bluuebunny/crossref_metadata_2025_split huggingface dataset:
Right ventricular myocardial work in patients with HFrEF
Authors: Butcher S.C , Fortuni F , Montero J.M , Ajmone Marsan N , Delgado V , Bax J.J 
Published: November 2020

Abstract

Background
Right ventricular myocardial work (RVMW) is a novel method of non-invasively quantifying right ventricular (RV) systolic function. Through the use of speckle tracking echocardiography-derived RV pressure-strain loops, RVMW provides a quantitative evaluation of afterload-dependent RV systolic function.

Purpose
To investigate RVMW in patients with heart failure and reduced ejection fraction (HFrEF) and compare to that of patients without cardiovascular disease (CVD) and a structurally and functionally normal heart.

Methods
Noninvasive analysis of RVMW was performed in 23 HFrEF patients and 23 patients without cardiovascular or structural heart disease. The novel indices of RV global constructive work (RVGCW), RV global work index (RVGWI), RV wasted work (RVWW) and RV global work efficiency (RVGWE) were analysed utilizing proprietary software originally developed for the assessment of left ventricular myocardial work by speckle tracking echocardiography. Parameters of RVMW were then compared between the two patient groups.

Results
The HFrEF group had lower left ventricular (LV) ejection fraction (18.7% [±6.7] vs 60.1% [±4.6], p&lt;0.0001), LV global longitudinal strain (−3.6% [±1.6] vs −20.4% [±2.1), p&lt;0.0001) and RV global longitudinal strain (−10.0% [±4.2] vs −22.0% [±3.1], p&lt;0.0001) when compared to those with no CVD. Estimated pulmonary artery systolic pressure (42.5mm Hg [±12] vs 22.5mm Hg [±3.7], p&lt;0.0001) and estimated right atrial pressure (8mm Hg (5 to 15) vs 5mm Hg (5 to 5), p&lt;0.0001) were significantly higher in the HFrEF group. RVGWI (259.7mmHg% [±135.0] vs 385.3mmHg% [±103.1], p=0.001), RVGWW (83.7mmHg% [±58.6] vs 14.5mmHg% [8.5 to 20.5], p&lt;0.0001) and RVGWE (77.2% [11.4] vs 95.5% [93.5 to 97], p&lt;0.0001) were significantly lower in the HFrEF group when compared to those without CVD. There was no statistically significant difference in RVGCW between the two groups (353.5mmHg% [±118.4] vs 417.2 [±102.1], p=0.057).

Conclusion
The novel parameters of RVGWI, RVGWW and RVGWE were significantly reduced in patients with HFrEF when compared to those without CVD. Further exploration of the clinical role and prognostic value of these afterload dependent parameters of RV systolic function is warranted.

Funding Acknowledgement
Type of funding source: None
Short term effect of Selexipag in comparison to parenteral prostacyclin analogues in pulmonary arterial hypertension patients started on double-combination therapy with ERA and PDE-5 inhibitors
Authors: Dardi F , Zuffa E , Palazzini M , Pasca F , De Lorenzis A , Guarino D , Magnani I , Ballerini A , Rotunno M , Manes A , Galie N 
Published: November 2020

Abstract

Background
The event-driven, phase 3, randomized, double-blind, placebo-controlled GRIPHON trial demonstrated that Selexipag reduces the risk of a composite end point of death or morbidity events in patients with pulmonary arterial hypertension (PAH). Despite the advantage of a per os formulation, its efficacy in comparison to parenteral prostacyclin analogues in patients already on oral double-combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5-I) is not known.

Purpose
The aim of this study was to compare the effects of Selexipag (S) vs subcutaneous Treprostinil (T) vs intravenous Epoprostenol (E) in PAH patients initially started with double-combination therapy with ERA and PDE5-I.

Methods
We enrolled patients on double combination therapy with ERA + PDE5-I starting S, T or E. Drugs were gradually uptitrated to the maximum tolerated/approved dose. All patients were systematically assessed with WHO-functional class (FC), six minute walk test (6MWT) and right heart catheterization before treatment and 3 months after reaching a stable dose of the drug. Baseline characteristics and changes in 6MWT and haemodynamic parameters were analyzed using Wilcoxon signed-rank test and compared between the 3 drugs with Kruskal-Wallis test.

Results
One hundred and seventy-one patients with PAH were enrolled. Results are shown in the Table. Patients with a complete re-evaluation were 61% of S, 85% of T, 79% with E.

