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We sought to evaluate interobserver concordance among experienced electrocardiogram (ECG) readers in predicting acute thrombotic coronary occlusion (ATCO) in the context of abnormal metabolic milieu (AMM) following resuscitated out of hospital cardiac arrest (OHCA).OHCA patients with initial shockable rhythm who underwent invasive coronary angiography (ICA) were included. AMM was defined as one of: pH 7.1, lactate 2 mmol/L, serum potassium 2.8 or 6.0 mEq/L. The initial ECG following ROSC but prior to ICA was adjudicated by 2 experienced readers using classic ST elevation myocardial infarction [STEMI] and expanded criteria and their combination to predict ATCO on ICA.152 consecutive patients (mean age 58 years, 76% male) met inclusion criteria. AMM was present in 77%; and 42% had ATCO on ICA. Sensitivity, specificity, PPV, NPV using classic STEMI criteria were 50%, 98%, 94%, 72% (c-statistic 0.74); whereas for combined (STEMI + expanded) criteria they were 69%, 88%, 81%, 79% respectively (c-statistic 0.79). Inter-observer agreement (kappa) was 0.7 for classic STEMI criteria, and 0.66 for combined criteria. Agreement between readers was consistently higher when ATCO was absent and with NMM (kappa 0.78), but lower in AMM (kappa 0.6).Despite experienced ECG readers, there was only modest overall concordance in predicting ATCO in the context of resuscitated OHCA. Significant interobserver variations were noted dependent on metabolic milieu and angiographic ATCO. These observations fundamentally question the role of the 12-lead ECG as primary triaging tool for early angiography among patients with OHCA.

ImportanceMany patients do not receive recommended services. Drive time to health care services may affect receipt of guideline-recommended care, but this has not been comprehensively studied.ObjectiveTo assess associations between drive time to care and receipt of guideline-recommended screening, diagnosis, and treatment interventions.Design, Setting, and ParticipantsThis cohort study used administrative data from the National Veterans Health Administration (VA) data merged with Medicare data. Eligible participants were patients using VA services between January 2016 and December 2019. Women ages 65 years or older without underlying bone disease were assessed for osteoporosis screening. Patients with new diagnosis of chronic obstructive pulmonary disease (COPD) indicated by at least 2 encounter codes for COPD or at least 1 COPD-related hospitalization were assessed for receipt of diagnostic spirometry. Patients hospitalized for ischemic heart disease were assessed for cardiac rehabilitation treatment.ExposuresDrive time from each patient’s residential address to the closest VA facility where the service was available, measured using geocoded addresses.Main Outcomes and MeasuresBinary outcome at the patient level for receipt of osteoporosis screening, spirometry, and cardiac rehabilitation. Multivariable logistic regression models were used to assess associations between drive time and receipt of services.ResultsOf 110 780 eligible women analyzed, 36 431 (32.9%) had osteoporosis screening (mean [SD] age, 66.7 [5.4] years; 19 422 [17.5%] Black, 63 403 [57.2%] White). Of 281 130 patients with new COPD diagnosis, 145 249 (51.7%) had spirometry (mean [SD] age, 68.2 [11.5] years; 268 999 [95.7%] men; 37 834 [13.5%] Black, 217 608 [77.4%] White). Of 73 146 patients hospitalized for ischemic heart disease, 11 171 (15.3%) had cardiac rehabilitation (mean [SD] age, 70.0 [10.8] years; 71 217 [97.4%] men; 15 213 [20.8%] Black, 52 144 [71.3%] White). The odds of receiving recommended services declined as drive times increased. Compared with patients with a drive time of 30 minutes or less, patients with a drive time of 61 to 90 minutes had lower odds of receiving osteoporosis screening (adjusted odds ratio [aOR], 0.90; 95% CI, 0.86-0.95) and spirometry (aOR, 0.90; 95% CI, 0.88-0.92) while patients with a drive time of 91 to 120 minutes had lower odds of receiving cardiac rehabilitation (aOR, 0.80; 95% CI, 0.74-0.87). Results were similar in analyses restricted to urban patients or patients whose primary care clinic was in a tertiary care center.Conclusions and RelevanceIn this retrospective cohort study, longer drive time was associated with less frequent receipt of guideline-recommended services across multiple components of care. To improve quality of care and health outcomes, health systems and clinicians should adopt strategies to mitigate travel burden, even for urban patients.

Background Integrating medical scribes with clinicians has been suggested to improve access, quality of care, enhance patient/clinician satisfaction, and increase productivity revenue. Objective Conduct a systematic review to evaluate the effects of medical scribes in emergency departments. Methods Electronic databases from 2010 through December 2019. Two individuals independently reviewed study eligibility, rated risk of bias, and determined overall certainty of evidence. Data abstracted included study and population characteristics, outcomes (efficiency, patient or clinician satisfaction, financial productivity, documentation quality, cost, and training time), and the effect of compensation structure, qualifications, duties, and setting on outcomes. Results Twenty studies (18 observational) were included; 12 from two institutions. All utilized in-person rather than virtual scribes. Fifteen were rated as serious or critical risk of bias; five were rated moderate. Findings indicate that scribes may increase patients seen per day and decrease length of stay; however, effects were small and may vary by setting and outcome measured (low certainty). Scribes may increase financial productivity; however, costs associated with developing, implementing, and maintaining scribe programs were not adequately reported. Results were mixed for door-to-room or door-to-provider time, patients left without being seen, and patient/clinician satisfaction. No studies examined the effects of scribes based on compensation structure, qualifications or duties. Conclusions Although information quality, quantity, and applicability are limited, in-person medical scribes may improve emergency department efficiency and financial productivity. There was no information on virtual scribes. There was little information on patient or clinician satisfaction, scribe documentation quality, or whether results vary by in-house vs. contracted hiring and training.

While torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared with furosemide remain unclear. We performed a systematic review and meta-analysis, including all published studies that compared torsemide and furosemide use in heart failure patients from January 1996 through August 2019. Nineteen studies (9 randomized control trials (RCTs) and 10 observational studies) with a total of 19,280 patients were included. During a mean follow-up duration of 15 months, torsemide was associated with a numerically lower risk of hospitalization due to heart failure (10.6% vs. 18.4%; odds ratio (OR) 0.72, 95% confidence interval (CI) (0.51, 1.03), p=0.07, I2=18%; number needed to treat (NNT) =23) compared with furosemide. Torsemide was associated with statistically significant more improvement in functional status from New York Heart Association (NYHA) class III/IV to I/II (72.5% vs. 58%; OR 2.32, 95% CI (1.32, 4.1), p=0.004, I2=27%; NNT=5) and lower risk of cardiac mortality (1.5% vs. 4.4%; OR 0.37, 95% CI (0.20, 0.66), p

Background Ultrafiltration is not commonly used because of higher incidence of worsening renal function without improved decongestion. We examined differential outcomes of high versus low fluid removal and preserved versus reduced ejection fraction (EF) in CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Methods and Results Baseline characteristics in the ultrafiltration arm were compared according to 24-hour ultrafiltration-based fluid removal above versus below the median. Patients were stratified by EF (40%). We compared clinical parameters of clinical decongestion during the hospitalization based on initial (40% group demonstrated larger increases of change in creatinine (P=0.023) and aldosterone (P=0.038) from baseline to 96 hours. Among patients with EF >40%, those with above median fluid removal (n=17) when compared with below median (n=17) had an increased rate of the combined end point (87.5% versus 47.1%, P=0.014). Conclusions In patients with acute heart failure, higher initial fluid removal with ultrafiltration had no association with worsening renal function. In patients with EF >40%, ultrafiltration was associated with worsening renal function irrespective of fluid removal rate and higher initial fluid removal was associated with higher rates of adverse clinical outcomes, highlighting variable responses to decongestive therapy. Dr. Fudim is supported by an American Heart Association Grant, 17MCPRP33460225; he consults for Coridea, AxonTherapies, Galvani, and Daxor. Dr. Greene has received research support from a Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis, Amgen, Bristol-Myers Squibb and Novartis; and serves on an advisory board for Amgen. Dr. Sharma has received research support from the Fonds de la recherche en sante du Quebec (FRSQ)-Junior 1, Jean Roy award in Cardiology (McGill University), Akcea, Pharma, Solutions, Alberta Innovates Health Solutions, Bayer-Canadian Cardiovascular Society, Boehringer-Ingelheim, Roche Diagnostics, and Takeda. Dr. Verbrugge was supported by a Fellowship of the Belgian American Educational Foundation. Dr. Martens has received consultancy fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Novartis, and Vifor Pharma and an unrestricted research grant from Vifor Pharma. Dr. Grodin receives research support from the Texas Health Resources Clinical Scholars fund and has received consultancy fees from Pfizer, Inc. Dr. Hernandez receives Grant/Research Support; Company Relationship; AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Luitpold Pharmaceuticals, Merck, Novartis. Honoraria; Company Relationship; Bayer, Boston Scientific, Novartis. Dr. Felker has received research funding from Otsuka, Novartis, Roche Diagnostics, Amgen, Merck, American Heart Association, and the National Heart, Lung, and Blood Institute; and has served as a consultant for Novartis, Roche Diagnostics, Amgen, Trevena, Cytokinetics, Madeliene, Myokardia, Bristol-Myers Squibb, Stealth Biotherapeutics, and GlaxoSmithKline. Dr. Mentz receives research support from the National Institutes of Health (U01HL125511-01A1, U10HL110312, and R01AG045551-01A1), Akros, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, Luitpold, Medtronic, Merck, Novartis, Otsuka, and ResMed; honoraria from Abbott, AstraZeneca, Bayer, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, and ResMed; and has served on an advisory board for Amgen, Luitpold, Merck, and Boehringer Ingelheim. The remaining authors have no disclosures to report. Fudim, M (corresponding author), 2301 Erwin Rd, Durham, NC 27713 USA. marat.fudim@gmail.com

Aims Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition, and tissue congestion manifested by oedema is not present in all patients. We compared clinical characteristics, exercise capacity, and outcomes in patients with HFpEF with and without oedema. Methods and results This study was a post hoc analysis of pooled data of patients with left ventricular ejection fraction of ≥50% enrolled in the DOSE, CARRESS‐HF, RELAX, ATHENA, ROSE, INDIE, and NEAT trials. Patients were dichotomized by the severity of oedema. Cox proportional hazard regression and generalized linear regression models were used to assess associations between oedema, symptoms, and clinical outcomes. The ambulatory cohort included 393 patients (228 with and 165 without oedema), and the hospitalized cohort included 338 patients (249 with ≥moderate oedema and 89 with mild or none). Among ambulatory patients, patients with oedema had a higher body mass index (35.2 kg/m2 [inter‐quartile range, IQR 30.5, 41.6] vs. 31.6 kg/m2 [IQR 27.9, 36.3], P

Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns.The purpose of this study was to determine the effects of HCQ treatment on QT interval.We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy.Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th-75th percentile) duration of HCQ therapy was 1006 (471-2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470-500 ms, and 12 (1.5%) had QTc500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc15% or on-treatment QTc500 ms. Over median 5.97 (3.33-10.11) years of follow-up, 269 patients (33%) died. QTc470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16-2.71; P = .008) in univariable but not in multivariable analysis.HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.

Background: Secondary mitral regurgitation (MR) arises from left ventricular (LV) dilatation and remodeling, and commonly is treated with transcatheter mitral valve repair. We examined the impact of MitraClip on reverse cardiac remodeling in patients with severe, symptomatic secondary MR.Methods:: An electronic search was performed through January 2018 for studies that reported cardiac chamber dimensions prior to and after treatment with MitraClip in patients with secondary MR. The mean difference (MD) with 95% CI was calculated using fixed or random inverse variance models. Outcomes of interest were changes in LV end-systolic and end-diastolic volumes (LVESV, LVEDV) and dimensions (LVESD, LVEDD). Secondary outcomes included left atrial (LA) volume, systolic pulmonary artery pressure (sPAP) and LV ejection fraction (LVEF).Results: A total of 16 studies with 1,266 patients were included in the present analysis. The weighted mean follow-up period (±SD) was 11.5 ± 7.2 months. MitraClip was associated...

