bluuebunny/crossref_metadata_2025 huggingface dataset:
121Clinical impact of residual SYNTAX score after physiology guided state-of-art PCI in 3VD: insight from the SYNTAX II trial
Authors: Kogame N , Modolo R , Chichareon P , Komiyama H , Taggart D , Escaned J , Banning A , Farooq V , Onuma Y , Serruys P W
Published: October 2019

Background

The clinical implication of residual SYNTAX score in patients treated with state-of- art PCI including hybrid iFR-FFR for three vessel disease is undetermined.

Purpose

The purpose of this study was to investigate the clinical impact of residual SYNTAX Score (rSS) after hybrid iFR-FFR guided state-of-art PCI in patients with three vessel disease (3VD).

Methods

The SYNTAX-II study was a multicentre, single arm study that investigated the impact of the state-of-art PCI strategy on clinical outcomes in 454 patients with de novo 3VD, without left main disease. All the patients treated with the state-of-art PCI in the SYNTAX II trial were retrospectively screened and analysed for rSS. The rSS was defined as the SYNTAX Score (SS) recalculated after PCI. The state-of-art PCI strategy included: 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 of this substudy was major adverse cardiac and cerebrovascular events (MACCE – a composite of all-cause death, any stroke, myocardial infarction, or revascularization) at 2 years. Patients with rSS were stratified according to angiographically complete revascularization (rSS of 0) and previously proposed rSS cut-off value of 8 (>0 to 8, and >8).

Results

A total of 454 patients were screened and rSS were analysable in 441 patients (97.1%). Before PCI, anatomical SS was 20.3±6.4 which was after PCI reduced to 3.9±4.5 (rSS). Only 67 patients (15.2%) had rSS >8 (mean 12.3±4.1). Two-year MACCE occurred in 58 patients (13.2%). Patients with MACCE had similar rSS to those without MACCE (2.0 (IQR: 0.0 to 6.0) vs. 2.0 (IQR: 0.0 to 5.0), p=0.313). Kaplan-Meier analysis showed similar 2- year incidence of MACCE with rSS stratifications (rSS of 0 (n=140): 15.0%, >0 to 8 (n=234): 12.0%, >8 (n=67): 13.4%, log-rank p for overall = 0.703).

Conclusion

After hybrid iFR-FFR guided state-of-art PCI in 3VD, residual SYNTAX Score was very low, suggesting that complete or reasonable incomplete revascularization was achieved in majority of cases. Previously proposed rSS cut-off value of 8 was not associated with a worse clinical outcome.

Acknowledgement/Funding

European Cardiovascular Research Institute (ECRI) with unrestricted research grants from Volcano and Boston Scientific
122Mechanism and impact of lesion morphology on the late lumen loss of drug-eluting resorbable magnesium scaffolds: a serial optical coherence tomography study
Authors: Ueki Y , Raber L , Otsuka T , Losdat S , Windecker S , Garcia-Garcia H , Byrne R , Landmesser U , Koolen J , Waksman R , Haude M , Joner M
Published: October 2019

Introduction

Resorbable Magnesium Scaffolds have demonstrated favourable clinical results with acceptable late lumen loss (LLL). However, the pathomechanisms influencing LLL of resorbable sirolimus-eluting metallic scaffold (Magmaris) have not been analyzed.

Purpose

Using serial optical coherence tomography (OCT), we investigated potential factors, i.e. the contribution of recoil versus neointimal hyperplasia (NIH).

Methods

Patients who were enrolled into BIOSOLVE-II, and underwent serial angiography and OCT (baseline and follow-up: 6-month and/or 1-year) were analyzed. Patients were divided into 2 groups based on angiographic in-scaffold LLL <0.5mm or ≥0.5mm. Endpoints were late absolute recoil and NIH area as assessed by OCT.

Results

A total of 70 patients (LLL <0.5mm: n=41, LLL ≥0.5mm: n=29) were serially analyzed. Patient and lesion characteristics were comparable and there was no significant difference in mean and minimal scaffold area between groups at baseline. Late absolute recoil was significantly smaller among patients with LLL <0.5mm (0.53±0.68 mm2) compared with those with LLL ≥0.5mm (1.48±1.20 mm2, P<0.001) (Figure). A small difference in NIH area at follow-up was observed (LLL <0.5mm: 1.47±0.33 mm2 vs. LLL ≥0.5mm: 1.68±0.34 mm2, P=0.013). In a matched-frame analysis (baseline and follow-up), late absolute recoil varied according to the underlying plaque type (lipid: 0.63±1.23 mm2, calcified: 0.81±1.44 mm2, and fibrous: 1.20±1.52 mm2, P<0.001), while there was no difference with regards to NIH area (P=0.132).

Conclusion

The main driver of late lumen loss of sirolimus-eluting absorbable metal scaffold was late scaffold recoil, while the contribution of NIH was modest. The degree of late scaffold recoil depended on the underlying plaque type and was highest among fibrotic lesions. Future studies will address the impact of procedural factors such as adequate lesion preparation and post-dilatation.

