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To curb transmission of SARS-CoV-2 and preserve hospital resources, elective procedures were postponed in the United States, affecting patients previously scheduled for electrophysiology (EP) procedures. We aimed to understand patients’ perceptions related to procedural postponements during the first wave of the SARS-CoV-2 pandemic. We performed a telephone survey between May 1-15 2020, of consecutive patients who experienced procedural postponement from March-April. Of 112 patients, 20% may have been lost to follow up and 12% lost interest in having their procedures done. The level of anxiety related to postponement was moderate to high in more than two thirds of patients.

Background: To curb transmission of SARS-CoV-2 and to preserve hospital resources, elective procedures were indefinitely postponed nationally, affecting many patients previously scheduled for electrophysiology (EP) procedures. Procedural wait times may affect patient satisfaction and retention, yet patient perceptions of procedural postponements during the SARS-CoV-2 pandemic are currently unknown. Methods: We performed a phone survey of consecutive patients who experienced EP procedural postponement from March – April 2020. Surveys were performed between May 1 – May 15. Sociodemographics, SARS-CoV-2 testing history, notification circumstances, and perceptions were obtained from patients. Results: Of 112 patients postponed, 77 patients consented to the survey, most of whom were minorities (black 43%, Hispanic 20%), 30% were below the poverty line, and 67% had ≤ high school education. Catheter ablation accounted for 33% of procedures and device procedure 44%. Half of patients (51%) were informed of their postponement by their electrophysiologist. In response to when patients thought their procedure would occur, 37% believed it would occur within 12 weeks of the survey. Perceptions and testing history are shown ( Figure ). Patients who had undergone SARS-CoV-2 testing were more likely to disagree with postponement than those who had not undergone testing (30% of those tested disagreed vs. 2% of those not tested, p Conclusion: Within an urban population, most patients agreed with procedural postponement and felt their procedure would occur soon. Interim SARS-CoV-2 testing was associated with disagreement with postponement and one third of patients had high anxiety about postponement. In our experience, patient retention was high.

Background Infection with the novel severe acute respiratory syndrome coronavirus 2 has been associated with a hypercoagulable state. Emerging data from China and Europe have consistently shown an increased incidence of venous thromboembolism (VTE). We aimed to identify the VTE incidence and early predictors of VTE at our high-volume tertiary care center. Methods We performed a retrospective cohort study of 147 patients who had been admitted to Temple University Hospital with coronavirus disease 2019 (COVID-19) from April 1, 2020 to April 27, 2020. We first identified the VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]) incidence in our cohort. The VTE and no-VTE groups were compared by univariable analysis for demographics, comorbidities, laboratory data, and treatment outcomes. Subsequently, multivariable logistic regression analysis was performed to identify the early predictors of VTE. Results The 147 patients (20.9% of all admissions) admitted to a designated COVID-19 unit at Temple University Hospital with a high clinical suspicion of acute VTE had undergone testing for VTE using computed tomography pulmonary angiography and/or extremity venous duplex ultrasonography. The overall incidence of VTE was 17% (25 of 147). Of the 25 patients, 16 had had acute PE, 14 had had acute DVT, and 5 had had both PE and DVT. The need for invasive mechanical ventilation (adjusted odds ratio, 3.19; 95% confidence interval, 1.07-9.55) and the admission D-dimer level ≥1500 ng/mL (adjusted odds ratio, 3.55; 95% confidence interval, 1.29-9.78) were independent markers associated with VTE. The all-cause mortality in the VTE group was greater than that in the non-VTE group (48% vs 22%; P = .007). Conclusions Our study represents one of the earliest reported from the United States on the incidence rate of VTE in patients with COVID-19. Patients with a high clinical suspicion and the identified risk factors (invasive mechanical ventilation, admission D-dimer level ≥1500 ng/mL) should be considered for early VTE testing. We did not screen all patients admitted for VTE; therefore, the true incidence of VTE could have been underestimated. Our findings require confirmation in future prospective studies.

Patient: Female, 58-year-old Final Diagnosis: Tumor embolism Symptoms: Dyspnea Medication:— Clinical Procedure: Percutaneous embolectomy • surgical embolectomy Specialty: Cardiac surgery • Cardiology • Critical Care Medicine • Oncology Objective: Rare disease Background: Tumor embolism is a rare neoplastic complication that occurs when there is intravenous invasion by a benign or malignant tumor. We present the case of an asymptomatic patient with an incidentally discovered leiomyosarcoma tumor emboli, which was initially misdiagnosed as “thrombus in transit.” Case Report: The patient was a 58-year-old woman who was incidentally found on echocardiogram to have a large tubular mass within the inferior vena cava and right atrium. Although initially characterized as “thrombus in transit”, this mobile right atrial mass was present without clinical, echocardiographic, or radiographic evidence of pulmonary embolism or increased pulmonary arterial impedance. Given that a thrombus in transit is nearly always associated with submassive or massive pulmonary emboli and their attendant right heart sequelae, these pertinent negative findings led us to seek an alternative diagnosis. After a trial of conservative management with anticoagulation and attempted removal of the mass with the AngioVac system, the patient ultimately underwent median sternotomy and surgical embolectomy on cardiopulmonary bypass to remove the mass, which was later identified on pathology as a leiomyosarcoma. Conclusions: With rare exceptions, “thrombus in transit” is accompanied by large pulmonary emboli and the presence of increased pulmonary artery pressure and right heart strain. The absence of clinical, echocardiographic, or radio-graphic evidence of these hemodynamic sequelae should raise suspicion for an alternative diagnosis. Tumor embolism should be considered in the differential diagnosis of any patient with a history of malignancy who presents with evidence of intracardiac mass or embolism.

