Search

Context: The amino acid L-arginine is a substrate for nitric oxide synthase and is increasingly used as a health supplement. Prior studies suggest that L-arginine has the potential to reduce vascular stiffness.Objective: To determine whether the addition of L-arginine to standard postinfarction therapy reduces vascular stiffness and improves ejection fraction over 6-month follow-up in patients following acute ST-segment elevation myocardial infarction.Design and Setting: Single-center, randomized, double-blind, placebo-controlled trial with enrollment from February 2002 to June 2004.Patients: A total of 153 patients following a first ST-segment elevation myocardial infarction were enrolled; 77 patients were 60 years or older.Intervention: Patients were randomly assigned to receive L-arginine (goal dose of 3 g 3 times a day) or matching placebo for 6 months.Main Outcome Measures: Change in gated blood pool-derived ejection fraction over 6 months in patients 60 years or older randomized to receive L-arginine compared with those assigned to receive placebo. Secondary outcomes included change in ejection fraction in all patients enrolled, change in noninvasive measures of vascular stiffness, and clinical events.Results: Baseline characteristics, vascular stiffness measurements, and left ventricular function were similar between participants randomized to receive placebo or L-arginine. The mean (SD) age was 60 (13.6) years; of the participants, 104 (68%) were men. There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either of the 2 groups, including those 60 years or older and the entire study group. However, 6 participants (8.6%) in the L-arginine group died during the 6-month study period vs none in the placebo group (P = .01). Because of the safety concerns, the data and safety monitoring committee closed enrollment.Conclusions: L-arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-arginine should not be recommended following acute myocardial infarction. Clinical Trial Registration ClinicalTrials.gov, NCT00051376. [ABSTRACT FROM AUTHOR]

Context: While current practice guidelines provide an evidence-based approach to management of acute coronary syndromes (ACS), application of the evidence by individual physicians has been suboptimal.Objective: To assess and synthesize the evidence regarding optimal management of non-ST-segment elevation ACS (NSTE-ACS).Data Sources: Systematic searches of peer-reviewed publications were performed in MEDLINE and the Cochrane Database from January 1990 through November 2004, with consultation by content experts. Search terms included antiplatelet therapy, antithrombotic therapy, angiotensin-converting enzyme inhibition, angiotensin receptor blockade, beta-blockade, hypertension, hyperlipidemia, cigarette smoking, diet, diabetes mellitus, exercise, myocardial ischemia, and coronary artery disease.Study Selection and Data Extraction: Criteria for selection of studies included controlled study design, English language, and clinical pertinence. Data quality was based on the publishing journal and relevance to clinical management of NSTE-ACS.Data Synthesis: While outcomes of controlled studies support a comprehensive approach in the management of patients with NSTE-ACS, many physicians perceive existing guidelines as lengthy and complex. After risk stratification to identify those patients most likely to benefit from an early invasive vs early conservative strategy, a comprehensive management plan can be assembled through an "ABCDE" approach. The elements of this include "A" for antiplatelet therapy, anticoagulation, angiotensin-converting enzyme inhibition, and angiotensin receptor blockade; "B" for beta-blockade and blood pressure control; "C" for cholesterol treatment and cigarette smoking cessation; "D" for diabetes management and diet; and "E" for exercise.Conclusion: An "ABCDE" approach for the management of NSTE-ACS provides a practical and systematic means to implement evidence-based medicine into clinical practice. [ABSTRACT FROM AUTHOR]

Acute coronary syndromes are a frequent cause of hospital admission for patients with coronary artery disease. The pathophysiology of acute coronary syndromes often involves plaque rupture or fissure with platelet aggregation. Recognition of the importance of platelet aggregation resulted in several large randomized trials testing 3 types of platelet antagonists, aspirin, glycoprotein IIb/IIIa inhibitors, and adenosine diphosphate inhibitors. A thorough understanding of the data, risks, and benefits of these therapies is important to optimize treatment of the patient with an acute coronary syndrome. Recognition that there is a great deal of interpatient variability in response to these antiplatelet therapies highlights the need for future research in this area. [ABSTRACT FROM AUTHOR]