AIMS Mechanical ultrafiltration (UF) involves the removal of an iso-osmotic filtrate from the blood. Its benefit in acute decompensated heart failure, however, remains inconclusive. We sought to better understand the direct effects of UF in comparison to an aggressive, urine output-guided pharmacological protocol for decongestion on fluid loss, renal function, and neurohormonal activation. METHODS AND RESULTS A per-protocol analysis of the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trial (n = 188) was performed. Participants were included if randomized to UF and had UF output collected, or if randomized to the pharmacological arm and had urine but not UF output collected. Using these definitions, there were 163 participants at 24 h, 156 at 48 h, 129 at 72 h, and 106 at 96 h. UF was associated with higher cumulative fluid loss (P = 0.003), net fluid loss (P = 0.001), and relative reduction in weight (P = 0.02). UF was also associated with higher serum creatinine and blood urea nitrogen by 72 h (P-interaction

The symptoms of and disability related to decompensated heart failure are manifestations of congestion. Therefore, congestion is the main treatment target and diuretics are recommended as first line therapy. Refractory congestion refers to situations in which diuretics fail to produce the desired clinical effect. In these circumstances, ultrafiltration may be appropriate for the relief of congestion and improved outcomes. This chapter will review the concept of refractory congestion; describe the use of diuretics and ultrafiltration in the treatment of congestion; and review the importance of case selection when choosing to treat refractory congestion with ultrafiltration.

Introduction: We embarked on a research project intending to compare healthcare and social care utilization and costs for people with congestive heart failure in the United States (US) and the Netherlands (NL). Our intention was to evaluate these characteristics at a national, regional, and person-specific level, comparing data from patients being cared for at Hennepin Healthcare (Minneapolis, MN, US) and Radboud University Medical Center (Nijmegen, NL). Because we focused on a specific clinical subpopulation in both countries, we expected to be able to make valid comparisons between these two patient populations. However, our experience with this project calls into question the accuracy and reliability of between-country healthcare comparisons. Methods: Spurious and unexpected results from the between-country database comparison prompted us to critically examine our findings. We used iterative group discussions to identify weaknesses and missing components in our comparative data. In addition to exploring specific examples from our own unpublished work, we went on to identify similar limitations in external, peer-reviewed publications. Results: We identified five domains that limited our ability to perform a valid between-country comparison. These included (1) differences in patient level characteristics both within and between countries; (2) variations in societal norms and values; (3) different systems of healthcare and social care organization and delivery; (4) variable definitions, implantation, and distribution of costs; and (5) limitations within the databases themselves. Discussion: Iterative group discussion and reflection were useful in understanding defining limitations in our between country database comparison. Acceptance of the database comparison would have led to erroneous conclusions about heart failure patients in the US and NL. Conclusions: There are five domains that limited our ability to perform a valid between-country comparison, including patient-level characteristics, societal norms and values, systems of healthcare and social care, costs, and databases. Lessons Learned: Our findings suggest that these domains should be considered prior to undertaking an international comparison of healthcare and social care. They may also provide a tool for critical analysis of published data. Limitations: The five domains we identified are based on a single study. However, we were able to identify external examples in peer-reviewed journals in each of the domains. Suggestions for future research: In order for us to continue to learn from other systems, international comparisons of healthcare and social care should continue, but particular attention must be given to ensuring that accurate and reliable comparisons are made. The domains we have identified may stimulate further research into quality assurance for international healthcare comparisons.

Background: The relationship between intensive volume removal in acute decompensated heart failure patients with preexisting worsening renal function (WRF) and renal tubular injury, postdischarge renal function, and clinical outcomes is unknown. Methods and Results: We used data from the multicenter CARRESS-HF trial (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) that randomized patients with acute decompensated heart failure and preexisting WRF to intensive volume removal with stepped pharmacological therapy or fixed rate ultrafiltration. Patients in the urinary renal tubular injury biomarker substudy (NAG [N-acetyl-b-D-glucosaminidase], KIM-1 [kidney injury molecule-1], and NGAL [neutrophil gelatinase-associated lipocalin]) were evaluated (N=105). The severity of prerandomization WRF was unrelated to baseline renal tubular injury biomarkers ( r =0.14; P =0.17). During randomized intensive volume removal, creatinine further worsened in 53% of patients. Despite a small to moderate magnitude increase in creatinine in most of these patients, postrandomization WRF was strongly associated with worsening in renal tubular injury biomarkers (odds ratio, 12.6; P =0.004). This observation did not differ by mode of volume removal (stepped pharmacological therapy versus ultrafiltration, P interaction =0.46). Increase in renal tubular injury biomarkers was associated with a higher incidence of hemoconcentration (odds ratio, 3.1; P =0.015), and paradoxically, better recovery of creatinine at 60 days ( P =0.01). Conclusions: In acute decompensated heart failure patients with preexisting WRF, intensive volume removal resulted in a further worsening of creatinine approximately half of the time, a finding associated with a rise in tubular injury biomarkers. However, decongestion and renal function recovery at 60 days were superior in patients with increased tubular injury markers. These data suggest that the benefits of decongestion may outweigh any modest or transient increases in serum creatinine or tubular injury markers that occur during intensive volume removal. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00608491.

Though commonly noted in clinical practice, it is unknown if decongestion in acute heart failure (AHF) results in increased serum bicarbonate.For 678 AHF patients in the DOSE-AHF, CARRESS-HF, and ROSE-AHF trials, we assessed change in bicarbonate (baseline to 72-96 hours) according to decongestion strategy, and the relationship between bicarbonate change and protocol-defined decongestion. Median baseline bicarbonate was 28 mEq/L. Patients with baseline bicarbonate ≥28 mEq/L had lower ejection fraction, worse renal function and higher N-terminal pro-B-type natriuretic peptide than those with baseline bicarbonate28 mEq/L. There were no differences in bicarbonate change between treatment groups in DOSE-AHF or ROSE-AHF (all P .1). In CARRESS-HF, bicarbonate increased with pharmacologic care but decreased with ultrafiltration (median +3.3 vs -0.9 mEq/L, respectively; P .001). Bicarbonate change was not associated with successful decongestion (P .2 for all trials).In AHF, serum bicarbonate is most commonly elevated in patients with more severe heart failure. Despite being used in clinical practice as an indicator for decongestion, change in serum bicarbonate was not associated with significant decongestion.

