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Luke C Kohan,1,* Vijaiganesh Nagarajan,1,* Michael A Millard,2 Michael J Loguidice,2 Nancy M Fauber,1 Ellen C Keeley1 1Division of Cardiology, 2Department of Medicine, University of Virginia, Charlottesville, VA, USA * These authors contributed equally to this work Objectives: To assess if a change in our cardiology fellowship program impacted our ST elevation myocardial infarction (STEMI) program. Background: Fellows covering the cardiac care unit were spending excessive hours in the hospital while on call, resulting in increased duty hours violations. A night float fellow system was started on July 1, 2012, allowing the cardiac care unit fellow to sign out to a night float fellow at 5:30 pm. The night float fellow remained in-house until the morning. Methods: We performed a retrospective study assessing symptom onset to arrival, arterial access to first device, and door-to-balloon (D2B) times, in consecutive STEMI patients presenting to our emergency department before and after initiation of the night float fellow system. Results: From 2009 to 2013, 208 STEMI patients presented to our emergency department and underwent primary percutaneous coronary intervention. There was no difference in symptom onset to arrival (150±102 minutes vs 154±122 minutes, p=0.758), arterial access to first device (12±8 minutes vs 11±7 minutes, p=0.230), or D2B times (50±32 minutes vs 52±34 minutes, p=0.681) during regular working hours. However, there was a significant decrease in D2B times seen during off-hours (72±33 minutes vs 49±15 minutes, p=0.007). There was no difference in in-hospital mortality (11% vs 8%, p=0.484) or need for intra-aortic balloon pump placement (7% vs 8%, p=0.793). Conclusion: In academic medical centers, in-house cardiology fellow coverage during off-hours may expedite care of STEMI patients. Keywords: door-to-balloon time, 24/7 in-house call, cardiology fellow

Ischemic heart disease is the most common cause of death in patients with chronic kidney disease (CKD). Patients with CKD who develop an acute coronary syndrome (ACS) have a poor prognosis, with >70% mortality at 2 years. Despite this heavy burden of disease, the optimal management of ACS in this patient population is unknown. Our goal was to compare the effect of coronary revascularization or medical therapy alone on the long-term survival of patients with CKD presenting with ACS. From 1990 to 1998, data were prospectively collected on 4,758 patients admitted to a coronary care unit with the diagnosis of ACS. Of these, 3,104 had preserved renal function, and 1,654 had significant renal dysfunction, as defined by the National Kidney Foundation in the Kidney Disease Outcomes Quality Initiative classification of kidney function as an estimated glomerular filtration rate of <60 ml/min/1.73 m(2). Long-term survival was assessed and outcomes were compared according to whether patients were treated with medical therapy alone or if they underwent a percutaneous or surgical revascularization procedure. Follow-up information was available in 99% of the patients up to 8 years after the index hospitalization. Of the 1,654 patients with significant renal dysfunction, 64 underwent coronary artery bypass surgery, 232 underwent percutaneous coronary revascularization, 280 underwent a diagnostic cardiac catheterization and were subsequently treated medically, whereas 1,078 were treated with medical therapy alone. Percutaneous coronary revascularization was associated with superior long-term survival. In conclusion, patients with severe CKD and ACS had improved long-term survival when treated with percutaneous coronary revascularization. [ABSTRACT FROM AUTHOR]

Background: Improving hypertension control is a public health priority. However, consistent identification of uncontrolled hypertension using computable definitions in electronic health records (EHR) across health systems remains uncertain., Methods: In this retrospective cohort study, we applied two computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥ 18 years) with hypertension (based on either ICD-10 codes of hypertension or two elevated blood pressure [BP] measurements) receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single BP measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit)., Results: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). A total of 24.1% of patients at YNHHS and 21.6% at OneFlorida had both diagnosis code for hypertension and elevated blood pressure measurements. Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p < 0.001; 49.7% versus 41.2% in OneFlorida; p < 0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p = 0.04; 42.2% versus 34.8% in OneFlorida; p < 0.001). Patients with controlled and uncontrolled hypertension had similar incidence rates of deaths, CVD events, and healthcare visits at 3, 6, 12, and 24 months. The two computable definitions generated consistent results., Conclusions: While the current EHR systems are not fully optimized for disease surveillance and stratification, our findings illustrate the potential of leveraging EHR data to conduct digital population surveillance in the realm of hypertension management., (© 2024. The Author(s).)

Omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) have garnered increased attention as a therapeutic option in cardiovascular disease. Most of the research to date has focused on their lipid altering effects and clinical benefits in patients with coronary artery disease, however, there are data supporting their use in the treatment of heart failure. We review the mechanisms through which Ω-3 PUFAs exert their positive effects on the cardiovascular system and highlight the observational and treatment studies that assessed their effects in patients with heart failure., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Fibrocytes, circulating bone-marrow derived cells that differentiate into fibroblasts and myofibroblasts, are a major source of hypertensive arterial fibrosis and correlate with left ventricular (LV) mass in subjects with hypertension. We tested whether circulating fibrocytes levels correlate with LV mass in middle-aged adults without hypertension., Methods: We measured peripheral blood fibrocyte levels and their activated phenotypes in 13 middle-aged, non-hypertensive adults and performed cardiac magnetic resonance imaging to assess LV mass., Results: There was a strong correlation between total fibrocyte levels (CD45 + Col1+) and LV mass index ( r  = 0.71, p  = 0.006), as well as fibrocyte subsets expressing the chemokine markers CCR2 ( r  = 0.60, p  = 0.032), CCR5 ( r  = 0.62, p  = 0.029), CCR7 ( r  = 0.60, p  = 0.034), co-expression of CXCR4 and CCR2 ( r  = 0.62, p = 0.029), α-SMA+ ( r  = 0.57, p  = 0.044), CD133 ( r  = 0.59, p  = 0.036), and pSTAT6 ( r  = 0.64, p  = 0.032)., Conclusions: Circulating fibrocytes are associated with LV mass index in middle-aged, non-hypertensive adults and may be a harbinger for the development of hypertension., Competing Interests: None., (© 2024 The Authors. Published by Elsevier Inc.)

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The ABCD-GENE score was developed to predict poor response to clopidogrel and includes Age, Body mass index, Chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m 2 ), Diabetes, and CYP2C19 GENE variants; a score ≥ 10 is predictive of reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). Estimation of GFR without a race variable via the CKD-EPI Scr 2021 equation is now recommended. We examined the impact of using the CKD-EPI Scr 2021 vs. 2009 equation on the ABCD-GENE score for post-PCI patients. A total of 4335 adult patients (n = 925 Black) who underwent PCI and CYP2C19 genotyping were included, with GFR estimated for each patient via the CKD-EPI Scr 2021 and CKD-EPI 2009 equations. The ABCD-GENE score, calculated based on each GFR estimation, was compared. With the CKD-EPI Scr 2021 vs. 2009 equation, median (IQR) eGFR was lower (74 [55-94] vs. 81 [60-103] mL/min/1.73 m 2 , P < 0.001), and CKD prevalence was higher (31% vs. 25%, P < 0.001) among Black patients, whereas eGFR was higher (85 [65-99] vs. 80 [61-94] mL/min/1.73m 2 , P < 0.001), and CKD prevalence was lower (20% vs. 24%, P < 0.001) in non-Black patients. This led to 12 (1%) Black patients being reclassified from low to high risk of poor clopidogrel response and 30 (1%) non-Black patients being recategorized from high to low risk (P < 0.001 for both comparisons). Removal of the race variable from GFR estimation significantly impacted the prediction of clopidogrel effectiveness via the ABCD-GENE score., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Background: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear., Methods and Results: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups., Conclusions: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.

