Publications by authors named "Justin M Vader"

32 Publications

Angiotensin II Type 1 Receptor Antibody Mediated Rejection Following Orthotopic Heart Transplant: A Single Center Experience.

Transplantation 2021 Feb 22. Epub 2021 Feb 22.

1Division of Cardiology, Department of Medicine 2Department of Pathology & Immunology 3Department of Developmental Biology Washington University in St. Louis, St. Louis, MO, 63130.

Background: Antibody mediated rejection (AMR) following orthotopic heart transplant (OHT) causes significant morbidity and mortality. There is limited data on antibodies to the angiotensin II type 1 receptor (AT1R-Ab) causing rejection following OHT.

Methods: This is a retrospective, single center study that presents our 2-year experience with a series of 11 patients with evidence of nonspecific graft dysfunction and pathologic levels of AT1R-Ab. The clinical outcomes and treatments were compared to a group of 10 patients, also with evidence of nonspecific graft dysfunction, but who had nonsignificant AT1R-Ab titers.

Results: The mean age of the AT1R-Ab cohort was 52 and 73% were bridged to transplant with an LVAD. The average LVEF at presentation was 45%, and most were not on an angiotensin receptor blocker (ARB). Endomyocardial biopsies in those with elevated AT1R-Ab levels frequently showed reactive endothelium/endocardium without C4d or intravascular CD68 staining. Ten patients (91%) were started on an ARB. Other therapies included plasmapheresis and IVIg (64%), with 4 patients also receiving rituximab. Most patients had symptom improvement, but minimal change in graft function at an average 6 months of follow-up.

Conclusions: The role of AT1R-Ab mediated rejection in OHT recipients remains poorly understood. More than half of patients at our center who presented with graft dysfunction in the absence of ACR or AMR were found to have elevated AT1R-Ab titers. Empiric AMR treatment in conjunction with ARB therapy may improve patient outcomes. Future studies are needed to better define the optimal treatment modalities for ATR1-Ab mediated AMR.
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http://dx.doi.org/10.1097/TP.0000000000003712DOI Listing
February 2021

Interim Analysis of the Phase II Study: Noninferiority Study of Doxorubicin with Upfront Dexrazoxane plus Olaratumab for Advanced or Metastatic Soft-Tissue Sarcoma.

Clin Cancer Res 2021 Mar 25. Epub 2021 Mar 25.

Cardio-Oncology Center of Excellence, Washington University in St. Louis, St. Louis, Missouri.

Purpose: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS).

Patients And Methods: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction.

Results: At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1-11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m (interquartile range, 300-750 mg/m).

Conclusions: At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4621DOI Listing
March 2021

Building Experience and Evidence: COVID-19 and Myocardial Injury.

Circ Cardiovasc Imaging 2021 01 19;14(1):e012220. Epub 2021 Jan 19.

Section of Heart Failure and Cardiac Transplantation, Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO.

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http://dx.doi.org/10.1161/CIRCIMAGING.120.012220DOI Listing
January 2021

Sacubitril/Valsartan in Advanced Heart Failure With Reduced Ejection Fraction: Rationale and Design of the LIFE Trial.

JACC Heart Fail 2020 10 10;8(10):789-799. Epub 2020 Jun 10.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).
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http://dx.doi.org/10.1016/j.jchf.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286640PMC
October 2020

Disparities and Impact of Medicaid Expansion on Left Ventricular Assist Device Implantation and Outcomes.

Circ Cardiovasc Qual Outcomes 2020 06 12;13(6):e006284. Epub 2020 May 12.

Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO (X.W., A.A.L., J.M.V., T.M.M., K.E.J.M.).

Background: Left ventricular assist device (LVAD) therapy is an increasingly viable alternative for patients who are not candidates for heart transplantation or who are waiting for a suitable donor. We aimed to determine whether there is an association between sex, race/ethnicity, insurance coverage, and neighborhood income and access to/outcomes of LVAD implantation. We further analyzed whether access to LVAD improved in states that did versus did not expand Medicaid.

Methods And Results: Retrospective cohort study using State Inpatient Databases to identify patients 18 to 85 years of age admitted for heart failure, cardiogenic shock, or LVAD implantation from 2012 to 2015. Logistic regression analyses adjusting for age, all the sociodemographic factors above, medical comorbidities, and a hospital random effect were used to quantify odds of receipt of LVADs, as well as outcomes conditional on receiving an LVAD, for the sociodemographic groups of interest. A total of 925 770 patients were included; 3972 (0.43%) received LVADs. After adjusting for age, comorbidities, and hospital effects, women (adjusted odds ratio [aOR], 0.45 [0.41-0.49]), black patients (aOR, 0.83 [0.74-0.92]), and Hispanic patients (aOR, 0.74 [0.64-0.87]) were less likely to receive LVADs than whites. Medicare (aOR, 0.79 [0.72-0.86]), Medicaid (aOR, 0.52 [0.46-0.58]), and uninsured patients (aOR, 0.17 [0.11-0.25]) were less likely to receive LVADs than the privately insured, and patients in low-income ZIP codes were less likely than those in higher income areas (aOR, 0.71 [0.65-0.77]). Among those who received LVADs, women (aOR, 1.78 [1.38-2.30]), patients of unknown race or race other than white, black, or Hispanic (aOR, 1.97 [1.42-2.74]), and uninsured patients (aOR, 4.86 [1.92-12.28]) had higher rates of in-hospital mortality. Medicaid expansion was not associated with an increase in LVAD implantation.