Conclusions
S was prescribed to the oldest and least severe PAH patients. E was prescribed to the youngest and most severe PAH patients and led to the strongest improvement of exercise capacity and haemodynamic profile. T has intermediate characteristics.
Table 1

Funding Acknowledgement
Type of funding source: None
Time trends of pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension
Authors: Hobohm L , Keller K , Munzel T , Konstantinides S.V , Lankeit M 
Published: November 2020

Abstract

Background and purpose
Chronic thromboembolic pulmonary hypertension (CTEPH) is considered as a rare but severe complication after acute pulmonary embolism (PE) and is potentially curable by pulmonary endarterectomy (PEA). We aimed to evaluate, over an 11-year period, time trends of in-hospital outcomes of PEA in CTEPH patients in the German nationwide inpatient sample.

Methods and results
We analyzed data on the characteristics, comorbidities, treatments and in-hospital outcomes for all CTEPH patients treated with PEA in Germany between 2006 and 2016. Overall, 1,398 inpatients were included. The annual number of PEA increased from 67 in 2006 to 194 in 2016 (β 0.69 [95% CI 0.51 to 0.86]; p&lt;0.001) in parallel with a significant decrease of in-hospital mortality (10.9% in 2008 to 1.5% in 2016; β −1.85 [95% CI: −2.46 to −1.24]; p&lt;0.001). Patients' characteristics shifted slightly towards older age and higher prevalence of chronic renal insufficiency and obesity over time, whereas duration of hospital stay decreased over time. Independent predictors of in-hospital mortality were age and right heart failure, and in-hospital complications such as ischemic stroke and bleeding events.

Conclusions
The number of CTEPH patients treated with PEA increased markedly in Germany between 2006 and 2016, in parallel with a decrease of in-hospital mortality. Our findings may suggest that the perioperative management of PEA and the general patients' selection have improved over time and might draw more attention to predictors for in-hospital mortality for CTEPH patients hospitalized for PEA.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1503).
Quality of life 3 and 12 months after acute pulmonary embolism: analysis of 617 patients from the prospective multicentre FOCUS study
Authors: Valerio L , Barco S , Jankowski M , Rosenkranz S , Lankeit M , Held M , Gerhardt F , Bruch L , Ewert R , Faehling M , Freise J , Ardeschir Ghofrani H , Gruenig E , Halank M , Konstantinides S.V 
Published: November 2020

Abstract

Background
Few data are available on the long-term course and predictors of quality of life (QoL) after acute pulmonary embolism (PE).

Aims
To evaluate the kinetics and determinants of QoL at 3 and 12 months after acute PE.

Methods
The Follow-Up after acute pulmonary embolism (FOCUS) study prospectively followed consecutive adult patients with objectively diagnosed PE. For this analysis, we considered patients who completed the Pulmonary Embolism QoL (PEmb-QoL) Questionnaire at two predefined visits 3 and 12 months after PE. PEmb-QoL, studied as total score and in its six dimensions, ranges from 0% (best QoL) to 100% (worst QoL). We studied the course of PEmb-QoL and the impact of baseline characteristics using multivariable linear regression.

Results
In 617 included patients (44% women, median age 62 years), overall QoL improved from 3 to 12 months, with a decrease of the mean PEmb-QoL score from 25.3% to 21.5% (p-value &lt;0.001). Intra-individual correlation between PEmb-QoL score at 3 and 12 months was high; Figure A. The improvement was consistent across all PEmb-QoL dimensions; Figure B. Female sex, cardiopulmonary diseases, and higher body mass index were the main factors associated with a worse QoL; Table. Age and smoking affected QoL only at 12 months. The improvement in QoL was faster in patients without cardiopulmonary diseases (−4.2%; 95% CI: −5.2% to −3.1%), without previous VTE (−4.3%; −5.5% to −3.2%), and in non-smokers (−4.2%; −5.3% to −3.1%).