Background: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear., Objectives: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y 12 inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI)., Methods: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y 12 inhibitor treatment were included. The primary outcome was major atherothrombotic events (MAE) within 1 year after PCI. Cox regression was performed to assess event risk in clopidogrel-treated (reference) vs alternatively treated patients, with stabilized inverse probability weights derived from exposure propensity scores after stratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype., Results: Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885)., Conclusions: These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Heart, Lung, and Blood Institute (grant R01HL149752) and the National Human Genome Research Institute (grant U01HG007269). Spartan Bioscience provided the genotyping platforms and kits for initial testing at the University of Florida Health Jacksonville site. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Franchi has received consulting fees or honoraria from AstraZeneca, Bayer, and Sanofi; and has received research grants to his institution from PLx Pharma and the Scott R. MacKenzie Foundation. Dr Johnson is on the United Health Group scientific advisory board. Dr Winterstein has received consulting fees from Arbor Pharmaceuticals, Bayer KG, Ipsen, and Genentech; and has received funding to her institution for research for which she served as principal investigator from Merck Sharp & Dohme. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and has received research grants to his institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex disease process influenced by metabolic disorders, systemic inflammation, myocardial fibrosis, and microvascular dysfunction. The goal of our study is to identify potential relationships between plasma biomarkers and cardiac magnetic resonance (CMR) imaging markers in patients with HFpEF., Methods: Nineteen subjects with HFpEF and 15 age-matched healthy controls were enrolled and underwent multiparametric CMR and plasma biomarker analysis using the Olink® Cardiometabolic Panel (Olink Proteomics, Uppsala, Sweden). Partial least squares discriminant analysis (PLS-DA) was used to characterize CMR and biomarker variables that differentiate the subject groups into two principal components. Orthogonal projection to latent structures by partial least squares (OPLS) analysis was used to identify biomarker patterns that correlate with myocardial perfusion reserve (MPR) and extracellular volume (ECV) mapping., Results: A PLS-DA could differentiate between HFpEF and normal controls with two significant components explaining 79% (Q2 = 0.47) of the differences. For OPLS, there were 7 biomarkers that significantly correlated with ECV (R2 = 0.85, Q = 0.53) and 6 biomarkers that significantly correlated with MPR (R2 = 0.92, Q2 = 0.32). Only 1 biomarker significantly correlated with both ECV and MPR., Discussion: Patients with HFpEF have unique imaging and biomarker patterns that suggest mechanisms associated with metabolic disease, inflammation, fibrosis and microvascular dysfunction., Competing Interests: LG is an employee of Ribo Life Science. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Siggins, Pan, Löffler, Yang, Shaw, Balfour, Epstein, Gan, Kramer, Keeley and Salerno.)

Coronary microvascular dysfunction is an underdiagnosed pathologic process that is associated with adverse clinical outcomes. There are data to suggest that coronary microvascular dysfunction, in some cases, may be genetically determined. We present an updated review of single nucleotide polymorphisms in coronary microvascular dysfunction.

Background: The appropriate use of pulmonary artery catheters (PACs) in critically ill cardiac patients remains debated., Objectives: The authors aimed to characterize the current use of PACs in cardiac intensive care units (CICUs) with attention to patient-level and institutional factors influencing their application and explore the association with in-hospital mortality., Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Between 2017 and 2021, participating centers contributed annual 2-month snapshots of consecutive CICU admissions. Admission diagnoses, clinical and demographic data, use of PACs, and in-hospital mortality were captured., Results: Among 13,618 admissions at 34 sites, 3,827 were diagnosed with shock, with 2,583 of cardiogenic etiology. The use of mechanical circulatory support and heart failure were the patient-level factors most strongly associated with a greater likelihood of the use of a PAC (OR: 5.99 [95% CI: 5.15-6.98]; P < 0.001 and OR: 3.33 [95% CI: 2.91-3.81]; P < 0.001, respectively). The proportion of shock admissions with a PAC varied significantly by study center ranging from 8% to 73%. In analyses adjusted for factors associated with their placement, PAC use was associated with lower mortality in all shock patients admitted to a CICU (OR: 0.79 [95% CI: 0.66-0.96]; P = 0.017)., Conclusions: There is wide variation in the use of PACs that is not fully explained by patient level-factors and appears driven in part by institutional tendency. PAC use was associated with higher survival in cardiac patients with shock presenting to CICUs. Randomized trials are needed to guide the appropriate use of PACs in cardiac critical care., Competing Interests: Funding Support and Author Disclosures Dr Solomon has received research support from the National Institutes of Health Clinical Center intramural research funds. Dr Morrow has received research grant support to Brigham and Women’s Hospital from Abbott and Abiomed; and has received consulting fees from Abbott Laboratories. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Coronary microvascular dysfunction is an underdiagnosed pathologic process that is associated with adverse clinical outcomes. Biomarkers, molecules measurable in the blood, could inform the clinician by aiding in the diagnosis and management of coronary microvascular dysfunction. We present an updated review of circulating biomarkers in coronary microvascular dysfunction representing key pathologic processes, including inflammation, endothelial dysfunction, oxidative stress, coagulation, and other mechanisms.