Acknowledgement/Funding

Biotronik
126Clinical outcomes at two years of the Absorb BRS vs. the Xience metallic DES in patients presenting with ACS vs. stable coronary disease - AIDA trial substudy
Authors: Tijssen R Y G , Van Der Schaaf R J , Vink M A , Kraak R P , Hofma S H , Arkenbout E K , Weevers A P J D , Kerkmeijer L S , Onuma Y , Serruys P W J C , Piek J J , Tijssen J G P , Henriques J P , De Winter R J , Wykrzykowska J J
Published: October 2019

AIMS Patients with acute coronary syndrome (ACS) might represent a specific subgroup, in which bioresorbable scaffold implantation in percutaneous coronary intervention, might lead to better outcomes when compared to conventional treatment. ACS patients (STE-ACS patients in particular) are generally younger, and most often have lesions with softer plaques, a lower plaque burden and less extensive coronary artery disease. In this pre-specified subgroup analysis of the AIDA trial, we evaluated the clinical outcomes of Absorb BVS versus Xience EES treated patients presenting with or without ACS.

Methods and results

This analysis includes the 2-year outcomes of all 1845 patients randomized in the AIDA trial subdivided by clinical presentation, a pre-specified subgroup analysis. We compared patients presenting with ACS with those presenting without ACS (ACS versus no-ACS patients). Patients presenting with ACS were further sub-categorized according to the presence or absence of ST-segment elevation at presentation (STE-ACS versus NSTE-ACS patients). Baseline status by clinical presentation was known in all patients, and 842 (45.6%) patients presented with ACS, 456 (25.2%) with STE-ACS and 377 (20.4%) with NSTE-ACS.The rate of the 2-year primary endpoint of target vessel failure (TVF) was similar after treatment with Absorb BVS or Xience EES in ACS patients (10.2% versus 9.0% respectively; p=0.49) and in no-ACS patients (11.7% versus 10.7% respectively; p=0.67) Definite or probable device thrombosis occurred more frequently with Absorb BVS compared to Xience EES in ACS patients (4.3% versus 1.7% respectively, p=0.03) as well as in no-ACS patients (2.4% versus 0.2% respectively; p=0.002). There were no statistically significant interactions between clinical presentation and randomized device modality for TVF (p=0.80) and for the endpoint of definite or probable device thrombosis (p=0.17).

Conclusions

In ACS patients within AIDA, we found no difference in rates of target vessel failure between the Absorb BVS and Xience EES groups. Rates of definite or definite/probable device thrombosis were higher in the Absorb BVS group throughout all clinical presentations. No significant interaction between ACS and no-ACS patients and the occurrence of TVF

Acknowledgement/Funding

The AIDA trial was financially supported by an unrestricted research grant from Abbott Vascular.
131Left atrial phasic function in heart failure with preserved ejection fraction: cardiac magnetic resonance myocardial feature tracking, invasive hemodynamics and outcome
Authors: Schoenbauer R , Kammerlander A A , Duca F , Aschauer S , Binder C , Zotter-Tufaro C , Nitsche C , Fiedler L , Roithinger F X , Loewe C , Hengstenberg C , Bonderman D , Mascherbauer J
Published: October 2019

Background

Global left atrial (LA) size and function have been shown to be associated with adverse events in heart failure with preserved ejection fraction (HFpEF). The machanism of coupling from left heart failure to pulmonary circulation is still controversially discussed.

Purpose

To study the prognostic most relevant determinant of LA size and function and its backward and forward interplay.

Methods

188 HFpEF patients were prospectively enrolled and underwent baseline clinical assessment, cardiac magnetic resonance imaging (CMR) and invasive hemodynamic assessment. Coronary artery disease was ruled out by coronary angiography. 92 patients were in atrial fibrillation (AF), 96 in sinus rhythm. LA size and function were assessed by CMR including LA strain imaging by myocardial feature tracking (Figure 1A & B).

Results

Patients in AF had more pronounced dilatation of all phasic LA volumes and reduction of all phasic LA functions when compared to sinus rhythm (each p<0.001 respectively).

After 31 (9–57) months 66 patients reached the combined endpoint defined as combination from hospitalization due to heart failure and cardiovascular death. In AF no atrial functional or volume parameter was correlated to outcome. In contrast in sinus rhythm several phasic LA volume and functional parameters were associated with outcome. After multivariate cox regression analysis only reduced total LA ejection fraction and conduit strain rate were still predictive for worse outcome (p=0.031 and <0.001 respectively). After adjustment for known risk factors in HFpEF like age, six minute walking distance (6MWD), systolic pulmonary artery pressure (sPAP) and right ventricular ejection fraction as derived by CMR only impaired LA conduit strain rate remained predicitve for cardiovascular events (p=0.001). In contrast to LA booster pump function LA conduit function parameters were significantly correlated to reduced 6MWD (Figure 1C) and coupled backwards to pulmonary vasculature via correlation to sPAP and pulmonary vascular resistance (PVR) but without coupling to CMR derived elevated LV extracellular volume and left ventricular end diastolic pressure.

Conclusion

Total LA ejection fraction plays a key role in the prognosis of HFpEF. This effect seems to be mainly related to its LA conduit function but not to LA booster pump function. LA conduit function correlates to impaired 6MWD, sPAP and PVR.
132Imaging criteria for the diagnosis of heart failure with midrange and preserved LVEF in the real life
Authors: Logeart D , Paven E , Damy T , Isnard R , Salvat M , Eicher J C , Roubille F , Tribouilloy C , Bauer F , Piccard F , Trochu J N
Published: October 2019

Background

According to last ESC guidelines, the diagnosis of heart failure with midrange and preserved left ventricular ejection fraction (HFmrEF-HF and HFpEF) requires at least one of the following imaging criteria: LV hypertrophy with LVMI >115g/m2 in men and 95g/m2 in women, left atria dilation with LAVI >34ml/m2, TDI e' wave average <9cm/s and E/e' average ≥13.

Purpose

We analyzed the prevalence of these imaging criteria in real life patients who are labeled HFmrEF or HFpEF by using a multicenter survey on HF.

