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Aim: The EMPULSE (EMPagliflozin in patients hospitalised with acUte heart faiLure who have been StabilizEd) trial showed that, compared to placebo, the sodium–glucose cotransporter 2 inhibitor empagliflozin (10 mg/day) improved clinical outcomes of patients hospitalized for acute heart failure (HF). We investigated whether efficacy and safety of empagliflozin were consistent across the spectrum of left ventricular ejection fraction (LVEF). Methods and results: A total of 530 patients hospitalized for acute de novo or decompensated HF were included irrespective of LVEF. For the present analysis, patients were classified as HF with reduced (HFrEF, LVEF ≤40%), mildly reduced (HFmrEF, LVEF 41–49%) or preserved (HFpEF, LVEF ≥50%) ejection fraction at baseline. The primary endpoint was a hierarchical outcome of death, worsening HF events (HFE) and quality of life over 90 days, assessed by the win ratio. Secondary endpoints included individual components of the primary endpoint and safety. Out of 523 patients with baseline data, 354 (67.7%) had HFrEF, 54 (10.3%) had HFmrEF and 115 (22.0%) had HFpEF. The clinical benefit (hierarchical composite of all‐cause death, HFE and Kansas City Cardiomyopathy Questionnaire total symptom score) of empagliflozin at 90 days compared to placebo was consistent across LVEF categories (≤40%: win ratio 1.35 [95% confidence interval 1.04, 1.75]; 41–49%: win ratio 1.25 [0.66, 2.37)] and ≥50%: win ratio 1.40 [0.87, 2.23], pinteraction = 0.96) with a favourable safety profile. Results were consistent across individual components of the hierarchical primary endpoint. Conclusion: The clinical benefit of empagliflozin proved consistent across LVEF categories in the EMPULSE trial. These results support early in‐hospital initiation of empagliflozin regardless of LVEF. [ABSTRACT FROM AUTHOR]

Aims: In patients hospitalized for acute heart failure (AHF) empagliflozin produced greater clinical benefit than placebo. Many patients with AHF are treated with mineralocorticoid receptor antagonists (MRAs). The interplay between empagliflozin and MRAs in AHF is yet to be explored. This study aimed to evaluate the efficacy and safety of empagliflozin versus placebo according to MRA use at baseline in the EMPULSE trial (NCT04157751). Methods and results: In this analysis all comparisons were performed between empagliflozin and placebo, stratified by baseline MRA use. The primary outcome included all‐cause death, heart failure events, and a ≥5 point difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score at 90 days, assessed using the win ratio (WR). First heart failure hospitalization or cardiovascular death was a secondary outcome. From the 530 patients randomized, 276 (52%) were receiving MRAs at baseline. MRA users were younger, had lower ejection fraction, better renal function, and higher KCCQ scores. The primary outcome showed benefit of empagliflozin irrespective of baseline MRA use (WR 1.46, 95% confidence interval [CI] 1.08–1.97 and WR 1.27, 95% CI 0.93–1.73 in MRA users and non‐users, respectively; interaction p = 0.52). The effect of empagliflozin on first heart failure hospitalization or cardiovascular death was not modified by MRA use (hazard ratio [HR] 0.58, 95% CI 0.30–1.11 and HR 0.85, 95% CI 0.47–1.52 in MRA users and non‐users, respectively; interaction p = 0.39). Investigator‐reported and severe hyperkalaemia events were infrequent (<6%) irrespective of MRA use. Conclusions: In patients admitted for AHF, initiation of empagliflozin produced clinical benefit and was well tolerated irrespective of background MRA use. These findings support the early use of empagliflozin on top of MRA therapy in patients admitted for AHF. [ABSTRACT FROM AUTHOR]

