bluuebunny/crossref_metadata_2025_split huggingface dataset:
2210Symptomatic severe aortic stenosis: predictor factors and outcomes
Authors: Almeida I , Gomes R , Joao I , Cruz I , Pereira R , Quadrado M , Pereira H 
Published: October 2019

Abstract

Introduction
The natural history in aortic stenosis (AS) is a slowly progressive process which begins as aortic sclerosis and subsequently progresses to severe opening restriction, conditioning symptoms development. At this time, surgical aortic valve replacement is strongly recommended due to its poor prognosis.

Purpose
Evaluation of predictor factors of symptomatic severe AS and its prognostic impact.

Methods
Single center retrospective analysis of patients' data accompanied in cardiology consultation due to severe AS diagnosed between 2015–2016. Data was collected regarding clinical and echocardiographic parameters to determine predictor factors of stablished endpoints.

Results
150 patients were reviewed, mean age 76.6±9.0 years, 72% males. 68.7% had hypertension, 42% dyslipidaemia and 32.7% diabetes. 64.7% of the patients had symptoms attributable to severe AS: 48% dyspnoea, 12% angina and 4.7% syncope. 7.3% of the patients were hospitalized due to acute heart failure in this context. Comparing echocardiographic parameters between symptomatic versus non-symptomatic patients with severe AS, symptomatic patients had higher values of aortic maximum velocity (4.5±0.5 vs 4.3±0.4 m/sec, p<0.001) and mean gradient (50.1±12.7 vs 43.2±7.7 mmHg, p<0.001). There were no significant differences regarding mean aortic valvular area neither left ventricle ejection fraction. At univariate analysis, predictor factors of symptoms attributable to severe AS development were: hypertension (odds ratio (OR) 2.044, confidence interval (CI) 1.004–4.161, p 0.049), anaemia (OR 0.420, CI 0.207–0.851, p 0.016), aortic maximum velocity (OR 5.497, CI 2.014–15.000, p 0.001) and mean gradient (OR 1.073, CI 1.029–1.118, p 0.001). At multivariate analysis, only aortic maximum velocity showed to be independent predictor factor of symptomatic severe AS (p 0.012). Hospitalization and all-cause mortality rates (respectively: 9.3 vs 9.4%, p 0.975; and 25.8 vs 34%, p 0.305) did not differ between groups.

Conclusion
In patients with severe AS, aortic maximum velocity showed to be the only independent predictor factor of symptoms development, however it was not associated with an increased hospitalization or mortality rates.
2227Limited impact of concomitant coronary artery by-pass grafting on long-term outcomes after surgical aortic valve replacement: a nationwide propensity matched study
Authors: Kyto V , Sipila J , Pikkarainen E , Rautava P , Gunn J 
Published: October 2019

Abstract

Objective
Coronary artery disease is a common comorbidity of aortic stenosis. Addition of coronary artery by-pass grafting (CABG) to surgical aortic valve replacement (SAVR) is viable solution for treating both. Modern era impact of concomitant CABG to long-term outcomes is however inadequately known. We set out to study long-term outcomes of patients with or without CABG added to SAVR.

Methods
Patients (excluding infective endocarditis) aged ≥50 years with isolated first-time SAVR with or without CABG in Finland between 2004–2014 (n=7060) were retrospectively studied using nationwide registries. Propensity score matching (1:1) was used to identify patients with comparable baseline features (n=2188 with and n=2188 without concomitant CABG). Outcomes were 10-year all-cause mortality, stroke, major bleeding and myocardial infarction. Median follow-up was 6.1 years.

Results
In matched population mortality after SAVR was comparable with or without CABG (31.0% vs. 32.7%; HR 1.05; CI 0.93–1.20; p=0.428). However, if CABG was performed solely with venous grafts mortality was higher (35.9%; HR 1.21; CI 1.02–1.43; p=0.030 vs. no-CABG). Myocardial infarction was more common in patients with CABG (13.4% vs. 6.9%; HR 1.62; CI 1.22–2.17; p=0.0008). Occurrence of stroke was comparable with or without CABG (15.1% vs. 13.5%; p=0.933). Rate on any major bleeding was also comparable (20.0% with vs. 21.9% without CABG; p=0.496). Gastrointestinal (8.1% vs. 10.3%; p=0.978) and intracranial bleeds (6.0% vs. 5.5%; p=0.383) were also comparable between study groups.

Conclusions
Matched patients with or without concomitant CABG had comparable long-term mortality, stroke and major bleeding rates after SAVR. Our results suggest that successful concomitant CABG has limited impact on long-term outcomes after SAVR.

