Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial.

BACKGROUND: Although beta-blockers are not recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) according to the latest European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers may adversely influence clinical outcomes by limiting chronotropic response in HFpEF. OBJECTIVES: This study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF. METHODS: In the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, a total of 6,263 patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) >40% were randomized to dapagliflozin or placebo across 20 countries. In this prespecified analysis, efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. RESULTS: Overall, beta-blockers were used in 5,177 patients (83%), with wide variation by geographic region. Beta-blocker use was associated with a lower risk of the primary outcome in covariate-adjusted models (HR: 0.70; 95% CI: 0.60-0.83). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR: 0.82; 95% CI: 0.72-0.94) and in patients not taking beta-blockers (HR: 0.79; 95% CI: 0.61-1.03; Pinteraction = 0.85), with similar findings for key secondary endpoints. Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. CONCLUSIONS: In patients with HFmrEF or HFpEF who were enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

Drive Time and Receipt of Guideline-Recommended Screening, Diagnosis, and Treatment.

Importance: Many 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. Objective: To assess associations between drive time to care and receipt of guideline-recommended screening, diagnosis, and treatment interventions. Design, Setting, and Participants: This 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. Exposures: Drive time from each patient's residential address to the closest VA facility where the service was available, measured using geocoded addresses. Main Outcomes and Measures: Binary 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. Results: Of 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 Relevance: In 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.

COVID-19 postacute care major organ damage: a systematic review.

BACKGROUND: Major organ complications have been reported in patients hospitalised for COVID-19; most studies lacked controls. OBJECTIVE: Examine major organ damage postdischarge among adults hospitalised for COVID-19 versus non-COVID-19 controls. DATA SOURCES: MEDLINE, Embase and Cochrane Library from 1 January 2020 to 19 May 2021. STUDY ELIGIBILITY CRITERIA: English language studies of adults discharged from hospital for COVID-19; reporting major organ damage. Single review of abstracts; independent dual review of full text. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Joanna Briggs Institute Appraisal Checklist for Cohort Studies. Outcome data were not pooled due to heterogeneity in populations, study designs and outcome assessment methods; findings are narratively synthesised. RESULTS: Of 124 studies in a full evidence report, 9 included non-COVID controls and are described here. Four of the nine (three USA, one UK) used large administrative databases. Four of the remaining five studies enrolled <600 COVID-19 patients. Mean or median age ranged from 49 to 70 years with 46%-94% male and 48%-78% White race; 10%-40% had been in intensive care units. Follow-up ranged from 4 weeks to 22 weeks postdischarge. Four used hospitalised controls, three non-hospitalised controls and two were unclear. Studies used various definitions of, and methods to assess, major organ damage outcomes. While the magnitude of effect differed across studies, incident cardiac, pulmonary, liver, acute and chronic kidney, stroke, diabetes, and coagulation disorders were consistently greater in adults hospitalised for COVID-19 compared with non-COVID-19 controls. LIMITATIONS: Applicability to subgroups (age, gender, COVID-19 severity, treatment, vaccination status) and non-hospitalised patients is unknown. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Postacute COVID-19 major organ damage is common and likely higher than controls. However, there is substantial uncertainty. More consistent reporting of clinical outcomes and pre-COVID health status along with careful selection of control groups are needed to address evidence gaps. PROSPERO REGISTRATION NUMBER: CRD42020204788.

Interobserver variability among experienced electrocardiogram readers to diagnose acute thrombotic coronary occlusion in patients with out of hospital cardiac arrest: Impact of metabolic milieu and angiographic culprit.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Effect of Medical Scribes in Emergency Departments: A Systematic Review.

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.

Implications of peripheral oedema in heart failure with preserved ejection fraction: a heart failure network analysis.

