bluuebunny/crossref_metadata_2025_split huggingface dataset:
278Clinical outcomes of state-of-the-art percutaneous coronary revascularization in patients with three-vessel disease: 3-year follow-up of the SYNTAX II study
Authors: Serruys P W J C , Walsh S , Sabate M , Davies J , Lesiak M , Moreno R , Cruz-Gonzalez I , West N , Piek J , Stables R , Van Mieghem N M , Farooq V , Escaned J , Banning A , Onuma Y 
Published: October 2019

Abstract

Background
The clinical implication of state-of-art PCI at long term follow-up in patients with three vessel disease is undetermined.

Purpose
The purpose of the study was to investigate whether the favourable outcomes of state-of-the-art PCI in the SYNTAX-II trial, demonstrated up to 2 years, are maintained at 3-year follow-up.

Methods
The SYNTAX-II study was a multicentre, single arm study that investigated the impact of a state-of-art PCI strategy on clinical outcomes in patients with de novo three vessel coronary artery disease, without left main disease. State-of-art PCI includes: heart team decision-making utilizing the SYNTAX score II, hybrid iFR-FFR decision-making strategy, intravascular ultrasound guided stent implantation, contemporary chronic total occlusion revascularization techniques and guideline-directed medical therapy. The primary endpoint is major adverse cardiac and cerebrovascular events (MACCE – a composite of all-cause death, any stroke, myocardial infarction, or revascularization) at 3 years. Clinical outcomes in SYNTAX-II were compared to the predefined PCI (SYNTAX-I PCI) and coronary artery bypass graft (SYNTAX-I CABG) cohorts from the landmark SYNTAX Trial (SYNTAX-I), selected on the basis of equipoise for long-term (4-year) mortality utilising the SYNTAX Score II.

Results
Between February 2014 and November 2015, 454 patients out of 708 screened patients were enrolled in SYNTAX-II. In SYNTAX-I, 643 (58.8%) patients with 3VD without left main disease had an equipoise recommendation for CABG or PCI based on the SYNTAX Score II and were used as the comparator. At 2 years, MACCE rate in SYNTAX-II was significantly lower compared to SYNTAX-I PCI (13.2% vs. 21.9%, p=0.001). Furthermore, similar two-year outcomes for MACCE were evident between SYNTAX II-PCI and SYNTAX-I CABG (13.2 vs. 15.1%, p=0.42). Three-year results will be presented at ESC2019.

Conclusions
Three-year results of his study may offer an attractive option of revascularization strategy in predefined patients with de novo 3VD (SYNTAX Score II inclusion) even if the patients have moderate to severe anatomical complexity (anatomic SYNTAX score >22).

Acknowledgement/Funding
European Cardiovascular Research Institute (ECRI) with unrestricted research grants from Volcano and Boston Scientific
279Clinical outcome after coronary bifurcation stenting: a systematic review and network meta-Analysis of PCI bifurcation techniques comprising 5572 patients
Authors: Di Gioia G , Sonck J , Colaiori I , Mizukami T , Kodeboina M , Barbato E , De Bruyne B , Collet C 
Published: October 2019

Abstract

Background
The optimal PCI technique for bifurcation lesions remains a matter of debate. Several RCT have compared different bifurcation PCI techniques. Provisional stenting has been recommended as the default technique for most bifurcation lesions. However, emerging data suggests that double-kissing crush technique can be considered in true left main bifurcation lesions and has been endorsed by the European Society of Cardiology Guidelines.

Purpose
To compare the clinical outcome between different bifurcation PCI techniques.

Methods
We searched MEDLINE for randomized clinical trials (RCT) comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE) defined as the composite of cardiac death, myocardial infarction (MI) and target vessel or lesion revascularization (TVR/TLR), and the individual components of MACE. Stent thrombosis was assessed as defined by the ARC. Stratification based on left-main or distal bifurcations was performed. We evaluated the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We estimated summary odds ratios (ORs) using pairwise and Bayesian network meta-analysis.

Results
We identified 263 studies and of these included 19 RCT including 5572 patients treated with 5 bifurcation PCI techniques namely provisional stenting, systematic T-stenting, crush, culotte and double-kissing crush. Median follow-up was 12 months (IQR 8 to 36). When all bifurcation lesions were combined, double-kissing crush technique reduced the occurrence of MACE (OR 0.42; CrI 0.28 to 0.61) compared to provisional stenting. This difference was driven by a reduction in TVR/TLR (OR 0.39; CrI 0.25 to 0.65). No differences were found in cardiac death, MI or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed between provisional stenting, systematic T-stenting, crush. In distal bifurcations (n=17 studies, 4634 patients), double-kissing crush also showed to reduce MACE (OR 0.48; CrI 0.29 to 0.67 vs. Provisional). In left-main bifurcations (n=3 studies, 938 patients) no differences in MACE were found between PCI techniques.