Acknowledgement/Funding
Finnish Cardiac Society, Finnish Cultural Foundation, Governmental VTR-funding
2395LGE CMR predicts sudden death and VT in adults with repaired tetralogy of Fallot - a prospective study with 3500 patient follow up years
Authors: Ghonim S , Gatzoulis M A , Smith G C , Heng E , Ernst S , Li W , Keegan J , Diller G P , Dimpoulos K , Moon J C , Pennell D J , Babu-Narayan S V 
Published: October 2019

Abstract

Background
Adults with repaired tetralogy of Fallot (rtoF) are at risk of ventricular arrhythmia and sudden cardiac death (SCD). Cross-sectional data suggest association of late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) with adverse clinical risk factors

Purpose
We sought to determine prognosis related to LGE CMR.

Methods
In this prospective cohort study the primary composite outcome comprised the first of cardiovascular death (SCD or heart failure-related), aborted SCD (successfully resuscitated cardiac arrest or appropriate AICD shock for ventricular fibrillation), and clinical sustained ventricular tachycardia (VT>30 seconds duration).

Results
In 531 rtoF patients (median age 32; 23–42, 296 (56%) male, NYHA≥II 17%) followed up after LGE CMR for median 5 (1.7–8.9) years, there were 39 primary composite outcomes: 10 SCD, 11 heart failure related deaths (2 perioperative RV failure), 2 aborted SCD and 16 clinical sustained VT events. At study end, there were 28 ventricular arrhythmic events in 28 rtoF patients (10 SCD, 16 clinical sustained VT, 2 aborted VF) that were significantly predicted by RV LGE extent (HR 1.45 CI: 1.3–1.6; P<0.001).
Univariable predictors of the primary outcome were RV LGE score; HR: 1.44 (1.31–1.57; p<0.001), (Figure) together with older age; HR: 1.05 (1.02–1.07; P<0.001), late repair; HR: 1.04 (1.02–1.07; p<0.001), lower RV ejection fraction; HR: 0.92 (0.89–0.95; p<0.001), larger RVOT akinetic length; HR: 1.04 (1.02–1.06; p<0.001) larger right atrial area; HR: 1.2 (1.12–1.29; p<0.001); higher BNP levels; HR: 1.01 (1–1.02; p<0.001), lower peak VO2; HR: 0.89 (0.83–0.96; p=0.001), prior atrial arrhythmia; HR: 5.3 (2.8–10.07; p<0.001), and non-sustained VT; HR: 4.1 (2.1–7.7; p<0.001). Inducible VT did not predict the primary outcome; HR: 2.1 (0.57–8; p=0.25)
In multivariable analysis both RV LGE score and indexed right atrial area (RAAi) only, remained predictive of the primary outcome (HR 1.29 CI: 1.12–1.49; p<0.001 and HR 1.1 CI: 1.02–1.12; p=0.01, respectively). Patients could accordingly be stratified such that supramedian RV LGE score (≥5) and RAAi ≥16cm2/m2 had 5-year event free survival 84% vs 94% for supramedian RV LGE score (≥5) and RAAi <16cm2/m2 or 98% for inframedian RV LGE score with RAAI<16cm2/m2. Figure.

Conclusions
For every unit increase in CMR defined RV fibrosis score there is a 44% increased risk of sudden cardiac death and VT. LGE CMR and maximal right atrial area should therefore be incorporated into risk stratification for sudden death in adults with rTOF.

Acknowledgement/Funding
British heart foundation
2422Outcome of histologically-proven fulminant versus acute non-fulminant myocarditis with left ventricular systolic dysfunction. Evidence from the International Registry on Acute Myocarditis
Authors: Ammirati E , Veronese G , Brambatti M , Merlo M , Potena L , Okumura T , Pinney S , Braun O , Van De Heyning C M , Montero S , Shimokawa H , Sinagra G , Adler E , Frigerio M , Camici P G 
Published: October 2019

Abstract

Background
Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular (LV) dysfunction requiring inotropes and/or mechanical circulatory support. Based on a retrospective single-center study published in 2000, patients with FM were considered to have better outcomes than those affected by acute non-fulminant myocarditis (NFM) presenting with LV systolic dysfunction (LVSD). Recently, this tenet was challenged, though substantial disagreement still exists.

Purpose
Aim of the present study is to provide additional evidence on the outcome of FM and to ascertain if patient stratification based on the main histologic subtypes can provide additional prognostic information.