Genetic variants of key hemostatic mediators increasingly have been proposed as risk factors for atherothrombosis. The Hormone and Estrogen/Progestin Replacement Study group recently reported that the initiation of estrogen replacement in postmenopausal women with known coronary heart disease is associated with an early increase in cardiovascular events. A putative genetic susceptibility factor has been proposed a potential mediator of this increased event risk. This review outlines the recent literature to support the premise for this important proposal. Genetic profiling has great potential to improve the safety and efficacy of individualized pharmacotherapy in postmenopausal women and other at-risk populations for the prevention of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication.Methods: We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months.Findings: At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001).Interpretation: TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied., Objectives: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, in a nationally representative sample from the National Health and Nutrition Examination Survey 1999 to 2004., Methods: We conducted a cross-sectional analysis of 2,134 women (546 pregnant) aged 20 to 40 years without a history of cardiovascular disease., Results: Among pregnant women in the first trimester, the prevalence of elevated NT-proBNP (>125 pg/mL) was 20.0% (SE, 6.6%) compared to 2.4% (SE, 0.8%) among women in the third trimester and 8.0% among nonpregnant women. After adjustment for demographics and cardiovascular risk factors, NT-proBNP was 44% higher (absolute difference 26.4 [95% CI: 11.2-41.6] pg/mL) in the first trimester of pregnancy compared to nonpregnant women. Among pregnant women only, adjusted NT-proBNP was 46% lower (absolute difference -22.2 [95% CI: -36.9 to -7.5] pg/mL) in women in the third trimester compared to women in the first trimester. NT-proBNP was inversely associated with body mass index and with systolic blood pressure., Conclusions: Women in the first trimester of pregnancy had significantly higher NT-proBNP than those in the third trimester and compared to similarly aged nonpregnant women. The dynamic nature of NT-proBNP should be taken into consideration when ordering NT-proBNP lab tests in pregnant women.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is a mediator of the immune response to sepsis. PCSK9 is also highly expressed in pneumocytes and pulmonary endothelial cells. We hypothesized that serum PCSK9 levels would be associated with death and ICU outcomes in patients with ARDS., Methods: Using data and plasma samples from the NIH BioLINCC data repository, we assembled a cohort of 1,577 patients with the acute respiratory distress syndrome (ARDS) enrolled in two previously completed clinical trials, EDEN and SAILS. We measured PCSK9 levels in plasma within 24 h of intubation using commercially available ELISA kits (R&D Systems). We assessed the association of PCSK9 with mortality using Cox proportional hazard models. We also assessed clinical factors associated with PCSK9 level and the association of PCSK9 with the number of days free of mechanical ventilation and days free of ICU care., Results: In 1,577 ARDS patients, median age was 53 years (IQR 42-65 years) and median APACHE III score 91 (72-111) connoting moderate critical illness. PCSK9 levels were 339.3 ng/mL (IQR 248.0-481.0). In multivariable models, race, cause of ARDS, body mass index, pre-existing liver disease, body temperature, sodium, white blood cell count and platelet count were associated with PCSK9 level. Presence of sepsis, use of vasopressors and ventilator parameters were not associated with PCSK9 level. PCSK9 levels were not associated with in-hospital mortality (HR per IQR 0.96, 95% CI 0.84-1.08, P = 0.47). Higher PCSK9 levels were associated with fewer ICU and ventilator free days., Conclusions: Plasma PCSK9 is not associated with mortality in ARDS, however higher PCSK9 levels are associated with secondary outcomes of fewer ICU free and ventilator free days. Clinical factors associated with PCSK9 in ARDS are largely unmodifiable. Further research to define the mechanism of this association is warranted., 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 Metkus, Kim, Jones, Martin, Schulman and Leucker.)

Maternal mortality is rising in the United States, and cardiovascular disease is the leading cause. Adverse pregnancy outcomes such as preeclampsia and gestational diabetes heighten the risk of cardiovascular complications during pregnancy and the peripartum period and are associated with long-term cardiovascular risks. The field of cardio-obstetrics is a subspecialty within adult cardiology that focuses on the management of women with or at high risk for heart disease who are considering pregnancy or have become pregnant. There is growing recognition of the need for more specialists with dedicated expertise in cardio-obstetrics to improve the cardiovascular care of this high-risk patient population. Current recommendations for cardiovascular fellowship training programs accredited by the Accreditation Council for Graduate Medical Education involve establishing core competency in the knowledge of managing heart disease in pregnancy. However, little granular detail is available of what such training should entail, which can lead to knowledge gaps. Additionally, dedicated advanced subspecialty training in this area is not commonly offered. Multidisciplinary collaborative teams have been shown to improve outcomes in cardiac patients during pregnancy, and cardiovascular fellows-in-training interested in cardio-obstetrics should have the opportunity to participate in and contribute to a pregnancy heart team. In this document, we describe a proposed specialized cardio-obstetrics training pathway that could serve to adequately prepare trainees to competently and comprehensively care for women with cardiovascular disease before, during, and after pregnancy., Competing Interests: Dr. Minhas was supported by the National Heart, Lung, and Blood Institute training grant T32HL007024, the Lou and Nancy Grasmick Research Fellowship, and the Marie-Josée and Henry R. Kravis Endowed Fellowship at the Johns Hopkins University. Dr. Goldstein is supported by The Thomas Anstrom Fellowship in Congenital Heart Disease Fund. Dr. Michos is funded by the Amato Fund in Women’s Cardiovascular Health Research at Johns Hopkins University. Dr. Lewey is funded by a grant from the National Heart, Lung, and Blood Institute (K23HL153667). Unrelated to this work, Dr. Michos serves on the advisory boards for AstraZeneca, Amarin, Bayer, Boehringer Ingelheim, Esperion, Novartis, Novo Nordisk, and Pfizer., (Copyright: © 2022 The Author(s).)