Methods

Our survey (NCT01956539) was carried out in 32 hospitals between 2015 and 2018 and included 2735 HF patients who gave their consent during consultation or hospitalization. The diagnosis of HF was left to the discretion of investigators. Besides clinical and biological data, echocardiographic data (<1 month before or <3 months after inclusion) was collected in an electronic database. No echographic variable except the LVEF was mandatory to be included.

Results

Among the 523 and 765 HF patients who were labeled respectively as HFmrEF-HF and HFpEF, the 4 echographic variables required for the diagnosis of HFmrEF or HFpEF were obtained in 512 patients. The median age was 74y [IQR 62–82], HF was de novo in 28%, AF in 34%, median NTproBNP was 1563 pg/mL [IQR 500–4372]. At least one of the 4 diagnostic criteria was present in all patients but 2, and patients had 2, 3 or 4 criteria in 43%, 37% and 1% of cases. The table shows only little differences between HFmrEF and HFpEF or de novo HF regarding the rate of each diagnostic criteria. There was no difference regarding the date of inclusion, i.e. before or after the last ESC guidelines.

Table 1 All HF patients De novo HF HFpEF HFmrEF mrEF or pEF (n=143) (n=293) (n=219) LVMI >115g/m2 (men) or 95g/m2 (women) 69.6% 64.3% 68.6% 70.2% LAVI >34ml/m2 74.2% 73.3% 80.4% 68.9% e' average <9cm/s 64.1% 55.3% 55.9% 76.1% E/e' average ≥13 35.4% 38.6% 37.3% 32.8%

Conclusion

The diagnosis of HFpEF or mrEF may be difficult and requires comprehensive echocardiography including all diagnostic variables because each single diagnostic criteria are present in only 33 to 80% cases.
247Safety and efficacy of high-sensitivity cardiac troponin for risk stratification in patients with suspected acute coronary syndrome
Authors: Bularga A , Anand A , Strachan F E , Lee K K , Stewart S , Ferry A V , Chapman A R , Marshall L , Shah A S V , Newby D E , Mills N L
Published: October 2019

Background

Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTn) assays for the risk stratification and rapid rule-out of myocardial infarction, but multiple approaches have been described. We previously demonstrated the utility of a single hs-cTnI concentration <5 ng/L at presentation to risk stratify patients with suspected acute coronary syndrome (ACS).

Purpose

To assess the safety and efficacy of a hs-cTnI concentration <5 ng/L at presentation in consecutive patients included in the High-STEACS (High-SensitivityTroponin in the Evaluation of patients with Acute Coronary Syndrome) randomised controlled trial.

Methods

The High-STEACS trial was a stepped wedge cluster randomised controlled trial in ten hospitals across Scotland that included 48,282 patients in whom high-sensitivity cardiac troponin was requested by the attending clinician for evaluation of suspected ACS. Patients with ST-segment elevation myocardial infarction (STEMI) were excluded. We evaluated the negative predictive value (NPV) and sensitivity of a presentation hs-cTnI <5 ng/L for a composite outcome of type 1 myocardial infarction, or subsequent type 1 myocardial infarction or cardiac death at 30 days. To assess safety, we report the one-year risk of type 1 myocardial infarction or cardiac death. To assess efficacy, we report the proportion of patients with cardiac troponin <5 ng/L at presentation.

Results

We included 47,101 consecutive patients in the analysis (mean 61±17 years old, 47% female). Of these patients, 27,500 (58%) had a cardiac troponin <5 ng/L at presentation. Overall, 4,313/47,101 (9%) patients had a composite outcome at 30 days, but the event rate was only 0.4% in those with troponin <5 ng/L (98/27,500). The NPV for the composite outcome in those <5 ng/L was 99.7% (95% confidence intervals [CI] 99.6–99.7) and the sensitivity was 98.0% (95% CI 97.6–98.4). In those without evidence of myocardial injury at presentation (hs-cTnI <99thcentile), type 1 myocardial infarction or cardiac death at one year occurred in 197 (0.7%) patients with cardiac troponin <5 ng/L, compared to 647 (5.5%) of those ≥5 ng/L. The NPV was unchanged across all age groups, although efficacy fell as fewer older patients had hs-cTnI concentrations below the risk stratification threshold (see Figure).

Conclusion

A hs-cTnI concentration <5 ng/L at presentation identifies the majority of patients with suspected ACS as low-risk of early or late cardiac events. Although the proportion identified as low risk is reduced in older populations, the safety of this risk stratification approach is maintained across patients of all ages.

Acknowledgement/Funding

British Heart Foundation
252Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome and multivessel coronary artery disease: a post-hoc analysis of the TROPICAL-ACS trial
Authors: Rizas K D , Gross L , Trenk D , Komocsi A , Baylacher M , Orban M , Loew A , Massberg S , Aradi D , Sibbing D
Published: October 2019

Background

The TROPICAL-ACS trial showed that platelet function testing (PFT) guided de-escalation of P2Y12-inhibitor is a safe alternative treatment strategy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). No specific data are available on the efficacy of this strategy in patients with multivessel coronary artery disease (CAD).

Purpose

To investigate the safety and efficacy of guided de-escalation of P2Y12-inhibitor treatment in patients with multivessel CAD.