Methods
Two hundred and twenty patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) presenting with LVSD were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The primary endpoint was the occurrence of cardiac death or heart transplant (HTx) within 60 days from admission and at long-term follow-up.

Results
Patients with FM (N=165) had significantly higher rates of cardiac death and HTx compared with those with NFM (N=55), both at 60 days (28.0% vs. 1.8%, p=0.0001) and at 7-year follow up (47.7% vs. 10.4%, p<0.0001; Figure). At Cox-multivariate analysis, the histologic subtype emerged as a further variable affecting outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis both at 60 days (62.5% vs. 26.3% vs. 21.0%) and at 3 years (81.3% vs. 39.9% vs. 37.3%, overall p<0.0001). In a sub-analysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with NFM both at 60 days (19.5% vs. 0%, p=0.005) and up to 7 years (41.4% vs. 3.1%, p=0.0004).
Outcome of FM vs NFM

Conclusions
The results of this international registry confirm that patients with FM have higher rates of cardiac death and HTx both in the short and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Acknowledgement/Funding
None
2425Evaluation of myocardial gene expression profiling for superior diagnosis of idiopathic giant cell myocarditis in a large cohort of patients with acute cardiac decompensation
Authors: Escher F , Pietsch H P , Gross U G , Lassner D L , Schultheiss H P 
Published: October 2019

Abstract

Background
Idiopathic giant cell myocarditis (IGCM) diagnostics is based on differential patterns of inflammatory cell infiltration, and multinucleated giant cells (GCs) in histological sections of endomyocardial biopsies (EMBs). However, the sampling error is high for the detection of focally GCs by histopathology. We report on a clinical evaluation of a recently published method for improved differential diagnosis of this frequently fatal disease by myocardial gene expression profiling.

Objective
This is to improve the diagnostics of IGCM by gene expression profiling, and to demonstrate the feasibility of this method in clinical practice in a large cohort of patients.

Methods
In this multicenter study, EMBs of n=427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age 47.03±15.69 years). In each patient, EMBs were analyzed by histology, immunohistology, molecular virology, and gene expression profiling.

Results
Out of the total of n=427 patient samples examined, GCs could be detected in 26 cases (6.0%) by histology. An established myocardial gene profile – consisting of 27 genes – was revealed resulting in a specified profile of 5 genes (chemokine receptor 5 (CCR5), chemokine receptor 6 (CCR6); carnitine palmitoyltransferase I (CPT1), toll-like receptor 8 (TLR8), and chemokine (C-C motif) ligand 20 (CCL20)) which identified histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Applying this newly established profiling on the remaining patient samples, additional n=31 (7.3%) patients were identified for IGCM without any histological proof of myocardial GCs.

Conclusions
Myocardial gene expression profiling is a reliable method in clinical practice to predict IGCM even without direct histological proof of GCs in EMB section. The gene profiling is of high clinical relevance to overcome the sampling error of purely histological examination, and to control the effectiveness of the therapy. The data clearly show the importance to take EMB in unexplained acute decompensation to get a diagnosis and improve the prognosis.
P1216Evaluation of alphavbeta3 integrin-targeted positron emission tomography and photoacoustic tracer for imaging of carotid plaque in apoE–/– mice
Authors: Yao Y , Li L B , Ji Y , Ma G , Wu Y , Hu X , Yang M , Fan Q 
Published: October 2019

Abstract

Background
Cardiovascular disease is the leading cause of death in the world. The majority of cardiovascular events result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. The integrin αVβ3 is expressed by activated macrophages and endothelial cells in atherosclerotic lesions and thus is a marker of high-risk plaques. Therefore, 89Zr-RGD-melanin nanoparticle (MNP) positron emission tomography (PET)/photoacoustic imaging (PAI) imaging of αVβ3 expression in plaques might provide a novel noninvasive biomarker of plaque vulnerability.

Purpose
In this study, the intrinsic photoacoustic signals and the native strong chelating properties with metal ions of MNP, positron-emitting metal ions 89Zr and αVβ3 integrins targeting ability of cyclic c (RGDfC) peptide was employed to construct an efficient nanoplatform. And we evaluated the feasibility of 89Zr-RGD-MNP PET/PAI of αVβ3 expression in vivo and in vitro.