Conclusions: There are meaningful sociodemographic disparities in access and outcomes for LVAD implantation. Medicaid expansion was not associated with an increase in LVAD rates.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006284DOI Listing
June 2020

Epidemiology of Left Ventricular Assist Device Infections: Findings From a Large Nonregistry Cohort.

Clin Infect Dis 2021 01;72(2):190-197

Division of Infectious Diseases, Washington University School of Medicine, St Louis, Missouri, USA.

Background: Infection is a major complication during circulatory support with a left ventricular assist device (VAD). Changes in device characteristics and treatment practices in the last decade can affect the epidemiology of infection. The International Society for Heart and Lung Transplantation (ISHLT) has published recommendations on the prevention and management of VAD infections, but data to support these recommendations remain sparse.

Methods: We performed a retrospective review of 455 patients who underwent VAD placement from 2009 to 2015. Infection episodes were defined using ISHLT criteria and were also grouped as endovascular or local. Analysis included descriptive statistics.

Results: There were 174 patients (38.6%) with a VAD infection. Infection incidence was 36.9 cases per 100 person-years of VAD support. The driveline was the most common infection site (67.2%). Systemic inflammatory response syndrome (SIRS) criteria were not satisfied in 29.2% of patients with endovascular infections, and computed tomography (CT) examinations were normal in 37.7% of cases. Gram-positive bacteria caused 65.6% of infections in patients with an available culture. Antimicrobial suppression was used in 72.3% of patients who survived treatment. Median survival after infection was 35 months for patients with VAD-related infections versus 14 months for patients with VAD-specific infections.

Conclusions: VAD infections continue to be a major complication after implantation. Clinical criteria alone were not predictive of serious infections, and many patients with confirmed infection had normal CTs. Patients with VAD-specific infections had lower median survival than patients with VAD-related infections.
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http://dx.doi.org/10.1093/cid/ciaa011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982342PMC
January 2021

Comparison of the Kansas City Cardiomyopathy Questionnaire and Minnesota Living With Heart Failure Questionnaire in Predicting Heart Failure Outcomes.

Am J Cardiol 2019 03 4;123(5):807-812. Epub 2018 Dec 4.

Washington University School of Medicine, St. Louis, Missouri. Electronic address:

Patient-reported outcome measures (PROMs) are relevant independent outcomes in heart failure (HF) care and are predictive of subsequent hospitalization and death in HF. The Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) are the 2 most widely adopted PROMs specific to HF. We compared their prognostic abilities in a prospective cohort of HF patients. A prospective cohort of subjects from a single-center registry was analyzed with regard to baseline KCCQ and MLHFQ scores and the outcomes of death, transplant, or left ventricular assist device implantation and hospitalization. A total of 516 subjects with reduced left ventricular ejection fraction (HFrEF) and 151 subjects with preserved left ventricular ejection fraction (HFpEF) were included. Discrimination was assessed using c-statistics based on time-to-event analyses and receiver-operator curves. The additive contribution of MLHFQ was assessed through the change in c-statistic, incremental discrimination index, and category-free net reclassification index. Overall, KCCQ was superior to MLHFQ for predicting death/transplant/ventricular assist device (c-statistic 0.702 [0.666 to 0.738] and 0.658 [0.621 to 0.695] respectively, p value for difference <0.001) and hospitalization (c-statistic 0.640 [0.613 to 0.666] and 0.624 [0.597 to 0.651], respectively, p value for difference 0.022). However, this difference was statistically nonsignificant in the HFpEF group alone. When analyzing the additional prognostic information afforded by adding MLHFQ to KCCQ in the overall, HFrEF, and HFpEF groups there was no significant improvement, although adding KCCQ to MLHFQ did significantly improve risk stratification. Scoring based upon the abbreviated KCCQ-12 did not reduce the prognostic accuracy of KCCQ. In conclusion, KCCQ is more prognostic of death/transplant/left ventricular assist device and hospitalization than MLHFQ in a combined cohort of patients with HFrEF and HFpEF, although the effect in HFpEF was less pronounced. KCCQ should be the preferred PROM for patients with HF if prognostication is a desired goal of using the PROMs.
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http://dx.doi.org/10.1016/j.amjcard.2018.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814384PMC
March 2019

Re-Thinking Re-Synching in Left Ventricular Assist Device Recipients.

J Am Heart Assoc 2018 06 15;7(12). Epub 2018 Jun 15.

Baylor University Medical Center, Dallas, TX.

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http://dx.doi.org/10.1161/JAHA.118.009591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220548PMC
June 2018

Outcomes and Predictors of Early Infection after Heart Transplantation.

Surg Infect (Larchmt) 2018 Jul 18;19(5):516-522. Epub 2018 May 18.

2 Department of Pharmacy, Barnes-Jewish Hospital , St. Louis, Missouri.

Background: Limited data exist on the incidence and outcome of early infection after orthotopic heart transplantation (OHT). The purpose of this study was to describe characteristics and outcomes of OHT recipients with an early infection and to identify predictors of such infections.

Methods: This retrospective, single-center study included patients greater than 18 years of age who underwent OHT from February 2009 to May 2014 and had an infection within 30 days of transplantation. Patient demographics, clinical variables, and outcomes were collected. Multivariable logistic regression was performed to identify independent predictors of infection.

