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• Pulmonary artery diastolic pressure (PADP) may approximate pulmonary capillary wedge pressure (PCWP). • The strength of this association has not been well described in cardiogenic shock (CS). • We observed a moderate correlation between PADP and PCWP in most patients with CS. • Right ventricular CS was the only CS phenotype in which the correlation was poor. • A PADP ≥ 24 mmHg infers a PCWP ≥ 18 mmHg with ≥ 90% confidence in most patients with CS. It is common for clinicians to use the pulmonary artery diastolic pressure (PADP) as a surrogate for the pulmonary capillary wedge pressure (PCWP). Here, we determine the validity of this relationship in patients with various phenotypes of cardiogenic shock (CS). In this analysis of the Critical Care Cardiology Trials Network registry, we identified 1225 people admitted with CS who received pulmonary artery catheters. Linear regression, Bland-Altman and receiver operator characteristic analyses were performed to determine the strength of the association between PADP and PCWP in patients with left-, right-, biventricular, and other non-myocardia phenotypes of CS (eg, arrhythmia, valvular stenosis, tamponade). There was a moderately strong correlation between PADP and PCWP in the total population (r = 0.64, n = 1225) and in each CS phenotype, except for right ventricular CS, for which the correlation was weak (r = 0.43, n = 71). Additionally, we found that a PADP ≥ 24 mmHg can be used to infer a PCWP ≥ 18 mmHg with ≥ 90% confidence in all but the right ventricular CS phenotype. This analysis validates the practice of using PADP as a surrogate for PCWP in most patients with CS; however, it should generally be avoided in cases of right ventricular-predominant CS. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that there is wide variability in cardiac intensive care unit (CICU) length of stay (LOS); however, these studies are limited by the absence of detailed risk assessment at the time of admission. Thus, we evaluated inter-hospital differences in CICU LOS, and the association between LOS and in-hospital mortality. Using data from the Critical Care Cardiology Trials Network (CCCTN) registry, we included 22,862 admissions between 2017 and 2022 from 35 primarily tertiary and quaternary CICUs that captured consecutive admissions in annual 2-month snapshots. The primary analysis compared inter-hospital differences in CICU LOS, as well as the association between CICU LOS and all-cause in-hospital mortality using a Fine and Gray competing risk model. The overall median CICU LOS was 2.2 (1.1-4.8) days, and the median hospital LOS was 5.9 (2.8-12.3) days. Admissions in the longest tertile of LOS tended to be younger with higher rates of pre-existing comorbidities, and had higher Sequential Organ Failure Assessment (SOFA) scores, as well as higher rates of mechanical ventilation, intravenous vasopressor use, mechanical circulatory support, and renal replacement therapy. Unadjusted all-cause in-hospital mortality was 9.3%, 6.7%, and 13.4% in the lowest, intermediate, and highest CICU LOS tertiles. In a competing risk analysis, individual patient CICU LOS was correlated (r2 = 0.31) with a higher risk of 30-day in-hospital mortality. The relationship remained significant in admissions with heart failure, ST-elevation myocardial infarction and non-ST segment elevation myocardial infarction. In a large registry of academic CICUs, we observed significant variation in CICU LOS and report that LOS is independently associated with all-cause in-hospital mortality. These findings could potentially be used to improve CICU resource utilization planning and refine risk prognostication in critically ill cardiovascular patients. [ABSTRACT FROM AUTHOR]

The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described. Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum. The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial. The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72). In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890 ; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634) [Display omitted] [ABSTRACT FROM AUTHOR]

Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting—but potentially unrecognized—LVH. Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up. The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions. NCT05713916. [ABSTRACT FROM AUTHOR]