Methods
We conjugated αVβ3 integrins, cyclic c (RGDfC) peptide, to MNP and chelated the long-lived positron-emitting nuclide 89Zr. The bio-stability and targeting action was detected in macrophages. And the PET/PAI imaging was performed in apoE−/− mice with partial carotid ligation leading to atherosclerosis. In PET imaging, tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side at different time points in vivo. In PAI, photoacoustic signal was measured in the atherosclerosis of the carotid arteries in vivo. Melanin staining and immunohistochemistry of αVβ3 expression were detected in atherosclerosis of the carotid arteries.

Results
89Zr-RGD-MNP showed excellent bio-stability and targeting action. PET imaging showed specific tracer accumulation at plaques in the left carotid artery, confirmed by competitive receptor blocking studies and the contrast in the right carotid artery. In the biodistribution studies, the left carotid (5.29%±0.78%) showed higher uptake than the right carotid (2.11%±1.55%). PAI showed the PA signal in the surgery group (452±85 a.u.) were stronger than the control (156±45 a.u.) and blocking group (254±66 a.u). The result was consistent with PET imaging and the presence of nanoparticles, as indicated by pathological examinations. These results presented good in vivo multimodality imaging (PET/PAI) properties.

Conclusions
We have developed 89Zr-labeled atherosclerotic plaques imaging agents based on the natural melanin nanoparticle. 89Zr-RGD-MNP demonstrates specific tracer accumulation in mice atherosclerotic carotid plaques. In this model, its uptake was associated with αVβ3 expression. 89Zr-RGD-MNP is a potential tracer for noninvasive imaging in atherosclerosis.

Acknowledgement/Funding
National Natural Science Foundation of China 81770452, 81470401
P1224Statin treatment in children with familial hypercholesterolemia in Scandinavia
Authors: Svendsen K , Walaas Krogh H , Bogsrud M P , Holven K B , Retterstol K 
Published: October 2019

Abstract

Introduction
New European guidelines recommend that patients with familial hypercholesterolemia (FH) should initiate treatment with statins at age 8–10 years. The number of children using statins has not yet been investigated. The aim of the present study was to describe the number of statin users <19 years of age in the Scandinavian countries: Sweden, Denmark and Norway.

Methods
In the Scandinavian countries, statins are only available by prescription, and there are national registries for the use of perscriptional drugs. In the present study, we assumed that the number of children using statins is equivalent to a positive FH diagnosis in these countries. Using the estimated frequency of FH of 1:250, we calculated the number of expected children with FH per year. Next, the percentage of all FH children who were treated according to the national registries were calculated. We also calculated changes between 2006 and 2016.

Results
As shown in Table 1, 1086 children 5–19 years in Scandinavia used statins in 2016. In the ages 10–19 years, statins were more frequent used in Norwegian FH children than in children from Denmark and Sweden (Figure 1). Nevertheless, the number of children aged 5–19 years using statins increased from about 2% to 4% between 2006 and 2016 in Sweden and Denmark (n=109 and n=136 respectively) and from about 5% to 10% in Norway (n=340).

Discussion
We observed a modest increase in statin users aged 5–19 years in the Scandinavian countries during a 10-year period. Nevertheless, our findings indicate that it will take decades to implement the current Statin-recommendation. Possible reasons for the difference in the degree of treatment between the countries will be discussed during the presentation, in particular with respect to genetic testing and cascade screening.
Table 1. Statin use according to age and gender Age (year) Male, N (%) Female, N (%) Both Sexes, N (%) 5–9 36 (3) 30 (3) 67 (6) 10–14 158 (15) 127 (12) 294 (27) 15–19 327 (30) 395 (36) 725 (67) 0–19 521 (48) 552 (51) 1086 (100)
Figure 1. Percent of FH children using statins

Conclusions
Despite increased statin use during the last years, there is still a severe undertreatment of children with FH in the Scandinavian countries.
P1234Weight fluctuation demonstrates residual atrial arrhythmogenic substrate despite final weight loss in a chronic sheep model: implications for epicardial fat and fibrofatty infiltrates
Authors: Agbaedeng T A , Twomey D J , Thanigaimani S , Linz D , Lau D H , Mahajan R , Sanders P 
Published: October 2019

Abstract

Background
Obesity-mediated epicardial adipose tissue (EAT) expansion drives fat cell infiltration which forms the unique substrate for atrial fibrillation (AF). The LEGACY study showed the benefits of weight loss but an attenuated response with weight fluctuation. How fluxes in weight impacts the atrial substrate in not known.

Objective
To investigate EAT and the atrial substrates due to weight fluctuation, with comparison to stable obesity.