Aims: The EMPULSE trial evaluated the clinical benefit of empagliflozin versus placebo using the stratified win ratio approach in 530 patients with acute heart failure (HF) after initial stabilization. We aim to elucidate how this method works and what it means, thereby giving guidance for use of the win ratio in future trials. Methods and results: The primary trial outcome is a hierarchical composite of death, number of HF events, time to first HF event, or a ≥5‐point difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score change at 90 days. In an overall (unstratified) analysis we show how comparison of all 265 x 265 patients pairs contribute to 'wins' for empagliflozin and placebo at all four levels of the hierarchy, leading to an unstratified win ratio of 1.38 (95% confidence interval [CI] 1.11–1.71; p = 0.0036). How such a win ratio should (and should not) be interpreted is then described. The more complex primary analysis using a stratified win ratio is then presented in detail leading to a very similar overall result. Win ratios for de novo acute HF and decompensated chronic HF patients were 1.29 and 1.39, respectively, their weighted combination yielding an overall stratified win ratio of 1.36 (95% CI 1.09–1.68) (p = 0.0054). Alternative ways of including HF events and KCCQ scores in the clinical hierarchy are presented, leading to recommendations for their use in future trials. Specifically, inclusion of both number of HF events and time‐to‐first HF event appears an unnecessary complication. Also, the use of a 5‐point margin for KCCQ score paired comparisons is not statistically necessary. Conclusions: The EMPULSE trial findings illustrate how deaths, clinical events and patient‐reported outcomes can be integrated into a win ratio analysis strategy that yields clinically meaningful findings of patient benefit. This has implications for future trial designs that recognize the clinical priorities of patient evaluation and the need for efficient progress towards approval of new treatments. [ABSTRACT FROM AUTHOR]

Aims Effective and safe decongestion remains a major goal for optimal management of patients with acute heart failure (AHF). The effects of the sodium–glucose cotransporter 2 inhibitor empagliflozin on decongestion-related endpoints in the EMPULSE trial (NCT0415775) were evaluated. Methods and results A total of 530 patients hospitalized for AHF were randomized 1:1 to either empagliflozin 10 mg once daily or placebo for 90 days. The outcomes investigated were: weight loss (WL), WL adjusted for mean daily loop diuretic dose (WL-adjusted), area under the curve of change from baseline in N-terminal pro-B-type natriuretic peptide levels, hemoconcentration, and clinical congestion score after 15, 30, and 90 days of treatment. Compared with placebo, patients treated with empagliflozin demonstrated significantly greater reductions in all studied markers of decongestion at all time-points, adjusted mean differences (95% confidence interval) at Days 15, 30, and 90 were: for WL −1.97 (−2.86, −1.08), −1.74 (−2.73, −0.74); −1.53 (−2.75, −0.31) kg; for WL-adjusted: −2.31 (−3.77, −0.85), −2.79 (−5.03, −0.54), −3.18 (−6.08, −0.28) kg/40 mg furosemide i.v. or equivalent; respectively (all P < 0.05). Greater WL at Day 15 (i.e. above the median WL in the entire population) was associated with significantly higher probability for clinical benefit at Day 90 (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline to 90 days) with the win ratio of 1.75 (95% confidence interval 1.37, 2.23; P < 0.0001). Conclusion Initiation of empagliflozin in patients hospitalized for AHF resulted in an early, effective and sustained decongestion which was associated with clinical benefit at Day 90. [ABSTRACT FROM AUTHOR]

