bluuebunny/crossref_metadata_2025_split huggingface dataset:
5943Mechanistic insights of papillary muscle dyssynchrony mediated function mitral regurgitation and modulation by cardiac resynchronization
Authors: Spinka G , Bartko P , Arfsten H , Heitzinger G , Pavo N , Strunk G , Gwechenberger M , Hengstenberg C , Binder T , Huelsmann M , Goliasch G 
Published: October 2019

Abstract

Abstract

Background
Mechanistic features of functional mitral regurgitation (FMR) include papillary muscle displacement due to left ventricular remodeling. Intraventricular conduction delay might further augment this condition by introducing interpapillary muscle dyssynchrony.

Objectives
To define this mechanism as a major contributing factor in FMR and prove the reversibility of FMR by interpapillary muscle resynchronization.

Methods
We enrolled 269 chronic HFrEF patients with conduction delay and comprehensively assessed dyssynchrony by complementary echocardiographic techniques. Opposing wall delay, calculated by speckle tracking, was determined as the time difference between peak longitudinal strain of the mid-anterior and inferior wall from a 2-chamber view. Furthermore, opposing wall delay was assessed as the time difference between peak strain values from tissue Doppler velocity-coded data of the mid-inferior septal and mid-lateral wall segments.

Results
Patients with severe FMR had markedly increased interpapillary longitudinal dyssynchrony (160ms [IQR 120–200]) compared to those with moderate (70ms [IQR 40–110]), no, or mild FMR (60ms [IQR 30–100]; P<0.001). Increased interpapillary muscle dyssynchrony was correlated with effective regurgitant orifice area (P<0.001; Figure A), regurgitant volume (P<0.001, Figure B) and vena contracta width (P<0.001, Figure C). Restoration of longitudinal papillary muscle synchronicity by cardiac resynchronization therapy (CRT) was correlated with FMR regression, as reflected by the reduction in regurgitant volume (P<0.001) and vena contracta width (P<0.001). Conversely, the improvement of FMR was associated with improved interpapillary radial (P=0.006) and longitudinal (P<0.001) dyssynchrony. The improvement of dyssynchrony-mediated FMR signified a better prognosis compared to no improvement in FMR during the 8-year follow-up period even after comprehensive adjustment by a bootstrap-selected confounder model (adj. HR of 0.41; 95% CI 0.18–0.91; P=0.028; Figure D). The results remained virtually unchanged after adjustment for left bundle branch block.
Figure 1. Dyssynchrony-FMR-CRT

Conclusion
Intraventricular dyssynchrony introduces unequal contraction by papillary muscle bearing walls, which has an adverse effect on FMR. CRT can effectively restore interpapillary balance and thus create a less tented leaflet configuration, resulting in a clinically meaningful reduction of FMR. The restoration of papillary muscle synchronicity in dyssynchrony-mediated FMR translates into a significantly better prognosis.
5944Mortality advantage of mitraclip in patients with heart failure and mitral regurgitation: an updated meta-analysis
Authors: Ashukem M , Bhavi Pandya M D , Verma Diva Ratyan M D 
Published: October 2019

Abstract

Background
In patients with symptomatic mitral regurgitation who are high risk for surgery, transcatheter mitral-valve repair has been shown to be safe and improve clinical outcomes. However, its impact on survival has shown conflicting results in recent trials.

Methods
PubMed, EMBASE and Google Scholar databases were queried for all trials about MitraClip compared with optimal medical therapy

Results
This meta-analysis of 9 trials including 3199 patients, found that patients treated with
MitraClip compared to optimal medical therapy had similar 30-day mortality (OR 0.64, 95% CI 0.32- 1.28) while at 12-months MitraClip was associated with significantly lower all-cause mortality (OR 0.46, 95% CI 0.33- 0.65). Absolute risk reduction was 13.9% and number needed to treat to save 1 life at 12 months was 7.2.
Figure 1

Conclusions
In this meta-analysis, transcatheter mitral valve repair with MitraClip was associated with significantly lower mortality at 12 months of follow up
5963Automated quantification of epicardial adipose tissue from non-contrast CT on multi-center and multi-vendor data using deep learning
Authors: Commandeur F , Goeller M , Razipour A , Cadet S , Hell M M , Kwiecinski J , Chen X , Chang H J , Marwan M , Achenbach S , Berman D S , Slomka P J , Tamarappoo B K , Dey D 
Published: October 2019

Abstract

Background
Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the coronary arteries, has been shown to promote the development of atherosclerosis in underlying coronary vasculature.