Among persons presenting to the emergency department with suspected acute myocardial infarction (MI), cardiac troponin (cTn) testing is commonly used to detect acute myocardial injury. Accelerated diagnostic protocols (ADPs) guide clinicians to integrate cTn results with other clinical information to decide whether to order further diagnostic testing. To determine the change in the rate and yield of stress test or coronary CT angiogram following cTn measurement in patients with chest pain presenting to the emergency department pre- and post-transition to a high-sensitivity (hs-cTn) assay in an updated ADP. Using electronic health records, we examined visits for chest pain at five emergency departments affiliated with an integrated academic health system 1-year pre- and post-hs-cTn assay transition. Outcomes included stress test or coronary imaging frequency, ADP compliance among those with additional testing, and diagnostic yield (ratio of positive tests to total tests). There were 7564 patient-visits for chest pain, including 3665 in the pre- and 3899 in the post-period. Following the updated ADP using hs-cTn, 862 (23.5 per 100 patient visits) visits led to subsequent testing versus 1085 (27.8 per 100 patient visits) in the pre-hs-cTn period, (P < 0.001). Among those who were tested, the protocol-compliant rate fell from 80.9% to 46.5% (P < 0.001), but the yield of those tests rose from 24.5% to 29.2% (P = 0.07). Among tests that were noncompliant with ADP guidance, yield was similar pre- and post-updated hs-cTn ADP implementation (pre 13.0%, post 15.4% (P = 0.43). Implementation of hs-cTn supported by an updated ADP was associated with a lower rate of stress testing and coronary CT angiogram. [ABSTRACT FROM AUTHOR]

The PARAGON-HF trial studied the effect of sacubitril/valsartan (Sac/Val) compared with valsartan (Val) on clinical outcomes in patients with chronic heart failure with preserved ejection fraction (HFpEF) or mildly reduced EF (HFmrEF). Further data are needed regarding the use of Sac/Val in these groups with EF and with recent worsening heart failure (WHF) events and in key populations not broadly represented in the PARAGON-HF trial, including those with de novo HF, the severely obese and Black patients. T he PARAGLIDE-HF trial is a multicenter, double-blind, randomized, controlled trial of Sac/Val vs Val that enrolled patients at 100 sites. Medically stable patients ≥ 18 years old with EF > 40%, amino terminal-pro B-type natriuretic peptide (NT-proBNP) levels ≥ 500 pg/mL and within 30 days of a WHF event were eligible for participation. Patients were randomly assigned 1:1 to Sac/Val vs Val. The primary efficacy endpoint is time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. Secondary endpoints include clinical outcomes during follow-up and additional biomarker assessments. Safety endpoints include symptomatic hypotension, worsening renal function and hyperkalemia. The trial enrolled 467 participants from June 2019 through October 2022 (52% women, 22% Black, age 70 ± 12 years, median (IQR) BMI 33 (27–40) kg/m2). The median (IQR) EF was 55% (50%–60%), 23% with HFmrEF (LVEF 41%–49%), 24% with EF > 60% and 33% with de novo HFpEF. Median screening NT-proBNP was 2009 (1291–3813) pg/mL, and 69% were enrolled in the hospital. The PARAGLIDE-HF trial enrolled a broad and diverse range of patients with heart failure with mildly reduced or preserved ejection fraction and will inform clinical practice by providing evidence about the safety, tolerability and efficacy of Sac/Val vs Val in those with a recent WHF event. • PARAGLIDE-HF is a randomized, controlled trial of sacubitril/valsartan vs valsartan that enrolled 467 participants with heart failure (52% women, 22% Black) and ejection fraction > 40% stabilized after a recent worsening heart failure event. • The primary efficacy endpoint was time-averaged proportional change in NT-proBNP from baseline through weeks 4 and 8; secondary endpoints included clinical outcomes during follow-up. • PARAGLIDE-HF enrolled a broad and diverse range of patients with heart failure with mildly reduced or preserved ejection fraction and will inform clinical practice by providing evidence on the safety, tolerability and efficacy of sacubitril/valsartan vs valsartan in those with a recent worsening heart failure event. [ABSTRACT FROM AUTHOR]

