Decreased Left Atrial Cardiomyocyte FGF13 Expression Increases Vulnerability to Postoperative Atrial Fibrillation in Humans.

Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and a significant cause of increased morbidity and mortality. The development of novel POAF therapeutics has been limited by an insufficient understanding of molecular mechanisms promoting atrial fibrillation. In this observational cohort study, we enrolled 28 patients without a history of atrial fibrillation that underwent mitral valve surgery for degenerative mitral regurgitation and obtained left atrial tissue samples along the standard atriotomy incision in proximity to the right pulmonary veins. We isolated cardiomyocytes and performed transcriptome analyses demonstrating 13 differentially expressed genes associated with new-onset POAF. Notably, decreased expression of fibroblast growth factor 13 (FGF13), a fibroblast growth factor homologous factor known to modulate voltage-gated sodium channel Na V 1.5 inactivation, had the most significant association with POAF. To assess the functional significance of decreased FGF13 expression in atrial myocytes, we performed patch clamp experiments on neonatal rat atrial myocytes after siRNA-mediated FGF13 knockdown, demonstrating action potential prolongation. These critical findings indicate that decreased FGF13 expression promotes vulnerability to POAF.

Volume-outcome relationship in septal myectomy for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Septal myectomy is the gold standard treatment for refractory hypertrophic obstructive cardiomyopathy. The present study characterized the association of septal myectomy volume and cardiac surgery volume with outcomes after septal myectomy. METHODS: Adults undergoing septal myectomy for hypertrophic obstructive cardiomyopathy were identified in the 2016 to 2019 Nationwide Readmissions Database. Centers were grouped into low-, medium-, and high-volume hospitals by tertiles based on institutional septal myectomy caseload. Overall cardiac surgery volume was similarly assessed. Generalized linear models were used to test the association between hospital septal myectomy or cardiac surgery volume and in-hospital mortality, mitral valve repair, and 90-day non-elective readmission. RESULTS: Of 3,337 patients, 30.8% underwent septal myectomy at high-volume hospitals, whereas 39.1% were managed at low-volume hospitals. Patients at high-volume hospitals had a similar burden of comorbidities at low-volume hospitals, although congestive heart failure was more prevalent at high-volume hospitals. Despite comparable rates of mitral regurgitation, patients more commonly avoided mitral valve intervention at high-volume hospitals compared with low-volume hospitals (72.9% vs 68.3%; P = .007). After risk adjustment, high-volume hospital status was associated with reduced odds of mortality (0.24; 95% CI, 0.08-0.77) and readmission (0.59; 95% CI, 0.3-0.97). Among cases requiring mitral intervention, high-volume hospital status was associated with greater odds of valve repair (5.33; 95% CI, 2.54-11.13) relative to low-volume hospitals. Overall cardiac surgery volume was not associated with any studied outcome. CONCLUSION: Greater septal myectomy volume, but not overall cardiac surgery volume, was associated with reduced mortality and greater mitral valve repair relative to replacement after septal myectomy. These findings suggest that septal myectomy for hypertrophic obstructive cardiomyopathy should be performed at centers with expertise in this operation.

Left atrial appendage closure during cardiac surgery: Safe but underutilized in California.

Objective: Left atrial appendage (LAA) closure is associated with reduced rates of stroke in patients with atrial fibrillation (AF). We evaluated trends in LAA closure, the association of LAA closure with stroke/systemic embolism, and its safety profile in patients with AF who underwent cardiac surgery in California. We further tested for hospital-level variation in concomitant LAA closure. Methods: Adults who underwent coronary artery bypass grafting and/or valve surgery with preoperative AF were identified in the 2016 to 2019 Office of Statewide Health Planning and Development databases. Propensity score matching was performed to study risk-adjusted associations of LAA closure with ischemic stroke/systemic embolism. Hospital-level variation was studied using intraclass correlation coefficients. Results: Among 18,434 patients with AF who underwent coronary artery bypass grafting/valve surgery, 47.7% received LAA closure. Rates of LAA closure increased from 44.4% to 51.4% from 2016 to 2019 (P < .001). In 4652 propensity score-matched patients, LAA closure was associated with reduced incidence of stroke/systemic embolism at discharge (1.6% vs 3.1%; P < .001) and readmission with stroke/systemic embolism at 1 year (2.9% vs 4.5%; P = .004). LAA closure was not associated with acute kidney injury, pulmonary complications, blood transfusion, reoperation, or in-hospital mortality. Approximately 18% of the risk-adjusted variation in LAA use was attributed to the hospital, with median center-level rate of 44.9% (interquartile range, 29.6%-57.4%). Conclusions: LAA closure was associated with minimal surgical morbidity, and reduced short- and midterm incidence of stroke/systemic embolism. Although the use of LAA closure has increased, substantial variation exists among programs in California, suggesting the need for further standardization of care.