Background: Little is known about the prevalence and post-surgical outcomes associated with cardiac intensive care unit (CICU) therapeutics among CICU patients referred for cardiac surgery., Objectives: The purpose of this study was to investigate the clinical characteristics and outcomes of CICU patients referred for cardiac surgery from the intensive care unit., Methods: We analyzed characteristics and outcomes of CICU admissions referred from the CICU for cardiac surgery during 2017 to 2020 across 29 centers. The primary outcome was in-hospital mortality., Results: Among 10,321 CICU admissions, 887 (8.6%) underwent cardiac surgery, including 406 (46%) coronary artery bypass graftings, 201 (23%) transplants or ventricular assist devices, 171 (19%) valve surgeries, and 109 (12%) other procedures. Common indications for CICU admission included shock (33.5%) and respiratory insufficiency (24.9%). Preoperative CICU therapies included vasoactive therapy in 52.2%, mechanical circulatory support in 35.9%, renal replacement in 8.2%, mechanical ventilation in 35.7%, and 17.5% with high-flow nasal cannula or noninvasive positive pressure ventilation. In-hospital mortality was 11.7% among all CICU admissions and 9.1% among patients treated with cardiac surgery. After multivariable adjustment, pre-op mechanical circulatory support and renal replacement therapy were associated with mortality, while respiratory support and vasoactive therapy were not., Conclusions: Nearly 1 in 12 contemporary CICU patients receive cardiac surgery. Despite high preoperative disease severity, CICU admissions undergoing cardiac surgery had a comparable mortality rate to CICU patients overall; highlighting the ability of clinicians to select higher acuity patients with a reasonable perioperative risk.

Hypertrophic cardiomyopathy is the most common genetic heart disease. Biomarkers, molecules measurable in the blood, could inform the clinician by aiding in diagnosis, directing treatment, and predicting outcomes. We present an updated review of circulating biomarkers in hypertrophic cardiomyopathy representing key pathologic processes including wall stretch, myocardial necrosis, fibrosis, inflammation, hypertrophy, and endothelial dysfunction, in addition to their clinical significance.