Methods

Two-thousand six-hundred-two biomarker-positive ACS patients were 1:1 randomized to either conventional treatment with prasugrel for 12 months (control group) or to a PFT guided de-escalation treatment strategy (guided de-escalation group). The primary endpoint (net clinical benefit) was defined as the composite of cardiovascular mortality (CVM), myocardial infarction (MI), stroke, and clinically overt bleeding (bleeding ≥ grade 2 according to the BARC criteria). The ischemic endpoint was defined as the composite of CVM, MI or stroke. We used log-rank statistics and Cox regression analysis with interaction testing to assess the effect of multivessel CAD on the primary and ischemic endpoints.

Results

Patients with multivessel (n=709) versus single-vessel CAD (n=1,901) exhibited a higher risk for the primary endpoint (10.2% vs. 7.6%; HR 1.36; 95% CI 1.02–1.81; p=0.034). Guided de-escalation was non-inferior to conventional treatment for the primary endpoint in both patients with single-vessel CAD (6.7% vs. 8.5%; pnon-inferiority = 0.001; Figure 1A) and multivessel CAD (9,5% vs. 10.9%; pnon-inferiority=0.041; Figure 1B). Moreover, there was no significant interaction in the prognostic value of guided de-escalation between single-vessel and multivessel CAD for both the primary (HR 0.78 [0.56–1.08]; p=0.137 in patients with single-vessel CAD vs. 0.86 [0.54–1.37; p=0.524 in patients with multivessel CAD; pinteraction=0.732) and combined ischemic endpoints (HR 0.80 [0.44–1.45]; p=0.456 in patients with single-vessel CAD vs. 0.71 [0.35–1. 46]; p=0.356 in patients with multivessel CAD; pinteraction=0.823).

Kaplan-Meier curves

Conclusion

A guided de-escalation of P2Y12-inhibitor appears to be safe and effective in ACS patients with both single-vessel and multivessel CAD.

Acknowledgement/Funding

Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.
284Outcomes after left atrial appendage occlusion with AMPLATZER Amulet and WATCHMAN device: Results from the ORIGINAL registry (saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure)
Authors: Kretzler L , Wunderlich C , Christoph M , Langbein A , Spitzer S G , Gerk U , Schellong S , Ketteler T , Neuser H , Schwefer M , Strasser R H , Mues C , Ibrahim K , Schoen S P
Published: October 2019

Aims

Left atrial appendage occlusion (LAAO) is a therapeutic option for patients with non-valvular atrial fibrillation (NVAF) and high risk of bleeding. This study reports outcomes of patients enrolled in the prospective multicentre, investigator initiated real life registry in the Free State of Saxony (saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure).

Methods and results

Data of all consecutive 521 patients (64.7% adult males, 35.3% adult females, mean age: 75.1 (SD 7.9) years with non-valvular atrial fibrillation undergoing interventional left atrial appendage occlusion procedure in the ORIGINAL prospective registry were analysed. The CHA2DS2-VASc and HAS-BLED scores were 4.3 (SD 1.5) and 3.7 (SD 1.1), respectively. 78.9% of the patients had a history of bleeding. 89.3% of the patients were considered as non-eligible for long term oral anticoagulation. A left atrial appendage occlusion device was successfully implanted in 97.5% of cases. A mean follow-up of 463 days could be reached in 386 patients. Among these, the distribution of the follow-up length reached was as follows: 1 year 205, 2 years 118, 3 years 65 and 4 years 17 patients. In the follow-up the annual frequency of stroke was very low (0.4%), which resulted in the 4.98% absolute risk reduction in the amount of thromboembolic strokes, which would have been expected according to the calculated CHA2DS2-VASc score in the hypothetic group not receiving any anticoagulant therapy. The occurrence of major and minor bleeding in the follow-up was 1.55% and 3.37% respectively.

Conclusions

In this prospective multicentre study we included the patients who are at high risk of stroke and bleeding. The annual ischemic stroke rate was 0.4%, the LAA could be sealed in 97.5%. Six months after the LAA closure only 3.63% of all patients were further on treated using oral anticoagulation. Considering the stroke reduction rates, the implantation of an LAAO device proves to be effective and safe in the clinical routine in the studied population.

Acknowledgement/Funding

None
287Diabetes mellitus is a risk factor for ischemic stroke in patients with and without coronary artery disease after coronary angiography
Authors: Olesen K K W , Madsen M , Gyldenkerne C , Thrane P G , Wurtz M , Thim T , Jensen L O , Eikelboom J W , Botker H E , Sorensen H T , Maeng M
Published: October 2019

Background

Diabetes (DM) and non-DM patients without coronary artery disease (CAD) by coronary angiography (CAG) have the same low risk of myocardial infarction.

Purpose

To study whether DM patients without CAD have the same risk of ischemic stroke as patients with neither DM nor CAD.

Methods

We conducted a cohort study of patients, who underwent CAG between 2004 and 2012 in the Western Denmark Heart Registry. Patients previously diagnosed with ischemic stroke or atrial fibrillation (AF) and those treated with an oral anticoagulant were excluded. Patients were stratified according to presence of DM and CAD. Follow-up started 30 days after CAG. We computed event rates and adjusted incidence rate ratios (IRRs) using patients with neither DM nor CAD as reference.

Results

A total of 68,829 patients were included. Median follow-up was 4.0 years. Patients with both DM and CAD were at the highest risk of ischemic stroke (1.25 events per 100 person-years; adjusted IRR 2.10, 95% CI 1.77–2.48) (Figure 1). Patients with CAD alone (0.70 events per 100 person-years; adjusted IRR 1.29, 95% CI 1.12–1.48) or DM alone (0.84 events per 100 person-years; adjusted IRR 1.79, 95% CI 1.41–2.26) were at intermediate risk while patients with neither DM nor CAD (0.46 events per 100 person-years) were at lowest risk. Among DM patients, extent of CAD was further predictive of risk (ptrend<0.001).

