Machine Learning - Based Bleeding Risk Predictions in Atrial Fibrillation Patients on Direct Oral Anticoagulants.

Importance: Accurately predicting major bleeding events in non-valvular atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) is crucial for personalized treatment and improving patient outcomes, especially with emerging alternatives like left atrial appendage closure devices. The left atrial appendage closure devices reduce stroke risk comparably but with significantly fewer non-procedural bleeding events. Objective: To evaluate the performance of machine learning (ML) risk models in predicting clinically significant bleeding events requiring hospitalization and hemorrhagic stroke in non-valvular AF patients on DOACs compared to conventional bleeding risk scores (HAS-BLED, ORBIT, and ATRIA) at the index visit to a cardiologist for AF management. Design: Prognostic modeling with retrospective cohort study design using electronic health record (EHR) data, with clinical follow-up at one-, two-, and five-years. Setting: University of Pittsburgh Medical Center (UPMC) system. Participants: 24,468 non-valvular AF patients aged ≥18 years treated with DOACs, excluding those with prior history of significant bleeding, other indications for DOACs, on warfarin or contraindicated to DOACs. Exposures: DOAC therapy for non-valvular AF. Main Outcomes and Measures: The primary endpoint was clinically significant bleeding requiring hospitalization within one year of index visit. The models incorporated demographic, clinical, and laboratory variables available in the EHR at the index visit. Results: Among 24,468 patients, 553 (2.3%) had bleeding events within one year, 829 (3.5%) within two years, and 1,292 (5.8%) within five years of index visit. We evaluated multivariate logistic regression and ML models including random forest, classification trees, k-nearest neighbor, naive Bayes, and extreme gradient boosting (XGBoost) which modestly outperformed HAS-BLED, ATRIA, and ORBIT scores in predicting clinically significant bleeding at 1-year follow-up. The best performing model (random forest) showed area under the curve (AUC-ROC) 0.76 (0.70-0.81), G-Mean score of 0.67, net reclassification index 0.14 compared to 0.57 (0.50-0.63), G-Mean score of 0.57 for HASBLED score, p-value for difference <0.001. The ML models had improved performance compared to conventional risk across time-points of 2-year and 5-years and within the subgroup of hemorrhagic stroke. SHAP analysis identified novel risk factors including measures from body mass index, cholesterol profile, and insurance type beyond those used in conventional risk scores. Conclusions and Relevance: Our findings demonstrate the superior performance of ML models compared to conventional bleeding risk scores and identify novel risk factors highlighting the potential for personalized bleeding risk assessment in AF patients on DOACs.

Beta blockers are associated with lower all-cause mortality among HFpEF patients.

BACKGROUND: The evidence regarding beta blocker (BB) benefit in heart failure with preserved ejection fraction (HFpEF) remains inconclusive, leading to consideration of BB withdrawal in this population. OBJECTIVES: In this study, we retrospectively analyzed the association of BB on all-cause mortality in HFpEF patients. METHODS: This is a single-center retrospective cohort study of 20,206 patients with left ventricular ejection fraction (EF) ≥ 50% who were hospitalized with decompensated HF between January 2011 and March 2020. Survival is reported at 30 days, 1 year, and 3 years. A secondary analysis comparing mortality for patients on BB with additional indications including hypertension (HTN), coronary artery disease (CAD), and atrial fibrillation (AF) was completed. Mortality was compared between patients on BB and additional therapies of spironolactone or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). RESULTS: BB showed lower all-cause mortality at 30 days, 1 year, and 3 years (p < 0.0001). This association with lower all-cause mortality was validated by a supplementary propensity score-matched analysis. At 3 years, there was significant mortality reduction with addition of BB to either spironolactone (p = 0.0359) or ACEi/ARBs (p < 0.0001). CONCLUSION: In a large single-center retrospective registry, BB use was associated with lower mortality in HFpEF patients with a recent decompensated HF hospitalization. The mortality benefit persisted in those treated with spironolactone or ACEi/ARBs, and in those with AF. This provocative data further highlights the uncertainty of the benefit of BB use in this cohort and calls for re-consideration of BB withdrawal, especially in those tolerating it well, without conclusive, large, and randomized trials showing lack of benefit or harm.

Association of pre-left ventricular assist device defibrillator shocks for ventricular arrhythmia with clinical outcomes after left ventricular assist device implantation.