The pathobiology of inflammation, thrombosis, and myocardial injury associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may be assessed by circulating biomarkers. However, their relative prognostic importance has been incompletely described. We analyzed data from patients hospitalized with COVID-19 from January 2020, to April 2021, at 122 US hospitals in the American Heart Association (AHA) COVID-19 cardiovascular (CV) disease registry. Patients with data for D-dimer, C-reactive protein (CRP), ferritin, natriuretic peptides [NP], or cardiac troponin (cTn) at admission were included. cTn quintiles were indexed to the assay-specific 99th percentile reference limits. Using multivariable logistic regression, we assessed the association between each biomarker by quintile [Q] and odds of in-hospital death and a cardiovascular and thrombotic composite outcome. Of 32,636 registry patients, 26,424 (81%) had admission values for ≥1 of the key biomarkers, of which 4,527 (17%) had admission values for all 5 biomarkers. Each biomarker revealed a significant gradient for in-hospital mortality from Q1 to Q5: D-dimer 14% to 35%, CRP 11%-32%, ferritin 11% to 30%, cTn 13% to 43%, and NPs 7% to 35% (P trend for each <.001). After adjustment for other biomarkers and clinical variables, Q5 for NPs (OR:4.67, 95% CI: 3.05-7.14) retained the greatest relative odds for death; cTn (OR:2.68, 95% CI: 2.00-3.59) and NPs (OR:7.14, 95% CI: 4.92-10.37) were associated with the greatest odds of the CV composite. Q5 for D-dimer was associated with the highest risk of thrombotic events (OR: 9.02, 95% CI: 5.36-15.18). Among patients hospitalized with COVID-19, cTn and NPs identified patients at high risk for an in-hospital adverse cardiovascular outcome, while elevations in D-dimer identified patients at risk for thrombotic complications. [ABSTRACT FROM AUTHOR]

In the United States, the frequency of using percutaneous mechanical circulatory support devices for acute myocardial infarction complicated by cardiogenic shock is increasing. These devices require large-bore vascular access to provide left, right, or biventricular cardiac support, frequently under urgent/emergent circumstances. Significant technical and logistical variability exists in device insertion, care, and removal in the cardiac catheterization laboratory and in the cardiac intensive care unit. This variability in practice may contribute to adverse outcomes observed in centers that receive patients with cardiogenic shock, who are at higher risk for circulatory insufficiency, venous stasis, bleeding, and arterial hypoperfusion. In this position statement, we aim to: 1) describe the public health impact of bleeding and vascular complications in cardiogenic shock; 2) highlight knowledge gaps for vascular safety and provide a roadmap for a regulatory perspective necessary for advancing the field; 3) propose a minimum core set of process elements, or "vascular safety bundle"; and 4) develop a possible study design for a pragmatic trial platform to evaluate which structured approach to vascular access drives most benefit and prevents vascular and bleeding complications in practice. [Display omitted] • Major bleeding and vascular complications are common in patients with AMI complicated by cardiogenic shock and contribute to morbidity and mortality. • There is substantial variability in practice relating to vascular access, cardiac critical care delivery, device removal, and vascular closure among institutions and individual operators. • Standardization of vascular access and closure techniques and approach to cardiac critical care management using "safety bundles" have the potential to favorably impact health outcomes during cardiogenic shock care. [ABSTRACT FROM AUTHOR]