Aim: The sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2 inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2 inhibitors on renal function during a hospital admission for acute heart failure remain largely unknown. Methods and results: Between 1 and 5 days after a hospitalization for acute heart failure, 530 patients with an eGFR >20 ml/min/1.73 m2 were randomized to 10 mg of empagliflozin or placebo and treated for 90 days. Renal function and electrolytes were measured at baseline, and after 15, 30 and 90 days. We evaluated the effect of empagliflozin on eGFR over time and the impact of baseline eGFR on the primary hierarchical outcome of death, worsening heart failure events and quality of life. Mean baseline eGFR was 52.4 ml/min/1.73 m2 in the empagliflozin group and 55.7 ml/min/1.73 m2 in the placebo group. Empagliflozin caused an initial decline in eGFR (−2 ml/min/1.73 m2 at day 15 compared to placebo). At day 90, eGFR was similar between empagliflozin and placebo. Investigator‐reported acute renal failure occurred in 7.7% of empagliflozin versus 12.1% of placebo patients. The overall clinical benefit (hierarchical composite of all‐cause death, heart failure events and quality of life) of empagliflozin was unaffected by baseline eGFR. Conclusion: In patients hospitalized for acute heart failure, empagliflozin caused an early modest decline in renal function which was no longer evident after 90 days. Acute renal events were similar in both groups. The clinical benefit of empagliflozin was consistent regardless of baseline renal function. [ABSTRACT FROM AUTHOR]

Aims: Improving the health status (symptoms, function, and quality of life) of patients with heart failure with reduced ejection fraction (HFrEF) is a primary treatment goal. Angiotensin receptor neprilysin inhibitors (ARNI) improve short‐term health status in clinical practice, but the sustainability of these improvements is unknown. Methods and results: In CHAMP‐HF, a multicentre observational study of outpatients with HFrEF, patients initiated on ARNI were propensity score matched 1:2 to patients not using ARNI with Cox regression modelling time to ARNI initiation, adjusted for sociodemographic and clinical variables, medical history, medications, and baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Repeated measures models for the overall KCCQ score and each domain compared the health status trajectories of patients initiated on ARNI vs. not. Among 3930 participants, 746 (19.0%) began ARNI, of whom 576 were matched to 1152 non‐ARNI patients. Prior to matching, participants initiated on ARNI were younger, non‐Hispanic, had lower EFs, more commonly had a history of ventricular arrhythmia, were less likely to be taking an ACEI/ARB, and more likely to be treated with beta‐blockers and mineralocorticoid receptor antagonists. There were no differences after matching. In the matched cohort, participants initiated on ARNI experienced improved health status by 3 months that persisted through 12 months [KCCQ Overall Summary Score (OSS) = 73.4 vs. 70.8; P < 0.001], with the largest benefit observed in the KCCQ Quality of Life domain (68.7 vs. 64.7; P < 0.001). Similar health status benefits were noted through 18 months (KCCQ‐OSS = 73.9 vs. 71.3; P < 0.001). A responder analysis showed that 12 patients would need to be initiated on ARNI for one to experience at least a large improvement (≥10 points) in health status benefit at 12 months. Conclusions: In outpatient practice, ARNI therapy was associated with improved health status by 3 months and continued to 18 months after initiating therapy. [ABSTRACT FROM AUTHOR]

Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular death or worsening heart failure (HF), and improve symptom burden, physical function and quality of life in patients with HF and reduced ejection fraction. The mechanisms of the HF benefits of SGLT2 inhibitors, however, remain unclear. In this substudy of the DEFINE‐HF trial, patients randomized to dapagliflozin or placebo had lung fluid volumes (LFVs) measured by remote dieletric sensing at baseline and after 12 weeks of therapy. A significantly greater proportion of dapagliflozin‐treated patients (as compared with placebo) experienced improvement in LFVs and fewer dapagliflozin‐treated patients had no change or deterioration in LFVs after 12 weeks of treatment. To our knowledge, this is the first study to suggest a direct effect of dapagliflozin (or any SGLT2 inhibitor) on more effective "decongestion", contributing in a meaningful way to the ongoing debate regarding the mechanisms of SGLT2 inhibitor HF benefits. [ABSTRACT FROM AUTHOR]