Figure 1

Conclusions

Not only CAD but also DM independently predict the risk of ischemic stroke after CAG. Their combination further increases the risk of ischemic stroke depending on the extent of CAD.
428In-hospital coronary angiography is associated with increased evidence based medications and better survival in patients hospitalized with acute heart failure - results from REALITY-AHF
Authors: Akiyama E , Konishi M , Okumura T , Kida K , Oishi S , Suzuki S , Yamamoto M , Kitai T , Matsue Y
Published: October 2019

Background

Coronary artery disease is a major cause of heart failure (HF). Urgent coronary angiography (CAG) is recommended for patients with acute HF (AHF) complicated with acute coronary syndrome (ACS); however, clinical usefulness of in-hospital CAG in AHF patients without ACS remains unknown.

Purpose

To investigate the association between in-hospital CAG and all-cause mortality at 1-year after hospital discharge and effects of medications at discharge on this association.

Methods

From the REALITY-AHF study, 1344 patients hospitalized with AHF were enrolled in this study and followed up for 1-year after hospital discharge.

Results

In-hospital CAG was undergone in 511 patients (38%). CAG group had a significantly lower 1-year mortality compared with non-CAG group (unadjusted hazard ratio [HR]; 0.30, 95%-confidence interval [CI] 0.21–0.43, P<0.001, after adjustment for MAGGIC score; HR 0.45, 95%-CI 0.29–0.70, P<0.001, in propensity-score matched 296 pairs; HR 0.60, 95%-CI 0.37–0.98, P=0.04). At discharge, aspirin, statins and beta blockers were prescribed more in CAG group compared with non-CAG group (aspirin 46% versus 30%, P<0.001, statins 51% versus 35%, P<0.001, and beta blockers 76% versus 65%, P=0.007). The prescription of aspirin or statins at discharge was associated with a better 1-year survival in patients with multivessel disease (P<0.001), but not in patients without significant stenosis or single vessel disease (P=0.95) (Figure).

CAG results, medications and mortality

Conclusions

In patients hospitalized with AHF, in-hospital CAG was associated with increased evidence based medications at discharge and a better long-term survival. Aspirin and statins at discharge might improve outcomes in AHF patients with multivessel disease.

Acknowledgement/Funding

This study was funded by The Cardiovascular Research Fund, Tokyo, Japan.
455Prediction of major bleeding in patients receiving DOACs for venous thromboembolism: a prospective cohort study
Authors: Vedovati M C , Mancuso A , Pierpaoli L , Paliani U , Conti S , Ascani A , Galeotti G , Di Filippo F , Caponi C , Agnelli G , Becattini C
Published: October 2019

Background

The accuracy of currently available bleeding scores in patients on treatment with direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) is undefined.

Purpose

In a prospective cohort of patients with VTE treated with DOACs, we evaluated the accuracy of the ATRIA, HAS-BLED, Kuijer, ORBIT, RIETE and VTE-BLEED risk scores in predicting major bleeding (according to ISTH definition).

Methods

The accuracy of different scores to correctly classify subjects into a defined risk category was assessed by the c-statistic.

Results

Overall, 1141 patients were evaluated and 1034 included in the study. The index event was pulmonary embolism in 509 patients (49.2%) and proximal deep vein thrombosis in the remaining patients (50.8%). During the 12-month study period, 26 major bleedings occurred in 25 patients (2.8% patient-year): 14 major bleedings occurred in the first 6 months of treatment and 12 from 6 to 12 months in the 654 patients remained on treatment.

In the 12-month study period, the VTE-BLEED score showed the best predictive value for bleeding complications (c-statistics 0.674, 95% CI 0.593–0.755). The lowest incidence of major bleeding (0.3%) was observed in the low risk category of VTE-BLEED which includes 38% of patients. The highest incidence of major bleeding (7.1%) was observed in the high-risk category of ORBIT which includes 10.9% of patients.

Conclusions

The VTE-BLEED score had the best accuracy in predicting major bleeding during treatment with DOACs for VTE. Whether the VTE-BLEED score can be used for decision making on anticoagulation should be tested in a management study.
456Risk of arterial calcification by conventional vitamin K antagonist treatment
Authors: Hasific S , Oevrehus K A , Gerke O , Hallas J , Busk M , Lambrechtsen J , Urbonaviciene G , Roennow Sand N P , Nielsen J S , Diederichsen L , Pedersen K B , Mickley H , Rasmussen L M , Lindholt J S , Diederichsen A
Published: October 2019

Background

Vitamin K antagonists (VKA) are the most frequently prescribed oral anticoagulants worldwide although new oral anticoagulants (NOAC) have become an important alternative. VKA inhibits Vitamin K1 necessary to produce coagulation factors but also Vitamin K2, which is essential in the activation of matrix-Gla protein, thought to be a strong local inhibitor of arterial calcifications.

Purpose

The aim was to investigate, whether VKA treatment is associated with coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD).

Methods

We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n=9,672) or research studies (n=14,166) in the period 2007–2017. Data on use of VKA and NOAC was obtained from the Danish National Health Service Prescription Database. The association between VKA treatment duration and categorized CAC score was investigated by ordered logistic regression while adjusting for covariates. The independent variables included in the model were: age, gender, smoking, body mass index (BMI), diabetes mellitus, hypertension, hypercholesterolemia and/or statin treatment, family history of CVD, estimated glomerular filtration rate, VKA treatment duration and NOAC treatment duration. The categorisation of CAC was: 0, 1–99, 100–399 and ≥400 AU, corresponding to no, mild, moderate and severe atherosclerotic plaque burden, respectively.

