bluuebunny/crossref_metadata_2025_split huggingface dataset:
6117Persistent LBBB and AV block with high-burden RV pacing following transcatheter aortic valve replacement are associated with new onset cardiomyopathy
Authors: Ananwattanasuk T , Ghannam M , Lathkar-Pradhan S , Latchamsetty R , Jame S , Jongnarangsin K 
Published: October 2019

Abstract

Background
Left bundle branch block (LBBB) and AV nodal block (AVB) requiring permanent pacemaker implantation occur frequently following transcatheter aortic valve replacement (TAVR) and may be associated with adverse clinical events.

Objectives
The study aims to assess the incidence of new onset cardiomyopathy among patients with normal left ventricular systolic function patients who developed LBBB or persistent AVB with high-burden right ventricular (RV) pacing (>80%) following TAVR procedure.

Methods
Consecutive patients who underwent TAVR procedure from January 2012 to June 2017 at the University of Michigan Health System were included in the retrospective analysis. Those who had a preexisting cardiac implantable electronic device (CIED), prior LBBB, left ventricular ejection fraction (LVEF) <50%, and follow up period less than 1 year were excluded from this analysis. New onset cardiomyopathy was defined by a left ventricular ejection fraction (LVEF) <45% within 1 year after TAVR.

Results
A total of 362 patients were included in the study (mean age 76.9±11.5 years, 56.1% male). Of these, 30 patients (8.3%) developed persistent AVB and required >80% RV pacing (pacing group), 61 patients (16.9%) developed persistent LBBB (LBBB group), and 271 patients (74.9%) did not have LBBB or AVB or required <80% RV pacing (control group). Baseline LVEF was 63.9+6.4% in pacing group (p=0.76) and 64.4+7.4% in LBBB group (p=0.89) compared to 64.3+6.5% in control group. Within 1 year after TAVR, 10/30 patients (33.3%) in pacing group (p<0.01) and 20/61 patients (32.8%) in LBBB (p<0.01) developed new onset cardiomyopathy compared to 9/271 patients (3.3%) in control group. LVEF at 1 year was 53.8+11.9% in pacing group (p<0.01) and 53.7+12.1% in LBBB group (p<0.01) compared to 64.8+7.7% in control group.

Conclusion
Among patients with normal baseline left ventricular systolic function, AV block required high-burden RV pacing and persistent LBBB following TAVR were associated with significantly higher incidence of new onset cardiomyopathy.
P4984The functional and coronary anatomic correlates of coronary flow velocity reserve during stress echocardiography
Authors: Ciampi Q , Zagatina A , Cortigiani L , Gaibazzi N , Borguezan Daros C , Zhuravskaya N , Wierzbowska-Drabik K , De Castro E Silva Pretto J L , D'Andrea A , Djordjevic-Dikic A , Simova I , Boshchenko A , Amor M , Merlo P B , Picano E 
Published: October 2019

Abstract

Background
The assessment of coronary flow velocity reserve (CFVR) on left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on regional wall motion abnormalities (RWMA).

Aim
To assess the feasibility and functional correlates of CFVR.

Methods
In a prospective, observational, multicenter study, we initially screened 3,410 patients (2061, 60%, male; age 63±11 years; ejection fraction, EF=61±9%) with known or suspected coronary artery disease (CAD) and/or heart failure (HF). All patients underwent SE (exercise, n=1288; vasodilator, n=1860; dobutamine, n=262) based on RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. We also assessed B-lines (a sign of pulmonary congestion) with lung ultrasound and left ventricular contractile reserve (LVCR) based on Force (systolic blood pressure/end-systolic volume).

Results
The success rate for CFVR on LAD was 3,002/3,410 (feasibility=88%): 1,025/1,288 for exercise (80%), 1,766/1,860 (95%) for vasodilator (dipyridamole, n=1,841 and adenosine= 18) and 211/262 (81%) for dobutamine (p<0.001 vs vasodilator, p=NS vs exercise). Imaging time was <3 min and analysis time <1 min per patient. Reduced (≤2.0) CFVR was found in 896/3,002 (30%) patients. At multivariate logistic regression analysis, age (odds ratio, OR: 1.025, 95% Confidence intervals, CI: 1.015–1.036, p<0.001), diabetes (OR: 2.271, 95% CI: 1.218–4.235, p=0.10), RWMA (OR: 6.550, 95% CI: 4.989–8.599, p<0.01), abnormal LVCR (OR: 3.446, 95% CI: 2.774–4.281, p<0.01) and stress-rest B-lines change (OR: 1.519, 95% CI: 1.174–1.99, p=0.01) were associated with reduced CFVR. In the 1149 patients with coronary angiographic information, a reduced CFVR was present in 103/455 patients (23%) with no CAD, 119/432 (27%) with 1-, 72/167 (43%) with 2-, and 62/95 (65%) with 3-vessel disease (p<0.001 by ANOVA for trend).
Figure 1

