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Objectives Extracorporeal membrane oxygenation (ECMO) is used to support patients in severe cardiogenic shock. In the absence of recovery, these patients may need to be listed for heart transplant (HT), which offers the best long-term prognosis. However, posttransplantation mortality is significantly elevated in patients who receive ECMO. The objective of the present study was to describe and risk-stratify different profiles of patients listed for HT supported by ECMO. Methods Patients listed for HT in the United Network for Organ Sharing database were analyzed. The primary outcome was 1-year survival and was assessed in patients bridged to transplant with ECMO (ECMOBTT) and patients who were previously supported on ECMO but had it removed before HT (ECMOREMOVED). Results Among 65,636 adult candidates listed for HT (between 2001 and 2017), 712 were supported on ECMO, 292 of whom (41%) underwent HT (ECMOBTT, n = 202; ECMOREMOVED, n = 90). Most of the patients with ECMOREMOVED were transplanted with a ventricular assist device. In ECMOBTT, recipient age (each 10-year increase), time on the waitlist (both defined as minor risk factors), need for dialysis, and need for mechanical ventilation (both defined as major risk factors) were independent predictors of mortality. ECMOREMOVED and ECMOBTT with no risk factors showed 1-year survival comparable to that in patients who were never supported on ECMO. Compared with patients who were never on ECMO, patients in ECMOBTT group with minor risk factors, 1 major risk factor, and 2 major risk factors had ~2-, ~5-, and >10-fold greater 1-year mortality, respectively (P Conclusions The HT recipients in the ECMOREMOVED and ECMOBTT groups with no risk factors showed similar survival as the HT recipients who were never supported on ECMO. In the ECMOBTT group, posttransplantation mortality increased significantly with increasing risk factors.

Background: Following treatment for acute decompensated heart failure, in-hospital observation on oral diuretics (OOD) is recommended, assuming it provides actionable information on discharge diuretic dosing and thus reduces readmissions. Methods: In the Mechanisms of Diuretic Resistance (MDR) cohort, we analyzed in-hospital measures of diuretic response, provider’s decisions, and diuretic response ≈30 days postdischarge. In a Yale multicenter cohort, we assessed if in-hospital OOD was associated with 30-day readmission risk. The main objective of this study was to evaluate the utility of in-hospital OOD. Results: Of the 468 patients in the MDR cohort, 57% (N=265) underwent in-hospital OOD. During the OOD, weight change and net fluid balance correlated poorly with each other ( r =0.36). Discharge diuretic dosing was similar between patients who had increased, stable, or decreased weight (decreased discharge dose from OOD dose in 77% versus 72% versus 70%, respectively), net fluid status (decreased discharge dose from OOD dose in 100% versus 69% versus 74%, respectively), and urine output (decreased discharge dose from OOD dose in 69% versus 79% versus 72%, respectively) during the 24-hour OOD period ( P >0.27 for all). In participants returning at 30 days for formal quantification of outpatient diuretic response (n=98), outpatient and inpatient OOD natriuresis was poorly correlated ( r =0.26). In the Yale multicenter cohort (n=18 454 hospitalizations), OOD occurred in 55% and was not associated with 30-day hospital readmission (hazard ratio, 0.98 [95% CI, 0.93–1.05]; P =0.51). Conclusions: In-hospital OOD did not provide actionable information on diuretic response, was not associated with outpatient dose selection, did not predict subsequent outpatient diuretic response, and was not associated with lower readmission rate. Additional research is needed to replicate these findings and understand if these resources could be better allocated elsewhere. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02546583.

Implantable cardioverter-defibrillators (ICDs) are recommended for patients with cardiac sarcoidosis (CS) with an indication for pacing, prior ventricular arrhythmias, cardiac arrest, or left ventricular ejection fraction35%, but data on outcomes are limited.Using data from the National Cardiovascular Data Registry ICD Registry between April 1, 2010 and December 31, 2015, we evaluated a propensity matched cohort of CS patients implanted with ICDs versus non-ischemic cardiomyopathies (NICM). We compared mortality using Kaplan-Meier survival curves and Cox proportional hazards models.We identified 1,638 patients with CS and 8,190 propensity matched patients with NICM. The rate of death at 1 and 2 years was similar in patients with CS and patients with NICM (5.2% vs 5.4%, P = 0.75 and 9.0% vs 9.3%, P = 0.72, respectively). After adjusting for other covariates, patients with CS had similar mortality at 2 years after ICD implantations compared with NICM patients (RR 1.03, 95% CI 0.87-1.23). Among patients with CS, multivariable logistic regression identified 6 factors significantly associated with increased 2-year mortality: presence of heart failure (HR 1.92, 95% CI 1.44-3.22), New York Heart Association (NYHA) Class III heart failure (HR 1.68, 95% CI 1.16-2.45), NYHA Class IV heart failure (HR 3.08, 95% CI 1.49-6.39), atrial fibrillation/flutter (HR 1.66, 95% CI 1.17-2.35), chronic lung disease (HR 1.64, 95% CI 1.17-2.29), creatinine2.0 mg/dL (HR 4.07, 95% CI 2.63-6.30), and paced rhythm (HR 2.66, 95% CI 1.07-6.59).Mortality following ICD implantation was similar in CS patients compared with propensity matched NICM patients. Presence of heart failure, NYHA class, atrial fibrillation/flutter, chronic lung disease, renal dysfunction, and paced rhythm at time of implantation were all predictors of increased 2-year mortality among CS patients with ICDs.