Background: Implantable cardioverter-defibrillation (ICD) shocks after left ventricular assist device therapy (LVAD) are associated with adverse clinical outcomes. Little is known about the association of pre-LVAD ICD shocks on post-LVAD clinical outcomes and whether LVAD therapy affects the prevalence of ICD shocks. Objectives: The purpose of this study was to determine whether pre-LVAD ICD shocks are associated with adverse clinical outcomes post-LVAD and to compare the prevalence of ICD shocks before and after LVAD therapy. Methods: Patients 18 years or older with continuous-flow LVADs and ICDs were retrospectively identified within the University of Pittsburgh Medical Center system from 2006-2020. We analyzed the association between appropriate ICD shocks within 1 year pre-LVAD with a primary composite outcome of death, stroke, and pump thrombosis and secondary outcomes of post-LVAD ICD shocks and ICD shock hospitalizations. Results: Among 309 individuals, average age was 57 ± 12 years, 87% were male, 80% had ischemic cardiomyopathy, and 42% were bridge to transplantation. Seventy-one patients (23%) experienced pre-LVAD shocks, and 69 (22%) experienced post-LVAD shocks. The overall prevalence of shocks pre-LVAD and post-LVAD were not different. Pre-LVAD ICD shocks were not associated with the composite outcome. Pre-LVAD ICD shocks were found to predict post-LVAD shocks (hazard ratio [HR] 5.7; 95% confidence interval [CI] 3.42-9.48; P <.0001) and hospitalizations related to ICD shocks from ventricular arrhythmia (HR 10.34; 95% CI 4.1-25.7; P <.0001). Conclusion: Pre-LVAD ICD shocks predicted post-LVAD ICD shocks and hospitalizations but were not associated with the composite outcome of death, pump thrombosis, or stroke at 1 year. The prevalence of appropriate ICD shocks was similar before and after LVAD implantation in the entire cohort.

Characteristics of Premature Myocardial Infarction Among Women With Prior Adverse Pregnancy Outcomes.

BACKGROUND: Adverse pregnancy outcomes (APOs), hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm birth are associated with ischemic heart disease in later life. OBJECTIVES: The authors aimed to study the features of premature myocardial infarction (MI) among women with and without prior APOs. METHODS: We performed a retrospective analysis of women with premature MI (<65 years of age) referred for left heart catheterization matched with a database of abstracted pregnancy data. We compared MI characteristics and epicardial coronary anatomy between women with and without APOs during their index pregnancy and evaluated time from delivery to MI. RESULTS: Of 391 women with premature MI and associated coronary angiography (age: 49 ± 8 years), 154 (39%) had a prior APO (hypertensive disorders of pregnancy n = 78, preeclampsia n = 35, gestational diabetes mellitus n = 28, and preterm birth n = 48). Women with APO history had a higher prevalence of diabetes (33% vs 16% without APO; P = 0.001) and presented earlier with MI following delivery (19.6 [IQR: 14.3-23.5] years vs those without APO 21.5 [IQR: 17.0-25.4] years; P = 0.012), driven by preeclampsia (17.1 [IQR: 12.7-22.4] years, P = 0.010). Women with and without APOs had similar MI features including rates of ST-segment elevation MI, obstructive and multi-vessel coronary artery disease, percutaneous coronary intervention, and shock. CONCLUSIONS: Among women with premature MIs, 39% had a history of an APO. Women with APO history presented sooner after pregnancy but had similar MI characteristics vs those without APOs. Pregnancy history may identify women who warrant early, aggressive cardiovascular disease prevention.

Long-term Outcomes of Percutaneous Coronary Intervention in Patients with Prior Coronary Artery Bypass Grafting.