AIMS The time course of changes in pulmonary artery (PA) pressure due to left ventricular assist devices (LVADs) is not well understood. Here, we describe longitudinal haemodynamic trends during the peri-LVAD implantation period in patients previously implanted with a remote monitoring PA pressure sensor. METHODS AND RESULTS We retrospectively studied PA pressure trends in patients implanted with CardioMEMS™ PA pressure sensor between October 2007 and March 2017 who subsequently had an LVAD procedure. Data are presented as mean ± standard deviation, and P-values are calculated using standard t-test with equal variance. Among 436 patients in cohort, 108 (age 58 ± 11 years, 82% male) received an LVAD and 328 (age 60 ± 13 years, 70% male) did not. The mean PA pressure at sensor implant was higher by 29% (P

Background: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N -acetyl-β- d -glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation–Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. Methods: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C. Results: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300–815 mg), which induced a urine output of 8425 mL (interquartile range, 6341–10 528 mL) over the 72-hour intervention period. Levels of N -acetyl-β- d -glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P >0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (−8.7 ng/mg; interquartile range, −169 to 35 ng/mg; P P =0.21), N -acetyl-β- d -glucosaminidase ( P =0.46), or kidney injury molecule 1 ( P =0.22). Increases in neutrophil gelatinase-associated lipocalin, N -acetyl-β- d -glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69–0.91; P =0.001). Conclusions: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

Background Long-term survivors after implantation of left ventricular assist devices (LVADs) are increasing in prevalence. We describe the characteristics and outcomes in patients surviving longer than 4 years on LVAD support. Methods We performed a multicenter, retrospective analysis of patients surviving at least 4 years on continuous-flow LVAD (CF-LVAD) support with a HeartMate II at centers participating in the Evolving Mechanical support Research Group. Results Between 2005 and 2010, 156 long-term survivors were identified with a mean survival of 7.1 years (95% confidence interval: 6.7 to 7.5 years). The mean age was 58.2 ± 15.2 years and 30.1% were women. Readmission rate was low at 1.1 events per patient per year with the most common reasons leading to readmission being infection (0.10 readmissions per patient per year) and gastrointestinal bleeding (0.07 readmissions per patient per year). Two years after implantation, 97% of patients were either New York Heart Association functional class I or II, with 92% at 4 years. Conclusions Patients surviving 4 years on CF-LVAD support can anticipate ongoing long-term survival with sustained improvements in functionality and low rates of rehospitalization.

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.

Background Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. Methods and Results We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67–0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77–1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57–4.03, P Conclusion The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies.

Aims Hyponatraemia is strongly associated with adverse outcomes in heart failure. However, accumulating evidence suggests that chloride may play an important role in renal salt sensing and regulation of neurohormonal and sodium-conserving pathways. Our objective was to determine the prognostic importance of hypochloraemia in patients with heart failure. Methods and results Patients in the BEST trial with baseline serum chloride values were evaluated (n = 2699). Hypochloraemia was defined as a serum chloride ≤96 mmol/L and hyponatraemia as serum sodium ≤135 mmol/L. Hypochloraemia was present in 13.0% and hyponatraemia in 13.7% of the population. Chloride and sodium were only modestly correlated (r = 0.53), resulting in only 48.7% of hypochloraemic patients having concurrent hyponatraemia. Both hyponatraemia and hypochloraemia identified a population with greater disease severity; however, renal function tended to be worse and loop diuretic doses higher with hypochloraemia. In univariate analysis, lower serum sodium or serum chloride as continuous parameters were each strongly associated with mortality (P

Objectives The aim of this analysis was to assess survival differences between men and women supported with Impella 2.5 (Abiomed Inc., Danvers) in the setting of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Background Data on sex differences in outcomes of CS with mechanical circulatory support are sparse. Methods Patients enrolled in the cVAD Registry who underwent percutaneous coronary intervention (PCI) and Impella 2.5 support for CS complicating an AMI were included. Differences between men and women were examined. Results In total, 180 patients were analyzed. Women (n = 49, 27.2%) were older (71.0 ± 12.8 years vs 63.8 ± 13.0, P = 0.001), smaller (BSA 1.82 ± 0.22 vs 2.04 ± 0.24 m2, P

