: All patients with a body mass index (BMI) of 18.5 kg/m2 or higher who underwent a cardiac surgical procedure between 2006 and 2013 were stratified into the following weight categories: normal (BMI 18.5 to 24.99 kg/m2), preobese (BMI 25 to 29.99 kg/m2), obese class I (BMI 30 to 34.99 kg/m2), obese class II (BMI 35 to 39.99 kg/m2), and obese class III (BMI ≥40 kg/m2). Comparisons between weight categories were done, and the risk-adjusted effect of weight category on prolonged ICU stay, prolonged ventilation, and ICU readmission was determined. RESULTS: Of the 5,365 included patients, 1,948 were obese. Patients with greater obesity experienced longer ICU time, longer ventilation time, and increased ICU readmission. After adjustment, increasing obesity remained independently associated with greater likelihood of prolonged ICU stay (obese class II: odds ratio [OR], 2.4; 95% confidence interval [CI], 1.55 to 3.61; obese class III: OR, 4.1; 95% CI, 2.38 to 7.05), prolonged ventilation (obese class III: OR, 3.4; 95% CI, 1.57 to 7.22), and ICU readmission (obese class II: OR, 3.0; 95% CI, 1.70 to 5.31; obese class III: OR, 2.9; 95% CI, 1.32 to 6.36). CONCLUSIONS: Increasing obesity was associated with a significant increase in ICU resource utilization after cardiac operations. Further study is needed to determine the mechanisms underlying this association and how the adverse effects of obesity may be mitigated.