bluuebunny/crossref_metadata_2025_split huggingface dataset:
4251Results from the Hungarian Cardiac Magnetic Resonance Registry of Structural Heart Disease and Aborted Sudden Cardiac Death in Athletes
Authors: Vago H , Szabo L , Czimbalmos C S , Dohy Z S , Csecs I , Toth A , Suhai I , Simor T , Becker D , Merkely B 
Published: October 2019

Abstract

Introduction
Sudden cardiac death (SCD) is the most common cause of death in athletes occurring usually during intensive training. Cardiac magnetic resonance (CMR) has a crucial role in the detection of structural myocardial abnormalities.

Aims
Our aim was to investigate the etiology of SCD and to estimate the prevalence of myocardial structural heart diseases among Hungarian athletes using CMR.

Methods
Between January 2011 and January 2019 we performed CMR scans on 228 athletes (199 males, age: 29.1±13.2) with suspected structural myocardial disease. Twelve athletes were investigated after aborted sudden cardiac death and normal coronary angiography.

Results
CMR confirmed the diagnosis of structural myocardial disease in 62 athletes (26.2%) (28.8±9.1 years, 59 male): hypertrophic cardiomyopathy (HCM) in 14 cases (22.6%), arrhythmogenic right ventricular cardiomyopathy (ARVC) in 9 cases (14.5%), noncompaction (NCCMP) in 6 cases (9.7%) and dilated cardiomyopathy (DCM) in 5 cases (8.1%). Subendocardial late gadolinium enhancement (LGE), reflecting myocardial scar, was typical of previous myocardial infarction (post MI) in 3 cases (5.5%). Acute myocarditis was found in 2 cases (3.6%). Nonischaemic LGE pattern was found in 20 cases (32.2%): patchy subepi-midmyocardial LGE suggesting previous myocarditis in 8 athletes, and with aspecific pattern in 12 athletes. Athletes with nonischaemic LGE had normal clinical and laboratory parameters without wall motion abnormalities, in their cases further investigations ruled out systemic disease. One athlete was diagnosed with Fabry-disease, one with coronary artery abnormality (anomalous origin of the left main coronary artery from the right sinus of Valsalva), one athlete showed pheochromocytoma-related Tako-Tsubo cardiomyopathy (each 1.6%). Five athletes with confirmed structural heart disease were investigated after sustained ventricular tachycardia, seven athletes after aborted SCD: ARVC (n=6), aspecific LGE pattern (n=4), HCM (n=1) and pheochromocytoma-related Tako-Tsubo cardiomyopathy (n=1) were diagnosed.
RVOT movie of an ARVC pts

Conclusion
In our national CMR registry the most common structural alteration was nonischaemic fibrosis, the most common cardiomyopathy was HCM, and the leading cause of SCD in Hungarian competitive athletes was ARVC. The national registers are highly important for a better understanding the etiology and the geographical differences of SCD in athletes.

Acknowledgement/Funding
Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary
4290Results of transcatheter mitral valve repair for severe mitral regurgitation from a real-world patient cohort according to COAPT and MITRA-FR trial inclusion criteria and echocardiographic parameter
Authors: Orban M , Stolz L , Orban M , Braun D , Stocker T , Stark K , Nabauer M , Massberg S , Hausleiter J 
Published: October 2019

Abstract

Background
Two randomized trials (MITRA-FR and COAPT) of transcatheter mitral valve repair (TMVR) for functional MR have shown symptomatic improvement but discordant results for heart failure hospitalizations compared to optimal medical therapy. Differences between real-world patients similar to the trial population in terms of symptomatic outcome and mortality have not been shown yet.

Purpose
Our study compared patients similar to both studies in terms of NYHA development and mortality at 1-year follow-up (FU).

Methods
In our center, 447 patients were treated with TMVR for MR grade 3 and 4 between 2012 and 2018. For the comparative analysis with MITRA-FR and COAPT, we applied filters to our database patients according to the published echocardiographic inclusion criteria and baseline data (COAPT: effective regurgitant orifice area [ERO]) 0.41±0.15cm2; left ventricular ejection fraction [LV-EF] 31.3±9.1%, left ventricular end-diastolic volume [LVEDV] 194.4±69.2ml; MITRA-FR: ERO 0.31±0.1 cm2; LV-EF 33.3±6.5, indexed LVEDV 136.2±37.4 ml).