Purpose
We evaluate the performance of deep learning (DL), a sub-group of machine learning algorithms, for robust and fully automated quantification of EAT on multi-center cardiac CT data.

Methods
In this study, 850 non-contrast calcium scoring CT scans, from multiple cohorts, scanners and protocols, with manual measurements of EAT from 3 different readers were considered. The DL method was based on a convolutional neural network trained to reproduce the expert measurement. DL global performance was first assessed using all the scans, and then compared to inter-observer variability on a subset of 141 scans. Finally, automated EAT progression was compared to manual measurement using baseline and follow-up serial scans available for 70 subjects. The proposed model was validated using 10-fold cross validation.

Results
Automated quantification was performed in 1.57±0.49 seconds compared to 15 minutes for manual measurement. DL provided high agreement with expert manual quantification for all scans (R=0.974, p<0.001) with no significant bias (0.53 cm3, p=0.13). EAT volume was higher in patients with hypertension (+18.02 cm3, p<0.001, N=442), with diabetes (+18.33 cm3, p<0.001, N=75) and with hypercholesterolemia (+7.33 cm3, p=0.039, N=508). Manual EAT volumes measured by two experienced readers on 141 scans were highly correlated (R=0.984, p<0.001) but presented a significant difference of 4.35 cm3 (p<0.001). On these 141 scans, DL quantifications were highly correlated to both experts' measurements (R=0.973, p<0.001; R=0.979, p<0.001) with significant and non-significant bias for readers 1 and 2 (5.19 cm3, p<0.001; 0.84 cm3, p=0.26), respectively. In 70 subjects, EAT progression quantified by DL correlated strongly with EAT progression measured by the expert reader (R=0.905, p<0.001) with no significant bias (0.64 cm3, p=0.43), and was related to increased non-calcified plaque burden quantified from coronary CT angiography (5.7% vs 1.8%, p=0.026).
Automated vs. manual EAT volume

Conclusion
Deep learning allows rapid, robust and fully automated quantification of EAT from calcium scoring CT. It performs as an expert reader and can be implemented for routine cardiovascular risk assessment.

Acknowledgement/Funding
1R01HL133616/01EX1012B/Adelson Medical Research Foundation
5970Morbidity and mortality in patients precluded for transvenous pacemaker implantation: experience with the Micra transcatheter pacemaker
Authors: Garg A , Koneru J N , Fagan D , Stromberg K , El-Chami M F , Piccini J P , Roberts P R , Soejima K , Cheng A , Ellenbogen K A 
Published: October 2019

Abstract

Background
The Micra transcatheter pacemaker has proven to be a safe and effective alternative to transvenous pacemakers (TVPs). However, the safety profile after Micra implantation in patients deemed poor candidates for TVPs is poorly understood.

Purpose
To evaluate the safety and all-cause mortality outcomes in Micra recipients stratified by whether or not they were precluded for therapy with TVP.

Methods
Micra patients from the Micra Transcatheter Pacing (IDE) Study, Continued Access (CA) study, and Post-Approval Registry (PAR) were divided into groups based upon whether or not the implanting physician considered the patient to be precluded from receiving a transvenous pacing system. All-cause mortality was compared between the Micra patient groups and patients receiving a single-chamber transvenous pacing system (SC-TVP) since 2010 from the Medtronic product surveillance registry using univariate and multivariate Cox models.

Results
Among 2,819 patients who underwent a Micra implant attempt, the overall major complication rate through 24 months was 3.5%. In these patients, 548 were deemed precluded from TVP implantation. Prior device infection or bacteremia (38.9%), venous access issues (36.1%) and thrombosis (10.2%) were amongst the most common causes of preclusion for TVP implantation. These patients were younger (71.7 vs. 76.7 years), more frequently on hemodialysis (26.3% vs. 2.5%), and more often had a prior CIED implanted (38.4% vs. 4.4%) than non-precluded patients. Over an average follow-up of 13.5±11.1 months, all-cause mortality was significantly higher in precluded Micra patients compared with SC-TVP patients (HR: 2.16, 95% CI: 1.54–3.2, P<0.001) (Figure 1). However, there was no significant difference in all-cause mortality when comparing non-precluded Micra patients and SC-TVP patients (HR: 1.12, 95% CI: 0.86–1.44, P=0.401). Acute all-cause death (within 1 month) among Micra patients was 2.74% and 1.32% in the precluded and non-precluded TVP groups, respectively. The procedure-related death rate was 0.55% for the TVP precluded group and 0.13% for the not precluded group (P=0.092). The major complication rate through 24-months was similar between the two Micra groups (4.0% vs 3.4%, P=0.630).
All-cause mortality for Micra and SC-TVP

Conclusion
The overall safety profile of Micra remains is in line with previously reported data. All-cause mortality risk (both acute and long term) appears to be higher in patients who were precluded from receiving TVP.