Conclusions
In this network meta-analysis, PCI bifurcation techniques were similar with respect to the occurrence of cardiac death, myocardial infarction and stent thrombosis. When all coronary bifurcations were combined, an advantage of double-kissing crush was observed in terms of MACE driven by lower rate of repeated revascularization. Further studies are required to define the best PCI bifurcation technique for left main coronary artery disease.
391Gadobutrol enhanced CMR to detect significant coronary artery disease defined by quantitative coronary angiography. Results from two blinded phase III clinical trials
Authors: Arai A 
Published: October 2019

Abstract

Background
The FDA regulated GadaCAD1 trial and the nearly identical GadaCAD2 clinical trial aimed to determine whether gadobutrol-enhanced CMR can detect significant CAD.

Methods
Two multicenter, international trials enrolled patients with known or suspected CAD and used cine MRI, gadobutrol enhanced stress/rest perfusion, and late gadolinium enhancement. Endpoints, primary, and secondary minimum performance thresholds versus QCA and stress cine MRI are summarized in the table. There were 3 blinded, core-lab CMR readers per trial (6 readers overall) and 2 core-lab QCA readers. A meta-analysis combined results from all 6 CMR readers.

Results
765 patients were analyzed (GadaCAD1: n=376, GadaCAD2: n=389). The meta-analysis of 6 readers had 79% sensitivity, 87% specificity, and AUC of 0.82 to detect a 70% QCA stenosis and met all study endpoints (figure & table). Versus a 50% QCA stenosis, the meta-analysis also met all study endpoints. At an individual reader level, all 6 readers met all study endpoints versus a 70% QCA stenosis. Versus a 50% QCA stenosis, only 1 of 6 readers exceeded the minimum performance threshold for sensitivity but all 6 readers met all other endpoints. For all readers, stress perfusion was more sensitive than stress wall motion (p<0.05).
Diagnostic Accuracy Results

Conclusions
CMR stress perfusion has high diagnostic accuracy for significant CAD. The ROC analysis and overall results support prior literature that a 70% QCA threshold is a more appropriate threshold for physiologically significant CAD.

Acknowledgement/Funding
Bayer
445Effects of losartan and beta-blockers on aortic root dilatation in patients with Marfan Syndrome - results of the extended COMPARE trial
Authors: Van Andel M M , Jalalzadeh J , Indrakusuma R , Balm R , Timmermans J , Van Den Berg M P , Scholte A J H A , De Waard V , Zwinderman A H , Mulder B J M , Groenink M 
Published: October 2019

Abstract

Introduction
Despite several randomized trials, beneficial effects of Losartan and β-blockers in adults with Marfan syndrome (MFS) are not entirely clear. The COMPARE trial previously showed a small but significant beneficial effect of Losartan on top of β-blocker use on aortic root dilatation rate. Yet, this effect was not reproduced by other trials, although in general a favourable effect of Losartan could be demonstrated. All trials in adults with MFS showed lower than expected aortic root dilatation rates, suggesting mildly affected study populations. Therefore we extended the follow-up period of the COMPARE trial up to 10 years and aimed to assess the clinical outcomes of the study cohort, as well as the effect of medication regimes on aortic root dilatation rates in the subgroup of patients with a native aortic root at initial randomization.

Methods
Patients previously enrolled in the COMPARE trial were retrospectively analyzed. Cardiovascular events (aortic dissections, ruptures and operations) and all-cause mortality were assessed. Individual aortic root dilatation rates were estimated in patients with a native aortic root at time of randomization on the basis of linear regression analysis of multiple transthoracic echocardiogram (TTE) results. Correlations between aortic root dilatation rates and cumulative Losartan or β-blocker treatment days were assessed with Spearman's rho (ρ).

Results
During a median follow-up of 8.0 years, two dissections and three deaths occurred in the 151 patients with a native aortic root at time of randomization. The 122 patients that were eligible for aortic root dilatation analysis, underwent a median of 6 TTEs. The median aortic root dilatation rate in these patients was 0.28 (interquartile range 0.09 - 0.59) mm/y. These patients were further classified as either patients with a stable aortic root (n=102) or with aortic root growth (n=20), based on the threshold of 0.9 mm per year. Patients with aortic root growth had significantly more aortic root replacements during follow-up (17/20 vs 18/102, P=0.001).
Furthermore, aortic root dilatation rate was negatively correlated with the number of Losartan treatment days (ρ=−0.272, P=0.003), β-blocker treatment days (ρ=−0.217, P=0.017) and with the duration of follow-up (ρ=−0.437, P<0.001).