Results
Out of our database, 91 patients were categorized as COAPT-like and 92 as MITRA-FR-like. COAPT-like patients had an ERO of 0.40±0.16cm2, LV-EF of 32.7±4.8%, LVEDV of 195±53.7ml and indexed LVEDV of 103.6±26.0ml/cm2 (Figure A). MITRA-FR-like patients had an ERO of 0.31±0.07 cm2, LV-EF of 31.7±5.0%, LVEDV of 221.7±60.8ml and indexed LVEDV of 117.9±29.1 ml/cm2. The difference of ERO and LVEDV between both groups was statistically significant. The majority of patients in both groups were in NYHA class III or IV at baseline (97% COAPT-like group, 98% MITRA-FR-like group, p=0.44).
MR reduction was equally effective in both groups, with 85 (93%) COAPT-like patients and 88 (96%) MITRA-FR-like patients having MR grade 1 or 2 at discharge. Clinical FU was available in 62 (68%) and 67 (73%) COAPT-like and MITRA-FR-like patients, respectively. The majority of patients improved symptomatically after TMVR. Before TMVR, 1 (98%) COAPT-like patient and 2 (97%) MITRA-FR-like patients were in NYHA class I or II compared to 36 (58%, p<0.01) COAPT-like patients and 38 (57%, p<0.01) MITRA-FR-like patients at FU (p=1.0 for intergroup comparison). Overall, 40 (65%) COAPT-like patients and 43 (64%) MITRA-FR-like improved at least one NYHA class (p=1.0 for intergroup comparison; Figure B). There were no differences in overall survival between groups with 68.9% of COAPT-like patients and 74.5% of MITRA-FR-like patients alive at 1-year FU (p=0.53, Figure C).
Figure 1

Conclusion
Our real-world data shows that TMVR leads to symptomatic improvement in both MITRA-FR-like and COAPT-like patients to a similar extent, despite substantial echocardiographic differences. Both patient groups have a similar survival rate.
4291Six-month outcomes from the multicenter, prospective study with the novel PASCAL transcatheter valve repair system for patients with mitral regurgitation in the CLASP study
Authors: Kar S , Lim S , Spargias K , Kipperman R , O Neill W , Ng M , Fam N , Raffel C , Webb J , Smith R , Rinaldi M , Latib A , Cohen G , Schaefer U , Feldman T 
Published: October 2019

Abstract

Background
Severe mitral regurgitation may lead to an impaired prognosis if left untreated. Transcatheter treatment options have emerged as an alternative to surgery and an adjunct to medical therapy. We report the six-month results of the PASCAL transcatheter valve repair system in treating patients with mitral regurgitation enrolled in the multicenter, prospective, single arm CLASP study.

Methods
The PASCAL Transcatheter Valve Repair System is a leaflet repair therapy that uses clasps and paddles to place a woven Nitinol spacer between the native valve leaflets to fill the regurgitant orifice via a transseptal approach. Eligible patients had clinically significant MR despite optimal medical therapy and were deemed candidates for transcatheter mitral repair by the local Heart Team. Safety, performance, and clinical outcomes were prospectively assessed at baseline, discharge, 30 days, and 6 months post-procedure. All major adverse events (MAE) were adjudicated by an independent clinical events committee and echocardiographic images were assessed by a core lab. The MAE rate was the primary safety endpoint, defined as the composite of cardiovascular mortality, stroke, MI, new need for renal replacement therapy, severe bleeding, and re-intervention for study device-related complications.

Results
Between June 2017 and September 2018, 62 patients were enrolled at 14 sites worldwide for transcatheter mitral valve reconstruction using the PASCAL system. The mean age was 76.5 years (62.9% male). All patients had MR grade ≥3+, with 59% functional, 34% degenerative, and 7% mixed etiology, and 51.6% of patients were in NYHA Class III/IV. Successful implantation of the PASCAL device was achieved in 95% of patients. At discharge, 95% of patients had MR grade ≤2+ with 81% grade ≤1+. There was one cardiovascular mortality and the MAE rate was 4.8%. At 30-day follow-up, paired analyses shows that 98% of patients had MR grade ≤2+ with 81% grade ≤1+ and 88% were in NYHA Class I/II (p<0.0001). The 6MWD improved by 38.9 m (p=0.0015) and was accompanied by average improvements in KCCQ and EQ5D scores by 14.1 points (p<0.0001) and 8.3 points (p=0.0028), respectively. The six-month data will be available for presentation.

Conclusions
In this early device experience, the PASCAL transcatheter valve repair system showed an acceptable safety profile and performed as intended in treating patients with mitral regurgitation. The PASCAL device resulted in significant MR grade reduction, which was associated with clinically and statistically significant improvements in functional status, exercise capacity, and quality of life. Continued follow-up is warranted to validate these initial promising results.