Results: Of the 172 eligible OHT recipients, 51 (29.7%) had an early infection. The median time to diagnosis was five days, with gram-negative organisms being slightly more common (58.2%). No differences in mortality rate, rejection, or re-admission were found between the groups. Longer durations of mechanical ventilation and lengths of stay were found in the infection group (p < 0.001). Patients with an early infection also had a higher incidence of mechanical circulatory support, history of drive-line infection, longer duration of mechanical ventilation, continuous renal replacement therapy (CRRT), and delayed chest closure (p < 0.05 for all). Pre-OHT left-ventricular assist device (adjusted odds ratio [AOR] 2.53; 95% confidence interval [CI] 1.015-6.286; p < 0.046), pre-OHT extracorporeal membrane oxygenation (AOR 14.10; 95% CI 1.38-150.5; p = 0.026) and post-OHT CRRT (AOR 3.98; 95% CI 1.67-9.52; p = 0.002) were found to be independent risk factors for an early infection. A total of 90% of the available susceptibility panels for the gram-negative isolates (26/29) were resistant to the standard peri-operative cephalosporin given.

Conclusions: Prior mechanical circulatory support and the acute need for CRRT may predispose OHT patients to an infection early in the post-operative period. Evaluation of peri-operative antimicrobial prophylaxis, based on an individual center's resistance panels, may be warranted.
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http://dx.doi.org/10.1089/sur.2017.295DOI Listing
July 2018

The Combination of Tricuspid Annular Plane Systolic Excursion and HeartMate Risk Score Predicts Right Ventricular Failure After Left Ventricular Assist Device Implantation.

ASAIO J 2019 Mar/Apr;65(3):247-251

From the Barnes-Jewish Hospital, Cardiovascular Division, Washington University, St. Louis., Missouri.

Right ventricular (RV) failure is difficult to predict and is a major determinant of poor outcomes after left ventricular assist device (LVAD) implantation. We evaluated the associations of the following variables with severe RV failure in LVAD patients: tricuspid annular plane systolic excursion (TAPSE), pulmonary artery pulsatility index (PAPi), simplified RV contraction pressure index (sRVCPI), and HeartMate Risk Score (HMRS). We performed a retrospective case-control study on 216 patients who underwent continuous-flow LVAD implantation between 2008 and 2014. The primary analysis assessed the ability of HMRS, PAPi, sRVCPI, and TAPSE to predict severe RV failure. A secondary analysis evaluated the incremental benefit of combining predictive variables. Seventy-four patients developed severe RV failure (24%). Compared with the control group, the severe RV failure group had lower TAPSE (1.30 vs. 1.55; p < 0.001), lower PAPi (1.77 vs. 2.47; p = 0.001), lower sRVCPI (42.71 vs. 57.82; p < 0.001), and higher HMRS (2.12 vs. 1.65; p < 0.001). All four variables had similar receiver operating characteristic curves with modest area under the receiver operating characteristic curve (0.63-0.67, all p values < 0.001). In the evaluation of combined predictive variables, the combination of TAPSE with HMRS was found to be best for predicting severe RV failure. In summary, patients at risk for severe RV failure after LVAD implantation were successfully identified using TAPSE, PAPi, sRCPI, and HMRS. The combination of TAPSE and HMRS-incidentally, the least invasive and most readily available variables-proved to be superior to RV-centric metrics for predicting severe RV failure. The predictive and clinical use of these two variables should be tested prospectively.
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http://dx.doi.org/10.1097/MAT.0000000000000808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203672PMC
March 2020

Internal driveline damage under the costal margin several years after HeartMate II implant: a series of three cases.

J Artif Organs 2018 Sep 3;21(3):359-362. Epub 2018 Mar 3.

Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8234, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA.

Although the incidence of driveline failure has been significantly reduced with the major modification to the driveline connection to the HeartMate II left ventricular assist device (LVAD), internal and external driveline damage continues to be a major reason for pump exchange or driveline repair. We report three cases of internal driveline damage under the costal margin and in the adjacent abdominal wall. All three cases developed occasional electrical disruptions 2-5 years after the original LVAD implant through the median sternotomy. Two patients underwent subcostal LVAD exchange and one had driveline externalization and repair. The driveline velour was well adhered to the costal margin and wire damage was found at the costal margin as well as the subsequent segment in the abdominal wall. Repeated ante-flex bending of the abdominal wall over years appeared to cause the chronic wear and tear of the vertically located driveline under the costal margin. This report will confirm a pitfall of the LVAD driveline location which can potentially cause driveline damage in the mid-to-long term.
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http://dx.doi.org/10.1007/s10047-018-1029-2DOI Listing
September 2018

Clinical Significance of Early Fluid and Weight Change During Acute Heart Failure Hospitalization.

J Card Fail 2018 09 11;24(9):542-549. Epub 2018 Jan 11.

Brigham and Women's Hospital, Division of Cardiology, Boston, Massachusetts; Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, Icahn School of Medicine, New York, New York. Electronic address:

Aims: To explore the association of changes in weight and fluid during treatment for acute heart failure (AHF) with clinical endpoints.

Methods And Results: Weight and net fluid changes recorded at 72-96 hours in 708 AHF patients enrolled in Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure, Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and Renal Optimization Strategies Evaluation in Acute Heart Failure studies were compared with freedom from congestion at 72-96 hours and a composite endpoint of death, rehospitalization, and unplanned hospital visit at 60 days. Weight loss was concordant with net fluid loss in 55%, discordant and less than expected for fluid loss in 34%, and paradoxically discordant or more than expected for fluid loss in 11% of patients. Weight loss, but not fluid loss, was associated with freedom from congestion (odds ratio per 1-kg weight loss = 1.11 [1.03-1.19]) and a nominal reduction in the composite endpoint (hazard ratio per 1-kg weight loss = 0.98 [0.95-1.00]). Outcomes were similar in patients with concordant and discordant weight-fluid loss.

