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To describe outcomes associated with bridging strategies in patients with acute decompensated heart failure-related cardiogenic shock (ADHF-CS) bridged to durable left ventricular assist device (LVAD) or heart transplant (HTx).Durable LVAD or HTx recipients from 2014 to 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by bridging strategy. The primary outcome was operative or 30-day post-operative mortality. Secondary outcomes included post-operative major bleeding. Exploratory comparisons between bridging strategies and outcomes were performed using overlap weighting with and without covariate adjustment. Among 9783 patients with pre-operative CS, 8777 (89.7%) had ADHF-CS. Medical therapy (N = 5013) was the most common bridging strategy, followed by intra-aortic balloon pump (IABP; N = 2816), catheter-based temporary mechanical circulatory support (TMCS; N = 417), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO; N = 465). Mortality was highest in patients bridged with VA-ECMO (22%), followed by catheter-based TMCS (10%), IABP (9%), and medical therapy (7%). Adverse post-operative outcomes were more frequent in LVAD recipients compared with HTx recipients.Among patients with ADHF-CS bridged to HTx or durable LVAD, the highest rates of death and adverse events during index hospitalization were observed in those bridged with VA-ECMO, followed by catheter-based TMCS, IABP, and medical therapy. Patients who received durable LVAD had higher rates of post-operative complications compared with HTx recipients. Prospective trials are needed to define optimal bridging strategies in patients with ADHF-CS. This article is protected by copyright. All rights reserved.

Background: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. Methods: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit–level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit–level COVID-19 rates. Results: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08–3.55]; P =0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32–0.99]; P =0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose ( P =0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P =0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56–1.48]; P =0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. Conclusions: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04409834.

Aims Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. Methods and results An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints ( 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17–1.31 and HR: 1.16, 95% CI: 1.05–1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90–1.06 and HR: 0.87, 95% CI: 0.39–1.92, respectively). Conclusion Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS.

Aims The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness. Methods and results The CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness. Conclusion The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population.

Heart failure (HF) is a growing public health problem and ischemic heart disease is an important risk factor. Understanding the epidemiology of HF in patients with atherosclerosis may help identify subgroups at greater risk who have the potential to derive greater benefit from preventive strategies.The TRA 2°P-TIMI 50 trial randomized 26,449 patients with stable atherosclerosis to the antiplatelet agent vorapaxar versus placebo. Hospitalization for HF (HHF) endpoints were adjudicated from serious adverse events by blinded structured review using established definitions. HHF incidence was estimated using Kaplan-Meier analysis. Independent predictors of HHF risk were identified using multivariable logistic regression. The effect of vorapaxar on HHF risk was explored using Cox regression. The estimated incidence of HHF at 3 years was 1.6%. Independent predictors of HHF included prior HF (adjusted odds ratio [adj-OR]: 8.31; 95% confidence interval [CI]: 6.56-10.54), age (adj-OR [per 10 years]: 1.67; 95% CI: 1.47-1.89), type 2 diabetes mellitus (T2DM; adj-OR: 2.55; 95% CI: 2.01-3.24), polyvascular disease (two-territory disease, adj-OR: 1.89; 95% CI: 1.46-2.44; three-territory disease, adj-OR: 2.68; 95% CI: 1.94-3.70), chronic kidney disease (CKD; adj-OR: 1.65; 95% CI: 1.30-2.11), body mass index (BMI; adj-OR [per 5 kg/mIn patients with stable atherosclerosis, prior HF, age, T2DM, polyvascular disease, CKD, BMI, prior MI, and hypertension are important predictors of HHF risk.

Acute heart failure (HF) is an important complication of coronavirus disease 2019 (COVID-19) and has been hypothesized to relate to inflammatory activation.We evaluated consecutive intensive care unit (ICU) admissions for COVID-19 across 6 centers in the Critical Care Cardiology Trials Network, identifying patients with vs without acute HF. Acute HF was subclassified as de novo vs acute-on-chronic, based on the absence or presence of prior HF. Clinical features, biomarker profiles and outcomes were compared.Of 901 admissions to an ICU due to COVID-19, 80 (8.9%) had acute HF, including 18 (2.0%) with classic cardiogenic shock (CS) and 37 (4.1%) with vasodilatory CS. The majority (n = 45) were de novo HF presentations. Compared to patients without acute HF, those with acute HF had higher cardiac troponin and natriuretic peptide levels and similar inflammatory biomarkers; patients with de novo HF had the highest cardiac troponin levels. Notably, among patients critically ill with COVID-19, illness severity (median Sequential Organ Failure Assessment, 8 [IQR, 5-10] vs 6 [4-9]; P = 0.025) and mortality rates (43.8% vs 32.4%; P = 0.040) were modestly higher in patients with vs those without acute HF.Among patients critically ill with COVID-19, acute HF is distinguished more by biomarkers of myocardial injury and hemodynamic stress than by biomarkers of inflammation.