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 < 0.001), greater burden of co-morbidities, higher intravascular pressures estimated on physical examination (elevated jugular venous pressure: 50% vs. 24.7%, P < 0.001), poorer renal function (creatinine: 1.2 mg/dL [IQR 0.9, 1.5] vs. 1 mg/dL [IQR 0.8, 1.3], P = 0.003), and lower peak VO2 (adjusted mean difference -1.04 mL/kg/min, 95% confidence interval [-1.71, -0.37], P < 0.003). Among hospitalized patients, despite greater in-hospital fluid/weight loss in the ≥moderate oedema group, there was no difference in the improvement in dyspnoea by the visual analogue scale or well-being visual analogue scale from baseline to 3-4 days and no statistically significant difference in the rate of 60 day rehospitalization/death (adjusted hazard ratio 1.44, 95% confidence interval [0.87, 2.39], P = 0.156). CONCLUSIONS: Patients with HFpEF and oedema display higher body mass, greater burden of co-morbidities, and more severe exercise intolerance, but clinical responses to treatment appear similar. Further research is required to better understand the nature of volume distribution in different HFpEF phenotypes.

Ultrafiltration in Acute Heart Failure: Implications of Ejection Fraction and Early Response to Treatment From CARRESS-HF.

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% or >40%). We compared clinical parameters of clinical decongestion during the hospitalization based on initial (≤24 hours) response to ultrafiltration. Cox-proportional hazards models were used to identify associations between fluid removal <24 hours and composite of death, hospitalization, or unscheduled outpatient/emergency department visit during study follow-up. The intention-to-treat analysis included 93 patients. Within 24 hours, median fluid removal was 1.89 L (Q1, Q3: 1.22, 3.16). The high fluid removal group had a greater urine output (9.08 versus 6.23 L, P=0.027) after 96 hours. Creatinine change from baseline to 96 hours was similar in both groups (0.10 mg/dL increase, P=0.610). The EF >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.

Effects of hydroxychloroquine treatment on QT interval.

BACKGROUND: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. OBJECTIVE: The purpose of this study was to determine the effects of HCQ treatment on QT interval. METHODS: 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. RESULTS: 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 QTc >500 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 QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33-10.11) years of follow-up, 269 patients (33%) died. QTc >470 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. CONCLUSION: 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.

An international comparison of factors affecting quality of life among patients with congestive heart failure: A cross-sectional study.

OBJECTIVE: To explore associations among twenty formal and informal, societal and individual-level factors and quality of life (QOL) among people living with congestive heart failure (CHF) in two settings with different healthcare and social care systems and sociocultural contexts. SETTING AND PARTICIPANTS: We recruited 367 adult patients with CHF from a single heart failure clinic within two countries with different national social to healthcare spending ratios: Minneapolis, Minnesota, United States (US), and Nijmegen, Netherlands (NL). DESIGN: Cross-sectional survey study. We adapted the Social Quality Model (SQM) to organize twenty diverse factors into four categories: Living Conditions (formal-societal: e.g., housing, education), Social Embeddedness (informal-societal: e.g., social support, trust), Societal Embeddedness (formal-individual: e.g., access to care, legal aid), and Self-Regulation (informal-individual: e.g., physical health, resilience). We developed a survey comprising validated instruments to assess each factor. We administered the survey in-person or by mail between March 2017 and August 2018. OUTCOMES: We used Cantril's Self-Anchoring Scale to assess overall QOL. We used backwards stepwise regression to identify factors within each SQM category that were independently associated with QOL among US and NL participants (p<0.05). We then identified factors independently associated with QOL across all categories (p<0.05). RESULTS: 367 CHF patients from the US (32%) and NL (68%) participated. Among US participants, financial status, receiving legal aid or housing assistance, and resilience were associated with QOL, and together explained 49% of the variance in QOL; among NL participants, financial status, perceived physical health, independence in activities of daily living, and resilience were associated with QOL, and explained 53% of the variance in QOL. CONCLUSIONS: Four formal and informal factors explained approximately half of the variance in QOL among patients with CHF in the US and NL.

Do not disregard the initial 12 lead ECG after out-of-hospital cardiac arrest: It predicts angiographic culprit despite metabolic abnormalities.