BACKGROUND Patients with a prior coronary artery bypass graft (CABG) may have a need for repeat revascularization, which is typically attempted first via percutaneous coronary intervention (PCI) of either a bypass graft or native vessel. Long-term outcomes of native vessel compared to graft PCI after CABG have not yet been explored in a large institution study. METHODS Patients with history of prior CABG who underwent PCI at our institution during 2010-2018 were included. Baseline characteristics and long-term outcomes of up to 5 years were compared between native vessel and bypass graft PCI groups. Cox regression was used to adjust for significant covariates in estimation of risk and calculation of hazard ratios. RESULTS During the study, 4,251 patients with a prior CABG underwent PCI. Native vessel PCI represented 67.1% (n=2,851) of the cohort. After adjusting for significant covariates, bypass graft PCI compared to native vessel PCI had a higher risk of overall mortality (HR 1.15; 95% CI, 1.04-1.29; p<0.05), all-cause readmission (HR 1.16; 95% CI, 1.1-1.3; p<0.05), readmission for PCI (HR 1.25; 95% CI, 1.13-1.38; p<0.05), readmission for heart failure (HR 1.16; 95% CI, 1.06-1.26; p<0.05), and composite of myocardial infarction and revascularization (HR 1.23; 95% CI, 1.12-1.35; p<0.05). CONCLUSIONS Among patients with prior CABG, bypass graft PCI compared to native vessel PCI was associated with higher risk of adverse long-term outcomes.

Outcomes in Multivessel Coronary Disease Stratified by The Society of Thoracic Surgeons Risk.

BACKGROUND: Surgical risk stratified outcomes after contemporary revascularization strategies have not been well described. We report these outcomes in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for multivessel coronary disease. METHODS: A total of 5836 patients with multivessel disease who underwent CABG (n = 4420) or PCI (n = 1416) were included in this retrospective observational analysis. Data were stratified based on The Society of Thoracic Surgeons risk score. A score less than 4% was considered low risk and a score greater than or equal to 4% was considered intermediate-high risk. Outcomes included mortality, inpatient readmissions, and repeat revascularizations. RESULTS: In the CABG population, 3863 (87.3%) were low risk and 557 (12.6%) were intermediate-high risk. The 5-year mortality for the low-risk cohort was 10.9% (95% confidence interval [CI], 9.83%-12.05%), and for the intermediate-high-risk cohort it was 40.1% (95% CI, 35.76%-44.54%). Among those undergoing PCI, 1163 (82.1%) were low risk, while 249 (17.6%) were intermediate-high risk. The 5-year mortality for the low-risk cohort was 21.6% (95% CI, 19.10%-24.26%), and for the intermediate-high-risk cohort it was 61.8% (95% CI, 54.72%-68.70%). CONCLUSIONS: This study reports outcomes stratified by surgical risk after PCI or CABG in patients with multivessel coronary disease. These data can help guide the revascularization strategy choice for individual patients.

Long term mortality and readmissions after transcatheter aortic valve replacement.

BACKGROUND: Readmissions following transcatheter aortic valve replacement (TAVR) are common but detailed analysis of cardiac and non-cardiac inpatient readmissions beyond thirty days to different levels of care are limited. METHODS: Our study population was 1,037 consecutive patients who underwent TAVR between 2011-2017 within a multi-hospital quaternary health system. A retrospective chart review was performed and readmissions were adjudicated and classified based on primary readmission diagnosis (cardiac versus noncardiac) and level of care [intensive care unit (ICU) admission vs. non-ICU admission]. Incidence, causes, and outcomes of readmissions to up to three years post procedure were evaluated. RESULTS: Of the 1,017 patients who survived their index hospitalization, there were readmissions due to noncardiac causes in 350 (34.4%) and cardiac causes in 208 (20.5%) during a mean 1.96 years of follow-up. The most common non-cardiac causes of readmission were sepsis/infection (14.3%), gastrointestinal (8.3%), and respiratory (4.8%), whereas heart failure (14.0%) and arrhythmias (4.6%) were the most common cardiac causes of readmission. A total of 191 (18.8%) patients were readmitted to the ICU and 372 patients (36.6%) were non-ICU readmissions. The risk of a noncardiac readmission was highest in the period immediately following TAVR (~4.5% per month) with an early high hazard phase that gradually declined over months. However, the risk of cardiac readmission remained stable at ~1% per month throughout. TAVR patients that were readmitted for any cause had markedly increased mortality; this was especially true for patients readmitted to an ICU. CONCLUSIONS: In TAVR patients who survived their index hospitalization, non-cardiac readmissions were more prevalent than cardiac. The risk of readmission and subsequent mortality was highest immediately post-procedure and declined thereafter. Readmission to ICU portends the highest risk of subsequent death in this cohort. Patient baseline co-morbidities are an important consideration for TAVR patients and play a significant role in readmissions and outcomes.

Association Between Black Race, Clinical Severity, and Management of Acute Pulmonary Embolism: A Retrospective Cohort Study.