Conclusion: During treatment for AHF, early changes in weight may be more useful for identifying response to therapy and for predicting outcomes than net fluid output. Nearly one-half of patients receiving decongestive therapies demonstrate discordant changes in weight and fluid; however, discordance was not associated with outcomes.
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http://dx.doi.org/10.1016/j.cardfail.2017.12.013DOI Listing
September 2018

Prospective Assessment of Frailty Using the Fried Criteria in Patients Undergoing Left Ventricular Assist Device Therapy.

Am J Cardiol 2017 Oct 1;120(8):1349-1354. Epub 2017 Aug 1.

Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri.

Frail patients are more prone to adverse events after cardiac surgery, particularly after implantation of left ventricular assist devices. Thus, frailty assessment may help identify patients unlikely to benefit from left ventricular assist device therapy. The purpose was to establish a suitable measure of frailty in adults with end-stage heart failure. In a prospective cohort of 75 patients (age 58 ± 12 years) with end-stage heart failure, we assessed the association between frailty (5-component Fried criteria) and the composite primary outcome of inpatient mortality or prolonged length of stay, as well as extubation status, time on ventilator, discharge status, and long-term mortality. Fried frailty criteria were met in 44 (59%) patients, but there was no association with the primary outcome (p = 0.10). However, an abridged set of 3 criteria (exhaustion, inactivity, and grip strength) was predictive of the primary outcome (odds ratio 2.9, 95% confidence interval 1.1 to 7.4), and of time to extubation and time to discharge. In patients with advanced heart failure, the 5-component Fried criteria may not be optimally sensitive to clinical differences. In conclusion, an abridged set of 3 frailty criteria was predictive of the primary outcome and several secondary outcomes, and may therefore be a clinically useful tool in this population.
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http://dx.doi.org/10.1016/j.amjcard.2017.07.074DOI Listing
October 2017

Clinical Decision Support for Heart Failure Referral-More Work, Better Outcomes?

J Card Fail 2017 10 23;23(10):727-728. Epub 2017 Aug 23.

Cardiovascular Division, Washington University, St. Louis, Missouri.

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http://dx.doi.org/10.1016/j.cardfail.2017.08.450DOI Listing
October 2017

Potential Expanded Indications for Neprilysin Inhibitors.

Curr Heart Fail Rep 2017 04;14(2):134-145

Cardiovascular Division, Washington University School of Medicine, 660 S. Euclid Ave., Box 8086, St Louis, MO, 63110, USA.

Purpose Of Review: The goal of this article is to review potential expanded indications for neprilysin inhibitors. This article reviews the rationale and design for ongoing and future trials of sacubitril/valsartan in cardiovascular and non-cardiovascular disease.

Recent Findings: Randomized trial data are lacking for use of sacubitril/valsartan in acute heart failure and advanced heart failure. Mechanistic data from animal studies suggest a role for neprilysin inhibition in the treatment of post-myocardial infarction systolic dysfunction and heart failure with preserved ejection fraction. Beyond the cardiovascular system, renal and neurological function may be impacted by neprilysin inhibition. Forthcoming randomized trials will address the clinical impact of sacubitril/valsartan on these conditions. Neprilysin inhibition with sacubitril/valsartan offers a new therapeutic strategy with a broad range of potential therapeutic actions. In PARADIGM-HF, the combination of neprilysin and RAAS inhibition was proven to be superior to enalapril for patients with stable NYHA class II-III heart failure and reduced left ventricular ejection fraction. Preliminary data suggests it may also have a role in other cardiovascular and non-cardiovascular disease. Several ongoing and planned studies will determine the extent of its benefit for these other indications.
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http://dx.doi.org/10.1007/s11897-017-0327-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645149PMC
April 2017

Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation.

Cancer 2017 05 6;123(10):1800-1809. Epub 2017 Mar 6.

Bone Marrow Transplant and Leukemia Program, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri.

Background: The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen-matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy-based HCT.

Methods: A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model.

Results: Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non-PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy.

Conclusions: The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy-based HCT. Cancer 2017;123:1800-1809. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30534DOI Listing
May 2017

Clinical outcomes associated with INTERMACS-defined right heart failure after left ventricular assist device implantation.

J Heart Lung Transplant 2017 04 30;36(4):475-477. Epub 2016 Dec 30.

Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri.

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http://dx.doi.org/10.1016/j.healun.2016.12.017DOI Listing
April 2017

Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial.

Eur J Heart Fail 2017 07 14;19(7):893-900. Epub 2017 Feb 14.

Duke Clinical Research Institute, Durham, NC, USA.

Background: While abnormal left ventricular (LV) global longitudinal strain (GLS) has been described in patients with heart failure with preserved ejection fraction (HFpEF), its prevalence and clinical significance are poorly understood.

Methods And Results: Patients enrolled in the RELAX trial of sildenafil in HFpEF (LV ejection fraction ≥50%) in whom two-dimensional, speckle-tracking LV GLS was possible (n = 187) were analysed. The distribution of LV GLS and its associations with clinical characteristics, LV structure and function, biomarkers, exercise capacity and quality of life were assessed. Baseline median LV GLS was -14.6% (25th and 75th percentile, -17.0% and -11.9%, respectively) and abnormal (≥ - 16%) in 122/187 (65%) patients. Patients in the tertile with the best LV GLS had lower N-terminal pro-brain natriuretic peptide (NT-proBNP) [median 505 pg/mL (161, 1065) vs. 875 pg/mL (488, 1802), P = 0.008) and lower collagen III N-terminal propeptide (PIIINP) levels [median 6.7 µg/L (5.1, 8.1) vs. 8.1 µg/L (6.5, 10.5), P = 0.001] compared with the tertile with the worst LV GLS. There was also a modest linear relationship with LV GLS and log-transformed NT-proBNP and PIIINP (r = 0.29, P < 0.001 and r = 0.19, P = 0.009, respectively). We observed no linear association of LV GLS with Minnesota Living with Heart Failure scores, 6-min walk distance, peak oxygen consumption, or expiratory minute ventilation/carbon dioxide excretion slope.