Background: Biomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood.Objectives: We examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures.Methods: FOURIER was a randomized trial of the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro-B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL).Results: When patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HRadj: 1.57 [95% CI: 1.38-1.78]; high score: HRadj: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HRadj: 1.33 [95% CI: 1.06-1.67]; high score: HRadj: 2.07 [95% CI: 1.52-2.83]) and its components (Ptrend <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each).Conclusions: A biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk coronary anatomy at the time of revascularization. These findings provide insight into the relationships between cardiovascular biomarkers, coronary anatomical complexity, and incident clinical events. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633). [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2010.06.010 Byline: Willibald Hochholzer (a)(b), David A. Morrow (a), Robert P. Giugliano (a) Abstract: The rapid evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome is of great clinical relevance. Biomarkers have become increasingly important in this setting to supplement electrocardiographic findings and patient history because one or both can be misleading. Today, cardiac troponin is still the only marker used routinely in this setting due to its myocardial tissue specificity and sensitivity, as well as its established usefulness for therapeutic decision making. However, even current generation troponin assays have certain limitations such as insufficient sensitivity for diagnosing unstable angina. Novel high-sensitivity assays for cardiac troponin have the potential to overcome these limitations. Further studies are needed to answer some critical questions regarding the best cutoffs for diagnosis and risk assessment and the optimal work-up for rule-out of acute myocardial infarction. Other nonmyocardial tissue-specific markers might help in this setting. Myeloperoxidase, copeptin, and growth differentiation factor 15 reflect different aspects of the development of atherosclerosis or acute ischemia. Each has demonstrated impact in risk stratification of acute coronary syndromes. Limited data also show that copeptin may, when used together with cardiac troponin, improve the sensitivity for diagnosing acute myocardial infarction, and growth differentiation factor 15 may help in selection of patients that benefit from invasive therapy. Further evaluation is needed before these markers can be adopted routinely in clinical practice. Author Affiliation: (a) TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (b) Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany Article History: Received 7 June 2010; Accepted 7 June 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2009.06.011 Byline: Sean R. Wilson (a), Marc S. Sabatine (a)(b), Eugene Braunwald (a)(b), Sarah Sloan (a), Sabina A. Murphy (a), David A. Morrow (a)(b) Abstract: At least 30% of patients with non-ST-elevation acute coronary syndrome present without evidence of myonecrosis using current generation troponin assays. A new generation of research assays for troponin that offer a >10-fold increase in analytical sensitivity has emerged. Author Affiliation: (a) TIMI Study Group, Brigham and Women's Hospital and Department of Medicine, Boston, MA (b) Cardiovascular Division, Brigham and Women's Hospital and Department of Medicine, Boston, MA Article History: Received 24 November 2008; Accepted 5 June 2009 Article Note: (footnote) Clinical trial registration: ClinicalTrials.gov no. NCT00250471.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2005.02.030 Byline: Marc S. Sabatine, David A. Morrow, Carolyn H. McCabe, Elliott M. Antman, C. Michael Gibson, Christopher P. Cannon Abstract: ST deviation and troponin are indicators of risk in unstable angina/non-ST-elevation myocardial infarction with related but distinct pathophysiology. We hypothesized that a combination of the two would offer complementary information regarding the benefit of an invasive strategy. Author Affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA Article History: Received 10 September 2004; Accepted 20 February 2005

Background: The interaction between thrombosis and inflammation appears central to COVID-19-associated coagulopathy and likely contributes to poor outcomes. Tissue factor is a driver of disordered coagulation and inflammatory signaling in viral infections and is important for viral replication; therefore, tissue factor may be an important therapeutic target in COVID-19.Study Design: ASPEN-COVID-19 (NCT04655586) is a randomized, prospective open-label blinded endpoint (PROBE), active comparator Phase 2b trial to evaluate the safety and efficacy of recombinant Nematode Anticoagulant Protein c2 (rNAPc2), a potent tissue factor inhibitor, in patients hospitalized with COVID-19 with elevated D-dimer levels. This report describes the design of the Phase 2b dose ranging and proof of concept study. Participants are randomly assigned, in a 1:1:2 ratio, to lower or higher dose rNAPc2 by subcutaneous injection on days 1, 3, and 5 or to heparin according to local standard of care; randomization is stratified by baseline D-dimer level (at 2X upper limit of normal). The primary efficacy endpoint for Phase 2b is proportional change in D-dimer concentration from baseline to Day 8 or day of discharge, whichever is earlier. The primary safety endpoint is major or non-major clinically relevant bleeding through Day 8. Phase 2b enrollment began in December 2020 and is projected to complete ∼160 participants by Q4 2021.Conclusions: ASPEN-COVID-19 will provide important data on a novel therapeutic approach that may improve outcomes in hospitalized COVID-19 patients beyond available anticoagulants by targeting tissue factor, with potential effects on not only thrombosis but also inflammation and viral propagation. [ABSTRACT FROM AUTHOR]

Environmental management systems standards are dominated by ISO 14001 in Europe to assess such processes, and for registering such programs, according to the Eco-Management & Audit Scheme (EMAS). Compares large multinational firms in the US and Europe with smaller domestic energy and gas companies in Germany. Includes tables.