Previous studies have suggested that torsemide lowers aldosterone level through its anti-mineralo-corticoid activity. However, the impact of torsemide on left ventricular (LV) reverse remodeling and renin-angiotensin-aldosterone system remains unclear with conflicting results. We performed a

Background We sought to study the prevalence of high‐sensitivity troponin and its association with cardiac structure and outcomes in ambulatory and hospitalized patients with heart failure with a preserved ejection fraction ( HF p EF ). Methods and Results A post hoc analysis utilized data from HF p EF patients: DOSE (Diuretic Optimization Strategies Evaluation) and CARRESS ‐ HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) enrolled patients hospitalized with acute HF p EF , and RELAX (Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) enrolled ambulatory patients with HF p EF . High‐sensitivity troponin I (hs‐TnI) was measured in hospitalized patients at baseline, at 72 to 96 hours, on day 7, and on day 60. In ambulatory patients hs‐TnI was measured at baseline and at week 24. In the ambulatory cohort, correlations between hs‐TnI and cardiac structure and function were assessed. The association between hs‐TnI and a 60‐day composite of emergency room visits, readmissions, and death was assessed for hospitalized patients using multivariable Cox proportional hazard models. The study population included 139 hospitalized and 212 ambulatory patients with HF p EF and hs‐TnI measured at baseline. The median (25th, 75th percentiles) baseline troponin was 17.6 (11.1, 41.0) ng/L in hospitalized patients and 9.5 (5.3, 19.7) ng/L in ambulatory patients ( P 99% percentile upper reference limit was 86% in hospitalized patients and 53% among ambulatory patients, with stable elevation in ambulatory patients during follow‐up. HF p EF patients with a hs‐TnI above the median were older with worse left ventricular hypertrophy and diastolic dysfunction. Continuously valued hs‐TnI (per doubling) was associated with increased risk of composite end point (adjusted hazard ratio 1.20, 95% confidence interval 1.00‐1.43; P =0.042). Conclusions Hs‐TnI is commonly elevated among both hospitalized and ambulatory patients with HF p EF . Increased hs‐TnI levels are associated with worse cardiac structure and increased risk of adverse events.

Rounds are an integral part of a physician’s life. Efficient conduct of rounds on the inpatient service is an important skill that trainees must harness as they transition from being physicians-in-training to becoming independent practitioners. Rounds are not only critical for learning the science

Background— Congestion is the most frequent cause for hospitalization in acute decompensated heart failure. Although decongestion is a major goal of acute therapy, it is unclear how the clinical components of congestion (eg, peripheral edema, orthopnea) contribute to outcomes after discharge or how well decongestion is maintained. Methods and Results— A post hoc analysis was performed of 496 patients enrolled in the Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trials during hospitalization with acute decompensated heart failure and clinical congestion. A simple orthodema congestion score was generated based on symptoms of orthopnea (≥2 pillows=2 points, P =0.038). Of the patients without orthodema at discharge, 27% relapsed to low-grade orthodema and 38% to high-grade orthodema at 60-day follow-up. Conclusions— Increased severity of congestion by a simple orthodema assessment is associated with increased morbidity and mortality. Despite intent to relieve congestion, current therapy often fails to relieve orthodema during hospitalization or to prevent recurrence after discharge. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00608491, NCT00577135.

Decompensated or acute heart failure (AHF) is characterized by increased ventricular and atrial pressures which may lead to and be caused by circulatory congestion. Unless due to a primary decrease in cardiac function, congestion arises from volume expansion or vasoconstriction. In turn, volume expansion and vasoconstriction are due to neurohormonal imbalance since both result from activation of the sympathetic nervous system, the renin-angiotensin-aldosterone axis and excess secretion of arginine vasopressin. Outcomes in AHF remain dismal. Loop diuretics are the mainstay of therapy for AHF and may themselves aggravate neurohormonal imbalance. No adjunctive pharmacotherapy has yielded improvement in outcomes in AHF despite many attempts with various vasodilators and inotropes. We, therefore, propose that insufficient attention has been paid to neurohormonal imbalance in AHF. As in chronic HF, rectifying the effects of neurohormonal imbalance may lead to better outcomes. The use of alternative decongestive strategies or adjunctive pharmacotherapy directed at neurohormonal activation could yield benefit.

Mechanical ultrafiltration (UF) involves the removal of an iso-osmotic filtrate from the blood. Its benefit in acute decompensated heart failure, however, remains inconclusive. We sought to better understand the direct effects of UF in comparison to an aggressive, urine output-guided pharmacological protocol for decongestion on fluid loss, renal function, and neurohormonal activation.A per-protocol analysis of the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trial (n = 188) was performed. Participants were included if randomized to UF and had UF output collected, or if randomized to the pharmacological arm and had urine but not UF output collected. Using these definitions, there were 163 participants at 24 h, 156 at 48 h, 129 at 72 h, and 106 at 96 h. UF was associated with higher cumulative fluid loss (P = 0.003), net fluid loss (P = 0.001), and relative reduction in weight (P = 0.02). UF was also associated with higher serum creatinine and blood urea nitrogen by 72 h (P-interaction0.05 for both), lower serum sodium by 48 h (P-interaction0.01) and increased plasma renin activity by 96 h (P = 0.04). The pharmacological arm was associated with higher serum bicarbonate after 24 h (P-interaction0.002). There were no differences in 60-day outcomes between the UF and pharmacological arms.Ultrafiltration vs. pharmacological therapy was associated with more fluid removal but also rise in serum creatinine and neurohormonal activation. Additionally, loop diuretic use vs. UF was associated with an increase in serum bicarbonate despite less decongestion, data which question the commonly held conception of a 'contraction alkalosis'.

