bluuebunny/crossref_metadata_2025 huggingface dataset:
P2563Effects of rivaroxaban on cardiac remodeling after experimental myocardial infarction in mice
Authors: Nakanishi N , Kaikita K , Ishii M , Oimatsu Y , Mitsuse T , Tsujita K
Published: October 2019

Background

Rivaroxaban, a direct activated factor X (FXa) inhibitor, has been established for prevention and treatment of arterial and venous thrombosis. Although FXa plays an important role in thrombosis, FXa also involves in inflammation via the protease-activated receptor (PAR)-1 and PAR-2 pathway. We assessed the hypothesis that rivaroxaban might protect cardiac remodeling after myocardial infarction (MI) in mice.

Methods

MI was induced in wild-type mice by permanent ligation of the left anterior descending coronary artery. At 1 day after MI, mice were randomly assigned to the rivaroxaban and vehicle groups. In the rivaroxaban group, the mice were provided with regular chow diet including rivaroxaban (2400ppm) after the randomization. We evaluated the cardiac function by echocardiography, expression of mRNA and protein in the infarcted and non-infarcted area 7 days after MI. Furthermore, we measured infarct size, infiltration of inflammatory cells by pathological analysis 7 days after MI.

Results

The fractional shortening (%FS) and Interventricular Septal thickness in diastole (IVSTd) was significantly improved 7 days after MI in the rivaroxaban group compared with the vehicle group (%FS, p=0.01; IVSTd, p=0.013). As for pathological analysis, rivaroxaban decreased infarct size (p=0.026) and the number of infiltrated macrophages in the non-infarcted area (p=0.011) compared with vehicle. The mRNA expression in tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β in the infarcted area and atrial natriuretic peptide (ANP) in the non-infarcted area was significantly lower in the rivaroxaban group compared with the vehicle (TNF-α, p=0.015; TGF-β, p=0.019; ANP, p=0.012). PAR-1 and PAR-2 mRNA expression in the infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (PAR-1, p=0.005; PAR-2, p=0.037). Furthermore, western blot analysis demonstrated that the phosphorylation of Extracellular Signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) in the non-infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (ERK, p=0.015; JNK, p=0.002).

Conclusions

The present study showed that rivaroxaban protected against cardiac dysfunction, probably due to the suppression of PAR-mediated increase of pro-inflammatory cytokines post-MI. Rivaroxaban might be potentially effective for improving the cardiac remodeling after MI.

Acknowledgement/Funding

This study was supported in part by trust-research grant from Bayer Yakuhin, Ltd.
P2576Sports in children and adolescents with congenital heart defects
Authors: Bauer U M M , Helm P , Siaplaouras J , Niessner C , Sticker E , Flemming M , Apitz C
Published: October 2019

Background

Age-appropriate physical activity is an important basis for healthy physical and mental development for children and adolescents with congenital heart defects (CHD)

Purpose

The main goal of this study was to learn more about the physical activity of young and adolescent CHD-patients to understand patient's needs physical activity and to improve the medical advice regarding physical activity and sports by taking the CHD-severity into account.

Methods

An online-questionnaire was developed. CHD patients registered in the German National Register for Congenital Heart Defects were invited by email/post to join the study. In total, 1,718 patients took part. 1,262 patients have finished the questionnaire and are included in the statistical analysis (average age: 11.6±3.1 years; 588 women). CHD severity: 411 patients with simple CHD, 423 with moderate CHD, 364 with complex CHD and 64 with unclassified CHD. The study participants were asked to answer questions regarding physical activity and (school) sports to evaluate their activity level and their individual needs regarding sports.

Results

We identified 831 (65.9%) patients who reported they were exercising sports for at least three days or more for 60 minutes or longer per week (simple CHD: 68.9%; moderate CHD: 64.5%; complex CHD: 63.5%; other CHD: 68.8%). Over all 47 patients (3.7%) stated that they had no regular school sports and 12 patients (1%) reported to have less than one regular sports lessen per week. Out of the 1,215 patients who reported to have regular school sports (simple CHD: 97.3%; moderate CHD: 98.1%; complex CHD: 94.5%; other CHD: 87.5%), the patients stated about how hard they usually work in a regular sports lesson as follows: “without sweating and without shortness of breath” (188 patients, 15.5%; simple CHD: 15.4%; moderate CHD: 17.1%; complex CHD: 14.8%; other CHD: 7.1%), “a little bit sweaty and a bit short of breath” (825 patients, 67.9%; simple CHD: 68.8%; moderate CHD: 65.3%; complex CHD: 68.9%; other CHD: 75%), “a lot of sweat and a lot of shortness of breath” (202 patients, 16.6%; simple CHD: 15.8%; moderate CHD: 17.6%; complex CHD: 16.3%; other CHD: 17.9%).