The Impact of COVID-19 on Racial and Ethnic Disparities in Cardiac Procedural Care.

OBJECTIVE: The primary objective of this study was to evaluate whether the COVID-19 pandemic altered the racial and ethnic composition of patients receiving cardiac procedural care. DESIGN: This was a retrospective observational study. SETTING: This study was conducted at a single tertiary-care university hospital. PARTICIPANTS: A total of 1,704 adult patients undergoing transcatheter aortic valve replacement (TAVR) (n = 413), coronary artery bypass grafting (CABG) (n = 506), or atrial fibrillation (AF) ablation (n = 785) from March 2019 through March 2022 were included in this study. INTERVENTIONS: No interventions were performed as this was a retrospective observational study. MEASUREMENTS AND MAIN RESULTS: Patients were grouped based on the date of their procedure: pre-COVID (March 2019 to February 2020), COVID Year 1 (March 2020 to February 2021), and COVID Year 2 (March 2021 to March 2022). Population-adjusted procedural incidence rates during each period were examined and stratified based on race and ethnicity. The procedural incidence rate was higher for White patients versus Black, and non-Hispanic patients versus Hispanic patients for every procedure and every period. For TAVR, the difference in procedural rates between White patients versus Black patients decreased between the pre-COVID and COVID Year 1 (12.05-6.34 per 1,000,000 persons). For CABG, the difference in procedural rates between White patients versus Black, and non-Hispanic patients versus Hispanic patients did not change significantly. For AF ablations, the difference in procedural rates between White patients versus Black patients increased over time (13.06 to 21.55 to 29.64 per 1,000,000 persons in the pre-COVID, COVID Year 1, and COVID Year 2, respectively). CONCLUSION: Racial and ethnic disparities in access to cardiac procedural care were present throughout all study time periods at the authors' institution. Their findings reinforce the continuing need for initiatives to reduce racial and ethnic disparities in healthcare. Further studies are needed to fully elucidate the effects of the COVID-19 pandemic on healthcare access and delivery.

Outcomes of heart transplant recipients bridged with percutaneous versus durable left ventricular assist devices.

BACKGROUND: The new United Network for Organ Sharing (UNOS) heart allocation policy prioritizes temporary percutaneous over durable left ventricular assist devices (LVAD) as bridge to transplant. We sought to examine 1-year outcomes of heart transplant recipients bridged with Impella versus durable LVADs. METHODS: All primary adult orthotopic heart transplant recipients registered in UNOS between January 2016 and June 2021 were analyzed. Recipients were identified as being bridged with isolated durable or percutaneous LVAD at the time of transplant. Baseline characteristics were compared and 1-year survival was examined using the Kaplan Meier method and multivariable Cox proportional hazards regression. RESULTS: During our study period, heart transplant recipients bridged with LVADs were divided between 5422(94%) durable and 324(6%) percutaneous options. Impella-bridged recipients were more likely to be status 1A under the old allocation system (98% vs. 70%, p < .01) and status 2 or higher under the new allocation system (99% vs. 24%, p < .01). Impella-bridged recipients were less likely to be obese (27% vs. 42%, p < .01), have ischemic cardiomyopathy (27% vs. 34%, p < .01), and were more likely to be on inotropic agents at the time of transplant (68% vs. 6%, p < .01). One-year post-transplant survival was not significantly different between the two groups on univariable (HR .87, 95% CI .56-1.37) or multivariable analysis (aHR .63, 95% CI .37-1.07). CONCLUSIONS: Following the UNOS allocation policy change, Impella utilization has increased with no significant difference in 1-year survival compared to bridge with durable LVADs. Impella may be a reasonable alternative to durable LVADs in select patients.

Transcatheter Aortic Valve Replacement for Severe Aortic Valve Stenosis: Do Patients Experience Better Quality of Life Regardless of Gradient?