IntroductionThe USA lags behind other high-income countries in many health indicators. Outcome differences are associated with differences in the relative spending between healthcare and social services at the national level. The impact of the ratio and delivery of social and healthcare services on the individual patient’s health is however unknown. ‘Reframing Healthcare Services through the Lens of Co-Production’ (RheLaunCh) will be a cross-Atlantic comparative study of the mechanisms by which healthcare and social service delivery may impact patient health with chronic conditions. Insight into these mechanisms is needed to better and cost-effectively organise healthcare and social services.MethodsWe designed a mixed methods study to compare the socioeconomic background, needs of and service delivery to patients with congestive heart failure and chronic obstructive pulmonary disease in the USA and the Netherlands. We will conduct: (1) a literature scan to compare national and regional healthcare and social service systems; (2) a retrospective database study to compare patient’s socioeconomic and clinical characteristics and the service use and spending at the national, regional and hospital level; (3) a survey to compare patient perceived quality of life, receipt and experience of service delivery and ability of these services to meet patient needs; and (4) multiple case studies to understand what patients need to better govern their quality of life and how needs are met by services.Ethics and disseminationEthics approval was granted by the ethics committee of the Radboud University Medical Center (2016–2423) in the Netherlands and by the Human Subjects Research Committee of the Hennepin Health Care System, Inc. (HSR #16–4230) in the USA. Multiple approaches will be used for dissemination of results, including (inter)national research presentations and peer-reviewed publications. A website will be established to support the development of a community of practice.

Introduction: People living with chronic illness require a wide range of resources to attain the QOL they desire, including living conditions, support from informal caregivers and the community, capabilities like self-regulation and resilience, and formal health and social care. However, the relative contribution of these resources to overall QOL is unknown. We designed a cross-national study to explore how a variety of resources influence QOL among people living with congestive heart failure (CHF) in two settings with different systems and sociocultural contexts: United States (US) and Netherlands (NL).Theory/Methods: We spoke with CHF patients in the US and NL to elicit resources needed to support their QOL and used the Social Quality Model (SQM) to organize them. The SQM depicts four quadrants that support QOL: Living Conditions (e.g., housing, education), Social Embeddedness (e.g., social support, trust), Societal Embeddedness (e.g., access to care, responsiveness of services), and Self-Regulation (e.g., physical health, resilience).We then developed a survey comprising validated instruments to assess constructs within each quadrant of the SQM, in addition to sociodemographics. We used Cantril’s Ladder to assess overall QOL. We administered the survey in-person or by mail to adult patients with CHF seen at Hennepin Healthcare, Minneapolis, Minnesota, US, or Radboud medical center, Nijmegen, NL.We compared sociodemographic characteristics using t-tests or Chi-squared, as appropriate. Next, we used backwards stepwise regression to identify characteristics within each SQM quadrant that were independently associated with QOL among US and NL participants (p

Background: Effective management of chronic, long-term illness largely depends on care that is shaped around the specific priorities, preferences, and routines of the individual patient. Evidence suggests that the coproduction of healthcare by patients and professionals may be effective in facilitating good health outcomes at lower costs. Furthermore, it is considered increasingly important to consider the social determinants of health and well-being. Our research team has conducted a cross-national mixed methods study to examine the health and social care needed to support people living with a chronic illness–specifically, congestive heart failure--in the United States and Netherlands. Translation of our research into practice includes a case-based teaching module to train health professionals and health professional students about coproduction of patient care. This presentation will provide: (1) an overview of our educational curriculum; (2) discuss our experiences teaching health professionals and health professional students about coproduction of healthcare services; (3) explore the individual knowledge, skills, and habits that are required to coproduce care with their patients and their patient’s families/informal caregivers; (4) summarize some of the guiding principles of coproduction. Target Audience: Health professionals, health professions students, and health professional educators Learnings/Take away: Our interactive, case-based workshop creates the foundation for healthcare professionals, educators, students, and researchers to consider new the role of coproduction in healthcare. This session will discuss an education module that can be replicated in other settings.

Background Loop diuretics are recommended by current guidelines for patients with symptomatic heart failure (HF) with NYHA class II-IV. While torsemide's oral bioavailability and half life theoretically render it a more efficacious drug than furosemide, the clinical outcomes of torsemide compared with furosemide in patients with HF remain unclear. Methods We performed a meta-analysis including all published randomized control trial (RCTs) and observational studies that compared torsemide and furosemide use in chronic HF patients from inception to February 2019. Results Fifteen studies (eight RCTs and seven observational studies) including 9758 patients were included. Over a weighted mean follow-up duration of 8±3 months, torsemide was associated with a lower risk of rehospitalization due to HF (8.6% vs. 12.7%, NNT=23) (OR 0.63, 95% CI (0.44, 0.91), p=0.01, I2=8%) and cardiac mortality (1.6% vs. 4.4%, NNT=37) (OR 0.37, 95% CI (0.20, 0.66), p Conclusion Torsemide use improved functional status and reduced rehospitalization due to HF compared with furosemide in chronic HF patients. Torsemide was also associated with reduced cardiac mortality, but this effect requires further study.

Mechanical heart valve thrombosis (MHVT) is rare but can lead to life threatening complications. Low-dose ultraslow tissue plasminogen activator (tPA) infusion is being used for treatment of MHVT as an effective alternative to surgery. There is however no guidance on management of MHVT in the

OBJECTIVE Methadone is associated with prolongation of the electrocardiographic QTc interval. QTc prolongation may be linked to cardiac dysrhythmia and sudden cardiac death. The rate of these events is unknown in methadone-maintained patients. METHODS This retrospective cohort study of 749 patients with opioid use disorder receiving methadone maintenance therapy through a single safety-net hospital, queried the electronic health record for electrocardiogram results, demographics, methadone dose, and diagnostic codes consistent with cardiac conduction disorder (International Classification of Disease, Ninth Revision [ICD-9] 426) and cardiac dysrhythmia (ICD-9 427). Factors associated with QTc interval were explored; Cox proportional-hazards regression models were used to analyze time to an event that may predispose to sudden cardiac death. RESULTS One hundred thirty-four patients had an electrocardiogram while on methadone, 404 while off methadone, and 211 both while on and off methadone. Mean QTc interval while on methadone (436 ms, SD 36) was significantly greater than while off methadone (423 ms, SD 33). Age and methadone dose were weakly associated with increased QTc interval (P

A B S T R AC T Background Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function. Methods We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days. Results Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P = 0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was −0.04±0.53 mg per deciliter (−3.5±46.9 μmol per liter) in the pharmacologictherapy group, as compared with +0.23±0.70 mg per deciliter (20.3±61.9 μmol per liter) in the ultrafiltration group (P = 0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1 kg [12.1±11.3 lb] and 5.7±3.9 kg [12.6±8.5 lb], respectively; P = 0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P = 0.03). Conclusions In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491.)