BACKGROUND: Improvement in renal function (IRF) in acute decompensated heart failure is associated with adverse outcomes. The mechanisms driving this paradox remain undefined. METHODS: Using the ROSE-AHF study (Renal Optimization Strategies Evaluation–Acute Heart Failure), 277 patients were grouped according to renal function, with IRF defined by a ≥20% increase (N=75), worsening renal function by a ≥20% decline (N=53), and stable renal function (SRF) by a RESULTS: Patients with IRF had the lowest admission estimated glomerular filtration rate (IRF, 37 [28 to 51] mL/min per 1.73 m 2 ; worsening renal function, 43 [35 to 55] mL/min per 1.73 m 2 ; and SRF, 43 [32 to 55] mL/min per 1.73 m 2 ; P trend =0.032) but greater cumulative urine output (IRF, 8780 [7025 to 11 208] mL; worsening renal function, 7860 [5555 to 9765] mL; and SRF, 8150 [6325 to 10 456] mL; P trend =0.024) and weight loss (IRF, –9.0 [–12.4 to –5.3] lb; worsening renal function, –5.1 [–8.1 to –1.3] lb; and SRF, –7.1 [–11.9 to –3.2] lb; P trend P trend =0.16). There were no differences in the relative change in NGAL, NAG, or KIM-1 between renal function groups ( P trend >0.19 for all). Patients with IRF had worse survival than patients with SRF (27% versus 54%; hazard ratio, 1.98 [1.10–3.58]; P =0.024). CONCLUSIONS: IRF during decongestive therapy for acute decompensated heart failure was not associated with improved markers of renal tubular injury and was associated with worsened survival, likely driven by the presence of greater underlying cardiorenal dysfunction and more severe congestion.

An 80-year-old man with a destination left ventricular assist device (LVAD) presented with decompensated heart failure. Evaluation demonstrated numerous LVAD high power spike events, significant aortic regurgitation, and hemolysis. He underwent successful aortic valve replacement with a novel transcatheter valve and LVAD pump exchange that resulted in an improvement in his clinical status. (Level of Difficulty: Advanced.), Central Illustration

To determine the predictive value of cardiac magnetic resonance (CMR) and echocardiographic parameters on left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients without cardiogenic shock and treated with mechanical LV unloading followed by immediate or delayed percutaneous coronary intervention (PCI)-mediated reperfusion.In STEMI, infarct size (IS) directly correlates with major cardiovascular outcomes. Preclinical models demonstrate mechanical LV unloading before reperfusion reduces IS. The door-to-unload (DTU)-STEMI pilot trial evaluated the safety and feasibility of LV unloading and delayed reperfusion in patients with STEMI.This multicenter, prospective, randomized, safety and feasibility trial evaluated patients with anterior STEMI randomized 1:1 to LV unloading with the Impella CP (Abiomed) followed by immediate reperfusion vs delayed reperfusion after 30 minutes of unloading. Patients were assessed by CMR at 3-5 days and 30 days post PCI. Echocardiographic evaluations were performed at 3-5 and 90 days post PCI. At 3-5 days post PCI, patients were compared based on IS as percentage of LV mass (group 1 ≤25%, group 225%). Selection of IS threshold was performed post hoc.Fifty patients were enrolled from April 2017 to May 2018. At 90 days, group 1 (IS ≤25%) exhibited improved LV ejection fraction (from 53.1% to 58.9%; P=.001) and group 2 (IS25%) demonstrated no improvement (from 37.6% to 39.1%; P=.55). LV end-diastolic volume and end-systolic volume were unchanged in group 1 and worsened in group 2. There was correlation between 3-5 day and 30-day CMR measurements of IS and 90-day echocardiography-derived LV ejection fraction.Immediate 3-5 day post-therapy IS by CMR correlates with 90-day echocardiographic LVEF and indices of remodeling. Patients with post-therapy IS25% demonstrated evidence of adverse remodeling. Larger studies are needed to corroborate these findings with implications on patient management and prognosis.

Background Most acute decompensated heart failure admissions are driven by congestion. However, residual congestion is common and often driven by the lack of reliable tools to titrate diuretic therapy. The authors previously developed a natriuretic response prediction equation (NRPE), which predicts sodium output using a spot urine sample collected 2 h after loop diuretic administration. Objectives The purpose of this study was to validate the NRPE and describe proof-of-concept that the NRPE can be used to guide diuretic therapy. Methods Two cohorts were assembled: 1) the Diagnosing and Targeting Mechanisms of Diuretic Resistance (MDR) cohort was used to validate the NRPE to predict 6-h sodium output after a loop diuretic, which was defined as poor ( 150 mmol); and 2) the Yale Diuretic Pathway (YDP) cohort, which used the NRPE to guide loop diuretic titration via a nurse-driven automated protocol. Results Evaluating 638 loop diuretic administrations, the NRPE showed excellent discrimination with areas under the curve ≥0.90 to predict poor, suboptimal, and excellent natriuretic response, and outperformed clinically obtained net fluid loss (p Conclusions Natriuretic response can be rapidly and accurately predicted by the NRPE, and this information can be used to guide diuretic therapy during acute decompensated heart failure. Additional study of diuresis guided by the NRPE is warranted.