BACKGROUND It is widely believed that a reduced cardiac index (CI) is a significant contributor to renal dysfunction in patients with heart failure (HF). However, recent data have challenged this paradigm.OBJECTIVES This study sought to determine the relationship between CI and renal function in a multicenter population of HF patients undergoing pulmonary artery catheterization (PAC).METHODS Patients undergoing PAC in either the randomized or registry portions of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial were included (n = 575). We evaluated associations between CI and renal function across multiple subgroups and assessed for nonlinear, threshold, and longitudinal relationships.RESULTS There was a weak but significant inverse correlation between CI and estimated glomerular filtration rate (eGFR), such that higher CI was paradoxically associated with worse eGFR (r = -0.12; p = 0.02). CI was not associated with blood urea nitrogen (BUN) or the BUN to creatinine ratio. Similarly, no associations were observed between CI and better renal function across multiple subgroups defined by indications for PAC or hemodynamic, laboratory, or demographic parameters. A nonlinear or threshold effect could not be identified. In patients with serial assessments of renal function and CI, we were unable to find within-subject associations between change in CI and eGFR using linear mixed modeling. Neither CI nor change in CI was lower in patients developing worsening renal function (p >= 0.28).CONCLUSIONS These results reinforce evidence that reduced CI is not the primary driver for renal dysfunction in patients hospitalized for HF, irrespective of the degree of CI impairment or patient subgroup analyzed. (C) 2016 by the American College of Cardiology Foundation.

Background Renal dysfunction (RD) is a potent risk factor for death in patients with cardiovascular disease. This relationship may be causal; experimentally induced RD produces findings such as myocardial necrosis and apoptosis in animals. Cardiac transplantation provides an opportunity to investigate this hypothesis in humans. Methods and Results Cardiac transplantations from the United Network for Organ Sharing registry were studied (n = 23,056). RD was defined as an estimated glomerular filtration rate 2 . RD was present in 17.9% of donors and 39.4% of recipients. Unlike multiple donor characteristics, such as older age, hypertension, or diabetes, donor RD was not associated with recipient death or retransplantation (age-adjusted hazard ratio [HR] = 1.00, 95% confidence interval [CI] 0.94–1.07, P = .92). Moreover, in recipients with RD the highest risk for death or retransplantation occurred immediately posttransplant (0–30 day HR = 1.8, 95% CI 1.54–2.02, P P = .33). Conclusions The risk for adverse recipient outcomes associated with RD does not appear to be transferrable from donor to recipient via the cardiac allograft, and the risk associated with recipient RD is greatest immediately following transplant. These observations suggest that the risk for adverse outcomes associated with RD is likely primarily driven by nonmyocardial factors.

Antibody-mediated rejection (AMR) of cardiac allografts mediated by anti-HLA Donor Specific Antibodies (DSA) is one of the major barriers to successful transplantation for the treatment of end-stage heart failure. Therapeutic plasma exchange (TPE) is a first-line treatment for pre-transplant desensitization. However, indications for treatment regimens and treatment end-points have not been well established. In this study, we investigated how sera dilutions could guide TPE regimens for effective peri-operative desensitization and early AMR treatment. Our data show that 1:16 dilutions of EDTA-treated sera and 1.5 volume TPE reduce anti-HLA class I and class II antibody levels in the same manner and, therefore, allows to predict which antibodies would respond to peri-operative TPE. We successfully applied this approach to transplanting three highly sensitized cardiac recipients (CPRA 85-93%) with peri-operative desensitization based on a virtual crossmatch performed on 1:16 diluted serum. Furthermore, we have used sera dilutions to guide DSA treatment post-transplant. Although these findings have to be confirmed in a larger prospective study, our data suggest that serum dilutions can serve as a predictive biomarker to guide peri-operative desensitization and post-transplant immunologic management.

Continuous-flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7 days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24-h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow-up did not differ between groups and patients with major bleeding were not more likely to have a supra-therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.

Background In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high‐dose loop diuretics. Methods and Results Patients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity‐adjusted analysis of all‐cause mortality. Secondary outcomes included hyponatremia (sodium mE q/L), hypokalemia (potassium mE q/L) and worsening renal function (a ≥20% decrease in estimated glomerular filtration rate). Of 13 898 admissions, 1048 (7.5%) used adjuvant metolazone. Metolazone was strongly associated with hyponatremia, hypokalemia, and worsening renal function ( P P =0.01). High‐dose loop diuretics were associated with hypokalemia and hyponatremia ( P P P =0.52). Conclusions During acute decompensated heart failure, metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function and increased mortality after controlling for the propensity to receive metolazone and baseline characteristics. However, under the same experimental conditions, high‐dose loop diuretics were not associated with hypokalemia, hyponatremia, or reduced survival. The current findings suggest that until randomized control trial data prove otherwise, uptitration of loop diuretics may be a preferred strategy over routine early addition of thiazide type diuretics when diuresis is inadequate.