Acknowledgement/Funding
Edwards Lifesciences
4311Decreased CD177 expression and its association with intravenous immunoglobulin resistance in Kawasaki disease
Authors: Huang Y 
Published: October 2019

Abstract

Kawasaki disease (KD) is the most common acute coronary vasculitis disease occurring in children. Its occurrence has been attributed to the combined effects of infection, genetics, and immunity. While the etiopathogenesis of KD remains unknown, we have performed a survey of global genetic DNA methylation status and transcripts expression in KD patients to address how they contribute to the pathogenesis of KD.

Methods
We recruited 148 participants for this study. The chip studies consisted of 18 KD patients that were analyzed prior to administering intravenous immunoglobulin (IVIG) treatment and at least 3 weeks afterward, as well as 36 non-KD control subjects. We performed a separate cohort of 94 subjects to validate real-time quantitative PCR.

Results
According to the microarray study, CD177, a neutrophil surface molecule, appeared to be most significantly upregulated in KD patients compared to controls with epigenetic hypomethylation. After patients received IVIG treatment, CD177 mRNA levels decreased significantly. PCR validation indicated that the expression of CD177 is consistent with the Transcriptome Array 2.0 results. Furthermore, the area under the curve values of CD177 between KD patients and controls is 0.937. We also observed significantly higher CD177 levels in typical KD than incomplete presentation, which was associated with IVIG resistance in KD patients.

Conclusion
The present study is the first to highlight the epigenetic hypomethylation of an increased CD177 transcript during the acute stage of KD. Furthermore, the higher expression of CD177 in a typical presentation of KD patients and was related to IVIG resistance.
4327Results of the DERIVATE study in non-ischemic dilated cardiomyopathy (NICM)
Authors: Guaricci A I , Masci P G , Lorenzoni V , Schwitter J , Pontone G 
Published: October 2019

Abstract

Background
Standard of care (SOC) suggests implanted cardioverter defibrillator (ICD) therapy based on the left ventricular ejection fraction (LVEF) cut-off value as detected by transthoracic echocardiography (TTE-LVEF)

Purpose
The aim of this study was to evaluate the additional prognostic value of a cardiac magnetic resonance (CMR) based score over SOC in a large cohort of non-ischemic cardiomyopathy (NICM) patients evaluated for primary ICD therapy

Methods
DERIVATE is an international, multicenter, prospective, observational registry including consecutive patients with chronic heart failure (HF) who undergo clinical evaluation. We included 1000 patients (derivation cohort) and 509 patients (validation cohort) with chronic heart failure (HF) with LVEF<50% affected by NICM enrolled in the period between January 2007 and October 2017. All-cause mortality and arrhythmic major adverse cardiac events (MACE) were the primary and the secondary endpoint, respectively.

Results
During a median follow-up of 959 days, all-cause mortality and combined MACE occurred in 72 (7%) and 93 (9%) patients respectively. Regarding to primary endpoint, age and number of myocardial segments with late gadolinium enhancement (LGE) midwall>3 were the only independent predictors of mortality (HR: 1.037, 95% CI: 1.018–1.057, p<0.001 and HR: 1.78, 95% CI: 1.062–3.005, p=0.029, respectively). Regarding to the secondary endpoint, gender, left ventricle end-diastolic volume indexed as detected by CMR (CMR-LVEDVi)>120.5 ml/m2, and number of myocardial segments with LGE midwall>2 were independent predictors of MACE (HR: 2.13, 95% CI: 1.231–3.690, p=0.007; HR: 3.16, 95% CI: 1.750–5.709, p<0.001 and HR: 1.69, 95% CI: 1.084–2.644, p<0.02 respectively). Accordingly, a weighted CMR score, including these three variables with a maximum of 7 points was calculated and when added to the model based on SOC provided a net reclassification improvement (NRI) of 63.7% (p<0.001). Finally, when the CMR-score was applied to validation cohort showed a NRI of 31.3% (p: 0.022) with a good prognostic stratification (p: 0.001) as compared to the SOC.

Conclusions
CMR provides additional prognostic stratification as compared to the SOC, which may have direct impact on the indication of ICD implantation. Further, prospective randomized trial should be addressed to test the cost-effectiveness of a CMR strategy as compared to SOC in patients undergoing ICD implantation.