Conclusions
CFVR is feasible with all SE protocols. The reduced CFVR is often accompanied by RWMA, abnormal LVCR and pulmonary congestion during stress.
P4992The ceramide-based Coronary Event Risk Test (CERT) predicts cardiovascular mortality in cardiovascular disease patients with type 2 diabetes mellitus as well as in those without diabetes
Authors: Leiherer A , Muendlein A , Saely C H , Laaksonen R , Laaperi M , Vonbank A , Larcher B , Mader A , Baumgartner I , Fraunberger P , Drexel H 
Published: October 2019

Abstract

Background
The recently introduced Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories.

Purpose
The purpose of this study was to investigate the power of CERT to predict cardiovascular mortality in patients with established cardiovascular disease (CVD) including patients with type 2 diabetes (T2DM).

Methods
We investigated a total of 1087 patients with established CVD, including 360 patients with T2DM.
At baseline, the prevalence of T2DM increased through CERT categories (29.1, 31.1, 37.4, and 53.4%, respectively, ptrend<0.001). Prospectively, cardiovascular deaths were recorded during a mean follow-up time of 8.1±3.2 years.

Results
A total of 130 cardiovascular deaths occurred. Overall, cardiovascular mortality increased with increasing CERT categories (figure) and was higher in T2DM patients than in those who did not have diabetes (17.7 vs. 9.4%; p<0.001). In Cox regression models, CERT categories predicted cardiovascular mortality in patients with T2DM (unadjusted HR 1.60 [1.28–2.01]; p<0.001; HR adjusted for age, gender, BMI, smoking, LDL cholesterol, HDL cholesterol, hypertension, and statin use 1.65 [1.27–2.15]; p<0.001) and in those without diabetes (unadjusted HR 1.43 [1.10–1.85]; p=0.008 and adjusted HR 1.41 [1.07–1.85]; p=0.015).
Cardiovascular survival of CVD patients

Conclusion
We conclude that CERT predicts cardiovascular mortality in CVD patients with T2DM as well as in those without diabetes.
P5001Acute cardiac fibrogenic response triggered by endotrophin, a type VI collagen signalling molecule
Authors: Reese-Petersen A L , Karsdal M , Genovese F 
Published: October 2019

Abstract

Background/Aim
Accumulation of extracellular matrix (ECM) proteins is the hallmark of cardiac fibrosis, causing stiffening of the ventricular wall, which can lead to heart failure and ultimately death. Many different cell types and growth factors are involved in this process but fibroblasts are the main source of ECM proteins. Here we present results from an in vitro model indicating that endotrophin (ETP), a collagen type VI fragment, activates cardiac fibroblasts and induces fibrogenesis.

Methods
The effect of ETP, transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF)-DD on ECM protein synthesis was assessed in a scar-in-a-jar (SiaJ) cell model using human cardiac fibroblasts isolated from the atrium of an adult healthy donor. Cells were seeded in 48-well plates at a density of 30.000 cells/well and incubated for 24H in Dulbecco's Modified Eagle's medium (DMEM) + 10% fetal bovine serum (FBS). Serum starvation was done by seeding the cells for further 24H in DMEM + 0.4% FBS. Fresh medium was added at day 0 with 37.5/25mg/mL Ficoll 70/400 and 1% ascorbic acid, containing 11.75 nM human recombinant ETP, 0.04 nM TGF-β, 0.39 nM PDGF-DD or a vehicle control. Medium was changed and collected at day 3 and 6. Biomarkers of type I (PRO-C1), III (PRO-C3), VI (PRO-C6) collagens and fibronectin (FBN-C) formation were assessed in the medium by ELISAs developed at Nordic Bioscience.

Results
ETP induced a significant increase in PRO-C1, PRO-C3 and FBN-C (comparable to TGF-β and PDGF-DD) within the first three days of the experiment, compared to the vehicle control. The levels remained significantly increased for PRO-C3 and FBN-C throughout the experiment, and non-significantly elevated for PRO-C1, compared to the vehicle control. PDGF-DD significantly induced synthesis of type VI collagen compared to the vehicle control, while TGF-β induced a small increase in synthesis from day 0–3, after which it seemed to inhibit synthesis.