Lipoprotein(a), or Lp(a), levels and the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on Lp(a) during the peri-infarction and early postinfarction period are not well characterized. This study aimed to describe the trajectory of Lp(a), as well as the effect of PCSK9 inhibition on that trajectory during the peri-infarction and early postinfarction period. Lp(a) levels were obtained within 24 hours of hospital admission as well as within 24 hours of hospital discharge and at 30 days from 74 participants who presented with a NSTEMI (troponin I >5 ng/ml) or with a STEMI and were enrolled in 2 randomized, double-blind trials of evolocumab and placebo (Evolocumab in Acute Coronary Syndrome [EVACS I]; ClinicalTrials.gov, NCT03515304 and Evolocumab in Patients With STEMI [EVACS II]; ClinicalTrials.gov Identifier: NCT04082442). There was a significant increase from the pretreatment level in the placebo-treated patients, from 64 (41,187) nmol/L to 80 (47, 172) nmol/L at hospital discharge and to 82 (37, 265) at 30 days. This was primarily driven by the results from participants with high Lp(a) at hospital admission (>75 nmol/L) in whom the median increase was 28% as compared with a 10% increase in those with pretreatment Lp(a) of <75 nmol/L. In contrast, there was no significant change from the pretreatment level in the evolocumab-treated patients regardless of pretreatment Lp(a) levels. In conclusion, Lp(a) rises during the peri-infarction and early postinfarction period in patients with acute myocardial infarction. The increase was prevented by a single dose of subcutaneous evolocumab given within 24 hours of hospital admission., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Despite technological and treatment advancements over the past 2 ​decades, cardiogenic shock (CS) mortality has remained between 40% and 60%. Our objective was to develop an algorithm that can continuously monitor heart failure patients and partition them into cohorts of high and low risk for CS., Methods: We retrospectively studied 24,461 patients hospitalized with acute decompensated heart failure, 265 of whom developed CS, in the Johns Hopkins Health System. Our cohort identification approach is based on logistic regression and makes use of vital signs, lab values, and medication administrations recorded during the normal course of care., Results: Our algorithm identified patients at high risk of CS. Patients in the high-risk cohort had 10.2 times (95% confidence interval, 6.1-17.2) higher prevalence of CS than those in the low-risk cohort. Patients who experienced CS while in the high-risk cohort were first deemed high risk a median of 1.7 ​days (interquartile range, 0.8-4.6) before CS diagnosis was made by their clinical team. To evaluate actionability , we randomly selected 50 patients designated as high risk who did develop CS and 50 who did not. On review of true positive cases, from the time of model identification as high risk to the eventual diagnosis of CS, 12% of patients had possible inappropriate therapy, and for 50% of patients, more tailored therapy options existed. On review of the false positive cases, 44% of cases were considered at high risk of CS or end-stage cardiomyopathy by their clinical teams or went onto develop other types of shock., Conclusions: This risk model was able to predict patients at higher risk of CS in a time frame that allowed a change in clinical care. The actionability evaluation demonstrates a possible opportunity to intervene as part of a CS algorithm for escalation of care., Competing Interests: Dr Suchi Saria reports a relationship with Bayesian Health that includes the founder and board member and with PatientPing that includes board membership. The other authors report no financial interests., (© 2022 The Authors.)

Introduction: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT)., Objective: The purpose of this study was to assess the nature of TCP in patients receiving CRRT., Methods: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria., Results: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU., Conclusion: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care., (© 2021 S. Karger AG, Basel.)

BACKGROUND: Some patients with acute heart failure (AHF) who are treated initially with noninvasive ventilation (NIV) will require endotracheal intubation, which indicates NIV failure. The incidence and prognosis of NIV failure in patients with AHF are not well characterized. METHODS: Using the National In-Patient Sample (NIS), we conducted a retrospective cohort study of subjects hospitalized with AHF between 2008 and 2014 who were treated with NIV within 24 h of hospital admission. We determined predictors of NIV failure and determined the association between NIV failure and in-hospital mortality using Cox proportional hazard models. RESULTS: Of 279,534 subjects hospitalized with AHF and treated with NIV, 4,257 (1.52%) failed NIV and required intubation. Cardiogenic shock (odds ratio 8.79, 95% CI 6.89-11.2) and in-hospital arrest (odds ratio 24.9, 95% CI 18.71-33.14) were associated with NIV failure. In-hospital mortality was 26.5% for NIV failure compared to 5.6% for those without NIV ( P < .001). After adjustment for demographics, comorbidities, cardiogenic shock, and in-hospital arrest, NIV failure was associated with nearly a 2-fold risk of in-hospital mortality (odds ratio 1.95, 95% CI 1.59-2.40). CONCLUSIONS: Intubation after initial NIV treatment was required in 1.5% of subjects hospitalized with AHF and treated with NIV, and was associated with high in-hospital mortality. These findings can guide future prospective interventional trials and quality improvement ventures., Competing Interests: Dr Metkus has disclosed relationships with BestDoctors, Oakstone/EBIX, and McGraw-Hill Publishing. The other authors have disclosed no conflicts of interest., (Copyright © 2020 by Daedalus Enterprises.)