Background Sensitized patients awaiting heart transplantation spend a longer time on the waitlist and have higher mortality. We are now able to further characterize sensitization by discriminating antibodies against class I and II, but the differential impact of these has not been assessed systematically. Methods and Results Using United Network for Organ Sharing data (2004–2015), we analyzed 17,361 adult heart transplant patients whose class I and II panel reactive antibodies were reported. Patients were divided into 4 groups: class I and II ≤25% (group 1); class I ≤25% and class II ˃25% (group 2); class II ≤25% and class I >25% (group 3); and both class I and II >25% (group 4). Outcomes assessed were treated rejection at 1-year mortality, all-cause mortality, and rejection-related mortality. Compared with group 1, only group 4 was associated with a higher risk of treated rejection at 1 year (odds ratio 1.31, 95% confidence interval [CI] 1.05–1.64), all-cause mortality (hazard ratio 1.24, 95% CI 1.06–1.46), and mortality owing to rejection (subhazard ratio 1.84, 95% CI 1.18–2.85), whereas groups 2 and 3 were not (P > .05). Conclusions Combined elevation in class I and II panel reactive antibodies seem to increase the risk of treated rejection and all-cause mortality, whereas risk with isolated elevation is unclear.

Lymphopenia has been implicated in poor outcomes in the heart failure population. However, the prognostic implication of lymphopenia in left ventricular assist device (LVAD) patients is unknown. We examine the impact of lymphopenia on all-cause mortality in this population over a 24-month period post-implantation. A total of 170 patients between June 2011 and July 2018 receiving permanent durable LVAD at a single center formed the study population. Criteria for lymphopenia on admission, defined as an absolute lymphocyte count (ALC)1500 cells/μl, was met in 99 patients. A total of 11 patients were excluded: two with ALC4800/μl and nine with incomplete data. Survival across groups was compared with a Kaplan-Meier plot and log-rank statistics. The Cox proportional hazard model was used to examine the association between lymphopenia and 24-month all-cause mortality. In the lymphopenia group, mean ALC was 909.6 ± 331.9 versus 2073.6 ± 501.1 in the non-lymphopenic group. Twenty-four-month all-cause mortality was significantly higher in the lymphopenia group (p = 0.009). The lymphopenic patients had worse unadjusted (hazard ratio [HR] = 2.14, confidence interval [CI] = 1.19-3.82; p = 0.01) and adjusted survival (HR = 2.07, CI = 1.13-3.79; p = 0.02). Further clinical investigations are required to assess the utility of continued clinical monitoring of ALC levels beyond LVAD placement.

Background: Sodium-glucose cotransporter-2 inhibitors improve heart failure–related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. Methods: Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. Results: Oral empagliflozin was rapidly absorbed as evidenced by a 27-fold increase in urinary glucose excretion by 3 hours ( P P =0.001), and there was a synergistic effect in combination with bumetanide (fractional excretion of sodium, 5.8±2.5% versus 3.9±1.9%; P =0.001). At 14 days, the natriuretic effect of empagliflozin persisted, resulting in a reduction in blood volume (−208 mL [interquartile range, −536 to 153 mL] versus −14 mL [interquartile range, −282 to 335 mL]; P =0.035) and plasma volume (−138 mL, interquartile range, −379 to 154±453 mL; P =0.04). This natriuresis was not, however, associated with evidence of neurohormonal activation because the change in norepinephrine was superior ( P =0.02) and all other neurohormones were similar ( P P =0.20) or renal dysfunction ( P >0.11 for all biomarkers), whereas both serum magnesium ( P P =0.008) improved. Conclusions: Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in patients with heart failure and may represent a mechanism contributing to the superior long-term heart failure outcomes observed with these agents. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03027960.

Objective: The objective of this study was to summarize the prevalence and the available management strategies for cardiogenic shock in the setting of severe aortic stenosis and their outcome. Introduction: Aortic stenosis (AS) is the most common valvular heart disease in older adults. Cardiogenic shock (CS) is a medical emergency, and while management for these two conditions has evolved over the years, little is known about the prevalence, management, and mortality of AS in combination with CS. Methods: We performed a systematic review to identify studies that included patients with severe AS presenting with CS using EMBASE, MEDLINE, and Scopus. Primary outcomes included in-hospital, 30-day, and 1-year mortality. Additional outcomes included procedure-related complications. We registered the study protocol at PROSPERO (CRD42018112245). Results: We included a total of 10 studies representing 338 patients. In-hospital mortality ranged from 43% to 77% in patients treated with Balloon Aortic Valvuloplasty (BAV), 0% in patients who underwent surgical valve replacement (SAVR), and 11% and Transcatheter aortic valve replacement (TAVR). In patients undergoing BAV, 30-day mortality varied between 50% and 55%, and between 19% and 33% in those treated with TAVR. There was limited evidence on the use of Mechanical Circulatory Support (MCS). Conclusion: AS presenting with CS is a rare but fatal condition, and no consensus exists regarding management strategy. Time to intervention on the valve is critical. Valve replacement through either SAVR or TAVR had better outcomes compared to BAV alone. There is limited evidence on MCS as a management strategy in patients with AS complicated by CS.