Background: p38 mitogen activated kinase (MAPK) mediates the response to pro-inflammatory cytokines following myocardial infarction (MI) and is inhibited by losmapimod.Methods: LATITUDE-TIMI 60 (ClinicalTrials.gov NCT02145468) randomized patients with MI to losmapimod or placebo for 12 weeks (24 weeks total follow-up). In this pre-specified analysis, we examined outcomes based on MI type [ST-segment elevation MI (STEMI) (865, 25%) and non-STEMI (2624, 75%)].Results: In patients with STEMI, inflammation, measured by hs-CRP, was significantly attenuated with losmapimod at 48 hours (P <0.001) and week 12 (P = 0.01). Losmapimod lowered NT-proBNP in patients with STEMI at 48 hours (P = 0.04) and week 12 (P = 0.02). The effects of losmapimod on CV death (CVD), MI, or severe recurrent ischemia requiring urgent coronary artery revascularization at 24 weeks [MACE] differed in patients with STEMI (7.0% vs 10.8%; HR 0.65, 95%CI 0.41 - 1.03; P= 0.06) and NSTEMI (11.4% vs 8.5%; HR 1.30, 95%CI 1.02 - 1.66; P = 0.04; p[int] = 0.009). CVD or HHF among patients with STEMI were 5.6% (losmapimod) and 8.3% (placebo) (HR 0.66; 95%CI 0.40 - 1.11; P = 0.12) and in NSTEMI were 4.8% (losmapimod) and 4.4% (placebo) (HR 1.09; 95%CI 0.76 - 1.56) in patients with NSTEMI.Conclusions: Patients with STEMI treated with losmapimod had an attenuated inflammatory response. Our collective findings raise the hypothesis that mitigating the inflammatory response may result in different outcomes in patients with STEMI and NSTEMI. While the difference in outcomes is exploratory, these findings do support separate examination of patients with STEMI and NSTEMI and increased emphasis on heart failure in future investigation of modulators of inflammation in MI. [ABSTRACT FROM AUTHOR]

This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended. [ABSTRACT FROM AUTHOR]

PIONEER-HF and the recently completed PARAGLIDE-HF both evaluated the efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF). This prespecified pooled analysis of PIONEER-HF (Ejection fraction [EF]≤40%) and PARAGLIDE-HF (EF>40%) examines outcomes with sacubitril/valsartan in patients stabilized after a worsening HF event across the spectrum of EF. Both PIONEER-HF and PARAGLIDE-HF were multicenter, double-blind, randomized, controlled trials of sacubitril/valsartan vs. control therapy (enalapril or valsartan, respectively). All participants in PIONEER-HF and 69% in PARAGLIDE-HF were enrolled after hemodynamic stabilization during a hospitalization for HF. The remainder in PARAGLIDE-HF were enrolled within 30 days of an episode of worsening HF (including an emergency department or urgent HF visit requiring intravenous diuretic) and included in this analysis. The primary endpoint of both trials was time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. Clinical endpoints in both trials were adjudicated by the same independent clinical events committee and analyzed in all randomized patients through end of follow-up, adjusting for trial. The pooled analysis included 1347 patients (881 from PIONEER-HF and 466 from PARAGLIDE-HF). The median age was 66y. Overall, 36% were women, 31% were Black, 34% had de novo HF. The median EF was 30% (92% with EF ≤60%). Among those with requisite NTproBNP results (n= 1130), the time-averaged reduction in the NT-proBNP was 24% greater with sacubitril/valsartan vs. control (ratio of change, 0.76; 95% confidence interval [CI], 0.69-0.83; p<0.0001; Fig-Left). The composite of cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs. control (HR 0.70; 95% CI 0.54-0.91; p=0.0077). The clinical effect of sacubitril/valsartan was consistent across the spectrum of EF≤60% (Fig-Right, overall HR among those w/ EF≤60% 0.59; 95% CI 0.44-0.79) and when restricted to those hospitalized with HF (n=1133, HR 0.73; 95% CI 0.55-0.98). Sacubitril/valsartan increased symptomatic hypotension (RR, 1.35; 95%CI, 1.05-1.72) but trended toward a lower rate of worsening renal function (Risk Ratio [RR], 0.80; 95%CI, 0.64-1.003). In a pooled analysis of randomized trials among patients hospitalized with HF, compared with control therapy, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP level and improved clinical outcome across the spectrum of EF≤60%. [ABSTRACT FROM AUTHOR]