Conclusions

Overall, young and adolescent patients with CHD appear to be exercising sports regularly and are well integrated into school sports. Although there are slight differences between the individual degrees of CHD severity. These differences can be interpreted as minor fluctuations.
P2609H2FPEF score as a prognostic value in HFpEF patients
Authors: Sueta D , Nishihara T , Yamamoto E , Tsujita K
Published: October 2019

Background

The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF).

Purpose

We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients.

Methods

This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50-months. The primary and secondary endpoints were composite cardiovascular/ cerebrovascular events (cardiovascular death, non-fatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation and non-fatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50-months, respectively.

Results

Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events in proportion to a higher H2FPEF score (log-rank test, P=0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P<0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (Table, hazard ratio, 1.179; 95% confidence interval, 1.066–1.305; P=0.001 and hazard ratio, 1.288; 95% confidence interval, 1.134–1.463; P=0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (Figure A, AUC 0.626, 95% CI 0.557–0.693; P<0.001) and HF-related events (Figure B, AUC 0.680, 95% CI 0.600–0.759; P<0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events.

Conclusion

The H2FPEF score is a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients.
P2617Activity of the adrenomedullin system to personalize post-discharge treatment in acute heart failure
Authors: Kozhuharov N , Wussler D , Sabti Z , Twerenbold R , Walter J , Du Fay De Lavallaz J , Strebel I , Breidthardt T , Mueller C
Published: October 2019

Objectives

Activity of the adrenomedullin system was quantified by using bioactive-adrenomedullin (bio-ADM), the biologically active moiety, and midregional proadrenomedullin (MR-proADM), a prohormone fragment, to 1) identify acute heart failure (AHF) phenotypes with disproportional benefit or harm from specific treatments at hospital discharge, 2) predict mortality, and 3) compare the prognostic utility of both biomarkers.

Methods

This prospective multicentre study using central adjudication of AHF measured bio-ADM in all patients and MR-proADM in a predefined subgroup in a blinded fashion on admission. Both biomarkers were measured at discharge as well. Interaction with specific treatments at hospital discharge and the biomarkers' prognostic utility during 365 days' follow-up were assessed.

Results

Among 1,886 patients with adjudicated AHF, 514 patients (27.3%) died during the 365 days' follow-up. Patients with bio-ADM plasma concentrations above the median were at a much higher risk of death (HR 1.87, 95% CI 1.57–2.24; p<0.001). After adjusting for age, creatinine plasma concentrations, and medical treatment at discharge, those patients derived disproportional benefit if treated with diuretics and/or angiotensin-converting-enzyme inhibitors/angiotensin receptor blocker (interaction p-values <0.05). These findings were confirmed only for the diuretics treatment when quantifying the adrenomedullin system using MR-proADM plasma concentrations (n=764). For predicting mortality, both biomarkers performed well and MR-proADM had a higher predictive accuracy as compared to bio-ADM (p<0.001).

Table 1. Interaction p-values in multivariate models using a cox proportional hazard analysis for predicting all-cause mortality at 365 days including age, bio-ADM or MR-proADM, creatinine at discharge, and medication at discharge Diuretics ACE inhibitors or ARB Beta blockers Aldosterone antagonists lg bio-ADM*, ng/l <0.001 0.011 0.760 0.175 lg bio-ADM†, ng/l <0.001 0.020 0.807 0.396 lg MR-proADM*, nmol/l 0.031 0.095 0.169 0.441 lg MR-proADM†, nmol/l 0.001 0.126 0.741 0.272 *At admission; †at discharge. ACE: Angiotensin-converting-enzyme; ARBs: Angiotensin receptor blocker; bio-ADM: bioactive adrenomedullin; MR-proADM: midregional proadrenomedullin.

Figure 1

Conclusion

Quantifying the activity of the adrenomedullin system helps to personalize post-discharge treatment and risk-prediction in AHF.