The medical complexity and critical care needs of patients admitted to cardiac ICUs are increasing, and prospective studies examining the underlying cardiac and noncardiac diagnoses, the management strategies, and the prognosis of cardiac ICU patients with respiratory failure are needed., Design: Prospective cohort study., Setting: The Critical Care Cardiology Trials Network is a research collaborative of cardiac ICUs across the United States and Canada., Patients: We included all medical cardiac ICU admissions at 25 cardiac ICUs during two consecutive months annually at each center from 2017 to 2019., Measurements: We evaluated the use of advanced respiratory therapies including invasive mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula versus no advanced respiratory support across admission diagnoses and the association with in-hospital mortality., Main Results: Of 8,240 cardiac ICU admissions, 1,935 (23.5%) were treated with invasive mechanical ventilation, 573 (7.0%) with noninvasive ventilation, and 281 (3.4%) with high-flow nasal cannula. Admitting diagnoses among those with advanced respiratory support were diverse including general medical problems in patients with heart disease as well as primary cardiac problems. In-hospital mortality was higher in patients who received invasive mechanical ventilation (38.1%; adjusted odds ratio, 2.53; 2.02-3.16) and noninvasive ventilation or high-flow nasal cannula (8.8%; adjusted odds ratio, 2.25; 1.73-2.93) compared with patients without advanced respiratory support (4.6%). Reintubation rate was 7.6%. The most common variables associated with respiratory insufficiency included heart failure, infection, chronic obstructive pulmonary disease, and pulmonary vascular disease., Conclusions: One-third of cardiac ICU admissions receive respiratory support with associated increased mortality. These data provide benchmarks for quality improvement ventures in the cardiac ICU, inform cardiac critical care training and staffing patterns, and serve as foundation for future studies aimed at improving outcomes., Competing Interests: Dr. Solomon received research support from the National Institutes of Health Clinical Center intramural research funds. Dr. Metkus received salary support from the National Institutes of Health-funded Institutional Career Development Core at Johns Hopkins (project number 5KL2TR003099-02). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background Heart failure with preserved ejection fraction (HFpEF) constitutes half of hospitalized heart failure cases and is commonly associated with obesity. The role of natriuretic peptide levels in hospitalized obese patients with HFpEF, however, is not well defined. We sought to evaluate change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels by obesity category and related clinical outcomes in patients with HFpEF hospitalized for acute heart failure. Methods and Results A total of 89 patients with HFpEF hospitalized with acute decompensated heart failure were stratified into 3 obesity categories: nonobese (body mass index [BMI] <30.0 kg/m 2 , 19%), obese (BMI 30.0-39.9 kg/m 2 , 29%), and severely obese (BMI ≥40.0 kg/m 2 , 52%), and compared for percent change in NT-proBNP during hospitalization and clinical outcomes. Clinical characteristics were compared between patients with normal NT-proBNP (≤125 pg/mL) and elevated NT-proBNP. Admission NT-proBNP was inversely related to BMI category (nonobese, 2607 pg/mL [interquartile range, IQR: 2112-5703]; obese, 1725 pg/mL [IQR: 889-3900]; and severely obese, 770.5 pg/mL [IQR: 128-1268]; P <0.01). Severely obese patients had the largest percent change in NT-proBNP with diuresis (-64.8% [95% CI, -85.4 to -38.9] versus obese -40.4% [95% CI, -74.3 to -12.0] versus nonobese -46.9% [95% CI, -57.8 to -37.4]; P =0.03). Nonobese and obese patients had significantly worse 1-year survival compared with severely obese patients (63% versus 76% versus 95%, respectively; P <0.01). Patients with normal NT-proBNP (13%) were younger, with higher BMI, less atrial fibrillation, and less structural heart disease than those with elevated NT-proBNP. Conclusions In hospitalized patients with HFpEF, NT-proBNP was inversely related to BMI with the largest decrease in NT-proBNP seen in the highest obesity category. These findings have implications for the role of NT-proBNP in the diagnosis and assessment of treatment response in obese patients with HFpEF.

The pulse amplitude ratio (PAR), the ratio of pulse pressure at the end of the Valsalva maneuver to before the onset, correlates with cardiac filling pressure. We have developed a handheld device that uses finger photoplethysmography to measure PAR and estimate left ventricular end diastolic pressure (LVEDP). Patients hospitalized with heart failure (HF) performed three 10-second trials of a standardized Valsalva maneuver (at 20 mm Hg measured via pressure transducer), while photoplethysmography waveforms were recorded, at admission and discharge. Combined primary outcome was 30-day HF hospitalization, intravenous diuresis, or death. Fifty-two subjects had discharge PAR testing; 12 met the primary outcome. Median PAR on admission was 0.55 (interquartile range: 0.40 to 0.70, n = 48) and on discharge was 0.50 (interquartile range: 0.36 to 0.69). Mean PAR-estimated LVEDP was significantly higher in subjects that had an event (20.2 vs 16.9 mm Hg, p = 0.043). Subjects with PAR-estimated LVEDP >19.5 mm Hg had an event rate hazard ratio of 4.57 (95% confidence interval 1.37, 15.19, p = 0.013) compared with patients with LVEDP 19.5 mm Hg or below, with significantly lower 30-day event-free survival (log-rank p = 0.006). In conclusion, noninvasively estimated LVEDP using the pulse amplitude response to a Valsalva maneuver in patients hospitalized for HF changes with diuresis and identifies patients at high risk for 30-day HF events. Detection of elevated filling pressures before hospital discharge may be useful in guiding HF management to reduce HF events., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Patients with influenza infection are at increased risk of acute myocardial infarction (AMI). There are limited data on the short-term prognosis and management of patients with AMI and concomitant influenza. We examined the National Inpatient Sample from 2010 to 2014 for adult patients with a diagnosis of AMI. Patients were stratified into those with or without concomitant influenza. In-hospital therapies and outcomes were compared between groups in unadjusted and adjusted analyses. Standardized differences of >10% and p values <0.05 were considered significant. Propensity matching was performed using a caliper radius of 0.01*sigma. Of 4,285,641 patients with a discharge diagnosis of AMI, 12,830 had concomitant influenza. Patients with influenza were older, had a higher burden of co-morbidities, and more often presented with non-ST elevation AMI (90% vs 74%) as compared with those without influenza. Coronary angiography (23% vs 54%) and revascularization (11% vs 41%) were less often pursued in AMI patients with influenza. Patients with AMI and influenza had elevated in-hospital mortality (14%) and multiorgan failure (33%). In a propensity-matched analysis of 23,415 patients, in-hospital mortality (odds ratio [OR] 1.26; p = 0.01), acute kidney injury (OR 1.36; p <0.01), multiorgan failure (OR 1.81; p <0.01), length-of-stay, and hospital costs were significantly higher in those with influenza. In conclusion, patients with AMI and concomitant influenza have an adverse in-hospital prognosis as compared with those without influenza., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Despite diet being a first-line strategy for preventing cardiovascular disease, the optimal macronutrient profile remains unclear. We studied the effects of macronutrient profile on subclinical cardiovascular injury and inflammation., Methods: OmniHeart was a randomized 3-period, crossover feeding study in 164 adults with high blood pressure or hypertension (SBP 120-159 or DBP 80-99 mm Hg). Participants were fed each of 3 diets (emphasizing carbohydrate (CARB), protein (PROT), or unsaturated fat (UNSAT)) for 6-weeks, with feeding periods separated by a washout period. Weight was held constant. Fasting serum was collected at baseline while participants ate their own diets and after each feeding period. High-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity C-reactive protein (hs-CRP) were measured in stored specimens., Results: The average age was 53.6 years, 55% were African American, and 45% were women. At baseline, the median (25th-percentile, 75th-percentile) hs-cTnI was 3.3 ng/L (1.9, 5.6) and hs-CRP was 2.2 mg/L (1.1, 5.2). Compared to baseline, all 3 diets reduced hs-cTnI: CARB -8.6% (95%CI: -16.1, -0.4), PROT -10.8% (-18.4, -2.5), and UNSAT -9.4% (-17.4, -0.5). Hs-CRP was similarly changed by -13.9 to -17.0%. Hs-cTnI and hs-CRP reductions were of similar magnitudes as SBP and low-density lipoprotein cholesterol (LDLc) but were not associated with these risk-factor reductions (P-values = 0.09). There were no between-diet differences in hs-cTnI and hs-CRP reductions., Conclusions: Healthy diet, regardless of macronutrient emphasis, directly mitigated subclinical cardiac injury and inflammation in a population at risk for cardiovascular disease. These findings support dietary recommendations emphasizing healthy foods rather than any one macronutrient., Trial Registration: This trial is registered at clinicaltrials.gov, number: NCT00051350; URL: https://clinicaltrials.gov/ct2/show/NCT00051350., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units., Methods: The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions., Results: Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%-50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%-100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use., Conclusions: There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.