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date.Design: COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771).Conclusion: In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes. [ABSTRACT FROM AUTHOR]

Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19. [ABSTRACT FROM AUTHOR]

Background: Critical care risk scores can stratify mortality risk among cardiac intensive care unit (CICU) patients, yet risk score performance across common CICU admission diagnoses remains uncertain.Methods: We evaluated performance of the Acute Physiology and Chronic Health Evaluation (APACHE)-III, APACHE-IV, Sequential Organ Failure Assessment (SOFA) and Oxford Acute Severity of Illness Score (OASIS) scores at the time of CICU admission in common CICU admission diagnoses. Using a database of 9,898 unique CICU patients admitted between 2007 and 2015, we compared the discrimination (c-statistic) and calibration (Hosmer-Lemeshow statistic) of each risk score in patients with selected admission diagnoses.Results: Overall hospital mortality was 9.2%. The 3182 (32%) patients with a critical care diagnosis such as cardiac arrest, shock, respiratory failure, or sepsis accounted for >85% of all hospital deaths. Mortality discrimination by each risk score was comparable in each admission diagnosis (c-statistic 95% CI values were generally overlapping for all scores), although calibration was variable and best with APACHE-III. The c-statistic values for each score were 0.85-0.86 among patients with acute coronary syndromes, and 0.76-0.79 among patients with heart failure. Discrimination for each risk score was lower in patients with critical care diagnoses (c-statistic range 0.68-0.78) compared to non-critical cardiac diagnoses (c-statistic range 0.76-0.86).Conclusions: The tested risk scores demonstrated inconsistent performance for mortality risk stratification across admission diagnoses in this CICU population, emphasizing the need to develop improved tools for mortality risk prediction among critically-ill CICU patients. [ABSTRACT FROM AUTHOR]

Background: The prevalence of renal disease in cardiac intensive care units (CICUs) is increasing, but little is known about the utilization, concurrent therapies, and outcomes of patients requiring acute renal replacement therapy (RRT) in this specialized environment.Methods: In the Critical Care Cardiology Trials Network, 16 centers submitted data on CICU admissions including acute RRT (defined as continuous renal replacement therapy and/or acute intermittent dialysis).Results: Among 2,985 admissions, 178 (6.0%; interhospital range 1.0%-16.0%) received acute RRT. Patients receiving RRT, versus not, were more commonly admitted for cardiogenic shock (15.7% vs 4.2%, P < .01), cardiac arrest (9.6% vs 3.7%, P < .01), and acute general medical diagnoses (10.7% vs 5.8%, P < .01), whereas acute coronary syndromes (16.9% vs 32.1%, P < .01) were less frequent. Variables independently associated with acute RRT included diabetes, heart failure, liver disease, severe valvular disease, shock, cardiac arrest, hypertension, and younger age. In patients receiving acute RRT, versus not, advanced therapies including mechanical ventilation (55.6% vs 18.0%), vasoactive support (73.0% vs 35.2%), invasive hemodynamic monitoring (59.6% vs 29.2%), and mechanical circulatory support (27.5% vs 8.4%) were more common. Acute RRT was associated with higher in-hospital mortality (42.1% vs 9.3%, adjusted odds ratio 3.74, 95% CI, 2.52-5.53) and longer median length of stay (10.0 vs 5.3 days, P < .01). In conclusion, acute RRT in contemporary CICUs was associated with the provision of other advanced therapies and lower survival.Conclusions: These data underscore the risks associated with the provision of renal support in patients with primary cardiovascular problems and the need to develop standardized indications and potential futility measures in this specialized population. [ABSTRACT FROM AUTHOR]