Conclusion
For the first time, a direct pro-fibrotic effect on fibroblasts induced by ETP has been shown. This novel pathway of activation could play an important role in regulating cardiac fibrosis, and thus prove to be a therapeutic target. This SiaJ model in combination with the investigated biomarkers of ECM formation could be used to further elucidate the mechanisms behind cardiac fibrosis.
P5004Peripheral neuropathy and increased risk of heart failure: a population-based longitudinal cohort study
Authors: Sun Y , Oxnard J , New B J , Mordi I R , Meng W , Tee A , Palmer C N , McCrimmon R , Doney A S , Lang C C 
Published: October 2019

Abstract

Background
One of the main pathophysiological processes thought to be implicated in the development of diabetic cardiomyopathy is a microvascular disease (MiVD) that is prevalent in type 2 diabetes (T2D). However, the role of MiVD in the development of heart failure (HF) is not known. T2D screening programmes identify three types of MiVD – retinopathy, nephropathy and neuropathy. Both retinopathy and nephropathy have been independently associated with the development of incident HF in observational cohort studies. There is less data on peripheral neuropathy and HF outcomes. This study aimed to determine the independent association of diabetic neuropathy with incident HF events in a large longitudinal population cohort of T2D patients with a detailed clinical follow-up that includes available echocardiographic data.
Design
This was a population-based longitudinal cohort study from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS) from 1996 to 2016. A total of 9,598 patients with T2D were included with data available on hospital admissions, prescribing and other clinical variables including age, gender, smoking history, duration of T2D, body mass index, systolic blood pressure, glycosylated haemoglobin (HbA1c), triglyceride, total LDL and HDL cholesterol levels. Neuropathy cases were identified using a well-validated record linkage method utilising neuropathic drug prescription records to identify cases of neuropathic pain and to monofilament testing that is used to diagnose neuropathy.

Results
There were 805 HF events. After adjustment for clinical variables, the presence of painful neuropathy related to a 57% increased risk of incident HF (HR 1.57, 95% CI = 1.32–1.89, p<0.001). A similar risk was also observed with diabetic neuropathy identified by monofilament testing with a 52% (HR 1.52, CI = 1.013–1.225, P<0.05) increased risk of incident HF.

Conclusions and relevance
Peripheral neuropathy, a feature of MiVD, may be pathophysiologically associated with the development of HF in patients with T2D and may be a therapeutic target.
P5006Metformin reduces the risk of hospitalization for heart failure in type 2 diabetes patients: a retrospective cohort analysis
Authors: Tseng C H 
Published: October 2019

Abstract

Background
A beneficial effect of metformin on heart failure requires confirmation.

Purpose
To investigate whether metformin might affect the risk of heart failure hospitalization in type 2 diabetes patients.

Methods
Patients with new-onset type 2 diabetes during 1999–2005 were enrolled from the reimbursement database of Taiwan's National Health Insurance and followed until December 31, 2011. Analyses were conducted in a propensity score (PS) matched-pair cohort (42,367 ever users and 42,367 never users) and hazard ratios were estimated by Cox's hazard regression analysis incorporated with the inverse probability of treatment weighting using the PS.

Results
A total of 1,592 never users and 987 ever users were hospitalized for heart failure for the first time during follow-up, with a respective incidence of 843.34 and 499.18 per 100,000 person-years. The overall hazard ratio was 0.588 (95% confidence interval: 0.543–0.637), and the hazard ratios for the first (<29.13 months), second (29.13–61.63 months), and third (>61.63 months) tertiles of cumulative duration were 1.018 (0.914–1.135), 0.575 (0.511–0.647), and 0.340 (0.297–0.390), respectively. Sensitivity analyses conducted in an unmatched cohort before and after excluding patients who received an irregular refill of metformin or who were treated with incretin-based therapies during follow-up consistently supported such a protective effect of metformin on heart failure.

Conclusion
Metformin use is associated with a lower risk of hospitalization for heart failure.

Acknowledgement/Funding
The study was partly supported by the Ministry of Science and Technology (MOST 107-2221-E-002-129-MY3) of Taiwan.
P5015Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events: A meta-analysis
Authors: Dykun I , Mincu R , Totzeck M , Rassaf T , Mahabadi A A 
Published: October 2019

Abstract

Background
Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors allow for reduction in LDL-cholesterol in addition to statin therapy.

Purpose
To perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome.

Methods
We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe or PCSK-9 inhibitor in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of November 2018, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were “ezetimibe”, “evolocumab”, “alirocumab”, or “bococizumab” and “cardiovascular events”.