Conclusions: Impaired LV GLS is common among HFpEF patients, indicating the presence of covert systolic dysfunction despite normal LV ejection fraction. Impaired LV GLS was associated with biomarkers of wall stress and collagen synthesis and diastolic dysfunction but not with quality of life or exercise capacity, suggesting other processes may be more responsible for these aspects of the HFpEF syndrome.
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http://dx.doi.org/10.1002/ejhf.754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511088PMC
July 2017

Global Outcome in Patients With Left Ventricular Assist Devices.

Am J Cardiol 2017 04 5;119(7):1069-1073. Epub 2017 Jan 5.

Department of Cardiovascular Outcomes Research, Saint Luke's Mid America Heart Institute, Kansas City, Missouri; Department of Cardiology, University of Missouri-Kansas City, Kansas City, Missouri.

Left ventricular assist devices (LVADs) improve survival and quality of life (QOL) for most, but not all, patients with advanced heart failure. We described a broader definition of poor outcomes after LVAD, using a novel composite of death, QOL, and other major adverse events. We evaluated the frequency of poor global outcome at 1 year after LVAD among 164 patients (86% Interagency Registry for Mechanically Assisted Circulatory Support profile 1 to 2; shock or declining despite inotropes) at a high-volume center. Poor global outcome (comprising death, poor QOL [Kansas City Cardiomyopathy Questionnaire <45], recurrent heart failure [≥2 heart failure readmissions], or severe stroke) occurred in 58 patients (35%): 37 died, 17 had poor QOL, 3 had recurrent heart failure, and 1 had a severe stroke. Patients with poor global outcomes were more likely designated for destination therapy (46% vs 24%, p = 0.01), spent more days hospitalized per month alive (median [interquartile range] 18.6 [5.0 to 31.0] vs 3.7 [1.8 to 8.3], p <0.001), and had higher intracranial (12% vs 2%, p = 0.031) and gastrointestinal (44% vs 28%, p = 0.056) hemorrhage rates over the year after implant. Although LVADs often improve survival and QOL, ∼1/3 of high-acuity patients experienced a poor global outcome over the year after LVAD. In conclusion, composite outcomes may better capture events that matter to patients with LVADs and thus support informed decisions about pursuing LVAD therapy.
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http://dx.doi.org/10.1016/j.amjcard.2016.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348271PMC
April 2017

Use of adenosine diphosphate receptor inhibitor prior to left ventricular assist device implantation is not associated with increased bleeding.

J Artif Organs 2017 Mar 9;20(1):42-49. Epub 2016 Nov 9.

Division of Cardiothoracic Surgery, Washington University School of Medicine, Campus Box 8234, 660 S Euclid Avenue, St. Louis, MO, 63110, USA.

Current guidelines recommend adenosine diphosphate receptor inhibitors (ADPRi) be discontinued 5-7 days prior to cardiac surgery due to increased bleeding events, rates of re-exploration, and transfusions. However, the risks of left ventricular assist device (LVAD) implantation in patients taking an ADPRi have not previously been studied. We retrospectively identified 134 eligible patients with ischemic cardiomyopathy that underwent LVAD implantation between July 2009 and August 2013. The cohorts received an ADPRi ≤5 days of surgery (n = 25) versus >5 days prior or not at all (n = 109). Subgroup analyses adjusted for differences in frequency of redo sternotomy between cohorts, excluded patients that received an ADPRi >1 year prior to surgery, and excluded patients with a redo sternotomy. The ADPRi and control groups did not have significant differences in the primary outcomes, intraoperative PRBC units transfused (3.0 vs. 4.0, p = 0.12) or chest tube output within 24 h of surgery (1.66 L vs. 1.80 L, p = 0.61). After adjusting for differences in frequency of redo sternotomy (ADPRi vs. control, 12 vs. 52%, p ≤ 0.001), no significant difference in PRBC units transfused (3.1 vs. 3.5, p = 0.59) or chest tube output (2.04 L vs. 2.04 L, p = 0.98) was seen. No significant difference in 30-day mortality (8.0 vs. 11.0%, p = 0.63), 90-day mortality (16.4 vs. 23.3%, p = 0.42), or length of stay (29.0 vs. 28.0, p = 0.61) was seen. In this single-center experience, use of an ADPRi ≤5 days prior to LVAD implantation was not associated with increased bleeding, length of stay, or mortality.
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http://dx.doi.org/10.1007/s10047-016-0932-7DOI Listing
March 2017

Timing and Causes of Readmission After Acute Heart Failure Hospitalization-Insights From the Heart Failure Network Trials.

J Card Fail 2016 Nov 28;22(11):875-883. Epub 2016 Apr 28.

Washington University School of Medicine, St. Louis, Missouri.

Background: Readmission or death after heart failure (HF) hospitalization is a consequential and closely scrutinized outcome, but risk factors may vary by population. We characterized the risk factors for post-discharge readmission/death in subjects treated for acute heart failure (AHF).