Conclusions
In a large cohort of patients with pulmonary embolism, we quantified the improvement of QoL between 3 and 12 months after diagnosis. We identified factors independently associated with lower QoL and slower recovery of QoL that may reflect special patient needs. These estimates may facilitate the planning and interpretation of clinical trials with QoL as a study outcome.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): University Medical Center of the Johannes Gutenberg University, Mainz, Germany; German Federal Ministry of Education and Research
Functional outcomes and quality of life during long-term follow-up after acute pulmonary embolism: analysis of the prospective multicentre FOCUS study
Authors: Barco S , Valerio L , Jankowski M , Hoeper M.M , Klok F.A , Leuchte H.H , Mayer E , Meyer F.J , Neurohr C , Opitz C , Seyfarth H.J , Trudzinski F , Wachter R , Wilkens H , Wild P.S 
Published: November 2020

Abstract

Background
It is unclear to which extent persistence of symptoms and/or residual haemodynamic impairment clinical course of pulmonary embolism are associated with worse quality of life (QoL).

Aims
To study the correlation between symptoms and haemodynamic impairment with QoL during the first year after acute pulmonary embolism (PE).

Methods
The Follow-Up after acute pulmonary embolism (FOCUS) study prospectively enrolled and followed consecutive adult patients diagnosed with acute symptomatic objectively diagnosed PE. In the present analysis, we considered patients who completed the Pulmonary Embolism QoL (PEmb-QoL) Questionnaire at predefined visits 3 and 12 months after acute PE. The PEmb-QoL score ranges from 0% (best QoL) to 100% (worst QoL). We evaluated at these two time points the correlation between persisting symptoms (group: symptoms), elevation of natriuretic peptides or residual right ventricular dysfunction (group: RVD), or their combination (group: symptoms + RVD) and QoL.

Results
A total of 617 patients were included; their median age was 62 years, 44% were women; 8% had active cancer, and 21% previous venous thromboembolism. At 3 months, patients with neither symptoms nor RVD (n=302) had the highest quality of life (median score 18%, 25th–75th percentile: 8%–34%), followed by those without symptoms but with RVD (n=255; median score 19%, 25th–75th percentile: 7%–34%), and by those with symptoms only (n=131; median PEmb-QoL 31%, 25th–75th percentile: 18%–49%). Patients with both symptoms and RVD (n=170) had the worst quality of life (median score 38%, 25th–75th percentile: 19%–53%); Figure 1A. At 12 months, we found an overall improvement of PEmb-QoL score. The degree of this QoL improvement varied across groups, being largest for patients who recovered from having symptoms + RVD at 3 months to normalization of at least one at 12 months. The change in QoL from 3 to 12 months was smaller both in patients who had neither symptoms nor RVD and in patients who had no recovery in either symptoms or RVD; Figure 1B.

Conclusions
Persistent symptoms after PE, especially in patients with elevated biomarkers or residual echocardiographic dysfunction, were the main drivers of QoL at 3 months as well as of the course of QoL over time.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): University Medical Center of the Johannes Gutenberg University, Mainz, Germany; German Federal Ministry of Education and Research
Combined pre- and post-capillary pulmonary hypertension defined by new criteria is worse prognosis group in patients with heart failure
Authors: Ibe T , Wada H , Sakakura K , Ugata Y , Yamamoto K , Seguchi M , Taniguchi Y , Mitsuhashi T , Momomura S , Fujita H 
Published: November 2020

Abstract

Background
The 6th World Symposium on Pulmonary Hypertension suggested major revision about definition of pulmonary hypertension (PH) as mean pulmonary artery pressure (mPAP) &gt;20 mmHg. The definitions of two subsets of PH due to left heart disease (PH-LHD) also revised. The aim of this study was to investigate clinical characteristics and outcomes of subsets of PH-LHD defined by new criteria.

Methods
We analyzed 701 patients admitted for symptomatic heart failure (NYHA ≥2) and underwent right heart catheterization at compensated stage between 2007 and 2016. These patients were divided into 4 groups as follows: (i) Isolated post-capillary PH (Ipc-PH); mPAP &gt;20 mmHg and pulmonary artery wedge pressure (PAWP) &gt;15 mmHg and pulmonary vascular resistance (PVR) &lt;3 WU, (ii) Combined pre- and post-capillary PH (Cpc-PH); mPAP &gt;20 mmHg and PAWP &gt;15 mmHg and PVR ≥3 WU, (iii) pre-capillary PH; mPAP &gt;20 mmHg and PAWP ≤15 mmHg, (iv) no PH; mPAP ≤20 mmHg. Kaplan-Meier curves were applied to investigate whether each groups predict heart failure (HF) death or HF readmission.