Background Existing evidence indicates Black patients have higher incidence of pulmonary embolism (PE) and PE-related mortality compared with other races/ethnicities, yet disparities in presenting severity and treatment remain incompletely understood. Methods and Results We retrospectively queried a multihospital healthcare system for all hospitalizations for acute PE (2012-2019). Of 10 329 hospitalizations, 8743 met inclusion criteria. Black patients (14.3%) were significantly younger (54.6±17.8 versus 63.1±16.6 years; P<0.001) and more female (56.1% versus 51.6%; P=0.003) compared with White patients. Using ordinal regression, Black race was significantly associated with higher PE severity after matching 1:3 on age and sex (1210:3264; odds ratio [OR], 1.08; 95% CI, 1.03-1.14), adjusting for clinical (OR, 1.13; 95% CI, 1.01-1.27), and socioeconomic (OR, 1.05; 95% CI, 1.05-1.35) characteristics. Among intermediate and high-severity PE, Black race was associated with a decreased risk of intervention controlling for the competing risk of mortality and censoring on hospital discharge. This effect was modified by PE severity (P value <0.001), with a lower and higher risk of intervention for intermediate and high-severity PE, respectively. Race was not associated with in-hospital mortality (OR, 0.84; 95% CI, 0.69-1.02). Conclusions Black patients hospitalized with PE are younger with a higher severity of disease compared with White patients. Although Black patients are less likely to receive an intervention overall, this differed depending on PE severity with higher risk of intervention only for life-threatening PE. This suggests nuanced racial disparities in management of PE and highlights the complexities of healthcare inequalities.

Area Deprivation Index and Cardiovascular Events: CAN CARDIAC REHABILITATION MITIGATE THE EFFECTS?

INTRODUCTION: Neighborhood socioeconomic status is associated with health outcomes. Cardiac rehabilitation (CR) provides a cost-effective, multidisciplinary approach to improve outcomes in cardiovascular disease. We aimed to evaluate the association of the Area Deprivation Index (ADI), a marker of neighborhood social composition, with risk of recurrent cardiovascular outcomes and assessed the modifying effect of CR. METHODS: We identified patients with a primary diagnosis of (1) myocardial infarction or (2) incident heart failure (HF) admitted to a large-sized regional health center during 2010-2018. We derived the ADI from home addresses and categorized it into quartiles (higher quartiles indicating increased deprivation). We obtained number of CR visits and covariates from the health record. We compared rehospitalization (cardiovascular, acute coronary syndrome [ACS], and HF) and mortality rates across ADI quartiles. RESULTS: We included 6957 patients (age 69.2 ± 13.4 yr, 38% women, 89% White race). After covariate adjustment, the ADI was significantly associated with higher incidence rates (IRs)/100 person-yr of cardiovascular rehospitalization (quartile 1, IR 34.6 [95% CI, 31.2-38.2]; quartile 4, 41.5 [95% CI, 39.1-44.1], P < .001). In addition, the ADI was significantly associated with higher rates of rehospitalization for HF (P < .001), ACS (P < .012), and all-cause mortality (P < .04). These differences in rehospitalization and mortality rates by the ADI were no longer significant in those who attended CR. CONCLUSIONS: We found the increased ADI was adversely associated with rehospitalizations and mortality. However, in individuals with CR, outcomes were significantly improved compared with those with no CR. Our findings suggest that CR participation has the potential to improve outcomes in disadvantaged neighborhoods.

Increased Mortality in Patients With Preoperative and Persistent Postoperative Pulmonary Hypertension Undergoing Mitral Valve Surgery for Mitral Regurgitation: A Cohort Study.