Cardiac rehabilitation following transcatheter aortic valve replacement (TAVR) is associated with improved outcomes; however, it remains relatively underutilized in this patient population. As part of a quality improvement initiative, we sought to increase the rate of cardiac rehabilitation referral after TAVR at our institution. We designed and implemented a multidisciplinary program that included education of cardiothoracic surgery providers discharging post-TAVR patients on the benefits of cardiac rehabilitation with participation of cardiac rehabilitation personnel during discharge rounds with the surgical team. The study period was defined as 12 months prior to and 6 months following the implementation of the education program. Overall referral rates increased from 5% to 56% ( P < 0.0001), and referrals placed before hospital discharge increased from 0.8% to 53% ( P < 0.0001) over the study period. In conclusion, a combination of education regarding the benefits of cardiac rehabilitation and cardiac rehabilitation personnel participation in discharge rounds significantly increased referral to cardiac rehabilitation after TAVR., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiac rehabilitation is a comprehensive program that treats patients with multiple cardiac conditions including post-myocardial infarction, stable angina, post-coronary artery bypass surgery, chronic heart failure, and peripheral vascular disease with structured exercise, and nutrition and risk factor counseling. It is an effective tool that has been shown to improve not only quality of life but also reduce adverse cardiac events, including death. While the value of cardiac rehabilitation is supported by a large body of evidence and its recommendation by the American Heart Association/American College of Cardiology it is significantly underutilized due to both patient and systemic factors. Continued efforts should be made to remove the obstacles to make cardiac rehabilitation available to all those who qualify., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The presence of coronary collateralization is heterogenous, even amongst those with similar degrees of epicardial coronary artery stenoses. We hypothesized that genetic variation of CXCL5, a chemokine that mediates angiogenesis, is associated with coronary collateralization., Methods: We genotyped subjects undergoing coronary angiography for single nucleotide polymorphisms of CXCL5 and determined the presence of spontaneously visible coronary collaterals., Results: Subjects with collaterals had less angina (46 % vs 59 %, p = 0.006), and prior percutaneous coronary intervention (34 % vs 47 %, p = 0.010), and more hyperlipidemia (90 % vs 82 %, p = 0.018), peripheral arterial disease (25 % vs 17 %, p = 0.041), congestive heart failure (16 % vs 8 %, p = 0.007), and multi-vessel coronary artery disease (41 % vs 24 %, p = 0.0001) compared to those without collaterals. Multi-vessel disease and hyperlipidemia were positive predictors of angiographically visible collaterals while being a carrier of the CXCL5 polymorphism was a negative predictor., Conclusions: Coronary collateralization may, at least in part, be genetically determined., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The coronary microvasculature is responsible for providing oxygen and nutrients to myocardial tissue. A healthy microvasculature with an intact and properly functioning endothelium accomplishes this by seemless changes in vascular tone to match supply and demand. Perturbations in the normal physiology of the microvasculature, including endothelial and/or vascular smooth muscle dysfunction, result in impaired function (vasoconstriction, antithrombotic, etc.) and structural (hypertrophic, fibrotic) abnormalities that lead to microvascular ischemia and potential organ damage. While coronary microvascular dysfunction (CMD) is the primary pathologic driving force in ischemia with non-obstructive coronary artery disease (INOCA), angina with no obstructive coronary arteries (ANOCA), and myocardial infarction with non-obstructed coronary arteries (MINOCA), it may be a bystander in many cardiac disorders which later become pathologically associated with signs and/or symptoms of myocardial ischemia. Importantly, regardless of the primary or secondary basis of CMD in the heart, it is associated with important increases in morbidity and mortality. In this review we discuss salient features pertaining to known pathophysiologic mechanisms driving CMD, the spectrum of heart diseases where it places a critical role, invasive and non-invasive diagnostic testing, management strategies, and the gaps in knowledge where future research efforts are needed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Cardiac remodeling is a process mediated, in part, by 18-hydroxyeicosapentaenoic acid (HEPE), a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA). We hypothesized that trans-myocardial levels of 18-HEPE could inform the pathophysiologic processes involved in heart failure with preserved ejection fraction (HFpEF)., Methods: We measured the concentration of 18-HEPE and EPA in trans-myocardial plasma samples from 10 subjects enrolled in The Women's Ischemia Syndrome Evaluation [WISE] Mechanisms of Coronary Microvascular Dysfunction Leading to Pre-HFpEF project., Results: Concentrations of 18-HEPE were significantly lower in coronary venous compared to the aortic plasma (270.5 pg/mL [212.8-480.8] vs. 430.5 pg/mL [299.5-655.8], p = 0.0039). There was a significant correlation between the concentrations of coronary venous EPA and aortic 18-HEPE ( r = 0.94, p = 0.0002), and aortic EPA and aortic 18-HEPE ( r = 0.82, p = 0.0058)., Conclusions: Results of this small pilot study support the suggestion that 