BACKGROUND: Aortic valve replacement improves survival for patients with low-gradient aortic valve stenosis, but there is a paucity of data on postoperative quality of life for this population. METHODS: In a single-center retrospective analysis of 304 patients with severe aortic valve stenosis who underwent transcatheter aortic valve replacement, patients were divided into 4 groups based on mean pressure gradient, left ventricular ejection fraction, and stroke volume index. Using the Kansas City Cardiomyopathy Questionnaire-12, quality of life was assessed immediately before and 1 month after transcatheter aortic valve replacement. RESULTS: Most patients in the low-flow, low-gradient group were men; this group had higher relative rates of cardiovascular disease and type 2 diabetes than the paradoxical low-flow, low-gradient group; the normal-flow, low-gradient group; and the high-gradient group. All-cause mortality did not differ significantly among the groups at 1 month after surgery, and all groups experienced a significant improvement in quality-of-life scores after surgery. The mean improvement was 27 points in the low-flow, low-gradient group, 25 points in the paradoxical low-flow, low-gradient group, 30 points in the normal-flow, low-gradient group, and 30 points in the high-gradient group (all P < .001). CONCLUSION: Quality of life improves significantly across all subgroups of aortic valve stenosis after trans-catheter aortic valve replacement, regardless of flow characteristics or aortic valve gradients.

An Unusual Case of Left Ventricular Outflow Tract Pseudoaneurysm.

Left ventricular outflow tract (LVOT) pseudoaneurysm is a rare condition with a wide range of causes and various clinical outcomes. The causes range from infections, trauma to the chest wall, and iatrogenic origins. We present a unique case of idiopathic LVOT pseudoaneurysm in a patient with no obvious clinical risk factors. (Level of Difficulty: Advanced.).

Impact of Pulmonary Complications on Outcomes and Resource Use After Elective Cardiac Surgery.

OBJECTIVE: To characterize the impact of pulmonary complications (PCs) on mortality, costs, and readmissions after elective cardiac operations in a national cohort and to test for hospital-level variation in PC. BACKGROUND: PC after cardiac surgery are targets for quality improvement efforts. Contemporary studies evaluating the impact of PC on outcomes are lacking, as is data regarding hospital-level variation in the incidence of PC. METHODS: Adults undergoing elective coronary artery bypass grafting and/or valve operations were identified in the 2016-2019 Nationwide Readmissions Database. PC was defined as a composite of reintubation, prolonged (>24 hours) ventilation, tracheostomy, or pneumonia. Generalized linear models were fit to evaluate associations between PC and outcomes. Institutional variation in PC was studied using observed-to-expected ratios. RESULTS: Of 588,480 patients meeting study criteria, 6.7% developed PC. After risk adjustment, PC was associated with increased odds of mortality (14.6, 95% CI, 12.6-14.8), as well as a 7.9-day (95% CI, 7.6-8.2) increase in length of stay and $41,300 (95% CI, 39,600-42,900) in attributable costs. PC was associated with 1.3-fold greater hazard of readmission and greater incident mortality at readmission (6.7% vs 1.9%, P <0.001). Significant hospital-level variation in PC was present, with observed-to-expected ratios ranging from 0.1 to 7.7. CONCLUSIONS: Pulmonary complications remain common after cardiac surgery and are associated with substantially increased mortality and expenditures. Significant hospital-level variation in PC exists in the United States, suggesting the need for systematic quality improvement efforts to reduce PC and their impact on outcomes.

Morbidity and Mortality Associated With Blood Transfusions in Elective Adult Cardiac Surgery.

OBJECTIVES: Perioperative transfusion thresholds have garnered increasing scrutiny as restrictive strategies have been shown to be noninferior. The study authors used data from a statewide academic collaborative to test the association between transfusion and 30-day mortality. DESIGN: All adult patients undergoing coronary artery bypass grafting (CABG) and/or valve surgeries between 2013 and 2019 in the authors' Academic Cardiac Surgery Consortium were examined. The relationship between the number of overall packed red blood cell (pRBC) and coagulation product (CP) (fresh frozen plasma, cryoprecipitate, platelets) transfusions on 30-day mortality was evaluated. Multivariate regression was used to evaluate predictors of transfusion and study endpoints. Machine learning (ML) models also were developed to predict 30-day mortality and rank transfusion-related features by relative importance. SETTING: At an Academic Cardiac Surgery Consortium of 5 institutions. PARTICIPANTS: Patients ≥18 years old undergoing CABG and/or valve surgeries. MEASUREMENTS AND MAIN RESULTS: Of the 7,762 patients (median hematocrit [HCT] 39%, IQR 35%-43%) who were included in the final study cohort, >40% were transfused at least 1 unit of pRBC or CP. In adjusted analyses, higher preoperative HCT was associated with reduced odds of mortality (adjusted odds ratio [aOR] 0.95, 95% CI 0.92-0.98), renal failure (aOR 0.95, 95% CI 0.92-0.98), and prolonged mechanical ventilation (aOR 0.97, 95% CI 0.95-0.99). In contrast, perioperative transfusions were associated with increased 30-day mortality after adjustment for preoperative HCT and other baseline features. The ML models were able to predict 30-day mortality with an area under the curve of 0.814-to-0.850, with perioperative transfusions displaying the highest feature importance. CONCLUSIONS: The present analysis found increasing HCT to be associated with a lower incidence of mortality. The study authors also found a direct dose-response association between transfusions and all study endpoints examined.