Background: The association of weight change and short-term readmission in patients hospitalized for heart failure (HF) has not been well studied. Methods: We collected clinical and weight data from patients admitted with decompensated HF to a single center (2012−2013). We performed logistic regression to determine the association between weight change and two outcomes: a total of 30-day HF-specific readmission and 30-day all-cause readmission. Results: Admission and discharge weights were documented in 479/658 patients (73%). Weight loss >2 kg was not associated with 30-day all-cause or HF-specific readmission when compared with more modest inpatient weight change (-2 kg to +2 kg; all-cause readmission odds ratio: 0.86; CI: 0.56−1.37; HF-specific readmission odds ratio: 1.15; CI: 0.61−2.16). Conclusion: Among HF inpatients, in-hospital weight loss was not associated with 30-day all-cause or HF-specific readmission.

Inferior vena cava (IVC) measurements correlate only modestly with right atrial pressure (RAP). Part of this inaccuracy is due to the high compliance of the venous system, where a large change in blood volume may result in only a small change in pressure. As such, the information provided by the IVC may be different rather than redundant.We analyzed patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial who had both pulmonary artery catheter and IVC measurements at baseline (n = 108). There was only a modest correlation between baseline RAP and IVC diameter (r = 0.41; P0.001). Hemoconcentration, defined as an increase in hemoglobin levels between admission and discharge, was correlated with decrease in IVC diameter (r = 0.35; P = 0.02) but not with a decrease in RAP (r = 0.01; P = 0.95). When patients had both IVC and RAP measurements that were below the median, survival rates were superior to the rates of those who had only 1 measurement below the median, and when both rates were above the median, patients fared the worst (P = 0.002).IVC and RAP have limited correlation with each another, and changes in intravascular volume appear to correlate better with IVC diameter rather than with RAP. Furthermore, complementary information is provided by pressure and volume assessments in acute decompensated heart failure.

Effective strategies to optimize Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS 1) patients are in much need. A novel awake venous-arterial extracorporeal membrane oxygenation (aVA ECMO) allows for clinical assessments while temporarily supporting biventricular function and stabilizing end-organ functions. The aim of the study was to assess outcomes of patients with aVA ECMO support before durable left ventricular assist device (LVAD) implantation. We evaluated 83 patients who received durable LVAD in 2012-2015, of whom 19 received aVA ECMO support before durable LVAD. Kaplan-Meier and Cox proportional hazards analyses were conducted to assess post-LVAD survival. No complications were observed during the mean aVA ECMO support of 2.7 days. Unadjusted survival of aVA ECMO-supported patients and non-aVA ECMO INTERMACS 1 patients at 1 year were 84.2% and 66.7%, respectively (p = 0.15). Survival of aVA ECMO patients was comparable with that of non-aVA ECMO INTERMACS 2 cohort (84.2% vs. 80.8%) at 1 year. Multivariate analysis demonstrated a significant reduction in the risk of death in aVA ECMO group compared with INTERMACS 1 non-aVA ECMO group (hazard ratio [HR]: 0.17; p = 0.035). Awake venous-arterial (VA) ECMO allows bridge to next therapy and improves outcomes in INTERMACS category 1 patients with an effect comparable with downgrading the disease severity on the INTERMACS scale.

Evidence regarding the utility of routine induction therapy on outcomes is not clear. This study aims to evaluate whether induction therapy is associated with a reduced risk of treated rejection and improved overall survival.We retrospectively analyzed all adult patients (age ≥ 18 years) that are included in the UNOS database who underwent heart transplantation between 2000 and 2017. Patients with prior transplants and dual organ transplants were excluded. 34,361 patients were included in the final analysis. We assessed the impact of induction therapy with T cell depleting agents (TC-DA), IL2 receptor antagonists (IL2R antagonist) and compared that to no induction therapy using Cox regression models adjusted for propensity scores. The primary outcome measure was all-cause mortality, whereas treated rejection at one year was analyzed as a secondary outcome measure (available in 77% of patients).A total of 52% of the cohort did not receive any induction therapy. A total of 27% received IL2R antagonist and the rest received TC-DA. Median age of the recipients was 55 (IQR: 46-62) years. A total of 25% of the population were women and 39% were supported on left ventricular assist device therapy at the time of transplantation. Median follow-up was 4.2 (IQR: 1.1-8.5) years with 32% reported mortality. Multivariate analysis with propensity score adjustment showed that TC-DA induction did not have any effect on mortality (HR = 0.98, 95% CI 0.93-1.03, p = 0.48). However, IL2R antagonist was associated with a modestly increased risk of all-cause mortality compared to no induction (HR = 1.06, 95% CI 1.01-1.11, p = 0.02, respectively). A total of 25% of patients were found to have treated rejection at one year, TC-DA induction was associated with reduced odds of rejection at one year (OR = 0.82, 95% CI 0.76-0.88, p0.001). However, induction with IL2R antagonist was not found to have a significant impact (OR = 1.03, 95% CI 0.96-1.11, p = 0.36).Compared to no induction therapy, induction with TC-DA was associated with reduction in risk of treated rejection at 1 year with no effect on mortality and IL2R antagonist was associated with a small but statistically significant increase in mortality without any impact on risk of rejection.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and18F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

The purpose of this review is to provide an update on cardiac sarcoidosis (CS) and to discuss the current recommendations and progress in diagnosis and management of this disease. Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Cardiac involvement is seen in at least 25% and is associated with poor prognosis. Manifestations of cardiac sarcoidosis (CS) can vary from presence of silent myocardial granulomas, which may lead to sudden death, to symptomatic conduction abnormalities, ventricular arrhythmias, and heart failure. We discuss newer imaging modalities such as cardiac magnetic resonance imaging and positron emission tomography in conjunction with clinical criteria increasingly used for diagnosing and prognosticating patients with CS. Immunosuppression (primarily corticosteroids) is recommended for treatment of CS; however, its efficacy has never been proven in prospective randomized studies. The role of imaging to guide the use of immunotherapy is unknown. Cardiac sarcoidosis continues to challenge clinicians due to its protean presentations, lack of diagnostic standards, and data for risk stratification and treatment. There is a need for prospective, randomized controlled trials to understand how best to diagnose and treat cardiac sarcoidosis.