Acknowledgement/Funding
funded by the Italian Ministry of Health, Rome, Italy (RC 2017 R659/17-CCM698
4331Safety and efficacy of sacubitril/valsartan by dose level in patients hospitalized with acute heart failure: Observations from PIONEER-HF
Authors: Morrow D A , Velazquez E J , Devore A D , Duffy C I , Gurmu Y , McCague K , Rocha R , Braunwald E 
Published: October 2019

Abstract

Background
In hemodynamically stabilized patients with acute decompensated heart failure (ADHF) enrolled in the PIONEER-HF trial, compared with enalapril, sacubitril/valsartan started in-hospital and continued for 8 weeks was well tolerated, achieved a greater reduction in NT-proBNP, and reduced cardiovascular death or rehospitalization for HF. Nearly 1/2 of patients achieved the target dose of blinded study drug. We performed an exploratory analysis of the safety and efficacy of sacubitril/valsartan according to the dose level dispensed at 4 weeks in PIONEER-HF

Methods
PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan vs. enalapril in 881 hospitalized ADHF pts following hemodynamic stabilization. Blinded study medication was administered for 8-weeks, with initial dosing selected based on the systolic blood pressure (SBP) at randomization (starting dose 24/26 or 49/51 mg twice daily vs 2.5 or 5 mg twice daily) and titrated toward a target of sacubitril/valsartan 97 mg/103 mg twice daily, or enalapril 10 mg twice daily with an algorithm using SBP along w/ the investigator's assessment of tolerability.

Results
At the week 4 visit, 199 patients (45.2%) in the sacubitril/valsartan group and 210 (47.6%) in the enalapril group were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. The prespecified adverse events of special interest were similar between sacubitril/valsartan and enalapril irrespective of dose level (Table) with no significant heterogeneity. In addition, there was no heterogeneity across dose levels in the favorable effect of sacubitril/valsartan on the change in NTproBNP by week 8 (Table, p-interaction=0.54) or the serious composite endpoint (p-interaction=0.71).
Efficacy and Safety by Dose-Tier

Conclusion
In hemodynamically stabilized patients with ADHF, the safety and efficacy of sacubitril/valsartan appears generally consistent among patients at various dose levels.

Acknowledgement/Funding
Novartis Pharmaceuticals
P3096The cardioprotective effect of FFR-significant multivessel disease detected by cardiac magnetic resonance imaging in patients following ST-segment elevation myocardial infarction. Results from DANAMI3
Authors: Ekstroem K , Nielsen J V W , Nepper-Christensen L , Ahtarovski K A , Kyhl K , Goeransson C , Bertelsen L , Ghotbi A A , Kelbaek H , Hoefsten D E , Koeber L , Schoos M M , Vejlstrup N , Loenborg J , Engstroem T 
Published: October 2019

Abstract

Background
In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), reperfusion injury accounts for a significant part of the final infarct size, which is directly related to patient prognosis. In animal studies brief periods of ischemia in non-infarct related coronary arteries protects the myocardium via remote ischemic perconditioning. Fractional flow reserve (FFR) measures functional significant coronary stenosis which may offer remote ischemic perconditioning of the myocardium. It has not previously been investigated if FFR-significant stenosis in non-culprit myocardium offers cardioprotection following STEMI.

Purpose
To investigate cardioprotective effect of FFR-significant multivessel disease (MVD) on final infarct size and myocardial salvage in a large contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI).

Methods and results
We included 509 patients with STEMI from the DANAMI-3 trial, divided into three groups: 388 (76%) patients had single vessel disease (SVD), 34 (7%) had non-FFR-significant MVD and 192 (17%) had FFR-significant MVD. CMR was performed at baseline and three months after primary PCI. There was no difference in final infarct size; mean infarct size (% left ventricular mass) SVD 9±3%; non-FFR-significant MVD 9±3%; and FFR-significant MVD 9±3%, p=0.95, or in myocardial salvage index (MSI) between groups, calculated as (area-at-risk – infarct size)/area-at-risk; mean index (%) SVD 67±23%; non-FFR-significant MVD 68±19%; and FFR-significant MVD 67±21%, p=0,99. In multivariable regression analyses FFR-significant MVD was not associated med larger MSI (p=0.84) or lower infarct size (p=0.60).
Figure 1. A. Late gadolinium (LGE) cardiac magnetic resonance (CMR) image of a mid-ventricular short-axis slice. Hyperintense signals (arrow) shows contrast enhancement in the anterior-septal segments, indicating myocardial infarction (MI). B. Same patient. T2-weighted image of the same mid-ventricular short-axis slice. Hyperintense signals (arrows) shows edema in the anterior-septal segments.

Conclusions
FFR-significant functional MVD of non-culprit myocardium does not offer cardioprotection in patients following STEMI.
P3103Cardiac rehabilitation referral after ACS, are women deprived?
Authors: Klein J , Farkash R , Bayya F , Taha L , Abeles N , Kischner A , Yaacobi E , Glikson M 
Published: October 2019

Abstract

Background
Referral and participation rates to Cardiac Rehabilitation (CR) after acute coronary syndrome (ASC) are low despite a Class I recommendation in the present guidelines. Our aim was to examine the role of gender on referral, participation and outcomes of CR.