Transcatheter and Surgical Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is not widely used in patients with bicuspid aortic valve (BAV) disease and has not yet been studied in randomized clinical trials. We characterized the rate of use and outcomes of TAVR and surgical aortic valve replacement (SAVR) in patients with BAV. METHODS: Adults with BAV stenosis receiving SAVR or TAVR procedures were abstracted from the 2012 to 2019 Nationwide Readmissions Database (NRD). Risk-adjusted analyses were performed with NRD-provided weights and inverse probability of treatment weights (IPTW) to examine the association of treatment strategy on inpatient mortality, complications, and hospitalization resource utilization. Nonelective readmissions within 90 days of discharge and reintervention at the first readmission were also examined. RESULTS: Of an estimated 56 331 patients with BAV requiring aortic valve replacement, 6.8% underwent TAVR. Unadjusted analysis demonstrated higher index hospitalization mortality for TAVR compared with SAVR. Upon risk adjustment using NRD-provided weights, the odds of pacemaker implantation remained significantly higher for TAVR patients compared with SAVR, with no significant difference in mortality. When NRD-provided survey weights were applied, TAVR had higher rates of 90-day readmission. Adjustment with inverse probability of treatment weights resolved these differences between the 2 groups. Regardless of the risk-adjustment method, the odds of reintervention were consistently higher among BAV TAVR patients compared with SAVR. CONCLUSIONS: The present analysis demonstrates comparable in-hospital mortality and morbidity for TAVR and SAVR patients in the moderate-risk era. With increasing TAVR use in BAV, surgeons must further refine selection criteria with consideration of concomitant aortopathy and implications of reintervention.

Regional Variation in the Use and Outcomes of Transcatheter Aortic Valve Replacement in California.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been widely adopted for management of aortic stenosis. The purpose of this study was to examine regional access to and outcomes following TAVR in California. METHODS: Patients undergoing TAVR or isolated surgical aortic valve replacement (SAVR) from 2008 to 2019 in California were identified in the Office of Statewide Health Planning and Development database. California was divided into seven regions: Northern California, San Francisco Bay Area, Central California, Los Angeles, Inland Empire, Orange, and San Diego. Regional TAVR volumes were normalized to Medicare beneficiaries or isolated SAVR volume. Outcomes included risk-adjusted 30-day mortality and major adverse cardiovascular and cerebral events (MACCE). Trends were studied using non-parametric tests, and regional outcomes using logistic regression. RESULTS: TAVR volume increased annually since 2011, with 7148 cases performed in California in 2019. After normalization, variation in utilization of TAVR was evident, with the least performed in Central California. TAVR to SAVR ratios in 2019 were greatest in Northern California, Los Angeles, and San Diego, and least in the Inland Empire. After risk adjustment, there were no significant regional differences in 30-day mortality, but lower 30-day MACCE in the San Francisco Bay Area. CONCLUSIONS: Regional differences in TAVR utilization exist, with limited access in Central California and the Inland Empire, but risk-adjusted outcomes are similar. Efforts to reach underserved areas through existing program expansion or regional referrals may distribute transcatheter technology more equitably across California.

Longitudinal profiling in patients undergoing cardiac surgery reveals postoperative changes in DNA methylation.

BACKGROUND: Cardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant pulmonary, cardiovascular, and neurologic complications. Commensurate with the immune and inflammatory response are changes in the heart and vasculature itself, which together drive postoperative complications through mechanisms that are poorly understood. Longitudinal DNA methylation profiling has the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass. RESULTS: While the vast majority of DNA methylation is unchanged by surgery after accounting for changes in cell-type composition, we identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. Paired statistical analysis, use of FACS data to support sufficient control of cell-type heterogeneity, and measurement of IL6 levels in a subset of patients add rigor to this analysis, allowing us to distinguish cell-type variability from actual changes in methylation. CONCLUSIONS: This study identifies significant changes in DNA methylation that occur immediately after cardiac surgery and demonstrates that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications. This research also establishes methods for controlling for cell-type variability in a large human cohort that may be useful to deploy in other longitudinal studies of epigenetic marks in the setting of acute and chronic disease.