Background Preoperative pulmonary hypertension (PH) is associated with excess mortality among patients with severe mitral regurgitation undergoing mitral valve surgery (MVS). However, the links between PH phenotype, pulmonary vascular remodeling, and persistent postoperative PH are not well understood. We aimed to describe the associations between components of pulmonary hemodynamics as well as postoperative residual PH with longitudinal mortality in patients with severe mitral regurgitation who received MVS. Methods and Results Patients undergoing MVS for severe mitral regurgitation from 2011 to 2016 were retrospectively identified within our health system (n=488). Mean pulmonary artery pressure and other hemodynamic variables were determined by presurgical right-heart catheterization. Postoperative pulmonary artery systolic pressure was assessed on echocardiogram 42 to 365 days post-MVS. Longitudinal survival over a mean 3.9 years of follow-up was evaluated using Cox proportional hazards modeling to compare survival after adjustment for demographics, surgical characteristics, and comorbidities. Pre-MVS prevalence of PH was high at 85%. After adjustment, each 10-mm Hg increase in preoperative mean pulmonary artery pressure was associated with a 1.38-fold increase in risk of death (95% CI, 1.13-1.68). Elevated preoperative pulmonary vascular resistance, transpulmonary gradient, and right atrial pressure were similarly associated with increased mortality. Among 231 patients with postoperative echocardiogram, evidence of PH on echocardiogram (pulmonary artery systolic pressure ≥35 mm Hg) was associated with increased risk of death (hazard ratio [HR], 2.02 [95% CI, 1.17-3.47]); however, this was no longer statistically significant after adjustment (HR, 1.55 [95% CI, 0.85-2.85]). Conclusions In patients undergoing MVS for mitral regurgitation, preoperative PH, and postoperative PH were associated with increased mortality.

Relationship between predicting bleeding complication in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score and mortality among patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: The predicting bleeding complication in patients undergoing stent implantation and subsequent dual antiplatelet therapy, PRECISE-DAPT (P-DAPT) score has been validated in large cohorts as an effective tool in predicting bleeding complication after dual antiplatelet therapy (DAPT) as well as in predicting in-hospital mortality. The implication of using this score to predict outcomes, including mortality in patients with atrial fibrillation (AF) undergoing PCI is unknown. OBJECTIVE: Role of P-DAPT score to study clinical outcomes, including mortality, hospitalization, and major bleeding, particularly among patients with AF. METHODS: This is a retrospective observational study of 18,850 consecutive patients who underwent percutaneous coronary intervention (PCI) across a large multihospital healthcare system from 2010 to 2019. Patients were stratified into four groups depending on the presence or absence of AF and P-DAPT score, with score ≥ 25 defined as high risk. The primary outcome was all-cause mortality. The secondary outcomes evaluated were hospitalization and major bleeding. RESULTS: In the unadjusted analyses, a P-DAPT score ≥ 25, in both AF and non-AF population, was associated with increased mortality, hospitalization, and bleeding. After adjusting for baseline covariates, no significant differences in major bleeding risk were found across the four groups. However, a P-DAPT score of ≥25 in AF patients was associated with a higher risk for hospitalizations related to cardiovascular causes (HR: 2.15 95% CI 2.00-2.3, p < .0001). Among AF patients, P-DAPT score ≥ 25 was found to be strongly associated with mortality (HR 3.5; 95% CI 2.95-4.25, p < .0001) as compared with AF patients with score < 25 (HR 1.18, 95% CI 0.88-1.54, p = .26). CONCLUSION: In this large cohort of patients undergoing PCI, the P-DAPT score can help to identify patients at high risk for long-term mortality, particularly among those with atrial fibrillation.

Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention in Patients With Diabetes.

As percutaneous coronary intervention (PCI) continues to evolve, comparative outcomes for PCI vs coronary artery bypass grafting (CABG) remain relevant in diabetic patients. All revascularization procedures in patients with coronary artery disease and diabetes mellitus from 2010 to 2018 were included. Propensity matching was used to identify equivalent cohorts to compare revascularization strategies. Primary outcomes included 30-day, 1-year, and 5-year mortality. Multivariable analysis was used to define factors associated with major adverse cardiovascular and cerebrovascular events (MACCE). A total of 2869 patients with diabetes were divided into PCI (n = 653) and CABG (n = 2216) cohorts. Propensity matching yielded a 1:1 match consisting of 552 patients in each cohort (CABG vs PCI). Total median follow-up was 3.28 years (range: 1.83-5.00). Following propensity matching in patients with no prior PCI (1:1; n = 279), mortality remained significantly higher in the PCI cohort at 1 year (13.98% vs 7.53%; P = 0.014) and 5 years (26.88% vs 16.85%; P < 0.004). Hospital readmissions were higher for PCI patients at 1 year (16.49% vs 9.32%; P < 0.0122) and 5 years (19.71% vs 11.83%; P = 0.011). MACCE occurred more frequently in the PCI cohort (32.97% vs 21.51%; P = 0.002). Need for subsequent revascularization (6.45% vs 2.51%; P = 0.024) were significantly higher in the PCI cohort, and time interval to revascularization was significantly longer in the CABG cohort (3.48 [2.11-5.17] vs 2.62 [1.33-4.25] years; P < 0.001). The current study reports improved survival, fewer long-term hospital readmissions, and reduced MACCE and need for repeat revascularization in the CABG cohort. Given these data, patients with diabetes mellitus and coronary artery disease may fare better with surgical revascularization, compared to PCI.