Worsening renal function is common among patients hospitalized for acute decompensated heart failure (ADHF). When this occurs, subsequent management decisions often pit the desire for effective decongestion against concerns about further worsening renal function. There are no evidence-based treatments or guidelines to assist in these difficult management decisions. Ultrafiltration is a potentially attractive alternative to loop diuretics for the management of fluid overload in patients with ADHF and worsening renal function.The National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network designed a clinical trial to determine if ultrafiltration results in improved renal function and relief of congestion compared with stepped pharmacologic care when assessed 96 hours after randomization in patients with ADHF and cardiorenal syndrome. Enrollment began in June 2008. This paper describes the rationale and design of the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF).Treating the signs and symptoms of congestion in ADHF is often complicated by worsening renal function. CARRESS-HF compares treatment strategies (ultrafiltration vs stepped pharmacologic care) for the management of worsening renal function in patients with ADHF. The results of the CARRESS-HF trial are expected to provide information and evidence as to the most appropriate approaches for treating this challenging patient population.

Introduction By blocking Na resorption in the thick ascending limb of the nephron, loop diuretics (LD) mediate volume loss through natriuresis. In contrast, extracorporeal isotonic volume removal by ultrafiltration (UF) is not renally mediated. Whether these therapies have a differential effect on renal sodium excretion in acute heart failure (AHF) is unknown. Hypothesis Diuretic-mediated decongestion will be associated with more sodium excretion than UF mediated decongestion. Methods A per-protocol analysis of CARRESS-HF (N=188) was performed. Participants were included if they had spot urine Na measured in the core lab and either randomized to UF and had UF output collected without concomitant intravenous LD use, or if randomized to the LD-based pharmacological arm and had urine but not UF output collected. There were N=61, 55, and 51 participants meeting this criteria at baseline, 24 h and 96 h, respectively. Mixed effects modelling determined the association of treatment on serial parameters. Results There were N=20 in the UF arm (age 67y [59-82], 80% male, 55% NICM, Cr 2.1 mg/dL [1.7-2.4], Na 137 mmol/L [134-139]) and N=41 in the pharmacological arm (age 65y [59-76], 73% male, 54% NICM, Cr 2.4 mg/dL [1.9-2.7], Na 138 mmol/L [135-140]). UF was associated with more relative weight loss by 96 h (%*time, P-interaction=0.003), lower urine sodium concentration over time by 24 and 96 h (UNa*time, P-interaction Conclusions Ultrafiltration, without concomitant LD use, is associated with less urinary sodium excretion in comparison to LD-based pharmacological decongestion in AHF. Yet, UF was also associated with greater weight loss, which may be reflective of greater cumulative sodium removal via UF. These observations highlight the differential response to sodium renal handling from extracorporeal volume removal than from LDs.

Introduction Accumulating data suggests that worsening renal function (WRF) during decongestion of acute decompensated heart failure (ADHF) patients is a benign and transient finding. However, it is unknown if continued aggressive volume removal in patients with preexisting WRF is harmful. Hypothesis Aggressive volume removal in ADHF patients with preexisting WRF will be associated with renal tubular injury. Methods We used data from the multicenter CARRESS-HF trial that randomized patients with ADHF and pre-existing WRF to aggressive volume removal with stepped pharmacologic therapy (SPT) versus fixed rate ultrafiltration (UF). Patients in the urinary renal tubular injury biomarker (NAG, KIM-1, and NGAL) sub-study were evaluated ( N =105). Results The severity of pre-randomization increase in creatinine was unrelated to baseline levels of renal tubular injury biomarkers (r=0.1, P =0.31). During randomized aggressive volume removal, creatinine further worsened in 53% of patients. Those with post-randomization WRF were highly likely to have a concurrent increase in renal tubular injury biomarkers (OR=12.6, P =0.004). This finding did not differ by mode of volume removal (SPT vs. UF, P interaction =0.47). Increase in renal tubular injury biomarkers during decongestion was associated with a higher incidence of hemoconcentration (OR=3.1, P =0.015), and paradoxically, better recovery of creatinine at 60 days ( P =0.01). Post-randomization WRF ( P =0.63) and worsening tubular injury biomarkers ( P =0.91) were not associated with death or rehospitalization at 60 days. Conclusions Aggressive volume removal in the setting of ADHF with preexisting WRF was associated with continued increase of creatinine in approximately half of patients. Worsened creatinine in this setting was accompanied by evidence of renal tubular injury. However, decongestion and renal function recovery at 60 days was superior in patients with worsening tubular injury markers. This suggests that increases in creatinine with effective decongestion may be clinically benign and transient, even when accompanied by renal tubular injury.

Excessive sympathetic drive is undoubtedly a major contributing factor to the pathophysiology of hypertension and heart failure. Much of the excessive sympathetic drive in these conditions is directed to the kidney, where it leads to inappropriate sodium retention, renin stimulation, and diminished renal function. Less well appreciated is the role the kidney itself plays in the generation of increased sympathetic activity by way of the renal somatic afferent nerves. The kidney therefore is both target and contributor to increased sympathetic activity in these conditions. Although some current pharmacotherapy indirectly targets this "sympathorenal axis," resistant hypertension remains a common problem, and the prognosis in heart failure remains poor, especially in more severe cases. It is now possible to directly target this axis via procedures, which directly interrupt renal sympathetic efferent and afferent signaling. Other procedures involving chronic carotid nerve stimulation may indirectly influence renal sympathetic tone and so improve renal sodium handling. These techniques have demonstrated early promise in hypertension and offer significant potential in heart failure as well. Should their early promise be borne out in controlled studies, the "sympathorenal axis" will have been proven to be a key element in the pathophysiology of these 2 very common, and dangerous, conditions.