Influence of center surgical aortic valve volume on outcomes of transcatheter aortic valve replacement.

Objective: The utilization of transcatheter aortic valve replacement (TAVR) technology has exceeded that of traditional surgical aortic valve replacement (SAVR). In addition, the role of minimum surgical volume requirements for TAVR centers has recently been disputed. The present work evaluated the association of annual institutional SAVR caseload on outcomes following TAVR. Methods: The 2012-2018 Nationwide Readmissions Database was queried for elective TAVR hospitalizations. The study cohort was split into early (Era 1: 2012-2015) and late (Era 2: 2016-2018) groups. Based on restricted cubic spline modeling of annual hospital SAVR caseload, institutions were dichotomized into low-volume and high-volume centers. Multivariable regressions were used to determine the influence of high-volume status on in-hospital mortality and perioperative complications following TAVR. Results: An estimated 181,740 patients underwent TAVR from 2012 to 2018. Nationwide TAVR volume increased from 5893 in 2012 to 49,983 in 2018. After adjustment for relevant patient and hospital factors, high-volume status did not alter odds of TAVR mortality in Era 1 (adjusted odds ratio, 0.94; P = .52) but was associated decreased likelihood of mortality in Era 2 (adjusted odds ratio, 0.83; P = .047). High-volume status did not influence the risk of perioperative complications during Era 1. However, during Era 2, patients at high-volume centers had significantly lower odds of infectious complications, relative to low-volume hospitals (adjusted odds ratio, 0.78; P = .002). Conclusions: SAVR experience is associated with improved TAVR outcomes in a modern cohort. Our findings suggest the need for continued collaboration between cardiologists and surgeons to maximize patient safety.

Parsimonious machine learning models to predict resource use in cardiac surgery across a statewide collaborative.

Objective: We sought to several develop parsimonious machine learning models to predict resource utilization and clinical outcomes following cardiac operations using only preoperative factors. Methods: All patients undergoing coronary artery bypass grafting and/or valve operations were identified in the 2015-2021 University of California Cardiac Surgery Consortium repository. The primary end point of the study was length of stay (LOS). Secondary endpoints included 30-day mortality, acute kidney injury, reoperation, postoperative blood transfusion and duration of intensive care unit admission (ICU LOS). Linear regression, gradient boosted machines, random forest, extreme gradient boosting predictive models were developed. The coefficient of determination and area under the receiver operating characteristic (AUC) were used to compare models. Important predictors of increased resource use were identified using SHapley summary plots. Results: Compared with all other modeling strategies, gradient boosted machines demonstrated the greatest performance in the prediction of LOS (coefficient of determination, 0.42), ICU LOS (coefficient of determination, 0.23) and 30-day mortality (AUC, 0.69). Advancing age, reduced hematocrit, and multiple-valve procedures were associated with increased LOS and ICU LOS. Furthermore, the gradient boosted machine model best predicted acute kidney injury (AUC, 0.76), whereas random forest exhibited greatest discrimination in the prediction of postoperative transfusion (AUC, 0.73). We observed no difference in performance between modeling strategies for reoperation (AUC, 0.80). Conclusions: Our findings affirm the utility of machine learning in the estimation of resource use and clinical outcomes following cardiac operations. We identified several risk factors associated with increased resource use, which may be used to guide case scheduling in times of limited hospital capacity.

Staged versus concomitant transcatheter aortic valve replacement and percutaneous coronary intervention: A national analysis.