Background: Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction. Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation to baseline hsTnT levels, and the effect of dapagliflozin on hsTnT levels. Methods: DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg daily) in patients with New York Heart Association class II to IV symptoms and left ventricular ejection fraction ≤40% (median follow-up, 18.2 months). hsTnT (Roche Diagnostics) was measured at baseline in 3112 patients and at 1 year in 2506 patients. The primary end point was adjudicated worsening heart failure or cardiovascular death. Clinical end points were analyzed according to baseline hsTnT and change in hsTnT from baseline to 1 year. Comparative treatment effects on clinical end points with dapagliflozin versus placebo were assessed by baseline hsTnT. The effect of dapagliflozin on hsTnT was explored. Results: Median baseline hsTnT concentration was 20.0 (25th–75th percentile, 13.7–30.2) ng/L. Over 1 year, 67.9% of patients had a ≥10% relative increase or decrease in hsTnT concentrations, and 43.5% had a ≥20% relative change. A stepwise gradient of higher risk for the primary end point was observed across increasing quartiles of baseline hsTnT concentration (adjusted hazard ratio Q4 versus Q1, 3.44 [95% CI, 2.46–4.82]). Relative and absolute increases in hsTnT over 1 year were associated with higher subsequent risk of the primary end point. The relative reduction in the primary end point with dapagliflozin was consistent across quartiles of baseline hsTnT ( P -interaction=0.55), but patients in the top quartile tended to have the greatest absolute risk reduction (absolute risk difference, 7.5% [95% CI, 1.0%–14.0%]). Dapagliflozin tended to attenuate the increase in hsTnT over time compared with placebo (relative least squares mean reduction, –3% [–6% to 0%]; P =0.076). Conclusions: Higher baseline hsTnT and greater increase in hsTnT over 1 year are associated with worse clinical outcomes. Dapagliflozin consistently reduced the risk of the primary end point, irrespective of baseline hsTnT levels. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.

Aims Increases in life expectancy, comorbidities, and survival with complex cardiovascular conditions have changed the clinical profile of the patients in cardiac intensive care units (CICUs). In this environment, palliative care (PC) services are increasingly important. However, scarce information is available about the delivery of PC in CICUs. Methods and results The Critical Care Cardiology Trials Network (CCCTN) Registry is a network of tertiary care CICUs in North America. Between 2017 and 2020, up to 26 centres contributed an annual 2-month snapshot of all consecutive medical CICU admissions. We captured code status at admission and the decision for comfort measures only (CMO) before all deaths in the CICU. Of 13 422 patients, 10% died in the CICU and 2.6% were discharged to palliative hospice. Of patients who died in the CICU, 68% were CMO at death. In the CMO group, only 13% were do not resuscitate/do not intubate at admission. The median time from CICU admission to CMO decision was 3.4 days (25th–75th percentiles: 1.2–7.7) and ≥7 days in 27%. Time from CMO decision to death was Conclusions In a contemporary CICU registry, comfort measures preceded death in two-thirds of cases, frequently without PC involvement. The high utilization of advanced intensive care unit therapies and lengthy times to a CMO decision highlight a potential opportunity for early engagement of PC teams in CICU.

Background: Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined. Methods: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria. Results: Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C–E: 19.0% to 83.7% and 14.6% to 52.2%, respectively; P trend P trend Conclusions: Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.

Purpose of review Cardiogenic shock is a complex clinical syndrome of end-organ hypoperfusion due to impaired cardiac performance. Although cardiogenic shock has traditionally been viewed as a monolithic disorder predominantly caused by severe left ventricular dysfunction complicating acute myocardial infarction (AMI), there is increasing recognition of the diverse causes of cardiogenic shock and wide spectrum of clinical severity. The purpose of this review is to describe the contemporary epidemiology of cardiogenic shock, including trends in clinical outcomes and recent efforts to refine risk assessment. Recent findings The incidence of cardiogenic shock among patients with AMI has remained remarkably stable at 3-10%; however, the proportion of cardiogenic shock cases related to AMI has decreased over time to ∼30%, while the proportion of cardiogenic shock cases due to acute decompensated heart failure has steadily increased. Estimated in-hospital mortality from cardiogenic shock in contemporary registries is approximately 30-40%, suggesting modest improvement in cardiogenic shock outcomes over the last decade. There is a wide spectrum of clinical severity among patients presenting with cardiogenic shock, which is described by the Society for Cardiovascular Angiography and Interventions clinical staging criteria. Summary Improved clinical characterization and risk assessment of patients with cardiogenic shock may facilitate more effective clinical investigations of this morbid clinical syndrome.

Background: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment–elevation myocardial infarction. Methods: REAL-TIMI 63B (A Randomized, Placebo‑controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment–elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. Results: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103–221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6–24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3–13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79–16.38; placebo: 10.48%, [IQR, 4.92–16.61], 1-sided P =0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA–1.10], 1-sided P =0.30). There was no significant difference in treatment emergent serious adverse events. Conclusions: Administration of MEDI6012 in patients with acute ST-segment–elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03578809.

Aims Interest in targeted screening programmes for atrial fibrillation (AF) has increased, yet the role of genetics in identifying patients at highest risk of developing AF is unclear. Methods and results A total of 36,662 subjects without prior AF were analyzed from four TIMI trials. Subjects were divided into quintiles using a validated polygenic risk score (PRS) for AF. Clinical risk for AF was calculated using the CHARGE-AF model. Kaplan–Meier event rates, adjusted hazard ratios (HRs), C-indices, and net reclassification improvement were used to determine if the addition of the PRS improved prediction compared with clinical risk and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Over 2.3 years, 1018 new AF cases developed. AF PRS predicted a significant risk gradient for AF with a 40% increased risk per 1-SD increase in PRS [HR: 1.40 (1.32–1.49); P < 0.001]. Those with high AF PRS (top 20%) were more than two-fold more likely to develop AF [HR 2.45 (1.99–3.03), P < 0.001] compared with low PRS (bottom 20%). Furthermore, PRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, ranging from a 3-year incidence of 1.3% in patients with low clinical and genetic risk to 8.7% in patients with high clinical and genetic risk. The subgroup of patients with high clinical risk, high PRS, and elevated NT-proBNP had an AF risk of 16.7% over 3 years. The C-index with the CHARGE-AF clinical risk score alone was 0.65, which improved to 0.67 (P < 0.001) with the addition of NT-proBNP, and increased further to 0.70 (P < 0.001) with the addition of the PRS. Conclusion In patients with cardiovascular conditions, AF PRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score and NT-proBNP.