18-HEPE is synthesized outside the heart and utilized within the myocardial bed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Microvascular dysfunction describes a varied set of conditions that includes vessel destruction, abnormal vasoreactivity, in situ thrombosis, and fibrosis, which ultimately results in tissue damage and progressive organ failure. Microvascular dysfunction has a wide array of clinical presentations, ranging from ischemic heart disease to renal failure, stroke, blindness, pulmonary arterial hypertension, and dementia. An intriguing unifying hypothesis suggests that microvascular dysfunction of specific organs is an expression of a systemic illness that worsens with age and is accelerated by vascular risk factors. Studying relationships across a spectrum of microvascular diseases affecting the brain, retina, kidney, lung, and heart may uncover shared pathologic mechanisms that could inform novel treatment strategies. We review the evidence that supports the notion that microvascular dysfunction represents a global pathologic process. Our focus is on studies reporting concomitant microvascular dysfunction of the heart with that of the brain, kidney, retina, and lung., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD-GENE score to predict the risk for atherothrombotic events in a diverse, real-world population of clopidogrel-treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD-GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD-GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient-years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23-2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient-years, adjusted HR 1.59, 95% CI 1.11-2.30, P = 0.013). Our diverse, real-world data demonstrate diminished clopidogrel effectiveness in post-PCI patients with an ABCD-GENE score ≥ 10., (© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.)

Aims: Contemporary cardiac intensive care unit (CICU) outcomes remain highly heterogeneous. As such, a risk-stratification tool using readily available lab data at time of CICU admission may help inform clinical decision-making., Methods and Results: The primary derivation cohort included 4352 consecutive CICU admissions across 25 tertiary care CICUs included in the Critical Care Cardiology Trials Network (CCCTN) Registry. Candidate lab indicators were assessed using multivariable logistic regression. An integer risk score incorporating the top independent lab indicators associated with in-hospital mortality was developed. External validation was performed in a separate CICU cohort of 9716 patients from the Mayo Clinic (Rochester, MN, USA). On multivariable analysis, lower pH [odds ratio (OR) 1.96, 95% confidence interval (CI) 1.72-2.24], higher lactate (OR 1.40, 95% CI 1.22-1.62), lower estimated glomerular filtration rate (OR 1.26, 95% CI 1.10-1.45), and lower platelets (OR 1.18, 95% CI 1.05-1.32) were the top four independent lab indicators associated with higher in-hospital mortality. Incorporated into the CCCTN Lab-Based Risk Score, these four lab indicators identified a 20-fold gradient in mortality risk with very good discrimination (C-index 0.82, 95% CI 0.80-0.84) in the derivation cohort. Validation of the risk score in a separate cohort of 3888 patients from the Registry demonstrated good performance (C-index of 0.82; 95% CI 0.80-0.84). Performance remained consistent in the external validation cohort (C-index 0.79, 95% CI 0.77-0.80). Calibration was very good in both validation cohorts (r = 0.99)., Conclusion: A simple integer risk score utilizing readily available lab indicators at time of CICU admission may accurately stratify in-hospital mortality risk., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

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 <24 h in 88%, with a median of 3.8 h (25th-75th 1.0-10.3). Before a CMO decision, 78% received mechanical ventilation and 26% mechanical circulatory support. A PC provider team participated in the care of 41% of patients who died., 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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Background: Infarct size following ST-elevation myocardial infarction (STEMI) is an important determinate of left ventricular (LV) dysfunction and cardiovascular morbidity and mortality. Cardiac magnetic resonance feature tracking (CMR-FT) is a technique that allows for the assessment of myocardial function via quantification of longitudinal, radial, and circumferential strain. We investigated the association between CMR-FT-derived myocardial global strain and myocardial recovery., Methods: A prospective study on patients presenting with STEMI treated with primary percutaneous coronary intervention (PCI) was conducted. CMR imaging was obtained at two interval time points, the baseline within 2 weeks of hospital discharge and follow-up at 6 months. Strain analysis was performed via FT-CMR, and recovery was quantified by the area of late gadolinium enhancement (LGE)., Results: A total of n = 14 patients met inclusion and exclusion criteria and were analyzed. There was a significant reduction in the infarct size, as measured by LGE mass percentage of the left ventricular muscle mass, between the initial and follow-up CMR (19.7%, IQR 12.2-23.9 vs. 17.1%, IQR 8.3-22.5, p = 0.04). Initial strain parameters were inversely correlated with the initial edema mass and the decrease in LGE mass between the initial and follow-up CMR. All LV global strains had high accuracy for the prediction of a reduction in LGE mass by 50% or more., Conclusions: LV global strains measured after primary PCI can predict the extent of myocardial recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Taha, Jeng, Salerno, Moguillansky, Keeley and Al-Ani.)