Acknowledgement/Funding

Swiss National Science Foundation, Swiss Heart Foundation, University of Base, Sphingotec
P2624Association between renal dysfunction and cardiac sympathetic innervation in patients with heart failure
Authors: Marsico F , Paolillo S , Gargiulo P , Esposito I , Dell'aversana S , Renga F , Esposito L , Perrone Filardi P
Published: October 2019

Introduction

In heart failure (HF) a strict interaction exists between heart and kidney. Previous studies reported a significant impact of sympathetic overdrive, that causes beta-adrenoceptor desensitization, in both renal and heart failure progression. It can be hypothesized that renal failure might be associated with impaired sympathetic activity assessed directly at the myocardial level in patients affected by HF.

Purpose

Aim of the present observational study was to assess the relationship between renal dysfunction and cardiac sympathetic innervation in HF patients with mildly and severely reduced ejection fraction (HFrEF and HFmEF).

Methods

Two-hundred and sixty-three patients (84% males; 66±10.8 years) with mild-to-severe HF (EF 31±6.8%) underwent iodine-123 meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart to mediastinum (H/M) ratios and washout rate. All patients also underwent clinical evaluation and venous blood sample collection for the assessment of serum creatinine and consequently the estimation of glomerular filtration rate (eGFR) by EPI formula.

Results

A direct correlation was found between EPI-eGFR and late H/M (r=0,215; p<0.001) (figure 1), with an inverse correlation between NYHA class and late H/M (r=0,152; p=0.013), and a direct correlation between left ventricular EF and late H/M (r=0,348; p<0.001). These results were not confirmed for early H/M, nor washout rate. Dividing the population in reduced eGFR and normal eGFR (cut-off ≤60 ml/min/1,73m2), a statistical significant reduction of late H/M value was found in patients with reduced eGFR (late H/M = 1,49±0,21) compared with patients with preserved eGFR (late H/M = 1,56±0,26) (p=0.020). In a multivariate model, adjusting eGFR for NYHA class and left ventricular EF, reduced eGFR and left ventricular EF remained significant predictors of reduced late H/M (p=0.006 and p<0.001, respectively).

Figure 1. linear regression curve

Conclusions

Patients with impaired renal function and HF show impaired cardiac sympathetic activity compared to HF patients with preserved renal function, and reduced eGFR estimated by EPI formula is a significant predictor of reduced late H/M evaluated by 123I-MIBG. Thus, in future studies, the combination of these two parameters might provide addictive prognostic information in HF patients.
P2630Incidence and prognostic impact of new-onset left bundle branch block in patients with heart failure and reduced ejection fraction
Authors: Kristensen S L , Roerth R , Jhund P S , Beggs S , Kober L , Abraham W T , Desai A , Solomon S , Packer M , Rouleau J , Zile M , Dickstein K , Petrie M C , McMurray J J V
Published: October 2019

Background

Cardiac resynchronization therapy (CRT) improves survival in patients with heart failure, reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). However, little is known about the incidence of LBBB in HFrEF and the risk factors for developing this. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials.

Methods

We identified 7703 patients with a non-paced rhythm on their baseline ECG, a QRS<130 ms, and at least one follow-up ECG (done at annual visits and end of study). Patients were stratified by baseline QRS duration (≤100 ms - reference; 101–115 ms and 116–129 ms) and followed until development of QRS duration ≥130 ms with a LBBB configuration or latest available ECG. The crude LBBB incidence rate per 100 person-years (py) was identified in the three QRS duration subgroups. Additionally, we examined risk of the primary composite outcome of cardiovascular death or HF hospitalization, and all-cause mortality, in patients with incident LBBB vs. no incident LBBB.

Results

Overall, 313 of 7703 patients (4%) developed LBBB during a mean follow-up of 2.7 years, yielding an incidence rate of 1.5 per 100 py. The rate ranged from 0.9 in those with QRS ≤100 ms to 4.0 per 100 py in patients with QRS 116–129 ms. Other predictors of incident LBBB included male sex, age, lower LVEF, HF duration and absence of AF. The risk of the primary composite endpoint was higher among those who developed incident LBBB vs no incident LBBB; event rates 13.5 vs 10.0 per 100 py, yielding an adjusted HR of 1.43 (1.05–1.96). For all-cause mortality the corresponding rates were 12.6 vs 7.3 per 100 py; HR 1.55 (1.16–2.07) (Table 1).