Conclusions
Our results support previous findings that Losartan and β-blockers appear to be equally effective on aortic root dilatation rate in Marfan Syndrome patients. The low event rate in the long term follow-up of this subgroup of the COMPARE trial represent a relatively mildly affected study population and an aggressive prophylactic surgical regime.
467FFR guided acute complete revascularization versus culprit lesion only treatment in patients presenting with STEMI; 3-year cost-analysis data from COMPARE-ACUTE trial
Authors: Smits P C , Abdel-Wahab M , Neumann F J , Boxma-De Klerk B M , Laforgia P L , Schotborgh C E , Wlodarczak A , Hambrecht R , Angeras O , Fischer H , Richardt G , Omerovic E 
Published: October 2019

Abstract

Background
Compare-Acute trial showed a 1-year superior outcome of FFR-guided acute complete revascularization (FFR-CR) compared to culprit-lesion-only revascularization (CLO) in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Long-term results and financial impact of this strategy are unknown.

Purpose
To evaluate if FFR-CR strategy is superior to CLO strategy in terms of health care costs at 3 year follow-up.

Methods
Compare-Acute is a multicenter, investigator-initiated prospective randomized controlled trial that involved 24 sites. Patients with STEMI and MVD were randomized 1:2 after successful primary PCI, towards FFR-CR or CLO treatment strategies (295 vs 590 pts). All stenosis ≥50% by angiography in the non-infarct artery were investigated by FFR in both arms. In the FFR-CR arm, all non-culprit (NC) lesions with a FFR ≤0.80 were treated by PCI. In the CLO arm pts underwent blinded FFR procedure of the NC lesions. Further treatment of these lesions was based on symptoms and/or ischemia testing during follow-up with an allowed treatment window of 45 days. The primary endpoint was defined as a composite of all-cause mortality, non-fatal myocardial infarction, any revascularization and cerebrovascular events (MACCE) at 12 months. The major secondary endpoints are MACCE and health care costs from both strategies up to 3-year follow-up. Cost-analysis is done from an insurance/governmental perspective in countries that use Diagnosis Related Group (DRG) costs: the Netherlands, Germany, Sweden and Poland.

Results
1-year results have already been published and showed superior outcome of patients in the FFR-CR arm. According to the Dutch system, at 1 year of follow-up the average cost per patient was 8.150€ in the FFR-CR arm, and 10.319€ in the CLO arm (−21%). The better cost-effectiveness of FFR-CR strategy remained at 3 years of follow-up: average cost per patient was 8.653€ in the FFR-CR arm and 11.100€ in the CLO arm (−22%). Same 3-year data was confirmed using DRG analysis according to the German system (FFR-CR 4.887€ vs CLO 5.200€; −6.0%) and the Swedish system (FFR-CR 6.205€ vs CLO 8.133€; −23.7%). FFR-CR strategy was not more costly according to the Polish system (FFR-CR 3.704€ vs CLO 3.685€; +0.5%). Moreover, the better outcome of the FFR-CR group was mantained at 3 year follow-up (data not shown).
Figure 1

Conclusion
Our cost-analysis of the Compare Acute Trial shows that the strategy of FFR-guided complete revascularization in patients with STEMI and MVD is not only superior in terms of outcome, but also in terms of health care costs at 1 year. This benefit is maintained at 3 years follow-up.
468Patients eligible for proprotein convertase subtilisin/kexin type9 inhibitors (pcsk9i) after acute myocardial infarction. The ESC position applied to patients included in the FAST-MI 2015 registry
Authors: Schiele F , Puymirat E , Ferrieres J , Onceanu S , Beard T , Marchand X , Landel J , Meneveau N , Simon T , Danchin N 
Published: October 2019

Abstract

Background
PCSK9i on top of high intensity statins have shown clinical benefit in patients after Acute Myocardial Infarction (AMI) who are not at LDL-c target. The ESC Task Force has defined guidance for the prescription of PCSK9i. Among patients discharged after AMI, the rate of those eligible for PCSCK9i is poorly documented.

Methods
We used data from the nationwide French FAST-MI 2015 registry. PSCK9-eligible patients were defined as those discharged with high intensity statins with expected-LDL>140 mg/dL, or >100mg/dL if they had additional high risk features such as diabetes with renal dysfunction or hypertension, multivessel coronary disease, associated peripheral artery disease or recurrent MI. The expected LDL-c was estimated from admission LDL-c and changes in lipid-lowering treatment. The rate of eligible patients was estimated from actual treatment and optimized treatment (i.e. addition of ezetimibe).