Results
A total of 100,610 patients from 9 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, SIPRE I, SPIRE II, ODYSSEY LONG TERM, OSLER-1 and OSLER-2, HIJ-PROPER) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 18% risk reduction in cardiovascular events (OR [95% CI]: 0.82 [0.75–0.89]). Effect sizes were similar for myocardial infarction (0.84 [0.76–0.92]) and even more pronounced for ischemic stroke (0.77 [0.67–0.83]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.94 [0.85–1.05]). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Comparing efficacy of LDL-reduction and relative risk redaction of cardiovascular events, a linear relationship was observed (figure).
Figure 1. Correlation of reduction of LDL-cholesterol at one year with relative risk reduction (95% confidence interval) of cardiovascular events in included trials.

Conclusion
Intensified LDL-lowering therapy with ezetimibe or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. There is a linear relationship between LDL reduction and cardiovascular risk reduction, confirming the beneficial effects of LDL lowering therapy beyond statins in secondary prevention.
P5022Dual-energy CT was effective to evaluate of microvasculopathy in chronic thromboembolic pulmonary hypertension
Authors: Onishi H , Taniguchi Y , Matsuoka Y , Yanaka K , Izawa Y , Mori S , Otake H , Satomi-Kobayashi S , Emoto N , Hirata K 
Published: October 2019

Abstract

Background
The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension (CTEPH) had been suggested. However, the impact of microvasculopathy for pathophysiology had been unknown. Recently dual-energy CT (DECT) can produce a sensitive iodine distribution map as blood perfusion in lung fields to quantify lung perfusion, also can suggest the existence of microvasculopathy according to poor subpleural perfusion which was published previously.

Methods
We retrospectively reviewed poor subpleural perfusion (defined as subpleural spaces either not or minimally perfused in all segments) and hemodynamics of 83 treatment-naïve CTEPH patients who underwent DECT from February 2014 to Jan 2019. Patients were divided according to poor subpleural perfusion: a microvasculopathy group (n=44) or a non-microvasculopathy group (n=39).
We assessed cardiopulmonary exercise test, right heart catheterization and DECT parameters as quantitative evaluation of pulmonary blood volume (PBV). PBV was calculated as the average of entire lung iodine density.

Results
PBV value in non-microvasculopathy group showed significant inverse correlation with pulmonary vascular resistance (PVR) (y = 14236 x-1.028 r=−0.530, p<0.01).
PBV, SvO2, and %DLCO/VA were significantly lower (22.0 vs. 26.4, p<0.01, 61.3 vs. 66.0, p<0.01, and 59.2 vs 75.9 p<0.01), and systolic pulmonary arterial pressure, PVR, VE/VCO2 slope, BNP were higher (69.3 vs 60.6 p=0.04, 834 vs 586 p<0.01, 45.5 vs. 37.8, p=0.02, and 440 vs 122 p=0.04) in microvasculopathy group, while the other parameters were similar between the two groups.
Multivariate analysis revealed that %DLCO/VA was the only predictor of microvasculopathy (OR,0.895 [95% CI, 0.835 - 0.960]; P<0.01).

Conclusion
Pulmonary blood flow of patients in non-micorvasculopathy group showed inverse correlation with PVR. DECT was effective to assess the microvasculopathy in CTEPH. In our experience, less than 60% of non-operable CTEPH patients have microvasculopathy.
P5024Pathogenic mechanism of DSG2-F531C mutation caused arrhythmogenic right ventricular cardiomyopathy
Authors: Wang D , Zhou X , Guo Y , Yang B 
Published: October 2019

Abstract

Objective
Mutations in the Desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We previously identified a highly conserved F531C (c.1592T>G) variant of the cardiac desmosome gene DSG2 in the proband with a positive family history. The aim of this study is to investigate the mechanism(s) of DSG2-F531C variant in the pathogenesis of ARVC.

Methods
A large Han Chinese family with five generations was enrolled in this study, physical and clinical examinations were performed. Seven members were diagnosed with ARVC. Subsequently five desmosomal genes (PKP2, DSG2, DSP, DSC2 and JUP), TMEM43 and PLN were sequenced directly from genomic DNA. Seven patients diagnosed with ARVC were homozygous for DSG2-F531C, while five members of the family with normal phenotype were heterozygous for DSG2-F531C. To further explore the role of DSG2-F531C in ARVC pathogenesis, we generated a knock-in (KI) mouse model, which was carrying the mouse equivalent form (DSG2-F536C) of this variant.