Acknowledgement/Funding
Supported by Medtronic
6089Increased vascular endothelial growth factor signalling following loss of endothelial endoglin leads to peripheral arteriovenous shunting and high output heart failure
Authors: Tual-Chalot S , Garcia-Collado M , Redgrave R E , Singh E , Davison B , Luli S , Jin Y , Wang Y , Lawrie A , Jakobsson L , Arthur H M 
Published: October 2019

Abstract

Background
Endoglin is a co-receptor for TGFbeta/BMP9/10 signalling and ENG mutations lead to the vascular disorder hereditary haemorrhagic telangiectasia type I (HHT). Endoglin is also required for normal vascular development and angiogenesis, but little is known about endoglin's role in quiescent adult vascular endothelium.

Purpose
The goal of this present study is to determine how endoglin maintains vessel calibre in adult life to prevent AVM formation and thereby protect heart function.

Methods
To investigate this role, tamoxifen was administered to adult Cdh5(PAC)-CreERT2; Engfl/fl mice to generate endothelial-specific depletion of endoglin (Eng-iKOe). Cardiac magnetic resonance imaging, myography, vascular casting, microsphere injection, immunohistology, qPCR and aortic telemetry were used to evaluate cardiovascular changes after endoglin knockdown.

Results
Endothelial-specific loss of endoglin leads to an enlarged heart and cardiomyocyte hypertrophy within 5 weeks, progressing to high output heart failure (HOHF). In vivo aortic telemetry revealed significant loss of aortic pressure within a few days of endoglin depletion. Increased cardiac size and reduced cardiac afterload were confirmed by ventricular pressure loop analysis. As HOHF could result from arteriovenous malformations (AVMs), and these are found primarily in mucocutaneous and pulmonary tissues in HHT, we systematically screened for AVMs using microspheres and vascular casting. Although AVMs were absent in the majority of tissues, they were observed in the pelvic region and may account for the rapid increase in cardiac output. The pelvic cartilaginous symphysis is a noncapsulated cartilage with a naturally high endogenous expression of vascular endothelial growth factor (VEGF). Development of pelvic AVMs in this region of high VEGF expression occurred because loss of endoglin in endothelial cells leads to increased sensitivity to VEGF and a hyper-proliferative response. Finally, we found that inhibition of VEGFR2 was protective against AVMs development, enlargement of the heart and dilatation of the ventricles.

Conclusion
Our results showed the essential role of endoglin in the maintenance of adult cardio-vasculature through crosstalk with the VEGF signalling pathway.

Acknowledgement/Funding
British Heart Foundation, Cure HHT, The Swedish Research Council, The Cardiovascular Programme at Karolinska Institutet, The Swedish Cancer Society
6091Chronic heart failure is associated with inflammatory deterioration of the bone marrow vascular niche
Authors: Hoffmann J , Abplanalp W , Rasper T , Fischer A , Assmus B , Wild P , Koeck T , Zeiher A M , Dimmeler S 
Published: October 2019

Abstract

Introduction
Inflammation plays a crucial role in many aspects of cardiovascular disease. Particularly, acquired mutations of hematopoietic stem cells (HSC) leading to clonal expansion of inflammatory cells (CHIP) are increased with age and are associated with an enhanced risk of cardiovascular disease. The bone marrow (BM) vascular niche plays a crucial role in maintenance and regulation of HSC functions. Previous studies in mice showed the reduction of a specific Endomucin-high (H-type) endothelial cells (EC) subpopulation by aging. However, the impact of cardiovascular disease is unclear. Therefore, we aimed to investigate the effects of age and heart failure (HF) on the vascular BM cell composition in mice and humans.