Background: With the improvement in outcomes for acute coronary syndrome (ACS), the practice of routine admission to cardiac intensive care units (CICUs) is evolving. We aimed to describe the epidemiology of patients with ACS admitted to contemporary CICUs. Methods: Using the CCCTN (Critical Care Cardiology Trials Network) Registry for consecutive medical CICU admissions across 26 advanced CICUs in North America between 2017 and 2020, we identified patients with a primary diagnosis of ACS at CICU admission and compared patient characteristics, resource utilization, and outcomes to patients admitted with a non-ACS diagnosis and across sub-populations of patients with ACS, including by indication for CICU admission. Results: Of 10 118 CICU admissions, 29.4% (n=2978) were for a primary diagnosis of ACS, with significant interhospital variability (range, 13.4%–56.6%). Compared with patients admitted with a diagnosis other than ACS, patients with ACS had fewer comorbidities, lower acute severity of illness with less utilization of advanced CICU therapies (41.3% versus 66.1%, P P P P Conclusions: In a registry of tertiary care CICUs, ACS represent ≈1/3 of all admissions with significant variability across hospitals. More than half of the ACS admissions to the CICU were for routine monitoring alone, with a low rate of complications and mortality. This observation highlights an opportunity for prospective studies to refine triage strategies for lower risk patients with ACS.

Background Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, which can be significantly reduced with anticoagulant treatment. Key goals in the clinical management of AF are the identification of patients at high risk for developing AF and accurate stratification of the risk of stroke and systemic embolic events (S/SEE) as well as treatment-related major bleeding. Content In this review, we describe the expanding evidence regarding the use of circulating biomarkers for predicting the risks of both incident AF and its clinically important complications of S/SEE and treatment-related major bleeding. We also review emerging biomarker-based scores for assessing these risks. Summary Patients with AF undergo progressive cardiac structural remodeling, which may precede the onset of the arrhythmia. Abnormal concentrations of circulating biomarkers reflecting the underlying pathophysiologic mechanisms of hemodynamic stress (i.e., natriuretic peptides), inflammation (i.e., C-reactive protein), and myocardial fibrosis identify patients at higher risk of developing AF. Circulating biomarkers can also be used to identify patients with AF who are at greatest risk for developing S/SEE or major bleeding. In particular, biomarkers of hemodynamic stress, myocardial injury (i.e., cardiac troponin), and coagulation activity (i.e., D-dimer) are key indicators of thromboembolic risk, and cardiac troponin and growth-differentiation factor-15 are strongly associated with risk of anticoagulant-related major bleeding. The biomarker-based age, biomarker, clinical history (ABC)-stroke and ABC-bleeding risk scores improve risk stratification for S/SEE and major bleeding, respectively, when compared with traditional clinical risk scores like the CHA2DS2-VASc and HAS-BLED scores.

Objectives This study sought to evaluate the efficacy and safety of sacubitril/valsartan according to dose level achieved in the PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode) trial. Background In patients hospitalized for acute decompensated heart failure (ADHF), in-hospital initiation and continuation of sacubitril/valsartan as compared with enalapril is well tolerated, achieves a greater reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP), and reduces the risk of cardiovascular death or rehospitalization for HF through 8 weeks. However, not all patients achieve the target dose of sacubitril/valsartan, and its efficacy and safety in such patients are of interest. Methods PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan versus enalapril in 881 patients stabilized during hospitalization for ADHF. Blinded study medication was administered for 8 weeks, with initial dosing selected based on the systolic blood pressure at randomization and titrated toward a target of sacubitril/valsartan 97/103 mg twice daily, or enalapril 10 mg twice daily, with an algorithm based on systolic blood pressure and the investigator’s assessment of tolerability. Results At 4 weeks, 199 (55%) patients allocated to sacubitril/valsartan and 211 (60%) patients allocated to enalapril were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. There was no heterogeneity across dose levels in the effect of sacubitril/valsartan on the reduction in NT-proBNP (pinteraction = 0.69), the reduction in cardiovascular death or rehospitalization for heart failure (pinteraction = 0.42), or the pre-specified adverse events of special interest through 8 weeks. Conclusions In hemodynamically stabilized patients with ADHF, the efficacy and safety of sacubitril/valsartan are generally consistent across dose levels. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890)

Prolonged use of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) has been shown to reduce the risk of major adverse cardiovascular events (MACE), but with increased bleeding. It remains unknown whether biomarkers of platelet activation may be useful for identifying patients at increased risk of MACE. The DAPT study was a randomized trial of 12 versus 30 months of DAPT in patients who underwent PCI. Serum biomarkers [myeloid-related protein (MRP)-8/14, P-selectin, soluble CD-40 ligand (sCD40L)] were assessed in 1399 patients early post-PCI. On-treatment platelet reactivity index (PRI) using VASP phosphorylation was assessed in 443 patients randomized to continued DAPT at 1 year. MACE was defined as CV death, MI, or ischemic stroke. Multivariable models were adjusted for baseline characteristics, index event, and stent type. A stepwise increase in the risk of MACE was observed with increasing tertiles of both MRP-8/14 and P-selectin (p-trend = 0.04 for both). After multivariable adjustment, the adjusted HR (95% CI) for MACE in patients in the top tertile was 1.94 (1.14–3.30) for MRP-8/14 and 1.62 (0.99–2.64) for P-selectin. In contrast, baseline sCD40L was not associated with CV risk. Among patients randomized to continued DAPT, higher on-treatment platelet reactivity was not significantly associated with risk of MACE (p-trend = 0.32; adj-HR T3 vs. T1 1.54, 95% CI 0.20–12.18) or bleeding (P-trend = 0.17; adj-HR 0.25, 95% CI 0.05–1.21). MRP-8/14 and soluble P-selectin may be useful for identifying patients at increased risk of MACE after PCI. The utility of on-treatment platelet function testing requires further study. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier NCT00977938.