The evolution of increasing serum bicarbonate is common during decongestive treatment for acute decompensated heart failure. However, animal models of metabolic alkaloses suggest that this evolution is not volume dependent. A per-protocol analysis of CARRESS-HF (N=188) was performed. Participants

Despite several studies, the clinical utility of ultrafiltration (UF) in acute heart failure (AHF) remains uncertain. Results from the Cardiorenal Rescue Study in Acute Decompensated Heart Failure trial (CARRESS-HF) did not demonstrate superior decongestive efficacy despite a rise in serum

Peripheral arterial disease (PAD) is common in patients with severe coronary artery disease (CAD) and is considered a relative contraindication to external enhanced counterpulsation (EECP), but there are no data that define the efficacy and safety of EECP in patients with PAD. The International EECP Patient Registry (IEPR) was used to compare initial post-therapy and 2-year follow-up clinical outcomes and adverse event rates in patients with and without PAD. From January 2002 to October 2004, 2126 patients were enrolled in the IEPR, of whom 493 (23%) had a history of PAD. Immediately following EECP, the reduction in angina (≥ 1 Canadian Cardiovascular Society class) was similar in patients with and without PAD (76.6% vs 79.0%, p = 0.27) as was improvement in the Duke Activity Score Index (DASI) score (+4.7% vs +6.1%, p < 0.001). Both angina reduction and DASI score improvement were sustained at 2 years. PAD patients discontinued EECP more frequently (12.0% vs 8.5%, p < 0.05), but lower extremity ulceration did not occur more frequently in patients with PAD (3.7% vs 2.7%, p = 0.26). Rates of death (17.1% vs 8.6%, p < 0.001) and myocardial infarction (9.5% vs 5.0%, p < 0.001) were, as expected, higher in patients with PAD compared to patients without PAD at 2 years. In conclusion, while PAD patients constitute a high-risk cohort with known higher adverse event rates, EECP led to similar short- and long-term improvements in angina and quality of life for individuals with PAD compared to those without PAD.

“If you have always done it that way, it is probably wrong.” — Charles F. Kettering, 1876–1958 The morbidity of decompensated heart failure is due to volume overload, a consequence of increased total body sodium.1,2 Failure to adequately reduce total body sodium contributes to progressive ventricular dysfunction, worsening heart failure, and excess morbidity. Ultrafiltration is the gold standard for sodium-volume removal and is the only intervention shown to improve outcomes in a randomized controlled trial of patients hospitalized with decompensated heart failure.3 Diuretics are inherently inferior because they produce hypotonic urine4,5and undesirable hemodynamic and neurohormonal changes.6,7 Therefore, ultrafiltration is the preferred initial treatment for patients hospitalized with decompensated heart failure and sodium-volume overload. Response by Shin and Dec on p 499 The earliest descriptions of heart failure date back more than 3500 years to the Egyptian civilization. Even then, symptoms were correctly attributed to volume excess.8 It was not until the early 20th century that researchers recognized the role of salt in the formation of edema. In 1901, researchers found that salt fed to patients with congestive heart failure could not be recovered as chloride in the urine.8 This represents one of the earliest descriptions of heart failure as a sodium avid state. Later, it was demonstrated that liberal salt intake increased congestive symptoms and pulmonary edema in patients with heart failure whereas patients on salt-restricted diets could tolerate large amounts of water without any further increases in congestion or edema.8 Other studies confirmed the primary role of salt, not water, in the formation of edema in heart failure. By 1948, sodium was widely recognized as the major determinant in extracellular fluid volume.1 Today, it is understood that sodium retention in heart failure is under the influence of the sympathetic and …

Relief of congestive symptoms is a primary goal in treating heart failure. Ultrafiltration is a tool that can be used to safely remove sodium and water from whole blood at a controlled rate. Ultrafiltration decreases symptoms, relieves congestion, and improves hemodynamics, neurohormonal balance, and exercise capacity. This article describes the importance of congestion as a therapeutic target in heart failure and outlines the development of ultrafiltration as a treatment to address this important physiologic state.

Background In 2013 the Minnesota Resuscitation Consortium developed an organized approach for the management of patients resuscitated from shockable rhythms to gain early access to the cardiac catheterization laboratory (CCL) in the metro area of Minneapolis‐St. Paul. Methods and Results Eleven hospitals with 24/7 percutaneous coronary intervention capabilities agreed to provide early (within 6 hours of arrival at the Emergency Department) access to the CCL with the intention to perform coronary revascularization for outpatients who were successfully resuscitated from ventricular fibrillation/ventricular tachycardia arrest. Other inclusion criteria were age >18 and P =0.03). Conclusions Early access to the CCL after cardiac arrest due to a shockable rhythm in a selected group of patients is feasible in a large metropolitan area in the United States and is associated with a 65% survival rate to hospital discharge with a good neurological outcome.

Background and Purpose We hypothesized that symptom improvement from enhanced external counterpulsation (EECP) is related to improved heart rate variability (HRV). Methods This prospective, multicenter study enrolled 27 patients with angina who underwent 48-hour ambulatory electrocardiogram monitoring at baseline, immediately after 35 hours of EECP, and at 1 month. Primary end points included change in time-domain (SD of normal-to-normal intervals) and frequency-domain HRV. Results Twenty-four patients completed the full course of EECP therapy and 3 ambulatory electrocardiograms. There were no significant changes in time-domain HRV measures after EECP. Patients younger than 65 years and those with heart failure had improved SD of normal-to-normal interval after EECP ( P = .02). Although frequency-domain HRV measures did not change in the overall cohort, patients with diabetes had improved daytime low-frequency power ( P = .016). Conclusions There was no significant change in the time- or frequency-domain HRV measures after EECP. In diabetic individuals, there was an increase in low-frequency HRV, which has been associated with reduced mortality.