Background: Gene expression profiling (GEP) and donor‐derived cell‐free DNA (dd‐cfDNA) are useful in acute rejection (AR) surveillance in orthotopic heart transplant (OHT) patients. We report a single‐center experience of combined GEP and dd‐cfDNA testing for AR surveillance. Methods: GEP and dd‐cfDNA are tested together starting at 2 months post‐OHT. After 6 months, combined testing was obtained before scheduled endomyocardial biopsy (EMB), and EMB was canceled with a negative dd‐cfDNA. This approach was compared to using a GEP‐only approach, where EMB was canceled with a negative GEP. We evaluated for frequency of EMB cancellation with dd‐cfDNA usage. Results: A total of 153 OHT patients over a 13‐month period underwent 495 combined GEP/dd‐cfDNA tests. 82.2% of dd‐cfDNA tests were below threshold. Above threshold results identified high‐risk patients who developed AR. 378 combined tests ≥6 months post‐OHT resulted in cancellation of 83.9% EMBs as opposed to 71.2% with GEP surveillance alone. There were 2 acute cellular and 2 antibody‐mediated rejection episodes, and no significant AR ≥6 months. Conclusion: Routine dd‐cfDNA testing alongside GEP testing yielded a significant reduction in EMB volume by re‐classifying GEP (+) patients into a lower risk group, without reduction in AR detection. The addition of dd‐cfDNA identified patients at higher risk for AR. [ABSTRACT FROM AUTHOR]

Aims: Treatment with sodium–glucose co‐transporter 2 (SGLT2) inhibitors improves outcomes in patients with chronic heart failure (HF) with reduced ejection fraction. There is limited experience with the in‐hospital initiation of SGLT2 inhibitors in patients with acute HF (AHF) with or without diabetes. EMPULSE is designed to assess the clinical benefit and safety of the SGLT2 inhibitor empagliflozin compared with placebo in patients hospitalized with AHF. Methods: EMPULSE is a randomized, double‐blind, parallel‐group, placebo‐controlled multinational trial comparing the in‐hospital initiation of empagliflozin (10 mg once daily) with placebo. Approximately 500 patients admitted for AHF with dyspnoea, signs of fluid overload, and elevated natriuretic peptides will be randomized 1:1 stratified to HF status (de‐novo and decompensated chronic HF) to either empagliflozin or placebo at approximately 165 sites across North America, Europe and Asia. Patients will be enrolled regardless of ejection fraction and diabetes status and will be randomized during hospitalization and after stabilization (between 24 h and 5 days after admission), with treatment continued up to 90 days after initiation. The primary outcome is clinical benefit at 90 days, consisting of a composite of all‐cause death, HF events, and ≥5 point change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ‐TSS), assessed using a 'win‐ratio' approach. Secondary outcomes include assessments of safety, change in KCCQ‐TSS from baseline to 90 days and change in natriuretic peptides from baseline to 30 days. Conclusion: The EMPULSE trial will evaluate the clinical benefit and safety of empagliflozin in patients hospitalized for AHF. [ABSTRACT FROM AUTHOR]