Cardiac arrest (CA) is a common reason for admission to the cardiac intensive care unit (CICU), though the relative burden of morbidity, mortality, and resource use between admissions with in-hospital (IH) and out-of-hospital (OH) CA is unknown. We compared characteristics, care patterns, and outcomes of admissions to contemporary CICUs after IHCA or OHCA.The Critical Care Cardiology Trials Network is a multicenter network of tertiary CICUs in the US and Canada. Participating centers contributed data from consecutive admissions during 2-month annual snapshots from 2017 to 2021. We analyzed characteristics and outcomes of admissions by IHCA vs OHCA.We analyzed 2,075 admissions across 29 centers (50.3% IHCA, 49.7% OHCA). Admissions with IHCA were older (median 66 vs 62 years), more commonly had coronary disease (38.3% vs 29.7%), atrial fibrillation (26.7% vs 15.6%), and heart failure (36.3% vs 22.1%), and were less commonly comatose on CICU arrival (34.2% vs 71.7%), p0.001 for all. IHCA admissions had lower lactate (median 4.3 vs 5.9) but greater utilization of invasive hemodynamics (34.3% vs 23.6%), mechanical circulatory support (28.4% vs 16.8%), and renal replacement therapy (15.5% vs 9.4%); p0.001 for all. Comatose IHCA patients underwent targeted temperature management less frequently than OHCA patients (63.3% vs 84.9%, p0.001). IHCA admissions had lower unadjusted CICU (30.8% vs 39.0%, p0.001) and in-hospital mortality (36.1% vs 44.1%, p0.001).Despite a greater burden of comorbidities, CICU admissions after IHCA have lower lactate, greater invasive therapy utilization, and lower crude mortality than admissions after OHCA.

Introduction: Circulating high-sensitivity cardiac troponin T (hsTnT) reflects myocardial injury, and higher levels are associated with an increased risk of worsening heart failure (HF) and death in patients with HF with reduced ejection fraction (HFrEF). Dapagliflozin reduces the rate of worsening HF or cardiovascular death in patients with HFrEF. The effect of dapagliflozin on the risk of worsening HF or CV death in relation to baseline concentration of hsTnT in patients with HFrEF is unknown. Methods: DAPA-HF was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg once daily) in patients with New York Heart Association class II, III, or IV HF and a left ventricular ejection fraction ≤40%. We measured hsTnT (Roche Diagnostics) at baseline in 3,138 patients randomized in DAPA-HF and at one year among 2,500 survivors. The primary outcome was adjudicated worsening HF or cardiovascular death. Secondary outcomes included each component individually, hospitalization for HF, and death from any cause. The median follow-up was 18.2 months. Results: By the time of this presentation, data will be available for presentation of the distribution of baseline hsTnT concentration and the clinical characteristics associated with strata of hsTnT concentration. The association between baseline hsTnT and 2-year outcomes will be presented and adjusted for potential confounders, including age, sex, eGFR, history of diabetes mellitus, and principal cause of HF (ischemic or non-ischemic). The effect of dapagliflozin on the change in hsTnT concentration from baseline to one year will be presented. The effect of dapagliflozin on the primary and secondary outcomes (both absolute and relative risk reductions) stratified by baseline hsTnT concentration will be analyzed. Conclusions: Biomarkers of myocardial injury identify patients with HFrEF at heightened risk of adverse outcomes. This analysis from a large, international, randomized, placebo-controlled trial will provide a robust assessment of the effect of dapagliflozin on hsTnT and the ability of dapagliflozin to improve outcomes in relation to baseline hsTnT concentration.

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor. Methods: We developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of P Results: Five clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0–7 points) using these predictors identified a >20-fold gradient of HHF risk ( P for trend P for trend=0.04), with high-risk (2 points) and very-high-risk (≥3 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively. Conclusions: Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01107886 and NCT01730534.

Burnout has become commonplace in residency training, affecting more than half of residents and having negative implications for both their well-being and their ability to care for patients. During the authors’ year as chief medical residents at Brigham and Women’s Hospital in 2017–2018, they became intimately familiar with the burnout epidemic in residency training. The authors argue that addressing resident burnout requires residency programs and teaching hospitals to focus not on the individual contributors to burnout, but instead on fostering meaning within residency to help residents find purpose and professional satisfaction in their work. In this Perspective, they highlight four important elements of residency that provide meaning: patient care, intellectual engagement, respect, and community. Patient care, intellectual engagement, and community provide residents with a focus that is larger than themselves, while respect is necessary for a resident’s sense of belonging. The authors provide examples from their own experiences and from the literature to suggest ways in which residency programs and teaching hospitals can strengthen each of these elements within residency and curb the epidemic of burnout.