Methods and results
Aging mice showed an age-dependent decrease of type H (Emcn-high) BM ECs (p=0.004), whereas the BM frequencies of type L (Emcn-low) ECs did not significantly differ (P=0.18). Importantly, we also observed a marked reduction of type H EC in chronic ischemic mice (P=0.016 vs. sham) indicating that chronic ischemic HF induces similar alterations of the vascular stem cell niche. Importantly, type H ECs were also significantly reduced in ischemic HF patients (n=16) compared with control subjects (n=8; P=0.0003). To gain insights into the mechanisms underlying the changes in the vascular niche, we performed single cells RNA sequencing of human BM ECs. These studies confirmed the decrease in Emcn-expressing ECs in ischemic HF patients, which was accompanied by significantly increased expression of inflammatory genes, including IL1b (P<0.0001 vs. control). Inflammatory EC phenotypes and IL1b expression in HF could be further confirmed at protein level using cytospin immunostainings. Finally, we comprehensively evaluated phenotype-associated differences in the bone marrow plasma proteomes of healthy individuals (n=19) and patients with chronic ischemic (n=22) and non-ischemic (n=19) HF, using proximity extension assays. Here, we identified 182 proteins significantly differentially regulated in CHF versus CTRL. Among the top upregulated proteins the BM environment of patients with CHF showed a striking enrichment of inflammatory and ECM remodeling components.

Conclusions
Our data show for the first time an impact of chronic heart failure on the bone marrow vascular niche in humans. These changes seem to be strongly associated with increased inflammatory response and bone matrix remodeling in CHF. Specifically, the induction of the inflammatory cytokine IL1b may contribute to the disturbed phenotype suggesting that inhibition of IL1b (e.g. by canakinumab) may be used as a novel strategy to prevent or reverse the deterioration of the vascular BM niche.
6097Aminoterminal proB-type natriuretic peptide: a key parameter to optimise therapeutic management of low-flow, low-gradient aortic stenosis
Authors: Annabi M S , Bergler-Klein J , Dahou A , Burwash I G , Ong G , Tastet L , Guzetti E , Orwat S , Baumgartner H , Bartko P E , Mascherbauer J , Mundigler G , Cavalcante J , Pibarot P , Clavel M A 
Published: October 2019

Abstract

Background
B-type natriuretic peptide (BNP) and aminoterminal-proBNP (NT-proBNP) are well established surrogates of LV function impairment. However, data are scarce regarding their prognostic value to risk-stratify patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS, with low left ventricular [LV] ejection fraction).

Methods
The TOPAS study is a prospective observational cohort of 240 patients with aortic valve area <0.6 cm2/m2, mean gradient<40 mmHg and LVEF<50%. True severe AS was adjudicated using flow independent grading schemes.

Results
BNP significantly predicted one-year (area under the receiver operating-characteristic curve [AUC]) 0.62±0.04, p=0.026) but not three-year mortality. After adjustment for the severity of AS, initial treatment (aortic valve replacement [AVR] vs. conservative management [ConsRx]), age, sex and the EuroSCORE (Model#1), BNP-ratio>550 pg/ml had a trend to predict time to death (HR=2.14 [1.00–4.58], p=0.05). In contrast, NT-proBNP ratio significantly predicted both one and three-year mortality (AUC=0.67±0.04 and 0.66±0.05, both p=0.001), and independently predicted time to death (HR=1.39 per 1 unit of Log transformed NT-proBNP [1.11–1.74], p=0.004). In a head-to-head comparison (108 patients with both biomarkers), the AUCs to predict one and thre-year mortality were significantly higher with NT-proBNP versus BNP (p<0.009). NT-proBNP but not BNP independently predicted mortality and significantly improved Model#1 (Likelihood ratio test Chi2=15.95, p<0.001). The category-free net reclassification index of NT-proBNP was 0.71 (p=0.008) versus 0.38 (p=0.15) for BNP. Furthermore, there was a marked survival benefit associated with AVR in patients with NT-proBNP ≥1700 pg/ml (adjusted hazard ratio (aHR) associated to AVR vs conservative management=0.52 [0.31–0.85], p=0.009), while those<1700 pg/ml had excellent one-year survival under ConsRx (only one death [4.5±4.4%] at one year as compared to 23 [37±6.2%] for ConsRx-NTproBNP>1700, aHR=0.11 [0.01–0.83], p=0.033). The survival benefit associated with AVR interacted with NT-proBNP (p<0.001) but not with true or pseudosevere AS (p=0.53 for interaction), suggesting that NT-proBNP might identify moderate AS patients but sufficiently severe valvulo-ventricular disease to justify AVR.
Survival according to NT-proBNP and AVR

Conclusion
NT-proBNP appears to be an excellent biomarker for the clinical purpose of risk-stratifying classical LFLG-AS. A threshold of 1700 pg/ml i.e. close to the diagnostic threshold for heart failure in acute dyspnea, was a strong independent determinant of the survival benefit associated with aortic valve replacement. Our findings suggest that NT-proBNP should be preferred over BNP.