Background Hypertrophic cardiomyopathy ( HCM ) is the most common inherited cardiomyopathy. Current guidelines endorse management in expert centers, but patient socioeconomic status can affect access to specialty care. The effect of socioeconomic status and specialty care access on HCM outcomes has not been examined. Methods and Results We conducted a retrospective cohort study that examined outcomes among HCM patients receiving care in the Yale New Haven Health System between June 2011 and December 2017. Patients were assigned to lower or higher socioeconomic status groups ( LSES / HSES ) based on medical insurance provider and to receivers of specialty care ( SC ) at Yale's Inherited Cardiomyopathy clinic or general cardiology care ( GC ). The primary outcome was all‐cause death, and the secondary outcome was all‐cause hospitalization. We identified 953 HCM patients; 820 (86%) were HSES and 133 (14%) were LSES . Forty‐three (4.5%) patients died from cardiac and noncardiac causes. LSES patients within the general cardiology care cohort had significantly higher all‐cause mortality compared with HSES patients (adjusted hazard ratio, [95% CI ]=10.06 [4.38–23.09]; P CI ]=2.87 [0.56–14.73]; P =0.21). The moderator effect of specialty care on mortality difference between LSES versus HSES , however, did not reach statistical significance (hazard ratio, 0.29 [0.05–1.77]; P =0.18). Specialist care was associated with increased hospitalization (adjusted hazard ratio, [95% CI ]=3.28 [1.11–9.73]; P =0.03 for LSES ; 2.19 [1.40–3.40]; P =0.001 for HSES ). Conclusions Socioeconomically vulnerable HCM patients had higher mortality when not referred to specialty care. Further study is needed to understand the underlying causes.

Despite efforts at early revascularization in acute coronary syndrome and advancing technologies in the field of temporary mechanical circulatory support (TMCS), the mortality from cardiogenic shock (CS) remains very high. Treatment of these patients involves understanding the trajectory of the condition and making complex decisions regarding the appropriate selection of medical and device therapies. The current definition of CS is not universally applicable and defines shock in absolute terms. CS should be thought of as a continuum rather than a binary diagnosis and is best defined as a clinical syndrome of tissue hypoperfusion resulting from cardiac dysfunction. Early intervention with appropriate timing and selection of apposite TMCS device may be the key to improving outcomes. TMCS device selection is a complex process requiring consideration of the severity of CS, patient-specific risks, technical limitations, overall goals of care, and assessment of futility of care. In this review, we discuss identification and pathophysiology of CS, and critically review acute management strategies, both medical and mechanical therapies and outline areas that need further investigation.

Purpose Evidence suggests that routine induction therapy does not improve long-term survival post-heart transplantation. The aim of this study was to evaluate if induction therapy would decrease the risk of treated rejection. Methods A retrospective analysis of 33,922 patients ≥ 18 years old in the UNOS database who underwent heart transplantation 2000-2017 was performed. Patients with prior transplants and dual organ transplants were excluded. The primary end point was treated rejection at one year. Patients were divided into three groups: no induction, induction with IL-2 receptor antagonists (daclizumab and basiliximab) and induction with T-cell depleting agents (alemtuzumab and anti-thymocyte globulins). Results 51% did not receive induction, 25% received IL-2 receptor antagonists and 25% received T-cell depleting agents. Female sex and black race were associated with increased odds of treated rejection at one year (OR 1.321, p Conclusion Induction with T-cell depleting agents reduces the risk of treated rejection at one year. This effect was not seen with IL-2 receptor antagonists. Female sex, higher degrees of HLA mismatch and black race are associated with increased risk of rejection and induction with T-cell depleting antibodies may reduce the risk of treated rejection in this group.

Background Loop diuretic resistance is a common barrier to effective decongestion in acute heart failure (AHF), and is associated with poor outcome. Specific mechanisms underlying diuretic resistance are currently unknown in contemporary AHF patients. We therefore aimed to determine the relative importance of defects in diuretic delivery vs. renal tubular response in determining diuretic response (DR) in AHF. Methods and results Fifty AHF patients treated with intravenous bumetanide underwent a 6-h timed urine collection for sodium and bumetanide clearance. Whole-kidney DR was defined as sodium excreted per doubling of administered loop diuretic and represents the sum of defects in drug delivery and renal tubular response. Tubular DR, defined as sodium excreted per doubling of renally cleared (urinary) loop diuretic, captures resistance specifically in the renal tubule. Median administered bumetanide dose was 3.0 (2.0–4.0) mg with 52 (33–77)% of the drug excreted into the urine. Significant between-patient variability was present as the administered dose only explained 39% of variability in the quantity of bumetanide in urine. Cumulatively, factors related to drug delivery such as renal bumetanide clearance, administered dose, and urea clearance explained 28% of the variance in whole-kidney DR. However, resistance at the level of the renal tubule (tubular DR) explained 71% of the variability in whole-kidney DR. Conclusion Defects at the level of the renal tubule are substantially more important than reduced diuretic delivery in determining diuretic resistance in patients with AHF.