A Dangerous Detour A 26-year-old woman with T-cell acute lymphoblastic leukemia and an indwelling port catheter presented with progressive dyspnea. She had received a diagnosis of pulmonary emboli ...

OBJECTIVE Heart failure (HF) is an impactful complication of type 2 diabetes mellitus (T2DM). We aimed to develop and validate a risk score for hospitalization for HF (HHF) incorporating biomarkers and clinical factor(s) in patients with T2DM. RESEARCH DESIGN AND METHODS We derived a risk score for HHF using clinical data, high-sensitivity troponin T (hsTnT), and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) from 6,106 placebo-treated patients with T2DM in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using Cox regression. The strongest indicators of HHF risk were included in the score using integer weights. The score was externally validated in 7,251 placebo-treated patients in DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events–Thrombolysis in Myocardial Infarction 58). The effect of dapagliflozin on HHF was assessed by risk category in DECLARE-TIMI 58. RESULTS The strongest indicators of HHF risk were NT-proBNP, prior HF, and hsTnT (each P < 0.001). A risk score using these three variables identified a gradient of HHF risk (P-trend CONCLUSIONS We developed and validated a risk score for HHF in T2DM that incorporated NT-proBNP, prior HF, and hsTnT. The risk score identifies patients at higher risk of HHF who derive greater absolute benefit from dapagliflozin.

The cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) have increased the focus of type 2 diabetes mellitus (T2DM) care on comprehensive cardiovascular risk reduction. Herein, we review the results of the cardiovascular outcomes trials of SGLT2i and GLP-1 RA, discuss the concepts of relative vs. absolute risk reduction in the context of these trials, and highlight the importance of individualized risk assessment when applying trial results to clinical practice. To enable personalized treatment approaches, multiple clinical risk scores have been developed to assess risk of atherosclerotic cardiovascular disease (ASCVD) outcomes and hospitalization for heart failure (HHF) in patients with T2DM. In addition, circulating biomarkers of myocardial injury (cardiac troponin) and hemodynamic stress (natriuretic peptides) have been shown to further refine risk prediction of these clinically important cardiovascular complications. When making decisions about whether to initiate SGLT2i and GLP-1 RA, clinicians should consider the anticipated relative and absolute treatment benefits from these antihyperglycemic therapies. Clinicians can use available clinical and biomarker-based risk tools when counseling patients about their individual cardiovascular risk profiles and when estimating absolute treatment benefits from SGLT2i and GLP-1 RA.

Single-center studies suggest that implementation of multidisciplinary cardiogenic shock (CS) teams is associated with improved CS survival.The aim was to characterize practice patterns and outcomes in the management of CS across multiple centers with versus without shock teams.The Critical Care Cardiology Trials Network is a multicenter network of cardiac intensive care units (CICUs) in North America. All consecutive medical admissions to each CICU (n = 24) were captured during annual 2-month collection periods (2017-2019; n = 6,872). Shock management and CICU mortality among centers with versus without shock teams were compared using inverse probability weighting.Ten of the 24 centers had shock teams. Among 1,242 CS admissions, 44% were at shock team centers. The groups were well-balanced with respect to demographics, shock etiology, Sequential Organ Failure Assessment score, biochemical markers of end organ dysfunction, and invasive hemodynamics. Centers with shock teams used more pulmonary artery catheters (60% vs 49%; adjusted odds ratio [OR]: 1.86; 95% CI: 1.47-2.35; P 0.001), less overall mechanical circulatory support (MCS) (35% vs 43%; adjusted OR: 0.74; 95% CI: 0.59-0.95; P = 0.016), and more advanced types of MCS (53% vs 43% of all MCS; adjusted OR: 1.73; 95% CI: 1.19-2.51; P = 0.005) rather than intra-aortic balloon pumps. The presence of a shock team was independently associated with lower CICU mortality (23% vs 29%; adjusted OR: 0.72; 95% CI: 0.55-0.94; P = 0.016).In this multicenter observational study, centers with shock teams were more likely to obtain invasive hemodynamics, use advanced types of MCS, and have lower risk-adjusted mortality. A standardized multidisciplinary shock team approach may improve outcomes in CS.

Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown.We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02).Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation.

Funding Acknowledgements Type of funding sources: None. OnBehalf Critical Care Cardiology Trials Network (CCCTN) registry Introduction Palliative care is a practice focused on providing relief of symptoms of illness, while optimizing the quality of life for patients and families. We aimed to quantify palliative care (PC) practices and end-of-life decision-making in critically ill cardiac patients in contemporary CICUs. Methods The CCCTN Registry is a network of tertiary care CICUs in the United States and Canada. Between 2017 and 2020, up to 26 centers contributed an annual 2-month snapshot of all consecutive admissions to the CICU. We captured code status, rates of palliative care consultation, and decisions for comfort measures only (CMO) before all deaths in the CICU. Results Of 8231 admissions, 10% ended with death in the CICU and 2.6% were discharges to hospice. Of deceased patients, 68% were CMO before death. The median age of CMO patients was 70y (25th-75th: 59-78) vs. 67 (56-77) among deaths without CMO. In the CMO group, only 13% were DNR/DNI at admission, and the remainder were full code. Respiratory insufficiency and non-cardiogenic shock were the CICU indications most frequently associated with CMO. The median time from CICU admission to CMO decision was 3.4 days (25th-75th: 1.2-7.7) and was ≥7 days in 27% (Figure). Time from CMO decision to death was Conclusions In contemporary CICUs, CMO preceded death in 2/3 of cases. The high use of advanced ICU therapies, lengthy times to a CMO decision, and the very short time from CMO to death, highlight a potential opportunity for greater PC consultation, as well as training programs to build skills in PC for practitioners in the CICU. Abstract Figure