Results
Among 5291 pts included, 4715 (89%) were discharged with statins, at high intensity in 3655 (71%). Expected LDL was 71mg/dL (IQ 56, 95). Among patients discharged with high intensity statins, 3146 (59%) had an expected LDL-c<100/mg (figure, in green). PCSK9-eligible patients were those with LDL-c>140mg/dL (n=178, 3.3%, in red) and, among those with LDL-c 100–140mg/dL (n=331, 6.2%, in yellow), patients who had additional risk features (n=227 (4%)). As a result, the population eligible for PSCK9i according to the ESC guidance would represent 7.6% (405 pts) of the population admitted with AMI. Expanding the indication to patients with statins, but not at high intensity would add 159 (3%). Conversely, optimizing discharge treatment with ezetimibe would reduce the rate of eligible patients to 3% (181 pts, in brown).

Conclusions
In real life, according to the ESC Task Force, 7.6% of the whole population admitted for AMI would be eligible for PCK9i. This rate could be reduced to 3% with the addition of ezetimibe.
480Right ventricular dysfunction is associated with late mortality in severe aortic stenosis: results from a multi-centre outcome study in patients undergoing aortic valve replacement
Authors: Rigolli M , Musa T A , Treibel T A , Loudon M , Vassiliou V S , Captur G , Singh A , Chin C , Dobson L E , Pica S , Malley T , Foley J R J , Bijsterveld P , Law G R , Myerson S G 
Published: October 2019

Abstract

Background
The right ventricle (RV) is relatively understudied and often not routinely assessed in aortic stenosis (AS). However, there are several potential reasons for its importance. RV function is sensitive to left-sided afterload changes which can result in pulmonary hypertension (PH) in severe AS. PH is also a recognised predictor of poor prognosis in AS, but RV afterload and function can be difficult to assess. Cardiovascular magnetic resonance (CMR) may reveal unrecognised RV dysfunction and simultaneously evaluate other prognostic markers in AS.

Purpose
To investigate preoperative RV function assessed by CMR in severe AS and its association with mortality after aortic valve replacement (AVR).

Methods
674 severe AS patients listed for either surgical or percutaneous AVR at six cardiothoracic centres underwent preoperative CMR (for ventricular function, mass and scar) along with echocardiography for valve severity. Scans were core-lab analysed for LV and RV volumes, function and scar quantification. Eight patients were excluded due to inadequate RV image quality for a total of 666 patients finally included. All-cause mortality was tracked for a minimum of 2 years after AVR.

Results
107 (16%) of severe AS undergoing invasive AVR had a RV ejection fraction (RVEF) <55%. CMR detected overt RV dysfunction (RVEF <50%) in 61 (9%) patients. During a median 3.6 years follow-up, 145 (22%) patients died. Baseline RV dysfunction was the most powerful predictor of all-cause mortality (hazard ratio [HR] 2.5, 95% CI 1.6–3.9, p<0.0001). RV function was independent from other clinical characteristics but associated with signs of LV maladaptation (LV ejection fraction [LVEF] and late gadolinium enhancement [LGE]). The strongest Cox multivariable model for all-cause mortality accounted for RV dysfunction, age and LGE (adjusted HRs 1.7, 1.1, 2.2, respectively). Even early stages of pre-procedural RV dysfunction (RVEF 45–50%) were associated with reduced long-term survival.
Cox and Kaplan-Meier for all-cause death

Conclusion
One out of 6 patients with severe AS undergoing valve replacement manifests a reduction in RV function detectable by CMR. Those with RV dysfunction (RVEF<50%) have a 2.5-fold increase in all-cause mortality after AVR at 3.6 years. Whilst RV dysfunction is associated with LV maladaptation (LGE, LVEF), it is a powerful independent factor associated with all-cause mortality and impacts survival even at early stages. Thus, the RV appears to be important in cardiac adaptation to AS and longevity after AS intervention.

Acknowledgement/Funding
British Heart Foundation and National Institute of Health Research
P305Prognostic value of relative apical sparing pattern of longitudinal strain in patients with severe aortic stenosis
Authors: Saito M , Imai M , Wake D , Higaki R , Sumimoto T , Inaba S 
Published: October 2019

Abstract

Background
The relative apical sparing pattern (RASP) of left ventricular longitudinal strain (LS) is determined on the strain polar map, while global longitudinal strain (GLS) is measured using speckle-tracking echocardiography and is frequently associated with cardiac amyloidosis (CA). According to recent reports, some elderly patients with aortic stenosis (AS) suffer from transthyretin CA and have a poor prognosis. Accordingly, we aimed to investigate the association of RASP and outcome of patients with severe AS.