Methods
We studied 24 sheep in 3 equal groups over 80 weeks: 1. Obesity induced by high calorie diet fed ad libitum; 2. Weight fluctuation induced by 20-week cycle of weight gain/loss (20:20:20:20); and 3. Lean controls fed quality hay to maintain baseline weight. All sheep underwent: daily weight measurement; haemodynamic and imaging assessments (cardiac MRI; dual-energy X-ray absorptiometry; and matrix assisted laser desorption infrared lipid imaging); electrophysiological studies and electroanatomic mapping; histological and structural analysis. Evaluations included: atrial voltage, conduction velocity, and refractoriness (7 sites, 2 cycle lengths), electrogram fractionation, EAT volume, fibro-fatty infiltration, myolysis of myocytes, and spatial distribution of intra-atrial lipids.

Results
The Table shows the group differences. Compared to reference controls, obesity demonstrated: Increased atrial volume and pressure, abnormal atrial electrical properties, expanded EAT and ensuing fibro-fatty infiltrations, and myolysis of myocytes. Despite comparable weight and EAT with controls, weight fluctuation resulted in extensive and severe fibro-fatty infiltrations, and twofold greater myolysis that persisted. Moreover, characteristic profiles and abundance of lipid species in the atrial myocardium were noted on further evaluation. More importantly, EAT and fibro-fatty infiltrates strongly correlated with increased atrial volume and pressure; with only fibro-fatty infiltrates correlating with fractionated electrograms (r=0.71, p<0.001) and conduction slowing (r=−0.59, p=0.006). Similarly, atrial myolysis exhibited significant correlations with atrial enlargement and haemodynamics, and electrical substrates (p<0.05 for all).

Conclusions
Obesity induces fibro-fatty replacement of atrial myocytes and deterioration of contractile units, which may drive impaired electrical remodeling. Despite final weight loss, weight fluctuation demonstrates residual electro-structural, fibro-fatty and contractile substrates.
P1251Percutaneous coronary intervention versus medical therapy for coronary lesions with positive fractional flow reserve (FFR) but preserved coronary flow reserve (CFR). A substudy of the COMPARE-ACUTE
Authors: Haeck J D , Zimmermann F M , Van 'T Veer M , Neumann F J , Triantafyllis A S , Abdel-Wahab M , Omerovic E , Boxma-De Klerk B M , Pijls N H , Richardt G , Tonino P A , Johnson N P , Smits P C 
Published: October 2019

Abstract

Introduction
International guidelines recommend performing percutaneous coronary intervention (PCI) on stable coronary lesions with a positive fractional flow reserve (FFR) to improve clinical outcomes. It remains unclear if FFR positive lesions with preserved coronary flow reserved (CFR) might be better treated medically.

Purpose
This study compared clinical outcomes between PCI and medical therapy for stable FFR-positive lesions with preserved CFR.

Methods
We performed a substudy of the randomized, multicenter COMPARE-ACUTE trial in which treated ST-elevation myocardial infarction patients with stable non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperaemic pressure gradients, we computed the so-called pressure bounded-CFR (pb-CFR) and classified lesions as low (<2) or preserved (≥2). Our primary end point was a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events (MACCE) at 12 months.

Results
A total of 980 lesions from 885 subjects were included in this sub-study due to availability of baseline and hyperaemic pressure gradients. For the 462 lesions with FFR≤0.80, 249 had a pb-CFR<2 while 29 had a preserved CFR (pb-CFR≥2). The rate of MACCE at 1 year did not differ significantly between subjects with FFR≤0.80 and pb-CFR<2 versus FFR≤0.80 and pb-CFR≥2 (24% vs. 30%, p=0.44). Because of randomization, baseline characteristics were well balanced between subjects with FFR≤0.80 and pb-CFR≥2 who were treated by PCI or medical therapy. Importantly for subjects with FFR≤0.80 and pb-CFR≥2, MACCE occurred more frequently when treated medically compared with PCI (50% vs. 0% respectively, p=0.01).

Conclusions
In this post-hoc substudy from a large randomized controlled trial of 885 subjects with 980 lesions, a preserved pb-CFR≥2 did not associate with an improved clinical outcome when FFR≤0.80. Subjects with FFR-positive coronary lesions but a preserved pb-CFR experienced significantly worse clinical outcomes when treated medically instead of with PCI. These data suggest that a stenosis with a FFR≤0.80, even when pb-CFR remains preserved, benefits from treatment with PCI.

Acknowledgement/Funding
Maasstad Cardiovascular Research, Abbott Vascular and St. Jude Medical