OBJECTIVES: The initial 12 lead electrocardiogram (ECG) following return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA), is often disregarded by clinicians in ability to predict acute thrombotic coronary occlusion (ATCO) due to markedly abnormal metabolic milieu (AMM). We sought to evaluate the accuracy of initial vs. follow-up ECG prior to invasive coronary angiography (ICA) to predict ATCO following resuscitated OHCA. METHODS: We included OHCA patients with initial shockable rhythm who underwent invasive coronary angiography (ICA). AMM was defined as one of: pH ​< ​7.1, lactate >2 ​mmol/L, serum potassium <2.8 or >6.0 mEq/L. Two ECGs A (initial) and B (follow-up) following ROSC but prior to ICA were adjudicated by 2 experienced readers using expanded ECG criteria to predict angiographic ATCO on ICA. RESULTS: 152 consecutive patients (mean age 58 years, 75% male) met inclusion criteria, 77% had AMM. Among those with both ECGs (n ​= ​102), overall accuracy, sensitivity, specificity, positive predictive value, negative predictive value for correctly predicting angiographic ATCO for ECG A was 72%, 63%, 81%, 61%, 83% and for ECG B was 71%, 50%, 91%, 73%, 80% respectively. Predictive accuracy for angiographic ATCO was similar between ECG A [odds ratio (OR) 7.31, CI 2.87-18.62, p ​< ​0.0001) and ECG B [OR 10.67; CI 3.6-31.61, p ​< ​0.0001], and consistent in AMM. CONCLUSIONS: In OHCA, despite AMM, the initial post ROSC ECG retains a statistically significant, and similar accuracy as the follow-up ECG to predict angiographic ATCO using expanded criteria.

Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure.

Although 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 <0.001, I2 = 0%, NNT = 40) compared with furosemide. However, there was no difference in all-cause mortality or medication side effects between the 2 groups. In conclusion, compared with furosemide, torsemide use was associated with significant more improvement in functional status and lower cardiac mortality; and numerically fewer hospitalizations in patients with heart failure.

Renal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function.

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, Pinteraction=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.

High-Sensitivity Troponin I in Hospitalized and Ambulatory Patients With Heart Failure With Preserved Ejection Fraction: Insights From the Heart Failure Clinical Research Network.

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<0.001). The prevalence of elevated hs-TnI (>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.

Direct comparison of ultrafiltration to pharmacological decongestion in heart failure: a per-protocol analysis of CARRESS-HF.

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 <0.05 for both), lower serum sodium by 48 h (P-interaction <0.01) and increased plasma renin activity by 96 h (P = 0.04). The pharmacological arm was associated with higher serum bicarbonate after 24 h (P-interaction <0.002). There were no differences in 60-day outcomes between the UF and pharmacological arms. CONCLUSIONS: 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'.

Neurohormonal Imbalance: A Neglected Problem-And Potential Therapeutic Target-In Acute Heart Failure.

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.

'Reframing Healthcare Services through the Lens of Co-Production' (RheLaunCh): a study protocol for a mixed methods evaluation of mechanisms by which healthcare and social services impact the health and well-being of patients with COPD and CHF in the USA and The Netherlands.

INTRODUCTION: The 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. METHODS: We 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 DISSEMINATION: Ethics 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.

Methadone and the QTc Interval: Paucity of Clinically Significant Factors in a Retrospective Cohort.

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 < 0.01 and P < 0.0005, respectively, adjusted R = 0.05). There were 44 ICD-9 426 and 427 events over 7064 patient-years (6.3 events/1000 patient-yrs). Having a QTc greater than sex-specific cut-off values was significantly associated with time to event (hazard ratio 3.32, 95% confidence interval 1.25-8.81), but being on methadone was not. CONCLUSIONS: Methadone is associated with QTc prolongation in a nonclinically significant dose-related manner. Cardiac events were rare and the sudden cardiac death rate was below that of the general population. Current recommendations for cardiac risk assessment in methadone-maintained patients should be reconsidered.