Purpose Less invasive extra-pericardial placement (LIEPP) of LVADs is being explored to address post-implant adverse events. We examined the differences in early 90-day right ventricular failure (RVF) between LIEPP versus standard median sternotomy (MS) approaches in a single-center experience. Methods A retrospective analysis of 173 LVAD patients implanted between June 2011 and September 2018 was conducted. Six patients were excluded: four with RVAD placement before LVAD, one with giant cell myocarditis, and one with >40% missing data. LIEPP was performed in 36 patients and 131 had MS implantation. Outcomes for RVF including RVAD need and bleeding were compared using Fisher's test for categorical variables, Mann-Whitney test for continuous variables, and multivariate for cause of RVF. Results Compared to the MS cohort, the LIEPP group consistent of patients with greater age (62.8 vs 57.9 yrs) p=0.03; higer INTERMACS profile (INTERMACS 1 =72.2% vs 30.5%) p=0.0004; greater IABP use (44.4% vs 26.0%) p=0.03; higher preop BUN (mg/dL) 36.5(25.5 - 56.0) vs 28.0 (19.0 - 41.0) p=0.01; and lower preop hemoglobin (g/dL) 10.0 (8.8 - 11.7) vs 10.6 (9.8 - 12.2) p=0.01. LIEPP showed a significantly lower rate of bleeding through chest tube output (p= Conclusion LIEPP reduces the early 90-day incidence of RVF and thus need for RVAD. With the integrity of the pericardium maintained, the LIEPP may prevent RV dilation and RVF. Likewise, a reduction in blood product use removes potential influence on pulmonary vascular resistance that can predispose to RVF. These trends were seen despite the worse pre-operative profile of the LIEPP group highlighting the preferred choice of LIEPP for poor surgical candidates.

Cardiac allograft vasculopathy (CAV) is a progressive fibroproliferative disease, which contributes to significant morbidity and mortality during long-term follow-up after heart transplantation. Mammalian target of rapamycin (mTOR) inhibitors have favorable effects on endothelial function and reduce intimal proliferation, and their early use after transplantation has been associated with a reduction in the risk of development and progression of CAV. However, there are conflicting reports on the efficacy of these agents in treating established CAV. Most of the data until recently have been based on short-term follow-up, and CAV was assessed by changes in intravascular ultrasound. In this study, we review the mechanism of action of mTOR inhibitors and their protective role in CAV and summarize some of the recent literature, which include long-term follow-up using this class of medications.

Purpose Gene expression profiling (GEP; AlloMap®) scores can be impacted in the presence of >20 mg/day of prednisone due to effects on steroid-responsive genes (IL-1R2, ITGAM, FLT3) and is not validated for use prior to 55 days post-heart transplant. Donor-derived cell-free DNA (dd-cfDNA) can be used as early as 14 days after heart transplant (HT), but the impact of early use and the impact of steroid dosing has not yet been demonstrated. Methods The dd-cfDNA (AlloSure®) from the Donor-Derived Cell-Free DNA Outcomes AlloMap Registry (D-OAR) and Surveillance Heart Care Outcome Registry (SHORE) registries had 17 visits 5-10, >10-15, >15-20, and >20 mg/day (n=1113, 542, 203, 82, and 30). Results For those = 55 days post-HT the median dd-cfDNA result was 0.15% (IQR: 0.15-0.15%) and 0.15% (0.15-0.19%), respectively (p=NS). When stratified by prednisone doses (0-5], (5-10], (10-15], (15-20], and (>20, there was also no difference in median dd-cfDNA: 0.12%, 0.12%, 0.15%, 0.15%, and 0.15%, respectively, p=0.7. Conclusion This preliminary data suggests that dd-cfDNA levels are not significantly affected when assessed earlier than 55 days post-HT or by varying prednisone dosage. Implementation of dd-cfDNA as an early biomarker of allograft injury and rejection may represent a valuable clinical tool during the early post-HT period.

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

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. Current prognostic models are not ideal, and identifying more accurate prognostic variables is needed. The objective of this study was to evaluate the relative prognostic value of the right atrial pressure/pulmonary artery wedge pressure (RAP/PAWP) ratio in PAH patients. We hypothesized that the RAP/PAWP ratio is more predictive of survival than any of the other measured or calculated hemodynamic variables.We performed a secondary analysis of a PAH cohort (Cohort 1) and validated our results in a separate cohort (Cohort 2). Cohort 1 included primarily patients enrolled in prospective, short-term, randomized clinical trials and subsequently followed long term. Cohort 2 included patients prospectively enrolled in a PAH registry at a tertiary PAH referral center.Cohort 1 (n = 847) and Cohort 2 (n = 697) had a mean age of 47 and 54 years, respectively. Most were female (78% and 73%, respectively), Caucasian (83% and 82%), with advanced functional class disease status (New York Heart Association Functional Class III/IV 85% and 68%) and with significantly elevated hemodynamics (mean RAP/PAWP ratio: 1.2 and 1.0; pulmonary vascular resistance: 13.5 and 9.4 Wood units). RAP/PAWP ratio indicated a 1-year hazard ratio of 1.44 (p = 0.0001) and 1.35, respectively (p0.0001), and was the most consistently predictive hemodynamic variable across the 2 cohorts. These results remain valid even when adjusted for other covariables in multivariable regression models.The RAP/PAWP ratio is a more specific predictor of survival than any other hemodynamic variable, and we recommend that it be used in clinical prognostication and PAH predictive models.