Prior studies have demonstrated that the cardiac intensive care unit (CICU) patient population has evolved over time. We sought to describe the temporal changes in comorbidities, illness severity, diagnoses, procedures and adjusted mortality within our CICU practice in recent years.Methods: We retrospectively reviewed unique CICU admissions at the Mayo Clinic from January 2007 to April 2018. Comorbidities, severity of illness scores, discharge diagnosis codes and CICU procedures and therapies were recorded, and temporal trends were assessed using linear regression and Cochran-Armitage trend tests. Trends in adjusted hospital mortality over time were assessed using multivariable logistic regression.Results: We included 12,418 patients with a mean age of 67.6 years (including 37.7% females). Temporal trends in the prevalence of several comorbidities and discharge diagnoses were observed, reflecting an increase in the prevalence of non-coronary cardiovascular diseases, critical care diagnoses, and organ failure (all P ≪ .05). The use of several CICU therapies and procedures increased over time, including mechanical ventilation, invasive lines and vasoactive drugs (all P ≪ .05). A temporal decrease in adjusted hospital mortality was observed among the subgroup of patients with (adjusted OR per year 0.97, 95% CI 0.94-0.99, P = .023) and without (adjusted OR per year 0.91, 95% CI 0.85-0.96, P = .002) a critical care discharge diagnosis.Conclusions: We observed an increasing prevalence of critical care and organ failure diagnoses as well as increased utilization of critical care therapies in this CICU cohort, associated with a decrease in risk-adjusted hospital mortality over time. [ABSTRACT FROM AUTHOR]

Background: Although the Seattle Angina Questionnaire (SAQ) has been widely used to assess disease-specific health status in patients with ischemic heart disease, it was originally developed in a predominantly male population and its validity in women has been questioned.Methods: Using data from 8892 men and 4013 women across 2 multicenter trials and 5 registries, we assessed the construct validity, test-retest reliability, responsiveness to clinical change, and predictive validity of the SAQ Summary Score (SS) and its 5 subdomains (Physical Limitation (PL), Anginal Stability (AS), Angina Frequency (AF), Treatment Satisfaction (TS), and Quality of Life (QoL)) separately in men and women.Results: Comparable correlations of the SAQ SS with Canadian Cardiovascular Society class was demonstrated in both men and women (-0.48 for men, -0.46 for women). Similar correlations between the SAQ PL scale with treadmill exercise duration and Short Form-12 (SF-12) Physical Component Summary were observed in women and men (0.34-0.63 and 0.40-0.63, respectively). SAQ AS scores were significantly lower for both men and women with acute syndromes compared with 1 month later. The SAQ AF scale was strongly correlated with daily angina diaries (0.62 for men and 0.66 for women). The SAQ QoL scores were moderately correlated with the EQ5D visual analog scale and SF-12 general health question in men (0.43-0.50) and women (0.33-0.39). All SAQ scales demonstrated excellent reliability (intraclass correlation ≥0.78) in both men and women with stable CAD and were very sensitive to change after percutaneous coronary intervention (≥15-point difference in scores, standardized response mean ≥ 0.67). The SAQ SS was similarly predictive of 1-year mortality and cardiac re-hospitalizations for both men and women.Conclusion: The SAQ demonstrates similar psychometric properties in men and women with CAD. These findings provide evidence for validity of the SAQ in assessing women with IHD. [ABSTRACT FROM AUTHOR]

Objective: The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF.Background: Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF.Methods: PIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF <40% and an amino terminal-pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia.Conclusion: The PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF. [ABSTRACT FROM AUTHOR]