Evolving Trends in Adult Heart Transplant With the 2018 Heart Allocation Policy Change.

Importance: The US heart allocation policy was changed on October 18, 2018. The association of this change with recipient and donor selection and outcomes remains to be elucidated. Objective: To evaluate changes in patient characteristics, wait list outcomes, and posttransplant outcomes after the recent allocation policy change in heart transplant. Design, Setting, and Participants: In this cohort study, all 15 631 adults undergoing heart transplants, excluding multiorgan transplants, in the US as identified by the United Network for Organ Sharing multicenter, national registry were reviewed. Patients were stratified according to prepolicy change (October 1, 2015, to October 1, 2018) and postpolicy change (October 18, 2018 or after). Follow-up data were available through March 31, 2020. Exposures: Heart transplants after the policy change. Main Outcomes and Measures: Competing risk regression for wait list outcomes was performed. Posttransplant survival was compared using the Kaplan-Meier method, and risk adjustment was performed using multivariable Cox proportional hazards regression analysis. Results: In this cohort study, of the 15 631 patients undergoing transplant, 10 671 (mean [SD] age, 53.1 [12.7] years; 7823 [73.3%] male) were wait listed before and 4960 (mean [SD] age, 52.7 [13.0] years; 3610 [72.8%] male) were wait listed after the policy change. Competing risk regression demonstrated reduced likelihood of mortality or deterioration (subhazard ratio [SHR], 0.60; 95% CI, 0.52-0.69; P < .001), increased likelihood of transplant (SHR, 1.38; 95% CI, 1.32-1.45; P < .001), and reduced likelihood of recovery (SHR, 0.54; 95% CI, 0.40-0.73; P < .001) for wait listed patients after the policy change. A total of 6078 patients underwent transplant before and 2801 after the policy change. Notable changes after the policy change included higher frequency of bridging with temporary mechanical circulatory support and lower frequency of bridging with durable left ventricular assist devices. Posttransplant survival was reduced after the policy change (1-year: 92.1% vs 87.5%; log-rank P < .001), a finding that persisted after risk adjustment (HR, 1.29; 95% CI, 1.07-1.55; P = .008). Conclusions and Relevance: Substantial changes have occurred in adult heart transplant in the US after the policy change in October 2018. Wait list outcomes have improved, although posttransplant survival has decreased. These data confirm findings from earlier preliminary analyses and demonstrate that these trends have persisted to 1-year follow-up, underscoring the importance of continued reevaluation of the new heart allocation policy.

Apoptosis of hematopoietic progenitor-derived adipose tissue-resident macrophages contributes to insulin resistance after myocardial infarction.

Patients with insulin resistance have high risk of cardiovascular disease such as myocardial infarction (MI). However, it is not known whether MI can initiate or aggravate insulin resistance. We observed that patients with ST-elevation MI and mice with MI had de novo hyperglycemia and features of insulin resistance, respectively. In mouse models of both myocardial and skeletal muscle injury, we observed that the number of visceral adipose tissue (VAT)-resident macrophages decreased because of apoptosis after these distant organ injuries. Patients displayed a similar decrease in VAT-resident macrophage numbers and developed systemic insulin resistance after ST-elevation MI. Loss of VAT-resident macrophages after MI injury led to systemic insulin resistance in non-diabetic mice. Danger signaling-associated protein high mobility group box 1 was released by the dead myocardium after MI in rodents and triggered macrophage apoptosis via Toll-like receptor 4. The VAT-resident macrophage population in the steady state in mice was transcriptomically distinct from macrophages in the brain, skin, kidney, bone marrow, lungs, and liver and was derived from hematopoietic progenitor cells just after birth. Mechanistically, VAT-resident macrophage apoptosis and de novo insulin resistance in mouse models of MI were linked to diminished concentrations of macrophage colony-stimulating factor and adiponectin. Collectively, these findings demonstrate a previously unappreciated role of adipose tissue-resident macrophages in sensing remote organ injury and promoting MI pathogenesis.