Acknowledgement/Funding
Canadian Institute of Health Research
6099Impact of aortic valve replacement on outcomes of patients with low-flow, low-gradient moderate aortic stenosis
Authors: Annabi M S , Dahou A , Bergler-Klein J , Burwash I G , Orwat S , Baumgartner H , Bartko P E , Mascherbauer J , Mundigler G , Cavalcante J , Ribeiro H B , Rodes-Cabau J , Clavel M A , Pibarot P 
Published: October 2019

Abstract

Background
Aortic valve replacement (AVR) is recommended for patients with low-flow, low-gradient (LFLG) and true-severe aortic stenosis (TSAS). However, there is very few data on the potential benefit of AVR in patients with LFLG pseudo-severe (i.e. moderate) AS (PSAS).

Methods
Consecutive patients with aortic valve area ≤0.6 cm2/m2, mean gradient <40 mmHg were prospectively recruited in a multicenter observational cohort study. The patients were categorized in TSAS vs. PSAS using previously reported thresholds of flow-independent parameters of AS severity (projected valve area at normal flow rate ≤1.0 cm2 and/or aortic valve calcium score by CT >1200 AU in women and >2000 AU in men). To account for between-treatment-group differences, inverse probability-of-treatment weighting was combined to Cox proportional hazards regression.

Results
Among the 430 patients included in this study, 297 (69%) were classified as TSAS and 274 (57%) underwent AVR. Of note, 21% of the patients treated by AVR were classified as PSAS. In patients managed conservatively (ConsRx), 52% had PSAS and 48% TSAS. During a median follow-up of 28 months [8–60], 198 patients died. The adjusted weighted hazard ratio (awHR) of death associated with AVR as compared to ConsRx was 0.42 [0.24–0.73] (p<0.0001, Figure1-Panel-A). This survival benefit associated with AVR was observed not only in patients with TSAS but also in those with PSAS (awHR: 0.29 [0.12–0.70]; p=0.006, Figure1-Panel-B).
Figure 1

Conclusion
The results of this study suggest that AVR is associated with a survival benefit not only in LFLG patients with TSAS but also in those with PSAS. Randomized trials are needed to confirm the benefit of AVR in patients with moderate AS and depressed LV systolic function.

Acknowledgement/Funding
Canadian Institute of Health Research
6111Optical coherence tomography derived predictors of restenosis after non-stenting coronary intervention with drug-coated balloon
Authors: Nakagama S , Niida T , Matsuda Y , Nakamura T , Sasaoka T , Hatano Y , Umemoto T , Lee T , Yonetsu T , Hirao K 
Published: October 2019

Abstract

Background
One of the limitations of metallic stents including contemporary drug eluting stents lies in the permanent existence of metallic materials within the coronary arteries, which may lead to neoatherosclerosis and a long-term use of dual antiplatelet therapy. Some reports have recently suggested the efficacy and safety of non-stent strategy with drug-coated balloon (DCB) angioplasty in combination with debulking devices for de novo lesions. However, little is known about the potential risk of restenosis after percutaneous coronary intervention (PCI) with DCB.

Purpose
We sought to assess the predictive factors of restenosis by optical coherence tomography (OCT) after PCI with DCB instead of metallic stents.

Methods
We retrospectively investigated 49 de novo lesions in 38 patients treated by DCB without stent implantation in whom OCT was performed immediately after PCI and follow-up angiography was performed at median of 5.6 (3.7–6.9) months. OCT findings after PCI and the incidence of restenosis at follow-up angiography were evaluated. By means of OCT images, medial coronary dissection was defined as a dissection which reached the medial layer of the vessel, and major dissection was defined as a dissection with more than 60 degrees of the circumference of the vessel or more than 3mm in length. Restenosis was defined as more than 50% diameter stenosis evaluated by Quantitative Coronary Angiography.

Results
Restenosis was observed in 13 of 49 lesions (27%). In univariate logistic regression analysis, major dissection and medial dissection at the final OCT were associated with restenosis (Odds ratio [OR] 10.0; 95% confidence interval [CI] 2.5–52.6; p<0.01 and OR 5.8; 95% CI 1.5–25.1; p=0.01, respectively). Lesion preparation prior to DCB were performed with rotational atherectomy (n=9), orbital atherectomy (n=2), directional atherectomy (n=4), excimer laser angioplasty (n=17), scoring balloon angioplasty (n=13), or balloon angioplasty (n=4). OCT-defined major dissection remained a significant predictor for restenosis independent of debulking devices used for the preparation (OR 8.1; 95% CI 1.2–70.2; p=0.03).

Conclusions
Major dissection was associated with restenosis after non-stenting PCI with DCB. Stent implantation should be considered in cases of OCT-defined major dissection.

Acknowledgement/Funding
None