Background: Ezetimibe improves cardiovascular (CV) outcomes in patients stabilized after acute coronary syndrome (ACS) when added to statin therapy. After ACS, patients vary considerably in their risk for recurrent CV events.Objectives: This study tested the hypothesis that atherothrombotic risk stratification may be useful to identify post-ACS patients who have the greatest potential for benefit from the addition of ezetimibe to statin therapy.Methods: The TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool, previously developed in a large population with atherothrombosis to predict CV death, myocardial infarction (MI), and ischemic stroke (CV death/MI/ischemic cerebrovascular accident [iCVA]). The current study applied this tool prospectively to 17,717 post-ACS patients randomized either to ezetimibe and simvastatin or to placebo and simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Treatment efficacy was assessed by baseline risk for CV death/MI/iCVA, the IMPROVE-IT composite endpoints (CE), and individual component endpoints at 7 years.Results: All 9 clinical variables in the TRS 2°P were independent risk indicators for CV death/MI/iCVA (p < 0.001). The integer-based scheme showed a strong graded relationship with the rate of CV death/MI/iCVA, the trial CE, and the individual components (p trend <0.0001 for each). High-risk patients (n = 4,393; 25%), defined by ≥3 risk indicators, had a 6.3% (95% confidence interval: 2.9% to 9.7%) absolute risk reduction in CV death/MI/iCVA at 7 years with ezetimibe/simvastatin, thus translating to a number-needed-to-treat of 16. Intermediate-risk patients (2 risk indicators; n = 5,292; 30%) had a 2.2% (95% confidence interval: -0.3% to 4.6%) absolute risk reduction. Low-risk patients (0 to 1 risk indicators; n = 8,032; 45%) did not appear to derive benefit from the addition of ezetimibe (p interaction = 0.010). Similar findings were observed for the IMPROVE-IT primary CE.Conclusions: Atherothrombotic risk stratification using the TRS 2°P identifies high-risk patients who derive greatest benefit from the addition of ezetimibe to statin therapy for secondary prevention after ACS. (Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878). [ABSTRACT FROM AUTHOR]

Temporary mechanical circulatory support (TMCS) bridging strategies are increasingly used for acute decompensated heart failure-related cardiogenic shock (ADHF-CS). However, the impact of bridging approach on post-operative outcomes in ADHF-CS patients who receive a durable left ventricular assist device (LVAD) or heart transplant (HT) is unknown. Durable LVAD or HT recipients from July 1, 2014 to December 31, 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by pre-operative TMCS strategy. Associations between TMCS strategies and post-operative outcomes were evaluated using propensity-score matching and adjustment for pre-selected covariates (pre-operative hemoglobin, platelets, albumin, bilirubin, international normalized ratio, creatinine, cardiopulmonary resuscitation, and operative status). A total of 8,777 ADHF-CS patients were bridged to LVAD (5,975; 68%) or HT (2,802; 32%). The composite of operative/30-day death following LVAD or HT was highest in patients managed with VA ECMO (22%) and lowest in those managed without TMCS (7%), with a stepwise gradient of incidence by level of hemodynamic support (Figure, top ). Other post-operative outcomes including major bleeding, cerebrovascular accident, cardiac arrest, prolonged mechanical ventilation, renal failure, and sepsis/pneumonia followed a similar pattern. However, after propensity score matching and adjustment, there were no differences in the odds of operative/30-day death or major bleeding with IABP versus no TMCS (Figure, bottom ). While there was no difference in operative/30-day death, odds of major bleeding were lower with catheter-based MCS compared with IABP (OR 0.70, 95% CI 0.53 - 0.92). ADHF-CS patients experience high rates of cardiac and non-cardiac adverse events post- LVAD and HT. A crude relationship between TMCS bridging strategy and post-operative outcomes was observed. However, after adjustment, pre-operative TMCS bridging strategy did not independently confer risk of near-term post-operative mortality among ADHF-CS patients who underwent HT or durable LVAD implantation. [ABSTRACT FROM AUTHOR]