Results
The homozygous KI mice (DSG2-F536C+/+) revealed a robust cardiomyopathy phenotype with left ventricular systolic dysfunction, histopathology showed accumulation of collagen, spotty calcification and fat droplets with extensive fibrosis in ventricular tissue in all DSG2-F536C+/+ mice. Further detections showed widening of the intercalated disc and regional loss of DSG2 in the hearts of these mice. The marked reduction in immunoreactive signal for sodium voltage-gated channel alpha subunit 5 (NaV1.5) was observed with no apparent changes in plakoglobin and connexin-43. In addition, dramatically elevated expression of transforming growth factor β1 (TGF-β1) was also found in the DSG2 mutant mice. Intriguingly, the heterozygous KI mice (DSG2-F536C+/−) expressed a similar level of TGF-β1 versus homozygous ones (DSG2-F536C+/+), but exhibited slight changes in morphology.

Conclusions
The DSG2-F536C KI mice produce a similar pathological phenotype of human ARVC, which supports DSG2-F531C as a causative mutation for ARVC. Additionally, the DSG2-F536C+/+ mutation induced cardiac fibrosis through the activation of TGF-β1 signaling will open new opportunities for further mechanistic and therapeutic studies in DSG2-related ARVC.

Acknowledgement/Funding
National Key R&D Program of China [2017YFC0909400); National Key Basic Research Program of China [973 program No. 2013CB531105]
P5027Prognosis and evaluation of the risk markers of arrhythmia in a large population of Brugada syndrome patients
Authors: Probst V , Anys S , Sacher F , Briand J , Guyomarch B , Tixier R , Berthome P , Babuty D , Thollet A , Mansourati J , Dupuis J M , Wiart F , Mabo P , Behar N , Gourraud J B 
Published: October 2019

Abstract

Introduction
Brugada syndrome (BrS) is an inherited arrhythmia syndrome with an increased risk of sudden cardiac death (SCD) despite a structurally normal heart. Many parameters have been suggested to be associated with the risk of ventricular arrhythmias, but only previous symptoms and spontaneous ECG pattern have been consistently associated with the risk of ventricular arrhythmia occurrence.

Objective
The aim of this study was to evaluate the association of these parameters with arrhythmic events in the largest cohort of BrS patients ever described.

Methods
Consecutive patients affected with BrS were recruited in a multicentric prospective registry in France (15 centers) between 1994 and 2016. Data were prospectively collected with an average follow-up of 6.5±4.7 years. ECGs were reviewed by 2 physicians blinded to clinical status.

Results
In this study, we enrolled a total of 1613 patients (mean age 45±15 years; 1119 males, 69%). At baseline, 462 patients (29%) were symptomatic (51 (3%) aborted SCD, 257 (16%) syncope). A spontaneous type 1 ECG pattern was present in 505 patients (31%). Implantable cardiac defibrillator was implanted in 477 patients (30%).
During the follow-up, 91 patients (6%) underwent arrhythmic events (16 SCD (10%), 48 appropriate ICD therapy (3%) and 27 ventricular arrhythmias (2%). Thirty-six patients (2%) died of non-arrhythmic causes. Mean age at the first event was 44±15 years.
In our cohort, event predictors were SCD (HR: 18.3; 95% CI: 11.2–29.8; p<0.0001), syncope (HR: 2.9; 95% CI: 1.8–4.9; p<0.0001), age >60 years (HR: 0.11; 95% CI: 0.032–0.377; p=0,0004), gender (HR: 2.96; 95% CI: 1.6–5.4; p=0.0005), spontaneous type 1 (HR: 2.14; 95% CI: 1.42–3.23; p=0.0003), type 1 ST elevation in peripheral ECG lead (HR: 3.6; 95% CI: 1.9–7.1; p=0,0001), fragmented QRS (HR: 3.37; 95% CI: 1.37–8.32; p=0,008), AvR sign (HR: 2.2; 95% CI: 1.4–3.8; p=0,0007), QRS >120ms in D2 lead (HR: 2.2; 95% CI: 1.4–3.6; p=0,001) and QRS >90ms in V6 (HR: 2.1; 95% CI: 1.3–3.3; p=0,001). All the others parameters including early repolarization pattern (ERP) and EPS were not predictor of events.

Conclusion
In the largest cohort of BrS patients ever described, we confirmed that symptoms, age, gender, spontaneous type 1, type 1 ST elevation in peripheral ECG lead, fragmented QRS, AvR sign, QRS >120ms in D2 and QRS >90ms in V6 are associated with arrhythmic events whereas ERP and EPS were not.