Background Patients with stable atherothrombotic disease vary in their risk of developing heart failure (HF). Circulating cardiovascular biomarkers may improve HF risk assessment and identify patients who may benefit from emerging HF preventive therapies. Methods and Results We measured high‐sensitivity cardiac troponin I and BNP (B‐type natriuretic peptide) in 15 833 patients with prior myocardial infarction, ischemic stroke, or peripheral artery disease from the TRA 2°P‐TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events‐Thrombolysis in Myocardial Infarction 50) trial, excluding patients with recent myocardial infarction (P LRT Conclusions Biomarkers of myocardial injury and hemodynamic stress are independent predictors of HHF risk in patients with stable atherothrombotic disease, with and without prior HF and/or type 2 diabetes mellitus. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00526474.

Importance Dapagliflozin has been shown to reduce the risk of cardiovascular death or worsening heart failure (HF) in patients with chronic HF and reduced ejection fraction (HFrEF). However, clinical inertia often underlies deferred initiation of effective therapies. Objective To examine timing of onset of clinical benefit with dapagliflozin and magnitude as a function of proximity to prior HF hospitalization. Design, Setting, and Participants This is a secondary analysis of a completed multinational trial. The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure trial was a double-blind, placebo-controlled randomized clinical trial of dapagliflozin in patients with chronic HFrEF (n = 4744). From February 2017 to August 2018, the study enrolled patients in New York Heart Association classes II through IV and with left ventricular ejection fraction of 40% or less; the median (range) follow-up time was 18.2 (0-27.8) months. Hazard ratios (HRs) were calculated for the primary efficacy outcome with dapagliflozin vs placebo by time following randomization. Efficacy and safety of dapagliflozin were assessed according to the timing of the most recent HF hospitalization prior to trial enrollment. Exposures None. Main Outcomes and Measures Composite of cardiovascular death or worsening HF. Results A total of 4744 patients were included (1109 women [23.4%]; mean [SD] age, 66.3 [10.9] years). The reduction in the primary outcome with dapagliflozin was rapidly apparent, with a sustained statistically significant benefit by 28 days after randomization (HR at 28 days, 0.51 [95% CI, 0.28-0.94];P = .03). A total of 2251 patients (47.4%) had been previously hospitalized for HF, and 1301 (27.4%) had been hospitalized within 12 months prior to enrollment. Among patients treated with placebo, there was a stepwise gradient of risk for the primary outcome according to timing of most recent HF hospitalization, with 2-year Kaplan-Meier rates of 21.1%, 25.3%, and 33.8% (adjustedP = .003) for patients with a prior HF hospitalization never, more than 12 months ago, and 12 or fewer months ago, respectively. Across these subgroups, dapagliflozin reduced the relative risk of the primary outcome by 16% (HR, 0.84 [95% CI, 0.69-1.01]), 27% (HR, 0.73 [95% CI, 0.54-0.99]), and 36% (HR, 0.64 [95% CI, 0.51-0.80]), respectively (P = .07 for trend). Accordingly, patients with a more recent HF hospitalization tended to experience greater absolute risk reductions with dapagliflozin at 2 years: 2.1% (95% CI, −1.9% to 6.1%), 4.1% (95% CI, −3.6% to 11.7%), and 9.9% (95% CI, 3.3%-16.5%), respectively (P = .05 for trend). Conclusions and Relevance In this study, treatment with dapagliflozin was associated with rapid reduction in the risk of cardiovascular death or worsening HF, with a sustained statistically significant benefit emerging very early after randomization. Patients with a more recent HF hospitalization were at particularly high risk and experienced greater relative and absolute risk reductions with dapagliflozin. Trial Registration ClinicalTrials.gov IdentifierNCT03036124

Background: In patients stabilized during hospitalization for acute decompensated heart failure (HF), initiation of sacubitril/valsartan compared with enalapril decreased the risk of cardiovascular death or rehospitalization for HF without increasing the risk of adverse events. It is unknown whether potentially high-risk subpopulations have a similar risk-benefit profile. Methods: PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP [N-terminal pro-B type natriuretic peptide] in Patients Stabilized From an Acute HF Episode) was a multicenter, randomized, double-blind trial of in-hospital initiation of sacubitril/valsartan (n=440) versus enalapril (n=441) in patients stabilized during hospitalization for acute decompensated HF. The composite of cardiovascular death or rehospitalization for HF was adjudicated. Safety outcomes included worsening renal function, symptomatic hypotension, and hyperkalemia. We evaluated heterogeneity in the effect of sacubitril/valsartan on these efficacy and safety outcomes in selected subgroups of clinical concern: patients with baseline systolic blood pressure ≤118 mm Hg (median; n=448), baseline NT-proBNP >2701 pg/mL (median; n=395), estimated glomerular filtration rate 2 (n=455), ≥1 additional hospitalization for HF within the prior year (n=343), admission to the ICU during the index hospitalization (n=96), inotrope use during the index hospitalization (n=68), and severe congestion (n=219). Results: The relative risk reduction in cardiovascular death or rehospitalization for HF with sacubitril/valsartan versus enalapril was consistent across all high-risk subgroups ( P interaction=non-significant [NS] for each). The risks of worsening renal function, symptomatic hypotension, and hyperkalemia with sacubitril/valsartan versus enalapril were also consistent in each high- versus low-risk subgroup ( P interaction=NS for each). Conclusions: In high-risk subpopulations admitted for acute decompensated HF, treatment with sacubitril/valsartan after initial stabilization conferred a consistent reduction in cardiovascular death or rehospitalization for HF and was well tolerated.