Methods And Results: A post hoc analysis was performed on data from 744 subjects enrolled in 3 AHF trials conducted within the Heart Failure Network (HFN): Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE-AHF), Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), and Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF). All-cause readmission/death occurred in 26% and 38% of subjects within 30 and 60 days of discharge, respectively. Non-HF cardiovascular causes of readmission were more common in the ≤30-day timeframe than in the 31-60-day timeframe (23% vs 10%, P = .016). In a Cox proportional hazards model adjusting a priori for left ventricular ejection fraction <50% and trial, the risk factors for all-cause readmission/death included: elevated baseline blood urea nitrogen, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) non-use, lower baseline sodium, non-white race, elevated baseline bicarbonate, lower systolic blood pressure at discharge or day 7, depression, increased length of stay, and male sex.

Conclusions: In an AHF population with prominent congestion and prevalent renal dysfunction, early readmissions were more likely to be due to non-HF cardiovascular causes compared with later readmissions. The association between use of ACEI/ARB and lower all-cause readmission/death in Cox proportional hazards model suggests a role for these drugs to improve post-discharge outcomes in AHF.
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http://dx.doi.org/10.1016/j.cardfail.2016.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085925PMC
November 2016

Clinical Implications of Serum Albumin Levels in Acute Heart Failure: Insights From DOSE-AHF and ROSE-AHF.

J Card Fail 2016 Nov 2;22(11):884-890. Epub 2016 Feb 2.

Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Background: Hypoalbuminemia is common in patients with chronic heart failure and, as a marker of disease severity, is associated with an adverse prognosis. Whether hypoalbuminemia contributes to (or is associated with) worse outcomes in acute heart failure (AHF) is unclear. We sought to determine the implications of low serum albumin in patients receiving decongestive therapies for AHF.

Methods And Results: Baseline serum albumin levels were measured in 456 AHF subjects randomized in the DOSE-AHF and ROSE-AHF trials. We assessed the relationship between admission albumin levels (both as a continuous variable and stratified by median albumin [≥3.5 g/dL]) and worsening renal function (WRF), worsening heart failure (WHF), and clinical decongestion by 72 hours; 7-day cardiorenal biomarkers; and post-discharge outcomes. The mean baseline albumin level was 3.5 ± 0.5 g/dL. Albumin was not associated with WRF, WHF, or clinical decongestion by 72 hours. Furthermore, there was no association between continuous albumin levels and symptom change according to visual analog scale or weight change by 72 hours. Albumin was not associated with 60-day mortality, rehospitalization, or unscheduled emergency room visits.

Conclusions: Baseline serum albumin levels were not associated with short-term clinical outcomes for AHF patients undergoing decongestive therapies. These data suggest that serum albumin may not be a helpful tool to guide decongestion strategies.
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http://dx.doi.org/10.1016/j.cardfail.2016.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970961PMC
November 2016

All-Payer Analysis of Heart Failure Hospitalization 30-Day Readmission: Comorbidities Matter.

Am J Med 2017 Jan 31;130(1):93.e9-93.e28. Epub 2016 Aug 31.

Division of Cardiology, Washington University School of Medicine, Saint Louis, Mo.

Background: Thirty-day readmission following heart failure hospitalization impacts hospital performance measures and reimbursement. We investigated readmission characteristics and the magnitude of 30-day hospital readmissions after hospital discharge for heart failure using the Healthcare Cost and Utilization Project State Inpatient Databases (SID).

Methods: Adults aged ≥ 40 years hospitalized with a primary discharge diagnosis of heart failure from 2007-2011 were identified in the California, New York, and Florida SIDs. Characteristics of patients with and without 7-, 8 to 30-, and 30-day readmission, and primary readmission diagnoses and risk factors for readmission were examined.

Results: We identified 547,068 patients with mean age 74.7 years; 50.7% were female, and 65.4% were White. Of 117,123 patients (21.4%) readmitted within 30 days (median 12 days), 69.7% had a non-heart failure primary readmission diagnosis. Patients with 30-day readmissions more frequently had a history of previous admission with heart failure as a secondary diagnosis, fluid and electrolyte disorders, and chronic deficiency anemia. There were no significant clinical differences at baseline between those patients whose first readmission was in the first 7 days after discharge vs in the next 23 days. The most common primary diagnoses for 30-day non-heart failure readmissions were other cardiovascular conditions (14.9%), pulmonary disease (8.5%), and infections (7.7%).

Conclusions: In this large all-payer cohort, ∼70% of 30-day readmissions were for non-heart failure causes, and the median time to readmission was 12 days. Future interventions to reduce readmissions should focus on common comorbid conditions that contribute to readmission burden.
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http://dx.doi.org/10.1016/j.amjmed.2016.07.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482409PMC
January 2017

A Case Series of Acute Myocardial Infarction in Left Ventricular Assist Device-Supported Patients.

ASAIO J 2017 Mar/Apr;63(2):e18-e24

From the *Department of Medicine, and †Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri.