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.

The prevalence and clinical characteristics of familial dilated cardiomyopathy (FDCM) among patients with end stage heart failure (ESHF) has yet to be elucidated. We sought to determine the prevalence of FDCM in ESHF in the United Network for Organ Sharing (UNOS) registry and compare this with center specific data from a large tertiary teaching hospital. Patients with a banked UNOS diagnosis of dilated cardiomyopathy (DCM) whose care originated at our center then underwent detailed pedigree analysis in order to determine the true prevalence of FDCM.A total of 16,091 patients with DCM from all centers were identified in the UNOS registry of whom 492 carried the diagnosis of FDCM (3.1%). Patients with the diagnosis of FDCM tended to be younger (42 versus 49 years old in idiopathic dilated cardiomyopathy (IDCM), p=0.001), were less likely to have diabetes (7.8% versus 16.5% in IDCM, p0.0001), had slightly lower creatinine (1.2 versus 1.4 in IDCM, p=0.0001) and were more likely to have a panel reactive antibody level ≥ 20% (62.1% versus 44.7% in IDCM, p0.0001). Consecutive living adult patients with ESHF were identified from the UNOS registry that had been treated at the Yale Center for Advanced Heart Failure (YCAHF). After excluding all diagnoses that did not include any form of non-ischemic DCM, 73 patients met the inclusion criteria. Center-specific UNOS data showed pre-pedigree analysis diagnosis of FDCM in 4.12% of patients (3 out of 73), consistent with that found in the UNOS database for all centers. However, after detailed family history and pedigree analysis, 19 (26%) of 73 patients were found to have FDCM, while the remaining 54 were found to have IDCM. Echocardiographic findings including mitral regurgitation, mitral valve annulus and left ventricular end diastolic dimension were not significantly different between groups when adjusting for multiple testing.The diagnosis of FDCM was missed in the majority of patients with end stage heart failure enrolled in the UNOS database, as sampled from a large, tertiary care teaching hospital in the United States. Echocardiographic findings are unlikely to aid in the differentiation between DCM and FDCM. Detailed pedigree analysis can successfully identify undiagnosed FDCM and should be encouraged prior to transplant listing as it has important implications for early detection and treatment of disease in family members.

Purpose Bleeding is the most common complication of left ventricular assist device (LVAD) placement. However, excessive transfusion has been linked to heart failure, stroke, and alloimmunization. We compared 90-day outcomes in patients receiving a blood conservation (BCS) versus liberal transfusion strategy during surgery and the subsequent 24 hours. Methods 173 LVAD implants at a single center between June 2011 and September 2018 were reviewed. Due to incomplete data, 3 patients were excluded. Results The BCS (≤1 packed red blood cell (pRBC)) was employed in 56/170 patients. In the liberal group, 41 received 2-5 units, 24 received 6-10 units, 24 received 11-15 units, and 25 received ≥15 units of PRBC. Anti-platelet use was equal across groups whereas anticoagulants were more readily used in the conservative group (55 vs 38%, p=0.04) at implantation. The liberal group had greater use of circulatory support devices (47 vs 29%, p=0.02) whereas the BCS group had larger ventricular size. Pre-operative laboratory values were similar among groups except for hemoglobin g/dL (12.6 conservative vs 11.6 liberal, p=0.02). Both the length of hospital and ICU stay were lower in the BCS group (17 vs 24 days, p 90-day mortality was significantly higher in the liberal group (p=0.03). However, multivariate analysis did not show a significant benefit of the BCS despite trend towards survival with a crude HR 2.23 (0.86-5.82, p=0.10) and adjusted HR 2.21 (0.82-5.75, p=0.10). Conclusion BCS at time of LVAD implant is associated with improved early survival. Identified transfusion triggers and standardized transfusion protocols for LVAD patients have the potential to reduce blood product utlization.

Predictors of survival in cardiogenic shock (CS) treated with intra-aortic balloon pump (IABP) are not clearly understood. In this retrospective study, we sought to evaluate patient characteristics and impact of timing of IABP in treatment of CS. Patients presenting to the Yale New Haven Hospital in CS who received IABP between February 2013 and April 2017 were included in the study. We assessed baseline characteristics and clinical predictors of 30-day mortality. Hundred ninety-three (n = 193) patients were included in this study. Mean age was 68.8 ± 14.5 years. Thirty percent (30%) were women, 38% had cardiac arrest, and left ventricular ejection fraction was 33.7 ± 14.9%. Overall 30-day mortality was 36%. Thirty-day mortality was 24% when IABP was placed within less than 1 hour of onset of CS versus 49% when implanted ≥1 hour after recognition of CS (p = 0.001). Mortality was 18%, 21%, 36%, and 74% for patient requiring 0, 1, 2, and 3 or more inotropes after IABP placement (p0.001). In multivariate analysis, advancing age, cardiac arrest on presentation, time to IABP implantation, and number of inotropes needed after IABP implantation predicted 30-day mortality. In the 193 patients, 134 (69.4%) presented with CS from ACS and 59 (30.6%) with CS from non-ACS-related causes. No difference in mortality was noted between the ACS and non-ACS groups 34.3% versus 40.7% (p = 0.39). In conclusion, early use of IABP in CS was associated with significant improvement in 30-day mortality regardless of the etiology of CS. Continued need for significant inotropic support after IABP is associated with worse prognosis and maybe used as an indicator for need to escalate to higher levels of support.