Sudden cardiac death (SCD) prevention in patients with newly diagnosed ventricular dysfunction or heart failure with reduced ejection fraction is an important clinical issue. A lack of strong evidence has led to uncertainty in medical decision making and variable clinical practice in the use of wearable cardioverter-defibrillators (WCDs). In this context, the results of VEST (Vest Prevention of Early Sudden Death Trial)1 at the American College of Cardiology Scientific Sessions on March 10, 2018, in Orlando, FL were highly anticipated. However, interpretations of the trial results have been presented that we find difficult to reconcile. We wish to call attention to what we think is the most rigorous interpretation of VEST: the primary results were negative. The WCD is designed for patients at risk of SCD who are not immediate candidates for implantable cardioverter-defibrillator (ICD) therapy. This is most commonly because of a new diagnosis of left ventricular dysfunction, often after acute myocardial infarction (MI).2 Although ICDs improve survival over years of treatment in appropriately selected patients, reductions in the first 40 days postinfarction have not been conclusively demonstrated.3,4 Despite this lack of evidence, the Food and Drug Administration approved the WCD for use in 2002, primarily because of the ability of this noninvasive technology to deliver appropriate shocks in laboratory settings and case series.5 Although the WCD may seem benign—prompting a philosophy among some of why not, or better safe than sorry—there are reasons its efficacy and value should be …

Purpose Cardiac resynchronization therapy (CRT) improves quality of life and survival in patients with heart failure, but it has not been rigorously investigated in LVAD patients. Furthermore, the effects of different pacing strategies on hemodynamics in LVAD recipients is unknown. Methods Hospitalized adult LVAD patients with a CRT device and a pulmonary artery catheter (PAC) in place were eligible to be enrolled. Patients who required vasopressor or high-dose inotropic support, or who had been shocked from their defibrillator in the prior 24 hours were excluded. The following pacing strategies were tested for each patient: right ventricular pacing (RVP), left ventricular pacing (LVP), biventricular pacing (BiVP), and no pacing. Right atrial pressure (RAP), pulmonary artery systolic (PASP) and mean (mPAP) pressures, pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) were measured after 5 minutes at each pacing setting. Mean values of each hemodynamic parameter were compared between the different settings. Results Between 9/1/2017 and 8/31/2018, 5 patients were enrolled. Mean age was 66.7 years and mean frequency of biventricular pacing at baseline was 71.8%. Two patients had HeartWare and 3 patients had HeartMate III LVADs. RAP appeared similar across all settings. PASP, mPAP, and PCWP were each slightly lower at the “no pacing” setting compared to RVP, LVP, or BiVP. CI was highest at the “no pacing” setting (Table). Statistical testing was not performed due to the small number of patients enrolled. No adverse events were observed. One patient developed atrial fibrillation during the study period that resolved spontaneously within 24 hours. Conclusion While all pacing strategies were safe and well tolerated acutely, the “no pacing” strategy was associated with a possible signal towards the most favorable hemodynamic profile. Whether these differences will persist upon further enrollment and meaningfully impact quality of life, exercise tolerance, or survival in LVAD recipients requires further study.

Worsening renal function (WRF), commonly observed during the treatment of patients with acute decompensated heart failure (ADHF), is associated with increased mortality, recurrent heart failure (HF) hospitalizations and frequently limits the institution and up-titration of clinically indicated

Background Effective decongestion of heart failure patients predicts improved outcomes, but high dose loop diuretics (HDLD) used to achieve diuresis predict adverse outcomes. In the DOSE trial, randomization to a HDLD intensification strategy (HDLD-strategy) improved diuresis but not outcomes. Our objective was to determine if potential beneficial effects of more aggressive decongestion may have been offset by adverse effects of the HDLD used to achieve diuresis. Methods and results A post hoc analysis of the DOSE trial (n=308) was conducted to determine the influence of post-randomization diuretic dose and fluid output on the rate of death, rehospitalization or emergency department visitation associated with the HDLD-strategy. Net fluid output was used as a surrogate for beneficial decongestive effects and cumulative loop diuretic dose for the dose-related adverse effects of the HDLD-strategy. Randomization to the HDLD-strategy resulted in increased fluid output, even after adjusting for cumulative diuretic dose (p=0.006). Unadjusted, the HDLD-strategy did not improve outcomes (p=0.28). However, following adjustment for cumulative diuretic dose, significant benefit emerged (HR=0.64, 95% CI 0.43–0.95, p=0.028). Adjusting for net fluid balance eliminated the benefit (HR=0.95, 95% CI 0.67–1.4, p=0.79). Conclusions A clinically meaningful benefit from a randomized aggressive decongestion strategy became apparent after accounting for the quantity of loop diuretic administered. Adjusting for the diuresis resulting from this strategy eliminated the benefit. These hypothesis-generating observations may suggest a role for aggressive decongestion in improved outcomes.