Objective: Although patients with significant coronary artery disease and aortic stenosis have traditionally undergone open valve replacement and bypass grafting, percutaneous coronary intervention (PCI) and transcatheter aortic valve replacement (TAVR) are increasingly considered. Because of the lack of data regarding timing of PCI/TAVR, in the present study we evaluated associations of staged and concomitant PCI/TAVR on outcomes in a nationally representative cohort. Methods: Adults who underwent TAVR and PCI were identified using the 2016 to 2018 Nationwide Readmissions Database. If PCI/TAVR occurred on the same day, patients were considered Concomitant and otherwise considered Staged. Staged were further classified as Early-Staged if both occurred in the same hospitalization or Late-Staged if TAVR ensued PCI in a subsequent hospitalization. Multivariable regression models were developed to evaluate the association of TAVR timing on outcomes. The primary end point was in-hospital mortality whereas perioperative complications including acute kidney injury and hospitalization costs were secondarily considered. Results: Of an estimated 5843 patients, 843 (14.4%) were Concomitant and 745 (12.7%) and 4255 (72.8%) were Early-Staged and Late-Staged, respectively. Although age and TAVR access were similar, Concomitant had a lower proportion of chronic kidney disease and more commonly underwent single-vessel PCI. Staged showed similar risk-adjusted mortality but greater odds of acute kidney injury (Early-Staged adjusted odds ratio: 2.68; 95% CI, 1.57-4.55 and Late-Staged: 1.97; 95% CI, 1.29-2.99) compared with Concomitant. Although post-TAVR hospitalization duration was similar, total length of stay and costs were increased in Staged. Conclusions: Concomitant PCI/TAVR was associated with similar rates of in-hospital mortality but reduced rates of acute kidney injury and lower resource utilization. While evaluating patient-specific factors, concomitant PCI/TAVR might be reasonable in select individuals.

Defining value in cardiac surgery: A contemporary analysis of cost variation across the United States.

Objective: Isolated coronary artery bypass grafting and aortic valve replacement are common cardiac operations performed in the United States and serve as platforms for benchmarking. The present national study characterized hospital-level variation in costs and value for coronary artery bypass grafting and aortic valve replacement. Methods: Adults undergoing elective, isolated coronary artery bypass grafting or aortic valve replacement were identified in the 2016-2018 Nationwide Readmissions Database. Center quality was defined by the proportion of patients without an adverse outcome (death, stroke, respiratory failure, pneumonia, sepsis, acute kidney injury, and reoperation). High-value hospitals were defined as those with observed-to-expected ratios less than 1 for costs and greater than 1 for quality, whereas the converse defined low-value centers. Results: Of 318,194 patients meeting study criteria, 71.9% underwent isolated coronary artery bypass grafting and 28.1% underwent aortic valve replacement. Variation in hospital-level costs was evident, with median center-level cost of $36,400 (interquartile range, 29,500-46,700) for isolated coronary artery bypass grafting and $38,400 (interquartile range, 32,300-47,700) for aortic valve replacement. Observed-to-expected ratios for quality ranged from 0.2 to 10.9 for isolated coronary artery bypass grafting and 0.1 to 11.7 for isolated aortic valve replacement. Hospital factors, including volume and quality, contributed to approximately 9.9% and 11.2% of initial cost variation for isolated coronary artery bypass grafting and aortic valve replacement. High-value centers had greater cardiac surgery operative volume and were more commonly teaching hospitals compared to low-value centers, but had similar patient risk profiles. Conclusions: Significant variation in hospital costs, quality, and value exists for 2 common cardiac operations. Center volume was associated with value and partly accounts for variation in costs. Our findings suggest the need for value-based care paradigms to reduce expenditures and optimize outcomes.

Ventricular Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy (Analysis Spanning 60 Years Of Practice): AJC Expert Panel.

Surgical myectomy remains the time-honored primary treatment for hypertrophic cardiomyopathy patients with drug refractory limiting symptoms due to LV outflow obstruction. Based on >50 years experience, surgery reliably reverses disabling heart failure by permanently abolishing mechanical outflow impedance and mitral regurgitation, with normalization of LV pressures and preserved systolic function. A consortium of 10 international currently active myectomy centers report about 11,000 operations, increasing significantly in number over the most recent 15 years. Performed in experienced multidisciplinary institutions, perioperative mortality for myectomy has declined to 0.6%, becoming one of the safest currently performed open-heart procedures. Extended myectomy relieves symptoms in >90% of patients by ≥ 1 NYHA functional class, returning most to normal daily activity, and also with a long-term survival benefit; concomitant Cox-Maze procedure can reduce the number of atrial fibrillation episodes. Surgery, preferably performed in high volume clinical environments, continues to flourish as a guideline-based and preferred high benefit: low treatment risk option for adults and children with drug refractory disabling symptoms from obstruction, despite prior challenges: higher operative mortality/skepticism in 1960s/1970s; dual-chamber pacing in 1990s, alcohol ablation in 2000s, and now introduction of novel negative inotropic drugs potentially useful for symptom management.

DNA Methylation-Based Prediction of Post-operative Atrial Fibrillation.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF. Methods: We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort. Results: A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort. Conclusions: We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.