Surgical versus percutaneous multivessel coronary revascularization in patients with chronic kidney disease.

OBJECTIVES: This study compared contemporary outcomes following surgical versus percutaneous coronary revascularization for multivessel coronary artery disease (MVCAD) in patients with chronic kidney disease. METHODS: Patients with MVCAD and a reduced glomerular filtration rate (<60 ml/min) undergoing coronary bypass surgery (CABG) or percutaneous coronary intervention (PCI) at a single institution between 2010 and 2017 were included. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) defined as a composite outcome of death, stroke, myocardial infarction or repeat revascularization. Multivariable Cox regression models were used for risk-adjustment and propensity matching was also performed. RESULTS: A total of 1853 patients were included in the study (1269 CABG, 584 PCI). CABG was associated with greater 5-year freedom from MACCE (70.1% vs 47.3%, P < 0.0001), a finding that persisted after risk-adjustment. The rates of early and late mortality and readmission were also lower with CABG as were individual rates of myocardial infarction and repeat revascularization. A propensity-matched analysis generated 704 well-matched patients (352 in each arm) with similar results, including greater 5-year freedom from MACCE (72.8% vs 45.8%, P < 0.0001), improved 5-year survival (73.9% vs 52.3%, P < 0.0001), lower readmission (cause-specific hazard ratio 0.68, 95% confidence interval 0.58-0.80; P < 0.0001), lower individual rates of myocardial infarction (2.6% vs 9.7%, P < 0.0001) and repeat revascularization (1.1% vs 7.4%, P < 0.0001). CONCLUSIONS: CABG is associated with a lower MACCE rate than that of PCI in patients with MVCAD and chronic kidney disease. Multidisciplinary discussions regarding the optimal revascularization strategy are important in MVCAD, particularly in more complex scenarios such as chronic kidney disease.

Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin in Patients With Chronic Kidney Disease and Atrial Fibrillation.

Patients with atrial fibrillation (AF) commonly have impaired renal function. The safety and efficacy of direct oral anticoagulants (DOACs) in patients with chronic kidney disease (CKD) and end-stage renal disease has not been fully elucidated. This study evaluated and compared the safety outcomes of DOACs versus warfarin in patients with nonvalvular AF and concomitant CKD. Patients in our health system with AF prescribed oral anticoagulants during 2010 to 2017 were identified. All-cause mortality, bleeding and hemorrhagic, and ischemic stroke were evaluated based on degree of renal impairment and method of anticoagulation. There were 21,733 patients with a CHA2DS2-VASc score of ≥2 included in this analysis. Compared with warfarin, DOAC use in patients with impaired renal function was associated with lower risk of mortality with a hazard ratio (HR): 0.76 (95% confidence interval [CI] 0.70 to 0.84, p value <0.001) in patients with eGFR >60, HR 0.74 (95% CI 0.68 to 0.81, p value <0.001) in patients with eGFR >30 to 60, and HR 0.76 (95% CI 0.63 to 0.92, p value <0.001) in patients with eGFR ≤30 or on dialysis. Bleeding requiring hospitalization was also less in the DOAC group with a HR 0.93 (95% CI 0.82 to 1.04, p value 0.209) in patients with eGFR >60, HR 0.83 (95% CI 0.74 to 0.94, p value 0.003) in patients with eGFR >30 to 60, and HR 0.69 (95% CI 0.50 to 0.93, p value 0.017) in patients with eGFR ≤30 or on dialysis. In conclusion, in comparison to warfarin, DOACs appear to be safe and effective with a lower risk of all-cause mortality and lower bleeding across all levels of CKD.

Impact of Chronic Kidney Disease and Anemia on Outcomes After Percutaneous Coronary Revascularization.