Objective: In this secondary analysis of the PACIFY randomized trial, we assessed whether dose and timing of fentanyl have implications for the pharmacokinetics and pharmacodynamics of ticagrelor loading during percutaneous coronary intervention (PCI)., Methods: Among 212 patients undergoing clinically indicated coronary angiography, a total of 70 required PCI and received 180 mg oral ticagrelor. Of these, thirty-two patients received no fentanyl and 38 received fentanyl (with variability in the timing of administration and cumulative dose among those randomized to fentanyl, given that both were provided at the interventional cardiologist's discretion). A time-weighted cumulative fentanyl exposure variable was calculated based on total dose of fentanyl and proximity in time of fentanyl administrations to the ticagrelor load. Patients were stratified based on receiving above or below the median time-weighted cumulative dose. Outcomes included ticagrelor concentrations by mass spectrometry (24-hour area under the curve) and platelet function measured using both VerifyNow platelet reactivity units (PRU) and light-transmission aggregometry (LTA)., Results: Unadjusted ticagrelor 24-hour area under the curve was significantly lower across the categories of increasing fentanyl exposure (P=.02). In adjusted regression models, this difference only remained when comparing the no-fentanyl group with the time-weighted cumulative dose above the median group (P=.04). Similarly, with the no-fentanyl group as the reference, adjusted models testing 2-hour PRU and LTA values demonstrated significant differences (with less platelet inhibition for both tests) only among those with time-weighted cumulative fentanyl exposures above the median value (5.1 μg/min)., Conclusions: We have previously shown that fentanyl slows absorption of oral ticagrelor, attenuating its effect on platelet inhibition. We now demonstrate this mechanism appears to be dose- and time-dependent.

Importance: Single-center and claims-based studies have described substantial changes in the landscape of care in the cardiac intensive care unit (CICU). Professional societies have recommended research to guide evidence-based CICU redesigns., Objective: To characterize patients admitted to contemporary, advanced CICUs., Design, Setting, and Participants: This study established the Critical Care Cardiology Trials Network (CCCTN), an investigator-initiated multicenter network of 16 advanced, tertiary CICUs in the United States and Canada. For 2 months in each CICU, data for consecutive admissions were submitted to the central data coordinating center (TIMI Study Group). The data were collected and analyzed between September 2017 and 2018., Main Outcomes and Measures: Demographics, diagnoses, management, and outcomes., Results: Of 3049 participants, 1132 (37.1%) were women, 797 (31.4%) were individuals of color, and the median age was 65 years (25th and 75th percentiles, 55-75 years). Between September 2017 and September 2018, 3310 admissions were included, among which 2557 (77.3%) were for primary cardiac problems, 337 (10.2%) for postprocedural care, 253 (7.7%) for mixed general and cardiac problems, and 163 (4.9%) for overflow from general medical ICUs. When restricted to the initial 2 months of medical CICU admissions for each site, the primary analysis population included 3049 admissions with a high burden of noncardiovascular comorbidities. The top 2 CICU admission diagnoses were acute coronary syndrome (969 [31.8%]) and heart failure (567 [18.6%]); however, the proportion of acute coronary syndrome was highly variable across centers (15%-57%). The primary indications for CICU care included respiratory insufficiency (814 [26.7%]), shock (643 [21.1%]), unstable arrhythmia (521 [17.1%]), and cardiac arrest (265 [8.7%]). Advanced CICU therapies or monitoring were required for 1776 patients (58.2%), including intravenous vasoactive medications (1105 [36.2%]), invasive hemodynamic monitoring (938 [30.8%]), and mechanical ventilation (652 [21.4%]). The overall CICU mortality rate was 8.3% (95% CI, 7.3%-9.3%). The CICU indications that were associated with the highest mortality rates were cardiac arrest (101 [38.1%]), cardiogenic shock (140 [30.6%]), and the need for renal replacement therapy (51 [34.5%]). Notably, patients admitted solely for postprocedural observation or frequent monitoring had a mortality rate of 0.2% to 0.4%., Conclusions and Relevance: In a contemporary network of tertiary care CICUs, respiratory failure and shock predominated indications for admission and carried a poor prognosis. While patterns of practice varied considerably between centers, a substantial, low-risk population was identified. Multicenter collaborative networks, such as the CCCTN, could be used to help redesign cardiac critical care and to test new therapeutic strategies.