Background: Cardiac arrest (CA) is a common reason for cardiac intensive care unit (CICU) admission and is associated with considerable morbidity, mortality, and resource use. Aim: To describe characteristics and outcomes of pts presenting to contemporary CICUs with in-hospital (IH) or out-of-hospital (OH) CA. Methods: The Critical Care Cardiology Trials Network (CCCTN) is a multicenter network of tertiary CICUs in North America (n=25). Participating centers contributed data from consecutive admissions during 2-month annual snapshots between 9/2017 and 8/2019 (n=8240). We analyzed characteristics and outcomes of pts with CA by IHCA vs OHCA. Results: Of 975 admissions with CA (48.9% OHCA), most were male (64.7%), Caucasian (63.4%) and smokers (60.6%). Acute coronary syndrome (ACS) was present in 30.6% and cardiomyopathy in 21.8%. Shockable rhythm was present in 54.1%, more commonly among those with reduced ejection fraction, ischemic cardiomyopathy, or ACS (pFig ] and CICU length of stay was longer for pts with OHCA (median 3.4 vs 3.1 days; p=0.049). In-hospital mortality was 41.2% and was higher in OHCA (44.7%) compared with IHCA (38.0%), p=0.03 [ Fig ]. Eventual discharge home or to rehab was more common among pts with IHCA (51.6% vs 49.1% for OHCA; p Conclusion: Despite advances in pre- and in-hospital care, pts presenting to contemporary CICUs with CA have high in-hospital mortality, with IHCA mortality only modestly lower than in OHCA. A better understanding of patterns may guide new approaches to improve patient outcomes.

Background: Circulating biomarkers reflecting pathways implicated in heart failure (HF) may improve HF risk assessment in patients with stable atherosclerotic cardiovascular disease (ASCVD). Hypothesis: We aimed to evaluate the performance of circulating biomarkers of hemodynamic stress, myocardial injury, and inflammation for the prediction of hospitalization for HF (HHF) in a large well-characterized cohort with stable ASCVD followed for a median of 4.1 years. Methods: HPS3/TIMI 55-REVEAL was a randomized, double-blind, placebo-controlled trial of the CETP inhibitor anacetrapib in patients with stable ASCVD. We performed a nested prospective biomarker study, measuring high-sensitivity troponin T (hsTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) (all Roche Diagnostics) at randomization (n=29,673). Hazard ratios were adjusted for covariates of a priori clinical relevance to HHF risk: age, prior HF, hypertension, diabetes mellitus, eGFR Results: A significant graded risk of HHF was observed with increasing deciles of hsTnT, NT-proBNP, and GDF-15 (p-trend Figure ). These associations remained significant after multivariable adjustment for clinical risk factors (p Conclusions: In patients with stable ASCVD, biomarkers of myocardial injury, hemodynamic stress, and inflammation provide incremental information for prediction of HHF. Future studies should address whether these patients are more likely to benefit from emerging HF preventive therapies.

Background: Percutaneous ventricular assist devices (VAD) are used in ~1/3 of patients (pts) with cardiogenic shock (CS). A percutaneous microaxial intracardiac VAD can offer hemodynamic support weighed against a risk of vascular complications. However, few studies have addressed the incidence of thrombotic complications, particularly in pts who require extended mechanical circulatory support (MCS). Methods: We conducted an observational cohort study to quantify the risk of thrombotic events during MCS in pts managed with a microaxial VAD for CS or mixed shock from 2015-2020 in a quaternary referral center. All consecutive pts were captured in a prospective registry of MCS and retrospectively reviewed for potentially device-related thrombotic events by 2 physician adjudicators. All pts received systemic anticoagulation with unfractionated heparin and/or bivalirudin. Results: The study included 106 pts (72% male, mean age 59.8). Peripheral artery disease, and a significant smoking history were present in 12% and 44% of cases respectively. The duration of microaxial VAD use was 5.3 days on average and >7 days in 25%. A concurrent microaxial VAD and other MCS were used in 28% of cases. Thrombotic/ischemic events were observed in 24.5% and were subcategorized into limb ischemia with visualized thrombus (n=6), limb ischemia without visualized thrombus (n=6), systemic embolism (n=6), intraventricular thrombus (n=2), device thrombus (n=6), and device dysfunction (n=3). Three pts had more than one complication. Moderate to severe thrombocytopenia ( Conclusion: Thrombotic events are common with a microaxial intracardiac VAD with an observed rate that was higher than previously reported. Larger studies of all-comers with MCS for CS are needed to better define the rate of MCS-associated complications.

Introduction: Although sex-specific differences in treatment and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) have been described, little is known about sex-specific differences in acute decompensated heart failure-related CS (ADHF-CS). Methods: The CCCTN is an investigator-initiated multicenter network of cardiac intensive care units (CICUs) in North America. Consecutive admissions (n=8240) to the CICU during annual snapshots (mostly 2 months) were submitted to the coordinating center (TIMI Study Group, Boston, MA). Patients were stratified by sex and type of CS. Adjustments were made for age and SOFA score. Results: Between 2017 and 2019, 1487 admissions were for CS of which 879 (33% women) were for ADHF-CS. In this cohort, age (median 62 y), race, and BMI (median 28 kg/m 2 ) did not differ by sex. Women and men also had similar SOFA and IABP-SHOCK II scores. Women were less likely to have CKD (28% vs 42%, p= Conclusions: Compared to men, women admitted to the CICU with ADHF-CS had higher mortality despite similar indices of illness severity. The reason(s) behind this difference merit further study.