Results

The final study population consisted of 17,254 participants (median 67 years old, 75% males) with no prior CVD, of which 1,748 (10%) and 1,144 (7%) had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories (Figure). For each cumulative year of VKA treatment, the odds of being in a higher CAC category, i.e. having more severe atherosclerosis, increased (odds ratio (OR)=1.032, 95% CI 1.009–1.057). All traditional cardiovascular risk factors were also associated with CAC. In contrast, NOAC treatment duration was not associated with CAC category (OR=1.004, 95% CI 0.937–1.075). In a sensitivity analysis of patients without statin treatment (n=12,143), the association between VKA treatment and CAC category remained unchanged. There was no significant interaction between VKA treatment duration and age on CAC category.

Conclusion

Adjusted for cardiovascular risk factors, VKA treatment – in contrast to NOAC - is associated with more severe CAC. Additional studies are required to clarify the clinical importance of this association in terms of hard cardiovascular endpoints.

Acknowledgement/Funding

Novo Nordisk Foundation and Independent Research Fund Denmark
458Real world persistence with direct oral anticoagulants in anticoagulation naive patients with atrial fibrillation
Authors: Denas G , Costa G , Ferroni E , Gennaro N , Fedeli U , Corti M C , Zoppellaro G , Padayattil Jose S , Pengo V
Published: October 2019

Introduction

Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications.

Purpose

To assess persistence levels of DOACs and look for possible predictors of treatment discontinuity in NVAF patients.

Methods

We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression.

Results

Overall, 17920 patients initiated anticoagulation with DOACs in the study period. Most patients were older than 74 years old, while gender was almost equally represented. Comorbidities included hypertension (72%), diabetes mellitus (17%), congestive heart failure (9%), previous stroke/TIA (20%), and prior myocardial infarction (2%). After one year, the persistence to anticoagulation treatment was 82.7%, while the persistence to DOAC treatment was 72.9% with about 10% of the discontinuations being due to switch to VKAs. On multivariate analysis, factors negatively affecting persistence were female gender, younger age (<65 years), renal disease and history of bleeding. Conversely, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction.

Persistence to DOAC therapy

Conclusion

This real-world data show that within 12 months, one out of four anticoagulation-naïve patients stop DOACs, while one out of five patients stop anticoagulation. Efforts should be made to correct modifiable predictors and intensify patient education.
460Edoxaban versus warfarin in atrial fibrillation patients with low, mid and high body weight: analysis of outcomes in the engage AF TIMI 48 trial
Authors: Boriani G , Ruff C T , Kuder J F , Shi M , Lanz H , Antman E M , Braunwald E , Giugliano R P
Published: October 2019

Background

The impact on outcomes of oral anticoagulants in pts at extremes of body weight have not been well-characterized.

Aim

To analyse the outcomes of pts with atrial fibrillation (AF) enrolled in ENGAGE AF-TMI 48 randomized to warfarin (W) targeting INR 2.0–3.0, higher (HDE) or lower dose regimens of edoxaban (LDE), focusing on subgroups of patients at the extremes of weight.

Methods and results

Among 21105 pts enrolled in the trial we identified 3 subgroups: 1082 with low body weight (LBW) (<5th percentile, <55kg), 2153 with mid body weight (MBW) (45–55th percentile, 80–84 kg), and 1093 patients with high body weight (HBE) (>95th percentile, >120 kg). Baseline characteristics differed markedly (LWB pts were older and more likely Asian, women, with prior TIA/stroke, renal dysfunction) resulting in a trend towards higher rates of stroke/systemic embolism (SSE: 6.5% vs 4.7% in MBW vs 1.6% in HBW) and major bleeding (MB: 9.3% vs 7.7% in MBW vs 6.5% in HBW) in the warfarin arm. The risks of SSE (Pint = 0.52) were similar between W and HDE regardless of body weight, while the relative reduction in MB was greatest in LBW patients (HR reduction45%, 23%, 1% across weight groups; Pint = 0.35) (Figure). Net clinical outcomes (SEE/major bleeding/death) tended to be most favourable for LBW pts (HR 0.67 [0.50–0.90]; Pint 0.084) (Figure).

Main outcomes during follow up

Conclusions

In ENGAGE AF-TIMI 48 the profile of AF pts with LBW markedly differed suggesting a more fragile clinical status. Use of dose-adjusted edoxaban, as compared to W, was associated with similar efficacy regardless of weight, while bleeding and net outcomes were most favourable in LBW pts.
464Optimal timing of invasive coronary angiography following NSTEMI
Authors: Mahendiran T , Nanchen D , Meier D , Gencer B , Klingenberg R , Raber L , Carballo D , Matter C , Luscher T , Windecker S , Mach F , Rodondi N , Muller O , Fournier S
Published: October 2019

Introduction

Current guidelines recommend angiography within 24 hours of hospitalisation for patients with non-ST elevation myocardial infarction (NSTEMI). The recent VERDICT study found that angiography within 12 hours of hospitalisation was associated with improved cardiovascular outcomes among high-risk patients. We aimed to obtain a real-world perspective of the impact of angiography timing on one-year outcomes of patients admitted with NSTEMI.