Background: Differentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/creat) can identify high- vs low-risk RD. Our objective was to determine if combining these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF.Methods and Results: A total of 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (> 1296 pg/mL) and BUN/creat ( > 17). In the group without RD, survival was similar regardless of BNP and BUN/creat (n = 430, adjusted P = .52). Similarly, in patients with both a low BNP and BUN/creat, RD was not associated with mortality (n = 250, adjusted hazard ratio [HR] = 1.0, 95% confidence interval [CI] 0.6-1.6, P = .99). However, in patients with both an elevated BNP and BUN/creat those with RD had a cardiorenal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared with patients without RD (n = 249, adjusted HR = 1.8, 95% CI 1.2-2.7, P = .008, P interaction = .005).Conclusions: In the setting of decompensated HF, the combined use of BNP and BUN/creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis.

Background Although atrial arrhythmias (AAs) are common in heart failure, the incidence of AAs subsequent to the placement of left ventricular assist devices (LVADs) has not been elucidated. Methods Patients receiving a HeartMate II LVAD in the bridge to transplant (n = 490) and destination therapy (n = 634) trials were included (n = 1125). AAs requiring treatment were recorded, regardless of symptoms. Using Cox models with and without a 60-day blanking period, risk factors for early and late AAs were determined. Results In total, there were 271 AAs in 231 patients (21%), most of which occurred within the first 60 days. Patients with and without AAs had similar survival (p = 0.16). Serum creatinine (hazard ratio [HR] = 1.49 per unit increase, 1.18 to 1.88; p

Background— Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. Methods and Results— We independently analyzed 2 cohorts: (1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of heart failure (n=657) and (2) patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) data set (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high versus low DE based on the median value. There was only a moderate correlation between DE and both intravenous diuretic dose and net fluid output (r 2 ≤0.26 for all comparisons), indicating that DE was describing unique information. With the exception of metrics of renal function and preadmission diuretic therapy, traditional baseline characteristics, including right heart catheterization variables, were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn: hazards ratio [HR], 1.36; 95% confidence interval [CI], 1.04−1.78; P =0.02; ESCAPE: HR, 2.86; 95% CI, 1.53−5.36; P =0.001). Conclusions— Although in need of validation in less-selected populations, low DE during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.

Normal aging results in a predictable decrease in glomerular filtration rate (GFR), and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age-related decreases in estimated GFR (eGFR) carry the same prognostic importance as disease-attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction limited data set (n = 6,337). The primary analysis focused on determining if the eGFR-mortality relation differed by the extent to which the eGFR was consistent with normal aging. Mean eGFR was 65.7 ml/min/1.73 m(2) (SD = 19.0). Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73 m(2)/year (95% confidence interval [CI] 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p for interaction0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted hazard ratio 1.0 per 10 ml/min/1.73 m(2), 95% CI 0.97 to 1.1, p = 0.53), whereas a disease-attributable decrease in eGFR above the median carried significant risk (adjusted hazard ratio 2.8, 95% CI 1.6 to 4.7, p0.001). In conclusion, in the setting of left ventricular dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis.

Objectives This study sought to determine if the timing of hemoconcentration influences associated survival. Background Indicating a reduction in intravascular volume, hemoconcentration during the treatment of decompensated heart failure has been associated with reduced mortality. However, it is unclear if this survival advantage stems from the improved intravascular volume or if healthier patients are simply more responsive to diuretics. Rapid diuresis early in the hospitalization should similarly identify diuretic responsiveness, but hemoconcentration this early would not indicate euvolemia if extravascular fluid has not yet equilibrated. Methods Consecutive admissions at a single center with a primary discharge diagnosis of heart failure were reviewed (N = 845). Hemoconcentration was defined as an increase in both hemoglobin and hematocrit levels, then further dichotomized into early or late hemoconcentration by using the midway point of the hospitalization. Results Hemoconcentration occurred in 422 (49.9%) patients (41.5% early and 58.5% late). Patients with late versus early hemoconcentration had similar baseline characteristics, cumulative in-hospital loop diuretic administered, and worsening of renal function. However, patients with late hemoconcentration versus early hemoconcentration had higher average daily loop diuretic doses (p = 0.001), greater weight loss (p Conclusions Only hemoconcentration occurring late in the hospitalization was associated with improved survival. These results provide further support for the importance of achieving sustained decongestion during treatment of decompensated heart failure.