Background: Patients (pts) with type 2 diabetes mellitus (T2DM) are at increased risk of heart failure (HF); however, the underlying mechanisms by which T2DM contributes to HF are incompletely understood. Hypothesis: We aimed to identify biological pathways associated with risk of hospitalization for HF (HHF) in a well-characterized cohort with T2DM followed for a median of 4.2 yrs. Methods: DECLARE-TIMI 58 was a randomized trial of dapagliflozin in pts with T2DM. We performed a nested case-control study of 184 candidate biomarkers (Olink CV II and CV III) in pts hospitalized for HF (n=432) and controls matched on age, sex, prior HF, prior CV disease, and f/u time (n=432). We evaluated associations between baseline biomarkers and HHF using logistic regression with a stringent threshold for significance (Bonferroni). Biomarkers were ranked according to Wald χ 2 values. ORs for the top 10 biomarkers were further adjusted for the components of the TIMI Risk Score for HF in Diabetes (AF, UACR, eGFR, CAD). ORs are per 1-SD. Results: 45 biomarkers were significantly associated with HHF. The 10 strongest associations were seen with N-terminal pro-B type natriuretic peptide (NT-proBNP), B type natriuretic peptide (BNP), spondin-1 (SPON1), insulin-like growth factor-binding protein 7 (IGFBP7), interleukin-6 (IL-6), fibroblast growth factor-23 (FGF-23), transferrin receptor protein 1 (TR), metalloproteinase inhibitor 4 (TIMP4), matrix metalloproteinase-2 (MMP-2), C-X-C motif chemokine 16 (CXCL16) ( Fig ). All 10 biomarkers were significantly associated with HHF both in pts with and without a history of HF. These proteins represent pathobiological axes implicated in hemodynamic stress, inflammation, myocardial hypertrophy, and cellular senescence, among others. Conclusions: A targeted proteomic approach identified established (NT-proBNP, BNP), investigational (IGFBP7, FGF-23, IL-6, TR, TIMP4, MMP-2, CXCL16), and novel (SPON1) biomarkers of HHF in pts with T2DM.

Introduction: Heart failure (HF) is a prognostically important complication of T2DM, the risk of which can be reduced by SGLT2 inhibitors. Clinical factors and circulating biomarkers of myocardial injury and hemodynamic stress predict risk of hosp for HF (HHF) in pts with T2DM. Aim: We aimed to develop and validate a biomarker-based risk score for HHF in pts with T2DM and to assess whether this score can identify high-risk pts with T2DM who have the greatest reduction in HHF risk with SGLT2 inhibition. Methods: Blood samples were prospectively collected from pts enrolled in SAVOR-TIMI 53 and DECLARE-TIMI 58 at randomization; high-sensitivity troponin T (hsTnT) and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. We derived a risk score in 6106 pts with T2DM in the placebo arm of SAVOR-TIMI 53. Candidate variables (n=27) were assessed using Cox regression. The strongest indicators of HHF risk (based on Wald χ;2 values) were selected for inclusion and assigned integer weights. We externally validated the score in 7251 T2DM pts in the placebo arm of DECLARE-TIMI 58. Hazard ratios (HR) and absolute risk reductions (ARR) in HHF with the SGLT2 inhibitor dapagliflozin were assessed by baseline risk group. Results: The strongest independent indicators of HHF risk were NT-proBNP and hsTnT concentrations, and prior HF (each pFig ). Conclusions: A novel biomarker-based risk score for HHF in pts with T2DM identifies pts at higher risk of HHF who derive greater absolute benefit from SGLT2 inhibitors.

Background Patients with atrial fibrillation (AF) have progressive cardiac structural changes that may be manifest by biomarkers of myocardial injury and hemodynamic stress. Baseline values of hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-brain natriuretic peptide) are associated with stroke risk and GDF-15 (growth differentiation factor-15) is associated with bleeding risk in patients with AF. However, the variability of these biomarkers over time and their associations with stroke or systemic embolism events (S/SEE) and bleeding in patients with AF remain unclear. Purpose We examined whether patients with AF demonstrate detectable changes in these biomarkers over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of S/SEE (hsTnT, NT-proBNP) and bleeding (GDF-15). Methods ENGAGE AF-TIMI 48 was a multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS2 score ≥2. We performed a nested prospective biomarker study in 6062 patients, analyzing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. Event rates were estimated and displayed with annualized event rates after 12 months. Results Of 6062 patients, hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/L change), GDF-15 in 45.6% (≥300 pg/L change) between baseline and 12 months. In addition, 7.7% in hsTnT shifted from low->high categories, 9.4% in NT-proBNP from low->high, 10.6% in GDF-15 from low->high over 12 months (Figure). Elevated hsTnT (≥14 ng/L) and NT-proBNP (≥900 pg/L) either at baseline or at 12 months were independently associated with higher rates of subsequent S/SEE, and elevated GDF-15 (≥1800 pg/L) either at baseline or at 12 months were independently associated with higher rates of subsequent bleeding (P Conclusions Serial assessment of hsTnT, NT-proBNP, and GDF-15 revealed a substantial proportion of patients with AF had dynamic values. Patients with either persistently elevated or dynamic values were at higher risk of adverse clinical outcomes. Those biomarkers may play a role in personalizing preventive strategies in patients with AF based on risk. Change in biomarkers and event rate Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Pharma Development