Methods

Data was obtained from the SPUM-ACS registry, a cohort of consecutive patients hospitalised with acute coronary syndromes in four university hospitals in Switzerland between 2009 and 2017. Patients without a door-to-catheter (DTC) time and those with life-threatening features were excluded. Cox proportional hazards models evaluated the impact of DTC time on the primary endpoint, defined as one-year major adverse cardiovascular events (MACE: cardiovascular mortality, myocardial infarction, stroke), and on one-year all-cause mortality.

Results

Of 2,672 NSTEMI patients, 1,832 met the inclusion criteria. Among them, 1,464 patients underwent angiography within 12 hours of admission (12h group) while 368 patients underwent angiography between 12 and 24 hours (12–24h group). After 2:1 propensity score matching, 736 patients from the 12h group and 368 patients from the 12–24h group were deemed equivalent in terms of main baseline clinical characteristics. Multiple logistic regression identified admission out-of-hours (night or weekend) as the most significant factor associated with delayed angiography. Cox models found no significant association between early angiography and one-year MACE (12h group: n=57 (7.7%) vs. 12–24h group: n=27 (7.3%), HR: 1.050, 95% CI 0.637- 1.733, p=0.847), or one-year all-cause mortality (12h group: n=25 (3.4%) vs. 12–24h group: n=17 (4.6%), HR: 1.514, 95% CI 0.774- 2.962, p=0.225) (Figure 1A). After stratification based on GRACE score (>140 vs. ≤140), there was no significant difference in one-year MACE or one-year all-cause mortality in the 12h group compared with the 12–24h group (p for interaction=0.601 and 0.463, respectively) (Figure 1A + 1B).

Figure 1

Conclusion

In an unselected real-world cohort of NSTEMI patients, angiography within 12 hours of hospitalisation was not associated with improved one-year outcomes when compared with angiography between 12 and 24 hours, even among patients with an elevated GRACE score.
477Partial fusion of two aortic valve leaflets is related to alterations in ascending aorta flow: 4D flow CMR study
Authors: Guala A , Galian L , Teixido Tura G , Dux-Santoy L , Ruiz Munoz A , Granato C , Valente F , La Mura L , Gutierrez L , Lopez Sainz A , Johnson K M , Wieben O , Sao Aviles A , Evangelista A , Rodriguez-Palomares J F
Published: October 2019

Introduction

Bicuspid aortic valve (BAV) is the most common congenital valve defect. It consists in the fusion of two aortic valve leaflets, and it is associated with a high prevalence of proximal aorta dilation. Dilation is highly prevalent (around 30%) in BAV patient relatives with a tricuspid valve (TAV) identified by echocardiography. However, the presence of partial aortic valve leaflet fusion (also called mini-raphe or forme fruste BAV, see figure 1A) is easily missed by echocardiography. A recent study reported that 44% of patients from a small cohort of BAV patient relatives with aortic dilation followed by CT showed mini-raphe.

Purpose

We aimed to use 4D flow CMR to assess if the presence of mini-raphe is associated with aortic flow alterations, which may be concurs in the etiology of aortic dilation in BAV patient relatives.

Methods

Twenty BAV patients first-degree relatives with partial fusion (<50%) of aortic valve leaflets and proximal aorta dilation were identified by CT or cine CMR and prospectively included. One-hundred twenty-five BAV and 95 patients with TAV from our prospective dataset of 4D flow CMR were included for comparison. Propensity score matching was used throughout the study to correct the comparisons between mini-raphe and BAV and mini-raphe and TAV patients for differences in age, maximum aortic diameter, sex, height, weight, proximal aortic pulse wave velocity and, only for BAV, fusion pattern. The hemodynamic parameters previously related to aortic dilation were computed. They were jet angle, normalized flow displacement and systolic flow reversal ratio (SFRR, identifying through-plane vortexes) were computed and compared in the ascending aorta and in the aortic arch.

Results

The presence of mini-raphe was statistically-significantly associated with increase in jet angle (Figure 1B), flow displacement (Figure 1C) and vortexes (Figure 1D) in most of the ascending aorta and aortic arch when mini-raphe patients were compared with TAV patients. The severity of flow asymmetry found in mini-raphe patients was lower than the one characteristic of BAV patients, but vortexes were even higher in a small region at the distal ascending aorta.

Figure 1

Conclusion

Partial fusion of the aortic valve leaflets is related to increase in proximal aorta flow eccentricity and vorticity. These flow abnormalities are not as marked as those associated with BAV. Data regarding prevalence of mini-raphe as evaluated with CT or cine CMR are needed, especially in familiar of BAV patients.

Acknowledgement/Funding

European FP7/People 267128; Spanish Ministry of Economy and Competitiveness RTC-2016-5152-1 and Instituto de Salud Carlos III PI14/0106
481Right ventricular longitudinal strain predicts symptoms in patients with chronic primary mitral regurgitation
Authors: Chilingaryan A L , Tunyan L G , Adamyan K G
Published: October 2019

Mitral regurgitation (MR) leads to subclinical changes that often cannot be detected by low sensitive conventional parameters and early predictors of deterioration could suggest a better timing for intervention.

Methods

We follow up 175 asymptomatic patients 56±13 years (79 female) with severe primary MR in sinus rhythm and without diabetes mellitus and renal disease for 2 years. Global longitudinal strain (LS) of left ventricle (LVGLS), right ventricular (RV) free wall LS (RVLS), and left atrial (LA) peak reservoir LS as average of two basal segments in 4 chamber view were measured by speckle tracking along with indexes of LV end-systolic and end-diastolic volumes, LV ejection fraction (EF), left atrial end-systolic volume index (LAVi) every 6 months. Normal reference values of LS were obtained from age and sex matched 40 healthy controls.