Few studies have evaluated outcomes after percutaneous coronary intervention (PCI) in patients with both anemia (hemoglobin < 12 g/dl in women; <13 in men) and chronic kidney disease (CKD, estimated glomerular filtration rate < 60 ml/min/1.73 m2). Patients with coronary artery disease who underwent PCI in our health system from 2010 to 2018 were included (n = 10,756), excluding those with ST-elevation myocardial infarction or shock. We evaluated the individual and combined effects of anemia and CKD on outcomes. Five-year mortality was highest in the cohort with both anemia and CKD and lowest in those with neither. After multivariate analysis, with the group with neither anemia nor CKD as a reference, the adjusted hazard ratio for mortality was 1.68 (95% confidence interval [CI] 1.45 to 1.95, p <0.001) for those with anemia alone, 1.33 (95% CI 1.15 to 1.53, p <0.001) for those with CKD alone, and 2.83 (95% CI 2.49 to 3.22, p <0.001) for those with both anemia and CKD. With respect to readmission and reintervention, similar tends were observed, with patients with both CKD and anemia having the highest risk for these outcomes. In conclusion, the combined effects of anemia and CKD on outcomes post-PCI appear to be worse than either of their effects individually.

Coronary Bypass Versus Percutaneous Revascularization in Multivessel Coronary Artery Disease.

BACKGROUND: This study focused on contemporary outcomes after coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease (MVCAD). METHODS: This was a propensity-matched retrospective, observational analysis. Patients with MVCAD who underwent CABG or PCI between 2010 and 2018 and for whom data were available through the National Cardiovascular Data Registry or The Society of Thoracic Surgeons Adult Cardiac Surgery Database were included. The primary outcome was overall survival. Secondary outcomes included freedom from inpatient readmission and freedom from repeat revascularization. RESULTS: Of the initial 6,163 patients with MVCAD, the propensity-matched cohort included 844 in each group. The estimated 1-year mortality was 11.5% and 7.2% (p < 0.001) in the PCI and CABG groups, respectively, with an overall hazard ratio for mortality of PCI versus CABG of 1.64 (95% confidence interval [CI], 1.29 to 2.10; p < 0.001). The overall hazard ratio for readmission for PCI versus CABG was 1.42 (95% CI, 1.23 to 1.64; p < 0.001). The overall hazard ratio for repeat revascularization for PCI versus CABG was 4.06 (95% CI, 2.39 to 6.91; p < 0.001). Overall major adverse cardiovascular events and individual outcomes of mortality, readmission, and repeat revascularization all favored CABG across virtually all major clinical subgroups. CONCLUSIONS: This contemporary propensity-matched analysis of patients undergoing coronary revascularization for MVCAD demonstrates a significant mortality benefit with CABG over PCI, and this benefit is consistent across virtually all major patient subgroups. Futures studies are needed reflecting routine practice to assess how best to approach shared decision making and informed consent when it comes to revascularization decisions in any patient with MVCAD.

Longitudinal Outcomes of Women Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVE: Recent data have suggested that women have a survival benefit at 1-year follow-up. However, long-term gender-based TAVR outcomes are lacking. METHODS: All patients undergoing isolated TAVR from 2011 to 2017 were included. Patients were stratified by gender. The primary outcomes of the study were 3-year mortality and 3-year hospital readmissions. Multivariable logistic regression analysis was used to evaluate the risk-adjusted impact of gender on TAVR outcomes. RESULTS: A total of 1,036 patients were divided into male (n = 518) and female (n = 518) cohorts. Women had a borderline significantly increased STS PROM (8.3% ± 5 vs. 7.7% ± 4.4; P = 0.05). The majority of procedures were performed under conscious sedation (male: 89% vs. female: 88%; P = 0.62) and via transfemoral access (male: 81.8% vs. female: 81.4%; P = 0.46). There was no difference in operative (30-day) mortality (male: 15 [3.3%] vs. female: 17 [3.7%]; P = 0.77) or 30-day readmissions (male: 40 [10.8%] vs. female: 44 [12.2%]; P = 0.56). Perioperative blood product usage was higher for women (male: 8.1% vs. female: 14.1%; P = 0.002). There was no significant difference in major vascular complications (male: 0.4% vs. female: 1.0%; P = 0.26) or major bleeding (male: 0.2% vs. female: 0.4%; P = 0.56). Permanent pacemaker placement was higher for males (11.6% vs. 7.0%; P = 0.01). On risk-adjusted multivariable analysis, gender was not a factor associated with mortality (HR 0.99 [0.76 to 1.30]; P = 0.99) or readmission (HR 0.90 [0.72 to 1.14]; P = 0.42) at 5 years. CONCLUSIONS: There was no difference in survival or readmissions on multivariable analysis for women undergoing TAVR at 3 years. Longitudinal multi-institutional data will be important to validate these findings.