Objectives This study was designed to compare the safety and efficacy of veno-venous ultrafiltration and standard intravenous diuretic therapy for hypervolemic heart failure (HF) patients. Background Early ultrafiltration may be an alternative to intravenous diuretics in patients with decompensated HF and volume overload. Methods Patients hospitalized for HF with ≥2 signs of hypervolemia were randomized to ultrafiltration or intravenous diuretics. Primary end points were weight loss and dyspnea assessment at 48 h after randomization. Secondary end points included net fluid loss at 48 h, functional capacity, HF rehospitalizations, and unscheduled visits in 90 days. Safety end points included changes in renal function, electrolytes, and blood pressure. Results Two hundred patients (63 ± 15 years, 69% men, 71% ejection fraction ≤40%) were randomized to ultrafiltration or intravenous diuretics. At 48 h, weight (5.0 ± 3.1 kg vs. 3.1 ± 3.5 kg; p = 0.001) and net fluid loss (4.6 vs. 3.3 l; p = 0.001) were greater in the ultrafiltration group. Dyspnea scores were similar. At 90 days, the ultrafiltration group had fewer patients rehospitalized for HF (16 of 89 [18%] vs. 28 of 87 [32%]; p = 0.037), HF rehospitalizations (0.22 ± 0.54 vs. 0.46 ± 0.76; p = 0.022), rehospitalization days (1.4 ± 4.2 vs. 3.8 ± 8.5; p = 0.022) per patient, and unscheduled visits (14 of 65 [21%] vs. 29 of 66 [44%]; p = 0.009). No serum creatinine differences occurred between groups. Nine deaths occurred in the ultrafiltration group and 11 in the diuretics group. Conclusions In decompensated HF, ultrafiltration safely produces greater weight and fluid loss than intravenous diuretics, reduces 90-day resource utilization for HF, and is an effective alternative therapy. (The UNLOAD trial; http://clinicaltrials.gov/ct/show/NCT00124137?order=1; NCT00124137).

Patients with refractory angina and left ventricular (LV) dysfunction exert an enormous burden on health care resources primarily because of the number of recurrent emergency department (ED) visits and hospitalizations. Enhanced external counterpulsation (EECP) therapy has emerged as a treatment option for patients with angina and LV dysfunction and has been shown to improve clinical outcomes and LV function. Improvements in symptoms and laboratory assessments in these patients, however, do not necessarily correlate with a reduction in ED visits and hospitalizations. This is the first study to assess the impact of EECP therapy on ED visits and hospitalization rates at 6-month follow-up. This prospective cohort study included 450 patients with LV dysfunction (ejection fractionor=40%) treated with EECP therapy for refractory angina. Clinical outcomes, number of all-cause ED visits, and hospitalizations within the 6 months before EECP therapy were compared with those at 6-month follow-up. Despite the unfavorable risk profile, refractory angina patients with LV dysfunction achieved a substantial reduction in all-cause ED visits and hospitalization rates at 6-month follow-up. EECP therapy appears to offer an effective adjunctive treatment option for this group of patients.

Background: Among survivors of out of hospital cardiac arrest (OHCA), the post resuscitation 12-lead electrocardiogram (ECG) is a widely used tool to identify acute thrombotic coronary occlusion (ACTO) and for appropriate triage to the catheterization laboratory. It is unknown how a post-resuscitation abnormal metabolic milieu impacts ECG accuracy. We studied inter-reader concordance in ECG interpretation as well as same-patient variation in interpretation between abnormal (A) and normal (N) metabolic milieus (MM). Methods: We performed a retrospective analysis of 125 consecutive patients with OHCA with a shockable rhythm undergoing coronary angiography in a single institution. Patients with AMM were defined as pH 6 mEq/L, vasoactive drug use or lactate >2 ng/ml. All post resuscitation ECGs recorded in both AMM and NMM for each patient prior to any invasive intervention were blindly interpreted by 2 experienced readers, classified into two categories: diagnostic for ATCO (ATCO +) and not diagnostic for ATCO (ATCO -) and compared to angiographic ATCO. The Cohen’s kappa scale was used to measure concordance. Results: Concordance between readers was 0.69 (95% CI 0.56-0.84) in AMM and 0.82 (95% CI 0.64-0.99) in NMM. Of 35 ECGs interpreted as diagnostic for ATCO (+) in AMM, 27 (77%) were reclassified as ATCO (-) after metabolic correction. Among 90 ECGs initially diagnosed as ATCO (-) in AMM, 2 (2%) were reclassified as ATCO (+) whereas 88 (98%) remained as ATCO (-) in NMM. Most ATCO (-) ECGs were in the setting of angiographic ATCO; see table. Conclusions: Despite acceptable inter-reader concordance (moderate in AMM, high in NMM) between experienced ECG readers, a significant proportion of angiographic ATCO was missed on post resuscitation ECGs. A high percentage of patients with angiographic ATCO were reclassified on ECG from ATCO (+) in AMM to ATCO (-) in NMM, suggesting possible interim blunting/resolution of typical diagnostic ECG changes in NMM.

Background— The ROSE AHF trial (Renal Optimization Strategies Evaluation in Acute Heart Failure) found that when compared with placebo, neither low-dose dopamine (2 µg/kg per minute) nor low-dose nesiritide (0.005 μg/kg per minute without bolus) enhanced decongestion or preserved renal function in AHF patients with renal dysfunction. However, there may be differential responses to vasoactive agents in AHF patients with reduced versus preserved ejection fraction (EF). This post hoc analysis examined potential interaction between treatment effect and EF (EF ≤40% versus >40%) on the ROSE AHF end points. Methods and Results— ROSE AHF enrolled AHF patients (n=360; any EF) with renal dysfunction. The coprimary end points were cumulative urine volume and the change in serum cystatin-C in 72 hours. The effect of dopamine (interaction P =0.001) and nesiritide (interaction P =0.039) on urine volume varied by EF group. In heart failure with reduced EF, urine volume was higher with active treatment versus placebo, whereas in heart failure with preserved EF, urine volume was lower with active treatment. The effect of dopamine and nesiritide on weight change, sodium excretion, and incidence of AHF treatment failure also varied by EF group (interaction P Conclusions— In this post hoc analysis of ROSE AHF, the response to vasoactive therapies differed in patients with heart failure with reduced EF and heart failure with preserved EF. Investigations of AHF therapies should assess the potential for differential responses in AHF with preserved versus reduced EF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01132846.