Results

Patients with MR had higher LV ejection fraction (EF), LVGLS, LALS and lower values of RVLS compared with controls (EF 67.4±5% vs 59.3±4%, p<0.05; LVGLS –25.2±2.3% vs –21.2±1.9%, p<0.03; LALS 46.2±5.1% vs 42.4±3.7%, p<0.04; RVLS –23.4±5.1% vs –27.3±2.8%, p<0.03). 53 (30%) patients developed symptoms at exercise during follow up. Symptomatic patients at baseline had higher values of RVLS compared with patients who remained asymptomatic during follow up without significant differences in EF, LVGLS, LALS (RVLS –21.4±2.6% vs –25.8±3.2%, p<0.02; EF 66.8±2.4% vs 68.1±3.1%, p>0.05; LVGLS –24.8±2.1% vs –25.3±2.3%, p>0.05; LALS 45.7±4.1% vs 46.5±4.4%, p>0.05). RVLS correlated with LAVi (r=0.53, p<0.01) and LALS (r=0.57, p<0.01). Regression analysis defined RVLS as an independent predictor of symptoms development (OR=3.2; 95% CI=1.37–7.63; p<0.01).

Conclusion

RV longitudinal strain predicts symptoms in patients with chronic primary mitral regurgitation.
P316The cardiac endothelial cell transcriptome in neonatal, adult, and remodeling hearts
Authors: Segers V F M , Vermeulen Z , Mateiu L , Dugaucquier L , De Keulenaer G W
Published: October 2019

Background

Cardiac microvascular endothelial cells (CMVECs) are the most numerous cells in the myocardium and orchestrate cardiogenesis during development, regulate adult cardiac function, and modulate pathophysiology of heart failure. It has been shown that the transcriptome of CMVECs differs from other endothelial cell types, but transcriptomic changes in cardiac endothelial cells during cardiac maturation and cardiac remodeling have not been studied earlier.

Purpose

To study changes in the transcriptome of CMVECs during cardiac maturation and cardiac remodeling, and to test the hypothesis that the fetal gene program is reactivated during cardiac remodeling in CVMECs.

Methods

CMVECs were isolated from rat hearts based on CD31 expression and were immediately processed for RNA sequencing, without an in vitro propagation step. We compared gene expression levels from primary CMVECs of neonatal hearts, normal adult hearts, and infarcted-hearts (4 weeks post LAD ligation).

Results

Between neonatal and adult CMVECs, 6838 genes were differentially expressed indicating that CMVECs undergo a substantial transformation during postnatal cardiac growth. A large fraction of genes upregulated in neonatal CMVECs are part of mitosis pathways, whereas a large fraction of genes upregulated in adult CMVECs are part of cellular response, secretory, signaling, and cell adhesion pathways. Between CMVECs of normal adult hearts and infarcted hearts, 159 genes were differentially expressed. We found a limited degree of overlap (55 genes) between the differentially expressed genes in neonatal and infarcted-hearts. Of 46 significantly upregulated genes in the infarcted heart, 46% were also upregulated in neonatal hearts relative to sham. Of 113 significantly downregulated genes in the infarcted-hearts, 30% were also downregulated in neonatal hearts relative to sham.

Conclusion

These data demonstrate that CMVECs undergo dramatic changes from neonatal to adult and more subtle changes between normal state and cardiac remodeling. During cardiac remodeling, a small part of the fetal gene program is reactivated in CMVECs.

Acknowledgement/Funding

IOF/SBO research grant (PID34923), Fund for Scientific Research Flanders (Application numbers 1501118N and 1842219N).
P325Incremental value of left atrial strain in predicting atrial fibrillation in heart failure with preserved ejection fraction
Authors: Jasic-Szpak E , Marwick T H , Przewlocka-Kosmala M , Jankowska E A , Ponikowski P , Kosmala W
Published: October 2019

Atrial fibrillation (AF) is a frequent comorbidity in heart failure with preserved ejection fraction (HFpEF), worsening the clinical course. Although various contributors to the development of AF have been identified, effective screening strategies to prevent this arrhythmia are ill-defined.

Aim

To investigate the factors associated with incident AF in a well-characterized HFpEF population, with special focus on left atrial (LA) strain.

Methods

170 pts with symptomatic HFpEF (mean age 65±8 yrs), free of baseline AF, underwent clinical evaluation, echocardiography and cardiopulmonary exercise testing. AF was diagnosed by clinical review, standard ECG, and single lead portable ECG monitoring.

Results

Over a median follow-up of 49 months, incident AF was identified in 39/170 pts (23%). Pts who developed AF were older, had higher clinical risk scores, BNP, creatinine, LA volume index (LAVI), LV mass, lower LA strain, exercise capacity, and more impaired LV diastolic function. The highest areas under ROC curves for AF prediction were for peak-atrial contraction strain (PACS; 0.76), total peak-atrial longitudinal strain (PALS; 0.71) and LAVI (0.72). Nested Cox regression models showed that the predictive value of LA strain was independent from and incremental to clinical data, LAVI and E/e' ratio estimating LV filling pressure (Figure). Addition of total PALS to the model including CHA2DS2VASc score, LAVI and E/e' improved classification by 37% (p=0.04), and subsequent addition of PACS improved classification by 54% (p=0.003).

Figure 1

Conclusions

LA strain, especially PACS, provides incremental predictive information about incident AF in HFpEF. The inclusion of LA strain to the diagnostic algorithm may help guide screening for AF risk in this population.