Background Prevention of adverse remodeling after myocardial infarction (MI) is an important goal of stem cell therapy. Clinical trial results vary, however, and poor cell retention and survival after delivery likely limit the opportunity to exert beneficial effects. To overcome these limitations, we built an implantable intravascular bioreactor (IBR) designed to protect contained cells from washout, dilution, and immune attack while allowing sustained release of beneficial paracrine factors. Methods and Results IBRs were constructed using semipermeable membrane adhered to a clinical-grade catheter shaft. Mesenchymal stem cell (MSC) viability in and paracrine factor release from IBRs were assessed in vitro and IBR biocompatibility and immune protection confirmed in vivo. In a porcine anterior MI model, IBRs containing 25 million allogeneic MSCs (IBR-MSCs) were compared with IBRs containing media alone (IBR-Placebo; n=8 per group) with adverse remodeling assessed by magnetic resonance imaging. Four weeks after MI, IBR-MSCs had no significant change in end-diastolic volume (+0.33±4.32 mL; P=0.89), end-systolic volume (+2.14±4.13 mL; P=0.21), and left ventricular ejection fraction (-2.27±2.94; P=0.33) while IBR-Placebo had significant increases in end-diastolic volume (+10.37±3.84 mL; P=0.01) and ESV (+11.35±2.88 mL; P=0.01), and a significant decrease in left ventricular ejection fraction (-5.78±1.70; P=0.025). Eight weeks after MI, adherent pericarditis was present in 0 of 8 IBR-MSCs versus 4 of 8 IBR-Placebo (P=0.02), suggesting an anti-inflammatory effect. In a separate study, 25 million allogeneic pig MSCs directly injected in the peri-infarct zone 3 days after MI (n=6) showed no significant benefit in adverse remodeling at 4 weeks compared with IBR-MSCs. Conclusions MSCs deployed inside an implantable, removable, and potentially rechargeable bioreactor in a large animal model remain viable, are immunoprotected, and attenuate adverse remodeling 4 weeks after MI.

Background: The incidence of complications and the outcomes of temporary transvenous pacemaker (TTP) placement in the modern era are not well established., Methods: To determine the current incidence of pericardial complications and the outcomes of patients undergoing TTP, we performed an analysis using the National Inpatient Sample (NIS), which is a US national database of hospital admissions. All patients who underwent TTP were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. A multivariate logistic regression model was constructed for a primary outcome of pericardial tamponade and another for a primary outcome of in-hospital mortality., Results: A total of 360,223 patients underwent TTP placement in the United States between 2004 and 2014. In-hospital mortality was 14.1%, and 37.9% later underwent permanent pacemaker implantation. Potential procedural complications included pericardial tamponade in 0.6% of patients, pneumothorax in 0.9% of patients, and non-pericardial bleeding in 2.4% of patients. In adjusted models, female sex (OR, 1.33 [95% CI, 1.09-1.64]; P = .005), in-hospital cardiac arrest (OR, 3.52 [95% CI, 2.76-4.48]; P < .001), teaching hospital status (OR, 1.91 [95% CI, 1.53-2.40]; P < .001), and previous coronary artery bypass grafting (OR, 0.26 [95% CI, 0.14-0.49]; P < .001) were associated with tamponade. Following multivariate adjustment, pericardial tamponade complicating TTP insertion was associated with a fivefold increase in risk for in-hospital death (OR, 5.00 [95% CI, 2.51-9.96]; P < .001)., Conclusions: TTP placement is generally safe with low pericardial complication rates. Clinicians should be mindful of infrequent but serious complications of TTP, and strategies to mitigate pericardial tamponade and other complications should be sought and implemented., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background Clinical investigations of shock in cardiac intensive care units (CICUs) have primarily focused on acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS). Few studies have evaluated the full spectrum of shock in contemporary CICUs. Methods and Results The Critical Care Cardiology Trials Network is a multicenter network of advanced CICUs in North America. Anytime between September 2017 and September 2018, each center (n=16) contributed a 2-month snap-shot of all consecutive medical admissions to the CICU. Data were submitted to the central coordinating center (TIMI Study Group, Boston, MA). Shock was defined as sustained systolic blood pressure <90 mm Hg with end-organ dysfunction ascribed to the hypotension. Shock type was classified by site investigators as cardiogenic, distributive, hypovolemic, or mixed. Among 3049 CICU admissions, 677 (22%) met clinical criteria for shock. Shock type was varied, with 66% assessed as cardiogenic shock (CS), 7% as distributive, 3% as hypovolemic, 20% as mixed, and 4% as unknown. Among patients with CS (n=450), 30% had AMICS, 18% had ischemic cardiomyopathy without AMI, 28% had nonischemic cardiomyopathy, and 17% had a cardiac cause other than primary myocardial dysfunction. Patients with mixed shock had cardiovascular comorbidities similar to patients with CS. The median CICU stay was 4.0 days (interquartile range [IQR], 2.5-8.1 days) for AMICS, 4.3 days (IQR, 2.1-8.5 days) for CS not related to AMI, and 5.8 days (IQR, 2.9-10.0 days) for mixed shock versus 1.9 days (IQR, 1.0-3.6) for patients without shock ( P<0.01 for each). Median Sequential Organ Failure Assessment scores were higher in patients with mixed shock (10; IQR, 6-13) versus AMICS (8; IQR, 5-11) or CS without AMI (7; IQR, 5-11; each P<0.01). In-hospital mortality rates were 36% (95% CI, 28%-45%), 31% (95% CI, 26%-36%), and 39% (95% CI, 31%-48%) in AMICS, CS without AMI, and mixed shock, respectively. Conclusions The epidemiology of shock in contemporary advanced CICUs is varied, and AMICS now represents less than one-third of all CS. Despite advanced therapies, mortality in CS and mixed shock remains high. Investigation of management strategies and new therapies to treat shock in the CICU should take this epidemiology into account.