Results
The study patients were divided into Ipc-PH (n=268), Cpc-PH (n=54), Pre-capillary PH (n=112), and no PH (n=267). Cpc-PH was significantly associated with HF death or HF readmission as compared to other groups (Figure).

Conclusions
Cpc-PH defined by new criteria was significantly associated with poor long-term clinical outcomes, which suggests new criteria of two subsets of PH-LHD could be strict risk stratification for symptomatic heart failure.
Figure1. Kaplan-Meier curves.

Funding Acknowledgement
Type of funding source: None
Long-term outcomes in newly diagnosed pulmonary arterial hypertension (PAH) patients receiving initial triple oral combination therapy: insights from the randomised controlled TRITON study
Authors: Galie N , Sitbon O , Doelberg M , Gibbs J.S.R , Hoeper M.M , Martin N , Mathai S.C , McLaughlin V , Perchenet L , Simonneau G , Chin K 
Published: November 2020

Abstract

Introduction
Long-term outcomes are important in PAH.

Purpose
To evaluate the long-term efficacy and safety of initial triple oral therapy with selexipag, macitentan and tadalafil vs initial double oral therapy with macitentan and tadalafil in PAH.

Methods
TRITON, a multicentre, double-blind, placebo-controlled, phase 3b study, randomised 1:1 newly diagnosed, treatment-naïve PAH patients to initial triple vs double therapy. Macitentan and tadalafil were initiated at randomisation and selexipag/placebo at day 15 (uptitrated to wk 12). Efficacy and safety were assessed in a blinded manner until the last patient randomised completed wk 26 (end of observation period). Pulmonary vascular resistance (PVR; primary endpoint) and 6-minute walk distance (6MWD) were assessed at wk 26. Other secondary endpoints included time to first disease progression event (centrally adjudicated) to end of observation period +7 days. Time to all-cause mortality up to end of observation period was analysed post-hoc.

Results
247 patients were randomised to initial triple (n=123) or initial double therapy (n=124); baseline characteristics were balanced between groups. Median follow-up was 77.6 (initial triple) and 75.8 wks (initial double). Initial triple and initial double therapy improved PVR (by 54% and 52%) and 6MWD (by 55 and 56 m), with no difference between groups. A 41% reduction in the risk of first disease progression event driven by PAH-related hospitalisation and all-cause death was observed with initial triple vs initial double therapy (hazard ratio 0.59, 95% CI 0.32–1.09, p=0.087; Figure). Two patients died in the initial triple vs 9 in the initial double therapy group (hazard ratio 0.23, 95% CI 0.05–1.04). Adverse events were consistent with the known safety profiles of the study drugs.

Conclusions
In TRITON, assessments at wk 26 showed marked improvements in both treatment arms, with no difference between groups. Exploratory analysis indicated a signal for improved long-term outcome with initial triple versus initial double therapy.

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): Actelion Pharmaceuticals Ltd.
Prognostic impact of neurohormonal inhibition in pulmonary arterial hypertension
Authors: Scagliola R , Rota I , Cheli M , Brunelli C , Balbi M , Ameri P 
Published: November 2020

Abstract

Background
Experimental evidence points towards a hyperactivity of the sympathetic nervous system and renin-angiotensin-aldosterone system in the pathobiology of pulmonary arterial hypertension (PAH), raising the hypothesis that blockade of neurohormonal axis may have favorable effects in this context.

Purpose
To assess the use and prognostic impact of neurohormonal inhibitors (NEUi) in a single centre cohort of subjects with PAH.

Methods
We analysed retrospectively collected data from our register of right heart catheterizations (RHC) performed consecutively from January 1st 2005 until October 31st 2018. We selected patients with PAH and complete information about demographics, biochemical data and drug therapy at the time of RHC. Patients on beta-blocker, angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or mineralocorticoid receptor antagonist (MRA) at the time of RHC were classified as NEUi users. Comparisons between NEUi recipients and non-recipients were drawn by chi-square or t-test, as appropriate. Death from any cause was assessed by Kaplan-Meier analysis.