Worsening renal function (WRF) is common during the treatment of heart failure (HF) and has been associated with decreased survival, hospitalization, and disease progression.1 There are several hypothetical mechanisms, including inflammation, oxidant stress, or induction of apoptosis by uremic toxins, by which a reduction in renal function could directly lead to mortality.2,3 However, patients who experience WRF also often exhibit multiple markers of increased HF disease severity and are less likely to respond to diuretics.4,5 As a result, it is difficult to determine whether the frequently observed association between WRF and adverse outcomes results directly from the reduction in glomerular filtration rate (GFR) or is merely serving as a marker of greater HF disease severity. See Article by Beldhuis et al Over the past several years, it been described that not all forms of WRF are prognostically equivalent and WRF that occurs in the setting of otherwise beneficial HF therapies, like renin–angiotensin–aldosterone system (RAAS) antagonists or aggressive diuresis, seems to have a negligible impact on outcomes.6–10 RAAS antagonists, a cornerstone of guideline-based medical therapy for HF with reduced ejection fraction (HFrEF), can lead to perturbations in glomerular hemodynamics, secondary to a more pronounced vasodilation of the efferent arteriole, yielding a decrease in filtration fraction and thus at times GFR.11 As a result, it is not surprising that WRF is commonly observed during treatment with these medications.7,12 Despite the increased frequency of WRF, we and others have found that WRF in the setting of HFrEF treated with RAAS antagonists is relatively benign compared with WRF unprovoked by RAAS antagonism.7,9,12 So although the evidence for prognostic subtypes of WRF is well established, questions remain as to what causes the difference in prognosis. Is …

Pump thrombosis (PT) is a severe complication of left ventricular assist device (LVAD) support. This study evaluated PT and bleeding after LVAD placement in patients responsive to a standard aspirin dose of 81 mg using platelet inhibition monitoring compared with initial nonresponders who were then titrated upward to achieve therapeutic response. Patients ≥ 18 years of age with initial placement of HeartMate II LVAD at our institution and at least one VerifyNow Aspirin test performed during initial hospitalization were included. The primary endpoints were bleeding and PT compared between initial aspirin responders and nonresponders. Of 85 patients, 19 (22%) were nonresponsive to initial aspirin therapy. Responders and nonresponders showed similar survival (p = 0.082), freedom from suspected/confirmed PT (p = 0.941), confirmed PT (p = 0.273), bleeding (p = 0.401), and incidence rates in PT and bleeding. Among the initial responders (

Understanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF (n=128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for in vivo assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine. The mean±SD prediuretic FELi was 16.2%±9.5%, similar to that in a control cohort without HF not receiving diuretics (n=52; 16.6%±9.2%; P=0.82). Administration of a median of 160 (interquartile range, 40-270) mg intravenous furosemide equivalents increased FELi by 12.6%±10.8% (P

Background— Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature. Methods and Results— Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride ( r =−0.46; P P =0.49). Hypochloremic versus nonhypochloremic patients exhibited renal wasting of chloride ( P =0.04) and of chloride relative to sodium ( P =0.01), despite better renal free water excretion (urine osmolality 343±101 mOsm/kg versus 475±136; P P Conclusions— Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardiorenal parameters. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02031354.

Background: Renal dysfunction (RD) is associated with reduced survival in HF; however, not all RD is mechanistically or prognostically equivalent. Notably, RD associated with "pre-renal" physiology, as identified by an elevated blood urea nitrogen to creatinine ratio (BUN/Cr), identifies a particularly high risk RD phenotype. Proteinuria, another domain of renal dysfunction, has also been associated with adverse events. Given that several different mechanisms can cause proteinuria, we sought to investigate whether the mechanism underlying proteinuria also affects survival in HF.Methods and Results: Subjects in the Studies of Left Ventricular Dysfunction (SOLVD) trial with proteinuria assessed at baseline were studied (n = 6439). All survival models were adjusted for baseline characteristics and estimated glomerular filtration rate (eGFR). Proteinuria (trace or 1+) was present in 26% and associated with increased mortality (HR = 1.2; 95% CI, 1.1-1.3, p = 0.006). Proteinuria >1+ was less common (2.5%) but demonstrated a stronger relationship with mortality (HR = 1.9; 95% CI, 1.5-2.5, p = 17.3), any proteinuria (HR = 1.3; 95% CI, 1.1-1.5, p = 0.008) and >1+ proteinuria (HR = 2.3; 95% CI, 1.7-3.3, p Conclusion: Analogous to a reduced eGFR, the mechanism underlying proteinuria in HF may be important in determining the associated survival disadvantage. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Obstructive sleep apnea (OSA) is a form of sleep disordered breathing in which pharyngeal muscle relaxation leads to recurrent nighttime apneas and hypopneas that, through increased afterload, intermittent hypoxia, and excess sympathetic activity, weaken the already failing heart. This review presents the current evidence regarding the complex relationship between OSA and heart failure (HF), including support for OSA as both a cause and consequence of HF. The impact of OSA on other cardiovascular diseases, such as hypertension, ischemic heart disease and arrhythmias, as they relate to HF development or exacerbation, also are reviewed.