Background: FDG PET is used in cardiac sarcoidosis (CS) diagnosis and management, including decisions about initiation and titration of immunosuppression. However, optimal methods to identify sarcoidosis-related inflammation on these scans is unknown. Traditional interpretive methods for FDG PET rely on qualitative visual analysis, but quantitative techniques including standardized uptake values (SUVs) may be more specific. This study evaluated the diagnostic reclassification of FDG PET studies using quantitative versus qualitative analysis and evaluated the potential impact of reclassification on downstream management and events. Methods: Cardiac-focused FDG PET examinations performed for the evaluation of CS were analyzed, comparing results from the clinically reported visual analysis to quantitative re-analysis using left ventricular maximal SUV values (SUVmax). Net diagnostic reclassification index (NDI) was calculated and compared to admissions, deaths, ICD placements, immunosuppression initiation/escalation. Of 154 exams, 22 were reclassified from positive to negative using quantitative re-analysis whereas only 2 clinically reported negative exams were quantitatively reclassified to positive, leading to a NDI of -13.0%. In the quantitatively negative/clinically reported positive group, 11 patients had immunosuppression adjusted after 22 exams and 4 ICDs were placed. Conclusions: Quantitative re-analysis of FDG PET for CS led to an overall negative diagnostic reclassification from positive to negative. Studies that were clinically reported as positive by visual analysis but reclassified as negative by quantitative analysis had numerous medical interventions but few clinical events. The low event rate suggests the use of quantitative interpretation of FDG PET for CS may help in providing providers with a more targeted therapeutic framework. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 342-353)

Purpose In patients with an established diagnosis of heart failure, lymphopenia can predict survival up to 1 year after measurement. Lymphocytes can be depleted through enteric losses secondary to splanchnic congestion or through exaggerated physiologic stress response. However, the prognostic role of lymphopenia in the outcome of LVAD patients has not been explored. We sought to examine the impact of lymphopenia on all-cause mortality in this population over a 24-month period post implantation. Methods At a single center, 170 patients received LVAD therapy between June 2011 and July 2018. 99 of these patients met criteria for lymphopenia on admission as defined as an absolute lymphocyte count (ALC) 4800/μL and nine with incomplete data. A Kaplan-Meir plot and log-rank statistics were used to compare survival across patient groups with and without lymphopenia. The association between lymphopenia and 24-month all-cause mortality was examined via unadjusted and adjusted cox models. Results In the lymphopenic group, mean ALC was 909.6± 331.9 and median (Interquartile range) of 910 (684.0 - 1164.8) versus 2073.6±501.1 and 1941.0(1679.5 - 2340.0) in the non-lymphopenic group. 24-month mortality was significantly higher in the lymphopenic group (Log-Rank p=0.009). On Cox-modelling, the lymphopenic patients had worse unadjusted survival [HR= 2.14 (1.19 - 3.82) (p=0.01)] and adjusted survival [2.01 (1.12 - 3.60) (p=0.02)] when age, race, gender, eGFR, INTERMACS category, serum sodium and LVEF were adjusted for. Conclusion Worse survival was seen in LVAD patients with lymphopenia at up to 24-months post procedure. Lymphocyte levels may be an important prognostic indicator and therapeutic target with future immune modulator therapy.

Purpose Abnormal chloride homeostasis is associated with worse survival in patients with chronic heart failure. Maladaptive neurohormonal responses and chronic diuretic use deplete serum chloride levels. However, the prognostic implications of serum chloride levels in LVAD patients is not fully elucidated. Our objective was to determine the effect of pre-LVAD hypochloremia on long term survival in LVAD patients. Methods We performed a retrospective analysis of all 166 LVAD implants between January 2011 and June 2018 at a single center. Patients were classified into either [hypochloremia (serum chloride 106mEq/L and one with incomplete data. Median chloride levels were used to assess the impact of LVAD therapy. Unadjusted and adjusted cox models were used to examine for association between hypochloremia and 2-year all-cause mortality . We compared survival between both groups using Kaplan-Meir plot and log-rank statistics. Results Chloride levels in group A normalized over three months and peaked at 24 months with a 7mEq/l rise from baseline. Group B levels remained normal with a marginal 0.5mEq/L rise from baseline at 24 months. No significant association between hypochloremia and survival was found [unadjusted HR= 1.01 (0.62 - 1.64), p=0.98] [adjusted HR= 0.88 (0.53 - 1.44), p=0.60]. Conclusion LVAD therapy normalizes chloride homeostasis via cardio-renal axis and stresses its prognostic value. Survival in the long run may be multi-factorial besides chloride levels alone.

Summary Frailty, a clinical syndrome that typically occurs in older adults, implies a reduced ability to tolerate biological stressors. Frailty accompanies many age‐related diseases but can also occur without overt evidence of end‐organ disease. The condition is associated with circulating inflammatory cytokines and sarcopenia, features that are shared with heart failure (HF). However, the biological underpinnings of frailty remain unclear and the interaction with HF is complex. Here, we describe the inflammatory pathophysiology that is associated with frailty and speculate that the inflammation that occurs with frailty shares common origins with HF. We discuss the limitations in investigating the pathophysiology of frailty due to few relevant experimental models. Leveraging current therapies for advanced HF and current known therapies to address frailty in humans may enable translational studies to better understand the inflammatory interactions between frailty and HF.

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.

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— 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.