Aims: The aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results: We leveraged data from CHAMP‐HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12 Overall Summary Scale (range from 0 to 100; ≥20‐point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient‐level characteristics as well as baseline KCCQ‐12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ‐12 score of 0–60 points had an OR = 0.86/5‐point higher score (CI 0.79, 0.93)], and those with a KCCQ‐12 score of 60–80 points had an OR = 0.61/5‐point higher score (0.45–0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05). Conclusions: We found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy—particularly in those with worse symptoms, function, and quality of life—and assessing treatment response are likely to be the best prospective strategy. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is emerging as one of the most common cardiovascular (CV) events in patients with type 2 diabetes (T2D), and the one associated with the worst prognosis. T2D and insulin resistance are strong predictors of incident HF, especially HF with preserved ejection fraction (HFpEF). Recent data suggest that even when all traditional risk factors for ASCVD are well controlled, patients with T2D continue to have a substantially greater risk of developing HF—indicating that traditional risk factor control is insufficient from a HF prevention standpoint, and highlighting the need for novel, more effective strategies for both prevention and treatment of heart failure in patients with T2D. Until recently, medications developed for glucose‐lowering had, at best, neutral effect on heart failure outcomes in patients with T2D, while several classes of T2D medications had little data in regards to HF risk, and others actually increased the risk of HF hospitalization. Sodium glucose cotransporter type 2 inhibitors (SGLT‐2i) have a novel and unique mechanism of action. By inhibiting sodium and glucose reabsorption in the proximal tubule, SGLT‐2i result in a number of downstream effects, including glucosuria, weight loss, osmotic diuresis and natriuresis, which should theoretically be beneficial in HF. Three CVOTs of various SGLT‐2i (EMPA‐REG OUTCOME, CANVAS and DECLARE‐TIMI 58) enrolled markedly different patient populations in terms of ASCVD risk, but have demonstrated robust and consistent benefits in reduction of hospitalization for HF. In a meta‐analysis of the three outcomes trials, SGLT‐2i significantly reduced the risk of cardiovascular death or hospitalization for HF by 23% and hospitalization for HF by 31%. Although the declines in HF hospitalization with SGLT‐2is are impressive, only a small proportion of patients with established HF were enrolled in these trials, and these benefits, therefore, represent primarily a HF prevention signal. Whether this prevention of HF benefit will translate to better outcomes for those patients with established HF (with or without diabetes), and whether it will extend across the spectrum of HF phenotypes (HFrEF and HFpEF) is yet to be determined, and is being actively investigated in several large ongoing trials. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular events (CVE) are among the most common and serious complications after implantation of continuous-flow left ventricular assist devices (CF-LVAD). We studied the incidence, subtypes, anatomical distribution, and pre- and post-implantation risk factors of CVEs as well as the effect of CVEs on outcomes after CF-LVAD implantation at our institution.Methods: Retrospective analysis of clinical and neuroimaging data of 372 patients with CF-LVAD between May 2005 and December 2013 using standard statistical methods.Results: CVEs occurred in 71 patients (19%), consisting of 35 ischemic (49%), 26 hemorrhagic (37%), and 10 ischemic+hemorrhagic (14%) events. History of coronary artery disease and female gender was associated with higher odds of ischemic CVE (OR 2.84 and 2.5, respectively), and diabetes mellitus was associated with higher odds of hemorrhagic CVE (OR 3.12). While we found a higher rate of ischemic CVEs in patients not taking any antithrombotic medications, no difference was found between patients with ischemic and hemorrhagic CVEs. Occurrence of CVEs was associated with increased mortality (HR 1.62). Heart transplantation was associated with improved survival (HR 0.02). In patients without heart transplantation, occurrence of CVE was associated with decreased survival.Conclusions: LVADs are associated with high rates of CVE, increased mortality, and lower rates of heart transplantation. Further investigations to identify the optimal primary and secondary stroke prevention measures in post-LVAD patients are warranted. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) has been defined classically as a condition in which the heart is unable to deliver sufficient oxygen to match the needs of the metabolizing tissues. Surprisingly, this definition has never been validated. The goal of this study was to determine the prevalence of elevated lactate levels in a cohort of patients with advanced heart failure.Methods and Results: We retrospectively analysed the arterio-venous oxygen difference (A-V O2 ), haemodynamics, and plasma lactate levels in stage D heart failure patients who were being evaluated for a left ventricular assist device (LVAD). We identified 359 patients with a right heart catheterization (RHC) performed prior to LVAD implantation. Plasma lactate was available for 96 patients. RHC showed that 93% of the patients had an A-V O2 above the upper limit of normal (>5 mL/100 mL). Among patients with measured lactate levels, the prevalence of elevated lactate (>2.1 mmol/L) was 25% (95% confidence interval 16.7-34.9). The A-V O2 was widened in all patients with elevated lactate, but plasma lactate did not correlate with A-V O2 (r = 0.02) and only 27% of patients with increased A-V O2 had elevated plasma lactate.Conclusions: Lactate levels were normal in ∼75% of the patients with advanced heart failure and a widened A-V O2 , suggesting that the cardiac output was sufficient to meet the metabolic needs of the peripheral metabolizing tissues. Given that ∼4% of heart failure patients are in NYHA class IV, these findings suggest that the classic definition of heart failure pertains to ∼1% of patients with HF. [ABSTRACT FROM AUTHOR]