Coronary microvascular dysfunction is a ubiquitous pathologic process that is operational in ischemia with no obstructive coronary artery disease and other cardiovascular disorders including heart failure with preserved ejection fraction. It may, in fact, be a manifestation of a multi-systemic condition of small vessel dysfunction that also affects the brain and kidneys. While the pathophysiology driving coronary microvascular dysfunction is multifactorial, chronic inflammation plays an important role. Resolution of inflammation is an active process mediated, in part, by a family of locally active mediators biosynthesized from omega-3 fatty acids, collectively referred to as specialized pro-resolving mediators. Omega-3 fatty acid treatment modulates inflammation and is associated with improved cardiovascular outcomes and attenuation of plaque progression on cardiovascular imaging. Whether omega-3 fatty acid treatment attenuates coronary microvascular dysfunction is unknown., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Resolvins and maresins, members of the specialized proresolving mediator (SPM) family, are omega-3 fatty acid-derived lipid mediators that attenuate inflammation. We hypothesized that they play a role in the pathophysiology of coronary microvascular dysfunction (CMD) in women with ischemia and no obstructive coronary disease. In a pilot study, we measured the D-series resolvins (D1, D2, D3, and D5), resolvin E1, maresin 1, docosahexaenoic acid, eicosapentaenoic acid (precursor of resolvin E1), and 18-hydroxyeicosapentaenoic acid by mass spectrometry in the peripheral blood of 31 women enrolled in the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial who had confirmed CMD assessed by coronary flow reserve. We compared SPM levels with 12 gender and age-matched reference subjects. Compared with the reference subject group, those with CMD had significantly lower plasma concentrations of resolvin D1 and maresin 1 and significantly higher levels of docosahexaenoic acid and 18-hydroxyeicosapentaenoic acid. In conclusion, insufficient or ineffective SPM production may play a role in the pathophysiology of CMD. If our results are validated in a larger cohort, omega-3 fatty acid supplementation could be tested as a novel treatment for these patients., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Objective: Infarct size is a strong predictor of outcomes after ST elevation myocardial infarction (STEMI). Circulating fibrocytes are bone marrow-derived progenitor cells associated with fibrotic processes. We tested whether fibrocytes correlate with infarct size in STEMI patients treated with primary percutaneous coronary intervention (PCI)., Design: Prospective observational study., Setting: Academic medical center., Participants: Subjects with STEMI treated with primary PCI., Interventions: Peripheral blood draw and cardiac magnetic resonance imaging (CMR)., Main Outcome Measure: Correlation of fibrocyte levels with infarct size., Methods: Peripheral blood fibrocytes were quantified at discharge from STEMI hospitalization and at 6 months follow-up using flow cytometry. Infarct size was determined within 2 weeks of discharge and at 6 months follow-up using late gadolinium enhancement on CMR., Results: Among 14 patients (median age 54 years, 79% men) with STEMI, there was a statistically significant positive correlation between fibrocyte levels at 6 months and 6-month infarct size on CMR (r = 0.58, p = 0.031). In addition, there was positive correlation between peak troponin I level (r = 0.85, p < 0.001), and white blood cell count (r = 0.55, p = 0.042) during the hospital stay and 6-month infarct size on CMR., Conclusions: Circulating fibrocytes measured 6 months after STEMI positively correlate with 6-month infarct size assessed by CMR., Competing Interests: Declaration of competing interest No authors reported conflict of interest.