Introduction Mixed lymphocytic and giant cell myocarditis is a rare devastating disease with a very high mortality rate. Case report A 59 year old male with no known past medical history presented with syncope. Electrocardiogram revealed complete heart block and a permanent pacemaker was placed. Cardiac MRI showed increased T2 signal in the basal septum with a normal left ventricular ejection fraction. Nine months later, the patient presented with shortness of breath unresponsive to outpatient antibiotics and bronchodilators. They were found to be in cardiogenic shock which required inotropic support. Pulse steroids were administered for presumed inflammatory cardiomyopathy. Right heart catheterization confirmed cardiogenic shock. An endomyocardial biopsy was performed. There was development of frequent episodes of ventricular tachycardia despite antiarrhythmic infusions and attempts to electrically pace the patient out of the rhythm. V-A ECMO and an intra-aortic balloon pump were inserted for mechanical support. An impella was placed on the right for right-ventricular support. The patient developed worsening cardiogenic shock leading to watershed infarcts of the brain and acute liver and kidney failure. The patient was determined to not be transplant candidate and the family decided to move care to comfort directed measures and expired. Results Post-mortem autopsy showed mixed lymphocytic and giant cell myocarditis. Lymphoid aggregates were composed of mature lymphocytes. Conclusions Initial presentation of lymphocytic or giant cell myocarditis is congestive heart failure and or ventricular arrhythmias. Survival rates without transplantation are extremely low. This case presents a patient with complete heart block as a result of mixed lymphocytic and giant cell myocarditis. It highlights the importance of early diagnosis with cardiac biopsy to allow for early bridge to transplant with mechanical circulatory assist devices in a disease state that has a very high mortality rate. Figure 1

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.

Background— Reduction in systolic blood pressure (SBP reduction) during the treatment of acute decompensated heart failure is strongly and independently associated with worsening renal function. Our objective was to determine whether SBP reduction or titration of oral neurohormonal antagonists during acute decompensated heart failure treatment negatively influences diuresis and decongestion. Methods and Results— SBP reduction was evaluated from admission to discharge in consecutive acute decompensated heart failure admissions (n=656). Diuresis and decongestion were examined across a range of parameters, such as diuretic efficiency, fluid output, hemoconcentration, and diuretic dose. The average reduction in SBP was 14.4±19.4 mm Hg, and 77.6% of the population had discharge SBP lower than admission. SBP reduction was strongly associated with worsening renal function (odds ratio, 1.9; 95% confidence interval, 1.2–2.9; P =0.004), a finding that persisted after adjusting for parameters of diuresis and decongestion (odds ratio, 2.0; 95% confidence interval, 1.3–3.2; P =0.002). However, SBP reduction did not negatively affect diuresis or decongestion ( P ≥0.25 for all parameters). Uptitration of neurohormonal antagonists occurred in >50% of admissions and was associated with a modest additional reduction in blood pressure (≤5.6 mm Hg). Notably, worsening renal function was not increased, and diuretic efficiency was significantly improved with the uptitration of neurohormonal antagonists. Conclusions— Despite a higher rate of worsening renal function, blood pressure reduction was not associated with worsening of diuresis or decongestion. Furthermore, titration of oral neurohormonal antagonists was actually associated with improved diuresis in this cohort. These results provide reassurance that the guideline-recommended titration of chronic oral medication during acute decompensated heart failure hospitalization may not be antagonistic to the short-term goal of decongestion.

Background: In decompensated heart failure (HF), reversible renal dysfunction (RD) is more frequently observed in patients with mild liver dysfunction likely due to the shared pathophysiologic factors involved. The objective of this study was to determine if these findings also apply to stable HF outpatients. Methods: Patients in the Beta-Blocker Evaluation of Survival Trial (BEST) were studied. Improvement in renal function (IRF) was defined as a 20% improvement in the estimated glomerular filtration rate from baseline to 3 months. Results: Elevated bilirubin (BIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly associated with signs of congestion or poor perfusion. IRF occurred in 12.0% of all patients and was more common in those with elevated BIL (OR = 1.5, p = 0.003), ALT (OR = 1.4, p = 0.01), and AST (OR = 1.4, p = 0.01). In a model containing all 3 liver parameters and baseline characteristics, including markers of congestion/poor perfusion, BIL (OR = 1.6, p = 0.001) and ALT (OR = 1.7, p < 0.001) were independently associated with IRF. Conclusions: Biochemical evidence of mild liver dysfunction is significantly associated with IRF in stable HF outpatients. Given the widespread availability and low cost of these markers, additional research is necessary to determine the utility of these parameters in identifying patients with reversible RD who may benefit from cardiorenal interventions.