Acute myocardial infarction (AMI) is an underrecognized phenomenon in patients with continuous-flow left ventricular assist devices (CF-LVAD). Previously, there has been an optimistic expectation of a benign clinical course; however, AMI in LVAD-supported patients can result in profound consequences and management remains controversial. We describe a case series of AMI in four CF-LVAD patients, each with a different presentation, clinical course, treatment, and outcome. The clinical variability and mixed outcomes of these patients highlights the unique challenges in diagnosis and management of AMI in this population, particularly the uncertain role of percutaneous intervention (PCI), and underscores the potentially poor prognosis of this entity. Several key points emerge from this review. First, LVAD-supported patients frequently have underlying abnormalities on the electrocardiogram (ECG) that obscure the diagnosis of AMI. Second, clinicians should have a high degree of suspicion for AMI in the presence of suggestive clinical features, elevated cardiac biomarkers, or new-onset ventricular arrhythmias. Third, the decision to proceed with PCI requires careful evaluation of the risk of hemorrhage, and strong consideration should be given to the use of bleeding avoidance strategies during and after PCI.
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http://dx.doi.org/10.1097/MAT.0000000000000401DOI Listing
January 2018

Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices.

Circ Heart Fail 2016 05;9(5)

From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO.

Background: We evaluated thrombotic and bleeding outcomes in patients with continuous-flow left ventricular assist devices (CF-LVADs), stratified by anticoagulation intensity. Previous studies of outpatients with CF-LVADs have suggested that target international normalized ratio (INR) values <2.5 (range, 2-3) may be used. However, recent studies reported an increase in pump thrombosis among CF-LVADs, especially within the first 6 months of implant.

Methods And Results: We retrospectively reviewed 249 outpatients at our center who received a CF-LVAD between January 2005 and August 2013. Using Poisson models, we analyzed their 10 927 INRs to determine INR-specific rates of thrombotic (ischemic stroke and suspected pump thrombosis) and hemorrhagic (gastrointestinal bleeding and hemorrhagic stroke) events occurring outside of the hospital. In multivariate analyses, we adjusted for age, sex, atrial fibrillation, coronary disease, and LVAD type as time-dependent Cox proportional hazard models. During a mean follow-up of 17.6±13.6 months, thrombotic events occurred in 46 outpatients. The highest event rate (0.40 thrombotic events per patient-year) was in the INR range of <1.5, but INR values of 1.5 to 1.99 also had high rates (0.16 thrombotic events per patient-year). INR was inversely associated with thrombotic events (hazard ratio, 0.40; 95% confidence interval, 0.22-0.72; P=0.002). The optimal INR based on weighted mortality of thrombotic and bleeding events was 2.6.

Conclusions: INR is inversely related to thrombotic events occurring outside of the hospital among patients supported with CF-LVADs. INR values <2.0 increase the rate of thrombotic events occurring outside of the hospital among patients supported with CF-LVADs.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860612PMC
May 2016

Serum Bicarbonate in Acute Heart Failure: Relationship to Treatment Strategies and Clinical Outcomes.

J Card Fail 2016 Sep 14;22(9):738-42. Epub 2016 Jan 14.

Duke Clinical Research Institute, Durham, North Carolina.

Background: Though commonly noted in clinical practice, it is unknown if decongestion in acute heart failure (AHF) results in increased serum bicarbonate.

Methods And Results: For 678 AHF patients in the DOSE-AHF, CARRESS-HF, and ROSE-AHF trials, we assessed change in bicarbonate (baseline to 72-96 hours) according to decongestion strategy, and the relationship between bicarbonate change and protocol-defined decongestion. Median baseline bicarbonate was 28 mEq/L. Patients with baseline bicarbonate ≥28 mEq/L had lower ejection fraction, worse renal function and higher N-terminal pro-B-type natriuretic peptide than those with baseline bicarbonate <28 mEq/L. There were no differences in bicarbonate change between treatment groups in DOSE-AHF or ROSE-AHF (all P > .1). In CARRESS-HF, bicarbonate increased with pharmacologic care but decreased with ultrafiltration (median +3.3 vs -0.9 mEq/L, respectively; P < .001). Bicarbonate change was not associated with successful decongestion (P > .2 for all trials).

Conclusions: In AHF, serum bicarbonate is most commonly elevated in patients with more severe heart failure. Despite being used in clinical practice as an indicator for decongestion, change in serum bicarbonate was not associated with significant decongestion.
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http://dx.doi.org/10.1016/j.cardfail.2016.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945480PMC
September 2016

Team-Based Care for Managing Noncardiac Conditions in Patients with Heart Failure.

Heart Fail Clin 2015 Jul;11(3):419-29

Division of Cardiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8086, St Louis, MO 63110, USA. Electronic address:

HF is a condition in which the prognosis and treatment are often defined by comorbidities, many of which are noncardiac. Knowledge of the interactions between HF and specific comorbidities is essential, yet to date the clinical trial evidence base for managing comorbidity in patients with HF is limited; further investigations are clearly needed. Perhaps the most pressing need is a focus on the overall multimorbidity state and its relationship to HF-a need that should be addressed in forthcoming trials. Successful navigation between HF and common interacting comorbidities requires coordination of care and team-based approaches that continually evolve to meet patient needs.
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http://dx.doi.org/10.1016/j.hfc.2015.03.006DOI Listing
July 2015

Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF).

Circ Heart Fail 2015 Jul 3;8(4):741-8. Epub 2015 Jun 3.

From the Division of Cardiology, Brigham and Women's Hospital, Boston, MA (A.L., L.W.S.); The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (A.L.); Duke Clinical Research Institute, Durham, NC (S.E.M., R.J.M., A.D.D., P.K., K.J.A., G.M.F., A.F.H.); Mayo Clinic, Rochester, MN (S.M.D., O.F.A., M.M.R.); Washington University School of Medicine, St Louis, MO (J.M.V.); and Hennepin County Medical Center, Minneapolis, MN (S.R.G., B.A.B.).