Background: Single-center studies suggest that implementation of multidisciplinary cardiogenic shock (CS) teams is associated with improved CS survival., Objectives: The aim was to characterize practice patterns and outcomes in the management of CS across multiple centers with versus without shock teams., Methods: 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., Results: 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)., Conclusions: 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., Competing Interests: Funding Support and Author Disclosures Dr Drakos has served as a consultant to Abbott. Dr Sinha has served as a consultant to the Abiomed Critical Care Advisory Board. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac rehabilitation is a class 1 recommendation for acute coronary syndrome (ACS) patients according to the American College of Cardiology/American Heart Association. However, only 1 in 5 ACS patients are referred for cardiac rehabilitation nationally, and even fewer at our institution. We sought to improve the number of referrals to cardiac rehabilitation for post-ACS patients admitted to our inpatient cardiology service, and ultimately their participation in the program. We designed a quality improvement initiative that included education of patients and house staff, automated referral order, and participation of cardiac rehabilitation staff members on multidisciplinary rounds. We compared the number of patients who received a referral to cardiac rehabilitation, had the first appointment scheduled before hospital discharge, and attended the program before and after our intervention. Six months after initiation of the project, the proportion of ACS patients referred to cardiac rehabilitation before hospital discharge increased from 10% to 43% (P < 0.001). The mean number of patients with a cardiac rehabilitation appointment scheduled before discharge was 2 before and 5 after the intervention (P < 0.001), and the mean number of patients who attended their scheduled appointment was 1 before and 3 after the intervention (P = 0.001). Run charts demonstrated that the number of referrals and the number of scheduled appointments remained above the median following the intervention. In conclusion, an initiative that included education, automated referrals, and direct one-on-one contact with cardiac rehabilitation staff before discharge increased the number of cardiac rehabilitation referrals, and appointments scheduled and attended in post-ACS patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We describe a case of a 42-year-old man who presented with anginal chest pain. He had objective evidence of ongoing cardiac injury. After initial treatment for coronary arterial disease, cardiac catheterisation revealed diffuse coronary arterial thrombosis with embolisation. Follow-up testing implicated new-onset antiphospholipid antibody syndrome as the aetiology., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Antihypertensive medication nonadherence is a prevalent issue but is very difficult to accurately assess. To clarify this problem among hypertensive patients attending a cardiovascular disease outpatient clinic, we utilized high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) to assess antihypertensive medication adherence and identify trends by sex and drug class., Methods: Serum was extracted from blood samples obtained from patients with either drug-controlled or drug resistant hypertension (RHTN) and analyzed via HPLC-MS for antihypertensive drugs which were categorized by drug class as beta blockers, aldosterone antagonists, diuretics, ACE inhibitor/ARBs, or calcium channel blockers. Clinic blood pressure (BP), sex, and prescription regimens were extracted from medical records at or near the time of blood collection. "Adherence" or "nonadherence" was determined by comparison of the patient's prescribed drug regimen and the presence/absence of prescribed drug(s) in their serum., Results: Among 76 patients (47 women; mean age 63; 53% white), nonadherence was confirmed in 29%. RHTN was more frequently identified in women than men (55% vs 38%) and nonadherence was higher in women than men (34% vs 21%). BP in those who were adherent to prescribed antihypertensive drugs was significantly lower than in those who were nonadherent (129/75 vs 145/83 mmHg, p  = 0.0015). Overall, ACE inhibitors/ARBs were associated with the least nonadherence. Among women, nonadherence was highest for aldosterone antagonists, whereas among men, nonadherence was highest for diuretics., Conclusion: We observed nonadherence was more frequent among older women in a cohort of HTN and RHTN patients with cardiovascular disease based on HPLC-MS confirmed drug levels., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that couple have appeared to influence the work reported in this paper., (© 2021 The Authors.)