Results
Complete data were available for 57 PAH patients. Mean pulmonary artery pressure, pulmonary artery wedge pressure, diastolic pressure gradient, pulmonary vascular resistance and cardiac index were 45.0±14.9 mmHg, 10.9±3.5 mmHg, 16.0±10.2 mmHg, 8.8±5.1 Wood units and 2.5±0.8 l/min/m2 respectively. Twenty-seven subjects (47.4%) were taking at least one NEUi when RHC was performed: 12 (21.1%) were on beta-blocker, 15 (26.3%) on ACEi/ARB and 6 (10.5%) on MRA. NEUi users were significantly older (67.6±11.9 vs. 58.3±15.2 years, p=0.039), had a higher body mass index (25.9±4.4 vs. 23.6±3.5, p=0.029), more frequently systemic arterial hypertension (74.1% vs. 40.0%, p=0.020), smoking habit (51.9% vs. 20.0%, p=0.025) and lower estimated glomerular filtration rate (58.7±22.7 vs. 73.7±24.7 ml/min/1.73 m2, p=0.022) than non-users. Moreover, 5 NEUi users (18.5%), but no NEUi non-users, had a history of coronary artery disease. Hemodynamic parameters were similar in NEUi recipients and non-recipients (p=NS). Seven patients (25.9%) died in the NEUi users group vs. 17 (56.7%) in the non-users one (p=0.038). Kaplan-Meier analysis confirmed that subjects not taking NEUi were more likely to die over the course of follow-up (Log-Rank p=0.020) (Figure 1).

Conclusions
Our data identify a subset of atypical PAH patients, with pre-capillary pulmonary hypertension and a comorbidity profile for left heart disease (LHD), in whom NEUi have shown to improve survival. A prognostic benefit of NEUi, due to their effects on cardiovascular comorbidities in this kind of patients, has been speculated. Future prospective studies are needed to identify the most appropriate treatment strategies for atypical forms of PAH, with subtle and probably covert LHD.
Figure 1. Kaplan-Meier survival curves

Funding Acknowledgement
Type of funding source: None
Identification of predictors of response to initial oral combination therapy in WHO-functional class II or III PAH patients: a post-hoc analysis of the AMBITION study
Authors: Hatano M , Abe K , Takahashi T , Tunmer G , Koike G 
Published: November 2020

Abstract

Background
AMBITION Study (NCT01178073) provided the first long-term clinical evidence for initial combination therapy with ambrisentan and tadalafil (COMB) compared with monotherapy of either agent (MONO), and the results contributed to the ESC/ERS guidelines recommending initial combination therapy in PAH patients with low and intermediate risk. However, predictors of response to initial oral combination therapy to identify PAH patients who benefit most from it have not been assessed.

Purpose
To identify potential predictors of response to initial combination therapy with ambrisentan and tadalafil (COMB) in PAH patients with WHO-FC II or III in the AMBITION study.

Methods
We examined 302 COMB patients from the modified intention to treat (mITT) population enrolled in the AMBITION study (n=605). The mITT population includes PAH patients with risk factors related to heart failure with preserved ejection fraction (Ex-PAS) who were excluded from the primary analysis set (PAS). A responder (i.e. event-free subject) was defined as not having a clinical failure event. Univariate and multivariate analyses were performed to identify the factors associated with responders. Multivariate logistic regression analysis was used to determine independent risk for each factor that showed a significant difference between cohorts by interactive backward selection. Odds ratio (OR), 95% confidence intervals (CIs) and p-values are presented.

Results
Univariate analysis showed that responders tended to be lower age, female, typical PAH (i.e. PAS), absence of coronary artery disease, non-use of oxygen therapy, and have better baseline parameters (i.e., lower NT-proBNP, longer 6-minute walk distance, low Borg index, high SaO2, WHO-FC II). A multivariate logistic regression analysis showed that female gender (OR=2.669, 95% CI: 1.291–5.518, P=0.0081), use of aldosterone antagonist diuretics (OR=2.535, 95% CI: 1.027–6.257, P=0.0436), lower log NT-proBNP (OR=0.704, 95% CI: 0.524–0.944, P=0.0190), and longer 6-minute walk distance (OR=1.006, 95% CI: 1.002–1.010, P=0.0039) were independent predictors of response to initial combination therapy.

Conclusion
These findings suggest that initial combination therapy with ambrisentan and tadalafil is beneficial, especially in less severe typical PAH patients. It also demonstrates that there is a potential contributing factor (i.e. use of aldosterone antagonist diuretics) which is not listed in the risk assessment table of the ESC/ERS guidelines.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): AMBITION study was funded by GlaxoSmithKline (GSK; study number 112565; trial registration number: NCT01178073) and Gilead Sciences, Inc. This analysis was funded by both companies.