Methods
Data of ACS patients hospitalized during 2007–2016 in our cardiology department were extracted and compared between referred to CR to those who were not. Multivariable models were used to assess the impact of gender on referral to CR and survival.

Results
Of the 6175 ACS patients, 1455 (23.6%) were female. Overall referral rate to CR was 66.5%, 51.3% among female and 70.0% in male; p<0.0001.
Female were more likely to have characteristics associated with lower referral rate; they were older, had lower rates of STEMI and higher rates of cardiac risk factors. Multivariable model, adjusted for those characteristics revealed that female gender is independently associated with lower referral rate to CR: OR = 0.77 95% CI [0.66–0.89]; p<0.0001. (Table 1)
Multivariable COX analysis showed that patients referred to CR had lower mortality hazard – HR = 0.427 95% CI [0.35–0.53]; p<0.0001, with no gender difference – HR=1.04 95% CI [1.04–1.06]; p=0.640.
Participation rate within referred patients, program duration as well as number of meetings were similar in female and male p=NS for all.
Independent predictors for CR referral OR 95% CI p-value Cath 6.5 5.3–8.0 <0.001 STEMI** 3.9 3.3–4.6 <0.001 NSTEMI** 2.1 1.8–2.4 <0.001 Smoker 1.9 1.6–2.1 <0.001 Age* 0.9 0.9–1.0 <0.001 Hypertension 0.8 0.7–0.9 0.023 Prior MI 0.8 0.7–0.9 0.032 Female gender 0.8 0.7–0.9 0.001 Prior CABG 0.7 0.6–0.9 0.003 CVA 0.7 0.6–0.9 0.010 PVD 0.7 0.52–0.9 0.033 CHF 0.7 0.6–0.9 0.001 *Age: continuous; **UA as reference group.

Conclusions
Referral of ACS patients to CR significantly lowers mortality rate. Referral rate of women to CR is significantly lower than men. Once referred to CR, no gender difference was found in CR participation rate and program compliance.

Acknowledgement/Funding
None
P3115Effect of calcitriol attenuates doxorubicin-induced cardiac dysfunction in mice model: focus on endothelial-to-mesenchymal transition
Authors: Tsai T H , Chen W Y 
Published: October 2019

Abstract

Objective
Doxorubicin (DOX) is an effective anti-neoplasm drug, but the early and late cardiac toxicity limits its clinical use. The Endothelial-to-mesenchymal transition (EndMT) has been found to involve in the process of heart failure. It's unclear whether EndMT plays a role in DOX-induced cardiomyopathy (DoIC). Calcitriol is an active form Vitamin D3, which blocks the growth of cancer cells via inhibiting Smad pathway. This study investigated the cardiac protective effect of calcitriol via inhibiting of EndMT in DoIC.

Methods/Findings
C57BL/6 mice and endothelial-specific labeled mice were administered Dox twice weekly for 4 weeks [intraperitoneally (i.p.), 32 mg/kg cumulative dose]and were subsequently treated with/without calcitriol for 12 weeks. The cardiac echography revealed diastolic dysfunction at 13 weeks following the first DOX treatment and was accompanied by increased of myocardial fibrosis and up-regulated pro-fibrotic proteins.(Figure A-C) Calcitriol attenuated DOX-induced myocardial fibrosis, down-regulated pro-fibrotic proteinsand diastolic function. Endothelial fate tracing revealed that endothelium-derived cells contributed DOX-induced cardiac remodelling through EndMT and Calcitriol attenuated this process without attenuating Dox-induced cardiac myocyte and endothelial cell damage.(Figure D) In vitro, we examined if calcitriol would inhibit EndMT and fibroblast-to-myofibroblast transition (FMT) through the Smad pathway. Human umbilical vein endothelial cells (HUVECs) and mouse cardiac fibroblasts were treated with TGF-beta with or without calcitriol. Morphological, immunofluorescence staining, and western blot analyses were carried out to evaluate EndMT and FMT. Calcitriol attenuated EndMT and FMT by inhibiting the Smad2 pathway. Taken together, calcitriol didn't reduced Doxorubicin induced damage of cardiomocyte and endothelial cells. But calcitriol inhibit doxorubicin induced heart failure by attenuating cardiac fibrosis through inhibiting Smad pathway.

Conclusion
Calcitriol attenuated DOX-induced cardiomyopathy partial through inhibiting EndMT process.

Acknowledgement/Funding
CMRPG8E0661-3