Background: Congestion is the most frequent cause for hospitalization in acute decompensated heart failure. Although decongestion is a major goal of acute therapy, it is unclear how the clinical components of congestion (eg, peripheral edema, orthopnea) contribute to outcomes after discharge or how well decongestion is maintained.

Methods And Results: A post hoc analysis was performed of 496 patients enrolled in the Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trials during hospitalization with acute decompensated heart failure and clinical congestion. A simple orthodema congestion score was generated based on symptoms of orthopnea (≥2 pillows=2 points, <2 pillows=0 points) and peripheral edema (trace=0 points, moderate=1 point, severe=2 points) at baseline, discharge, and 60-day follow-up. Orthodema scores were classified as absent (score of 0), low-grade (score of 1-2), and high-grade (score of 3-4), and the association with death, rehospitalization, or unscheduled medical visits through 60 days was assessed. At baseline, 65% of patients had high-grade orthodema and 35% had low-grade orthodema. At discharge, 52% patients were free from orthodema at discharge (score=0) and these patients had lower 60-day rates of death, rehospitalization, or unscheduled visits (50%) compared with those with low-grade or high-grade orthodema (52% and 68%, respectively; P=0.038). Of the patients without orthodema at discharge, 27% relapsed to low-grade orthodema and 38% to high-grade orthodema at 60-day follow-up.

Conclusions: Increased severity of congestion by a simple orthodema assessment is associated with increased morbidity and mortality. Despite intent to relieve congestion, current therapy often fails to relieve orthodema during hospitalization or to prevent recurrence after discharge.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00608491, NCT00577135.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.001957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512849PMC
July 2015

Treatment of secondary pulmonary hypertension with bosentan after left ventricular assist device implantation.

Cardiovasc Ther 2015 Apr;33(2):50-5

Division of Cardiology, Washington University School of Medicine, St. Louis, MO, USA.

Introduction: Secondary pulmonary hypertension (PH) and right ventricular dysfunction are common and associated with poor prognosis in HF patients with left ventricular assist devices (LVADs). The role of pulmonary vasodilator therapy for these patients is currently unclear.

Aims: We sought to evaluate the safety and clinical course of patients treated with bosentan, an endothelin receptor antagonist, after the implementation of a LVAD.

Results: Between 10/2008 and 5/2011, 50 consecutive patients with mean PAP >25 mmHg were treated with bosentan after LVAD implantation for a mean duration of 15.7 (±12.4) months. Ten patients discontinued the drug for possible side effects, including three for LFT abnormalities. Comparison of baseline to 6-month follow-up data revealed laboratory evidence for decongestion with a decrease in bilirubin (2.3-0.6, P < 0.0001) and an improvement in pulmonary hemodynamics with echocardiographically calculated mean PVR decreasing 1.4 woods units (3.93 ± 1.53 to 2.58 ± 1.05, P < 0.0001).

Conclusion: In this single-centered retrospective case series, we provide evidence that the tolerability of bosentan in LVAD-supported patients with secondary PH is comparable to prior experience in patients with heart failure.
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http://dx.doi.org/10.1111/1755-5922.12111DOI Listing
April 2015

Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure.

JACC Heart Fail 2015 Feb 31;3(2):97-107. Epub 2014 Oct 31.

Duke Clinical Research Institute, Durham, North Carolina.

Objectives: The purpose of this study was to assess the relationship between biomarkers of renin-angiotensin-aldosterone system (RAAS) activation and decongestion strategies, worsening renal function, and clinical outcomes.

Background: High-dose diuretic therapy in patients with acute heart failure (AHF) is thought to activate the RAAS; and alternative decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate this RAAS activation.

Methods: This study analyzed 427 AHF patients enrolled in the DOSE-AHF (Diuretic Optimization Strategies in Acute Heart Failure) and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) trials. We assessed the relationship between 2 markers of RAAS activation (plasma renin activity [PRA] and aldosterone) from baseline to 72 h and 96 h and decongestion strategy: high- versus low-dose and continuous infusion versus bolus furosemide for DOSE-AHF and UF versus stepped pharmacologic care for CARRESS-HF. We determined the relationships between RAAS biomarkers and 60-day outcomes.

Results: Patients with greater RAAS activation at baseline had lower blood pressures, lower serum sodium levels, and higher blood urea nitrogen (BUN) concentration. Continuous infusion furosemide and UF were associated with greater PRA increases (median: +1.66 vs. +0.66 ng/ml/h with continuous vs. bolus infusion, respectively, p = 0.021; +4.05 vs. +0.56 ng/ml/h with UF vs. stepped care, respectively, p = 0.014). There were no significant differences in RAAS biomarker changes with high- versus low-dose diuretic therapy (both: p > 0.5). Neither baseline log PRA nor log aldosterone was associated with increased death or HF hospitalization (hazard ratio [HR] for a doubling of 1.05; 95% confidence interval [CI]: 0.98 to 1.13; p = 0.18; and HR: 1.13; 95% CI: 0.99 to 1.28; p = 0.069, respectively). The change in RAAS biomarkers from baseline to 72 and 96 h was not associated with outcomes (both: p > 0.5).

Conclusions: High-dose loop diuretic therapy did not result in RAAS activation greater than that with low-dose diuretic therapy. UF resulted in greater PRA increase than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated with short-term outcomes in this cohort. (Determining Optimal Dose and Duration of Diuretic Treatment in People With Acute Heart Failure [DOSE-AHF]; NCT00577135; Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal Syndrome [CARRESS]; NCT00608491).
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http://dx.doi.org/10.1016/j.jchf.2014.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324057PMC
February 2015