Aims Heart failure ( HF) has been defined classically as a condition in which the heart is unable to deliver sufficient oxygen to match the needs of the metabolizing tissues. Surprisingly, this definition has never been validated. The goal of this study was to determine the prevalence of elevated lactate levels in a cohort of patients with advanced heart failure. Methods and results We retrospectively analysed the arterio-venous oxygen difference (A-V O2), haemodynamics, and plasma lactate levels in stage D heart failure patients who were being evaluated for a left ventricular assist device ( LVAD). We identified 359 patients with a right heart catheterization ( RHC) performed prior to LVAD implantation. Plasma lactate was available for 96 patients. RHC showed that 93% of the patients had an A-V O2 above the upper limit of normal (>5 mL/100 mL). Among patients with measured lactate levels, the prevalence of elevated lactate (>2.1 mmol/L) was 25% (95% confidence interval 16.7-34.9). The A-V O2 was widened in all patients with elevated lactate, but plasma lactate did not correlate with A-V O2 ( r = 0.02) and only 27% of patients with increased A-V O2 had elevated plasma lactate. Conclusions Lactate levels were normal in ∼75% of the patients with advanced heart failure and a widened A-V O2, suggesting that the cardiac output was sufficient to meet the metabolic needs of the peripheral metabolizing tissues. Given that ∼4% of heart failure patients are in NYHA class IV, these findings suggest that the classic definition of heart failure pertains to ∼1% of patients with HF. [ABSTRACT FROM AUTHOR]

Objective An inflammatory response after cardiac surgery is associated with worse clinical outcomes, but recent trials to attenuate it have been neutral. We evaluated the association between systemic inflammatory response syndrome (SIRS) and mortality after transcatheter (TAVR) and surgical aortic valve replacement (SAVR) for aortic stenosis (AS) and evaluated whether diabetes influenced this relationship. Methods Patients (n=747) with severe AS treated with TAVR (n=264) or SAVR (n=483) between January 2008 and December 2013 were included and 37% had diabetes mellitus. SIRS was defined by four criteria 12-48 h after aortic valve replacement (AVR): (1) white blood cell count <4 or >12; (2) heart rate >90; (3) temperature <36 or >38°C; or (4) respiratory rate >20. Severe SIRS was defined as meeting all four criteria. The primary endpoint was 6-month all-cause mortality (60 deaths occurred by 6 months). Inverse probability weighting (IPW) was performed on 44 baseline and procedural variables to minimise confounding. Results Severe SIRS developed in 6% of TAVR patients and 11% of SAVR patients (p=0.02). Six-month mortality tended to be higher in those with severe SIRS (15.5%) versus those without (7.4%) (p=0.07). After adjustment, severe SIRS was associated with higher 6-month mortality (IPW adjusted HR 2.77, 95% CI 2.04 to 3.76, p<0.001). Moreover, severe SIRS was more strongly associated with increased mortality in diabetic (IPW adjusted HR 4.12, 95% CI 2.69 to 6.31, p<0.001) than non-diabetic patients (IPW adjusted HR 1.74, 95% CI 1.10 to 2.73, p=0.02) (interaction p=0.007). The adverse effect of severe SIRS on mortality was similar after TAVR and SAVR. Conclusions Severe SIRS was associated with a higher mortality after SAVR or TAVR. It occurred more commonly after SAVR and had a greater effect on mortality in diabetic patients. These findings may have implications for treatment decisions in patients with AS, may help explain differences in outcomes between different AVR approaches and identify diabetic patients as a high-risk subgroup to target in clinical trials with therapies to attenuate SIRS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]