Objectives: This study sought to compare a continuous infusion diuretic strategy versus an intermittent bolus diuretic strategy, with the addition of low-dose dopamine (3 μg/kg/min) in the treatment of hospitalized patients with heart failure with preserved ejection fraction (HFpEF)., Background: HFpEF patients are susceptible to development of worsening renal function (WRF) when hospitalized with acute heart failure; however, inpatient treatment strategies to achieve safe and effective diuresis in HFpEF patients have not been studied to date., Methods: In a prospective, randomized, clinical trial, 90 HFpEF patients hospitalized with acute heart failure were randomized within 24 h of admission to 1 of 4 treatments: 1) intravenous bolus furosemide administered every 12 h; 2) continuous infusion furosemide; 3) intermittent bolus furosemide with low-dose dopamine; and 4) continuous infusion furosemide with low-dose dopamine. The primary endpoint was percent change in creatinine from baseline to 72 h. Linear and logistic regression analyses with tests for interactions between diuretic and dopamine strategies were performed., Results: Compared to intermittent bolus strategy, the continuous infusion strategy was associated with higher percent increase in creatinine (continuous infusion: 16.01%; 95% confidence interval [CI]: 8.58% to 23.45% vs. intermittent bolus: 4.62%; 95% CI: -1.15% to 10.39%; p = 0.02). Low-dose dopamine had no significant effect on percent change in creatinine (low-dose dopamine: 12.79%; 95% CI: 5.66% to 19.92%, vs. no-dopamine: 8.03%; 95% CI: 1.44% to 14.62%; p = 0.33). Continuous infusion was also associated with greater risk of WRF than intermittent bolus (odds ratio [OR]: 4.32; 95% CI: 1.26 to 14.74; p = 0.02); no differences in WRF risk were seen with low-dose dopamine. No significant interaction was seen between diuretic strategy and low-dose dopamine (p > 0.10)., Conclusions: In HFpEF patients hospitalized with acute heart failure, low-dose dopamine had no significant impact on renal function, and a continuous infusion diuretic strategy was associated with renal impairment. (Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction [ROPA-DOP]; NCT01901809)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Morphine delays oral P2Y 12 platelet inhibitor absorption and is associated with adverse outcomes after myocardial infarction. Consequently, many physicians and first responders are now considering fentanyl as an alternative. We conducted a single-centre trial randomizing cardiac patients undergoing coronary angiography to intravenous fentanyl or not. All participants received local anaesthetic and intravenous midazolam. Those requiring percutaneous coronary intervention (PCI) with stenting received 180 mg oral ticagrelor intra-procedurally. The primary outcome was area under the ticagrelor plasma concentration-time curve (AUC 0-24 hours ). The secondary outcomes were platelet function assessed at 2 hours after loading, measured by P2Y 12 reaction units (PRUs) and light transmission platelet aggregometry. Troponin-I was measured post-PCI using a high-sensitivity troponin-I assay (hs-TnI). All participants completed a survey of pain and anxiety. Of the 212 randomized, 70 patients required coronary stenting and were loaded with ticagrelor. Two participants in the no-fentanyl arm crossed over to receive fentanyl for pain. In as-treated analyses, ticagrelor concentrations were higher in the no-fentanyl arm (AUC 0-24 hours 70% larger, p  = 0.03). Platelets were more inhibited by 2 hours in the no-fentanyl arm (71 vs. 113 by PRU, p  = 0.03, and 25% vs. 41% for adenosine diphosphate response by platelet aggregation, p  < 0.01). Mean hs-TnI was higher with fentanyl at 2 hours post-PCI (11.9 vs. 7.0 ng/L, p  = 0.04) with a rate of enzymatic myocardial infarction of 11% for fentanyl and 0% for no-fentanyl ( p  = 0.08). No statistical differences in self-reported pain or anxiety were found. In conclusion, fentanyl administration can impair ticagrelor absorption and delay platelet inhibition, resulting in mild excess of myocardial damage. This newly described drug interaction should be recognized by physicians and suggests that the interaction between opioids and oral P2Y 12 platelet inhibitors is a drug class effect associated with all opioids., Clinical Trial Registration:  https://clinicaltrials.gov/ct2/show/NCT02683707 (: NCT02683707)., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: To characterize patient profile and hemodynamic profile of those undergoing intra-aortic balloon pump (IABP) for cardiogenic shock and define predictors of hemodynamic failure of IABP support., Background: Clinical characteristics of IABP support in cardiogenic shock not related to acute myocardial infarction (AMI) remain poorly characterized., Methods: We retrospectively studied a cohort of 74 patients from 2010 to 2015 who underwent IABP insertion for cardiogenic shock complicating acute decompensated heart failure not due to AMI., Results: In the overall cohort, which consisted primarily of patients with chronic systolic heart failure (89%), IABP significantly augmented cardiac index and lowered systemic vascular resistance (P<.05). Despite this improvement, 28% of these patients died (24%) or require urgent escalation in mechanical circulatory support (MCS) (4%). Multivariable regression revealed that baseline left ventricular cardiac power index (LVCPI), a measure of LV power output derived from cardiac index and mean arterial pressure (P=.01), and history of ischemic cardiomyopathy (P=.003) were significantly associated with the composite adverse-event endpoint of death or urgent MCS escalation. An IABP Failure risk score using baseline LVCPI <0.28 W/m 2 and ischemic history predicted 28-day adverse events with excellent discrimination., Conclusion: Despite hemodynamic improvements with IABP support, patients with non-AMI cardiogenic shock still suffer poor outcomes. Patients with ischemic cardiomyopathy and low LVPCI fared significantly worse. These patients may warrant closer observation or earlier consideration of more advanced hemodynamic support., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Morphine reduces and delays the absorption of oral P2Y 12 platelet inhibitors. Fentanyl is another opiate often administered during percutaneous coronary interventions (PCI). The PACIFY study will test whether intravenous fentanyl also impairs the absorption and action of oral P2Y 12 inhibitors., Methods: PACIFY is a single-center trial randomizing adults undergoing clinically-indicated coronary angiography to have the procedure with or without fentanyl. All patients will receive local anesthetic and intravenous midazolam. Doses of all drugs are at the discretion of treating providers. Patients that require PCI receive 180mg of oral ticagrelor during the angiography procedure. The primary outcome is area under the ticagrelor plasma concentration-time curve. Secondary outcomes include platelet inhibition 2-h after loading, measured both by VerifyNow® (Accriva Diagnostics, San Diego, California) and by light-transmission platelet aggregometry. We will also survey patient comfort and measure high-sensitivity troponin levels. Patients and outcomes assessors are blinded, treating providers are not., Results: A total of 212 patients are participating, 70 of whom required PCI. Baseline characteristics are numerically well balanced in both study arms. Mean age is 63years and 27% are female. There were no differences in total midazolam dose during the index PCI procedure, whereas mean total fentanyl dose was 9 mcg in the no-fentanyl arm (2 participants in this arm required fentanyl for bailout treatment of pain) versus 96 mcg in the fentanyl arm., Conclusions: This study will provide important information on the impact of fentanyl administered during PCI on the absorption of ticagrelor and its antiplatelet activity., Trial Registration: clinicaltrials.gov Identifier: NCT02683707., (Copyright © 2017 Elsevier Inc. All rights reserved.)