The patient was a frail-appearing woman slumped in a wheelchair, surrounded by her 3 children. Her head tilted slightly in greeting, but beyond her rapid and deep respiratory effort, she was too weak to move. She had been discharged 3 days previously from an outside hospital where she was confined for 3 weeks and had arrived at the academic medical center for a posthospital visit. The recent admission followed 4 others in the previous 6 months. Now, she was living at home in hospice care. The family arrived that day hoping that, as they heard from a church friend, the heart failure (HF) specialist might be able to help. The patient was more accepting, saying, “The doctors told me that I am dying, and there is nothing that they can do. I am at peace; I don’t want to be a bother to no one.” There are 5.7 million patients with HF in the United States over half of whom are women. Each year 33 700 women will die from this disease, representing 58% of all annual HF deaths.1–3 Although women and men are equally likely to have HF, women are more likely to die from it. Despite these facts, many Americans think that men are at greater risk for heart disease and that women are more likely to die from breast cancer. Why is the risk of HF in women underappreciated? The substantial numbers of women with HF with preserved ejection fraction (HFpEF) may be a contributor. It is known that HF with reduced EF (HFrEF) accounts for only a portion of patients with symptomatic HF. In a cohort of patients from Olmsted County, MN, HFrEF accounted for only 57% of patients with HF, whereas 43% of patients had an ejection fraction of >50%. Patients with …

Renal dysfunction (RD) in heart failure portends adverse outcomes and often limits aggressive medical and decongestive therapies. Despite the high prevalence in this population, not all forms of RD are prognostically or mechanistically equivalent: RD can result from irreversible nephron loss secondary to diabetic or hypertensive kidney disease or it can develop secondary to heart failure (HF) itself, i.e., the cardiorenal syndrome. Furthermore, filtration is only one aspect of renal performance such that significant renal impairment secondary to cardiorenal syndrome can exist despite a normal glomerular filtration rate. Renal biomarkers have the potential to inform some of the intricacies involved in accurately assessing cardiorenal interactions. This article discusses novel biomarkers for cardiorenal syndrome and their utility in the prognosis, diagnosis, and targeted treatment of heart failure-induced RD.

Ventricular assist devices (VADs) are an increasingly used therapy for advanced heart failure in the United States; over 10,000 patients have durable mechanical circulatory support since 2006. Renal dysfunction is common in these patients, particularly those who are not candidates for cardiac transplantation and receive a VAD as a destination therapy. Presence of baseline renal dysfunction translates into a greater risk of acute kidney injury (AKI) following VAD placement, which in turn portends a poor prognosis. However, the majority of patients actually experience a relative improvement in renal function with mechanical support suggesting that a significant burden of reversible heart failure-induced renal dysfunction was present in these patients at baseline. The clinical significance of post-VAD improvements in renal function remains poorly understood. This chapter describes the changes in renal function after VAD implantation, their association with mortality, and the potential influence of continuous-flow technology on these renal outcomes.

Background— The long-term durability and prognostic significance of improvement in renal function after mechanical circulatory support (MCS) has yet to be characterized in a large multicenter population. The primary goals of this analysis were to describe serial post-MCS changes in estimated glomerular filtration rate (eGFR) and determine their association with all-cause mortality. Methods and Results— Adult patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with serial creatinine levels available (n=3363) were studied. Early post-MCS, eGFR improved substantially (median improvement, 48.9%; P P P =0.002) and worsening in eGFR (adjusted HR, 1.63; 95% CI, 1.15–2.13; P =0.004). Conclusions— Post-MCS, early improvement in renal function is common but seems to be largely transient and not necessarily indicative of an improved prognosis. This pattern was observed with both pulsatile and continuous-flow devices. Additional research is necessary to better understand the mechanistic basis for these complex post-MCS changes in renal function and their associated survival disadvantage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00119834.

Differentiation of HF-induced renal dysfunction (RD) from irreversible intrinsic kidney disease is challenging, likely related to the multifactorial pathophysiology underlying HF-induced RD. In contrast, HF-induced liver dysfunction results in characteristic laboratory abnormalities. Given that similar pathophysiologic factors are thought to underlie both conditions, and that the liver and kidneys share a common circulatory environment, patients with laboratory evidence of HF-induced liver dysfunction may also have a high incidence of potentially reversible HF-induced RD.Hospitalized patients with a discharge diagnosis of HF were reviewed (n = 823). Improvement in renal function (IRF) was defined as a 20% improvement in estimated glomerular filtration rate (eGFR). An elevated international normalized ratio (INR; odds ratio [OR] 2.8; P.001), bilirubin (BIL; OR 2.2; P.001), aspartate aminotransferase (AST; OR 1.8; P = .004), and alanine aminotransferase (ALT; OR 2.1; P = .001) were all significantly associated with IRF. Among patients with baseline RD (eGFR ≤45 mL min(-1) 1.73 m(-2)), associations between liver dysfunction and IRF were particularly strong (INR: OR 5.7 [P.001]; BIL: OR 5.1 [P.001]; AST: OR 2.9 [P = .005]; ALT: OR 4.8 [P.001]).Biochemical evidence of mild liver dysfunction is associated with reversible RD in decompensated HF patients. In the absence of methodology to directly identify HF-induced RD, signs of HF-induced dysfunction of other organs may serve as an accessible method by which HF-induced RD is recognized.

Background— Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results— Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8; P P =0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8; P =0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate P P =0.59; p interaction=0.03). Conclusions— An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.