Methods
We retrospectively studied 157 consecutive patients (age: 81±10 years, 33% men) with severe AS (mean transaortic pressure gradient: 49 mmHg) and preserved ejection fraction (>50%). After measuring GLS, RASP was semi-quantitatively and quantitatively assessed. Semi-quantitative RASP (sRASP) was defined as reduction of LS (more than −10%), showing light red or blue in ≥5 segments out of the basal six segments, relative to apical LS (less than −15%) showing red. This analysis was independently performed in a blinded manner by two observers. Quantitative RASP (qRASP) was calculated using the following formula: average apical LS/(average basal LS + average mid-ventricle LS), then qRASP ≥1 was determined as positive according to the previous paper. Patients were followed up to determine their outcomes, i.e., sudden cardiac death or unexpected admission due to heart failure over a median duration of 1.9 years. Concordance of sRASP was assessed using the kappa statistic, and a Cox proportional hazards model was used to assess the association between the parameters and primary outcome.

Results
The consistency in the observations of the two sonographers in identifying sRASP was found to be excellent (κ = 1.00). sRASP and qRASP were observed in 24 (15%) and 42 (27%) patients, respectively, and were significantly associated with the primary outcome (n=44; 28%). The representative case is shown in figure (left panel). Further, positive sRASP was associated with the outcome after adjusting for the Euro score, NYHA ≥II, and GLS (hazard ratio = 2.69, p=0.01). The model based on these covariates significantly improved following the addition of sRASP (Figure; right panel). In addition, sRASP was observed in four patients out of 50 patients who underwent aortic valve replacement. Of these, one patient had the primary outcome (25%). On the other hand, in the remaining 46 patients without sRASP, four patients had the outcome (9%).
Figure 1

Conclusions
RASP was observed in some patients with severe AS and has been shown to have increasing importance in predicting adverse cardiac events in such patients.
P314Osteopontin stimulates cell cycle in neonatal cardiomyocytes
Authors: Rotem I , Schary Y , Shaihov - Teper O , Konfino T , Leor J 
Published: October 2019

Abstract

Introduction
Macrophages control myocardial regeneration in the neonatal heart and repair in the adult heart. Osteopontin (OPN) is a macrophage-derived protein which is upregulated following tissue injury. While OPN regulates cell adhesion, spreading and migration, its role in myocardial regeneration is unknown.

Purpose
We aimed to test the hypothesis that OPN stimulates cardiomyocyte proliferation.

Methods and results
Mouse neonatal cardiomyocytes were treated with a serum-free medium for 24 hours. Immunofluorescent staining showed that these cells expressed the OPN receptor CD44 (Fig. 1A). To assess cell expansion, we used MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colorimetric assay. OPN preserved cardiomyocyte count in a low glucose medium for 24 hours, compared with no OPN treatment (Fig. 1B). Staining for phosphohistone (pH)3, a marker of nucleus division, showed a higher expression of pH3 in cardiomyocytes after OPN treatment (Fig. 1C). Immunoblotting revealed that OPN induced the phosphorylation of cell-cycle activity proteins, known as yes-associated protein (YAP)1, and extracellular signal-regulated kinase (ERK)2, while it decreased the phosphorylation of the YAP1 inhibitor, the large tumor-suppressor kinase (LATS)1/2 (Figs. 1D and 1E). Gene expression analysis revealed that OPN upregulated the transcriptional enhancer factor TEF-1 (TEAD1), which interacts with YAP1 (Fig. 1F), connective tissue growth factor (CTGF) and cyclin-dependent kinase 1 (CDK1), which are YAP downstream targets (Figs. 1G and 1H). Furthermore, OPN significantly upregulated cyclin B1, a regulator of the mitotic (M) phase (Fig. 1I). Moreover, OPN may promote positive feedback by upregulating the expression of CD44, SPP-1 (Figs. 1J and 1K). Finally, administration of OPN to adult mouse improved cardiac remodeling and function after myocardial infarction.

Conclusions
OPN stimulates cell-cycle activity in neonatal cardiomyocytes through YAP1 activity, independently from the HIPPO-YAP signaling pathway. Because macrophages are a major source of OPN after injury, our findings could explain the essential role of macrophages in neonatal heart regeneration and adult heart repair.

Acknowledgement/Funding
Israel Science Foundation