With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, morphine is the analgesic mainstay for patients with nitrate resistant chest pain due to acute Myocardial Infarction (MI). However, observational data suggest that morphine administration during MI may have negative consequences. While vomiting, hypotension and respiratory depression are established side effects, recent reports have demonstrated attenuated and delayed oral anti-platelet agent absorption, as well as suboptimal reperfusion after MI, all of which may translate into adverse cardiovascular outcomes. These data have resulted in reduced support for morphine in recent European and U.S. clinical practice guidelines for MI; despite the absence of any prospective randomized outcomes trials addressing this question. As such, randomized trials are now necessary to confirm whether or not morphine, which is administered in up to 30% of MI cases, causes adverse clinical outcomes in these patients. However, given that placebo-controlled randomized trial designs evaluating morphine in MI are limited by an ethical requirement for appropriate analgesia, alternative investigational approaches may be necessary. In this article we review the updated evidence for morphine in MI and outline novel strategies that may facilitate future investigation of this clinical dilemma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Opinion Statement: Resuscitated cardiac arrest continues to carry a poor prognosis despite advances in medical care. One such advance, therapeutic hypothermia, is neuroprotective and has been demonstrated to improve clinical outcomes in patients who remain unresponsive despite return of spontaneous circulation after arrhythmogenic cardiac arrest. Two landmark randomized controlled trials, both reported in 2002, led to endorsements by major American and European guidelines for therapeutic hypothermia as a viable treatment option for the prevention of adverse outcomes related to anoxic encephalopathy. Since then, significant research has been conducted to better understand the optimum strategies to maximize the neuroprotective effects of hypothermia. However, dissemination of therapeutic hypothermia guideline recommendations into clinical practice has been slow and incomplete. In this review article, we discuss the historical background and physiologic rationale for therapeutic hypothermia, review the recent literature supporting this intervention, and outline practical considerations.

Heart failure with preserved ejection fraction (HFpEF) has been described as a disease of elderly subjects with female predominance and hypertension. Our clinical experience suggests patients with HFpEF from an urban population are far more heterogenous, with greater co-morbidities and significant inhospital morbidity. There are limited data on the hospitalization course and outcomes in acute decompensated HFpEF. Hospitalizations for acute heart failure at our institution from July 2011 to June 2012 were identified by International Classification of Diseases, Ninth Revision, codes and physician review for left ventricular ejection fraction ≥50% and were reviewed for patient characteristics and clinical outcomes. Worsening renal function (WRF) was defined as creatinine increase of ≥0.3 mg/dl by 72 hours after admission. Hospital readmission and mortality data were captured from electronic medical records and the Social Security Death Index. Of 434 heart failure admissions, 206 patients (47%) with HFpEF were identified. WRF developed in 40%, the highest reported in HFpEF to date, and was associated with higher blood pressure and lower volume of diuresis. Compared to previous reports, hospitalized patients with HFpEF were younger (mean age 63.2 ± 13.6 years), predominantly black (74%), and had more frequent and severe co-morbidities: hypertension (89%), diabetes (56%), and chronic kidney disease (55%). There were no significant differences in 1- and 12-month outcomes by gender, race, or WRF. In conclusion, we found hospitalized patients with HFpEF from an urban population develop a high rate of WRF are younger than previous cohorts, often black, and have greater co-morbidities than previously described., (Copyright © 2015 Elsevier Inc. All rights reserved.)