Table 1. Risk of outcomes according to incident LBBB during follow-up No. events Crude rate per 100py Adjusted* HR (95% CI) HF hospitalization or CV death   No incident LBBB 2145 10.0 (9.6–10.4) 1.00 (ref.)   Incident LBBB 43 13.5 (10.0–18.2) 1.43 (1.05–1.96) All-cause mortality   No incident LBBB 1662 7.3 (6.9–7.6) 1.00 (ref.)   Incident LBBB 48 12.6 (9.5–16.7) 1.55 (1.16–2.07)

Conclusion

Among patients with HFrEF, the annual incidence of new-onset LBBB (and a potential indication for CRT), was around 1.5%, ranging from 1% in those with QRS duration below 100 ms to 4% in those with QRS 116–129 ms. Incident LBBB was associated with a much higher risk of adverse outcomes, highlighting the importance of repeat ECG monitoring in patients with HFrEF.

Acknowledgement/Funding

Novartis
P2634Prognostic value of admission left ventricular outflow tract velocity time integral in hospitalized heart failure patients with preserved ejection fraction: a report from the JASPER registry
Authors: Omote K , Nagai T , Kamiya K , Aikawa T , Tsujinaga S , Kato Y , Komoriyama H , Kobayashi Y , Iwano H , Yamamoto K , Yoshikawa T , Saito Y , Anzai T
Published: October 2019

Background

There are little effective treatment strategies for heart failure with preserved ejection fraction (HFpEF) to achieve a reduction of morbidity and mortality. Thus, accurate prognostication of patients with HFpEF could help improve their outcomes by identifying high-risk patients who might potentially benefit from intensive inpatient and outpatient monitoring and early referral for advanced HFpEF therapy. The left ventricular outflow tract velocity time integral (LVOT-VTI) is a representative non-invasive parameter for evaluating stroke volume, which can be a determinant of adverse outcomes in hospitalized patients with heart failure. However, the prognostic implication of admission LVOT-VTI for hospitalized HFpEF patients is undetermined.

Purpose

The aim of the present study was to investigate whether admission LVOT-VTI could predict poor clinical outcomes in hospitalized patients with HFpEF.

Methods

We examined consecutive 535 hospitalized HFpEF patients (left ventricular ejection fraction ≥50%) due to acute decompensated heart failure from the JASPER (JApanese heart failure Syndrome with Preserved Ejection fRaction) multicenter registry, obtained between November 2012 and March 2015. Patients without accessible LVOT-VTI data on admission were excluded. Finally, 214 patients were examined. The primary outcome of interest was composite of all-cause death and rehospitalization due to heart failure.

Results

Mean age was 78±11 years, 100 were male, and median plasma brain-type natriuretic peptide level was 400 (interquartile range [IQR] 223–711) pg/ml. During a median follow-up period of 688 (IQR 162–810) days, adverse events occurred in 83 patients (39%), including 47 (22%) all-cause death, 51 (24%) rehospitalization due to heart failure. The c-index of LVOT-VTI for predicting the composite of adverse events was 0.59 (95% CI 0.51 to 0.67), and the optimal cut-off value of LVOT-VTI was 15.8 cm. Low LVOT-VTI (≤15.8 cm) was significantly associated with higher adverse events compared to high LVOT-VTI (>15.8 cm) (Figure). Multivariable Cox regression analysis revealed that lower LVOT-VTI was an independent determinant of adverse events (HR 0.94, 95% CI 0.91 to 0.98, P=0.005) even after adjustment for pre-specified confounders including age, sex, systolic blood pressure, serum sodium, albumin, plasma brain-type natriuretic peptide and renal function.

Figure 1

Conclusions

Lower admission LVOT-VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT-VTI on admission could be a useful marker for risk stratification in these patients.
P2641Renal and cardiovascular benefits of treatment with angiotensin receptor blockers in patients with hypertension and chronic kidney disease: A systematic review and meta-analysis
Authors: Burnier M , Ruilope L R , Bader G B , Durg S D , Brunel P B
Published: October 2019

Background

Blood pressure (BP) control is critical in delaying the progression of chronic kidney disease (CKD), which otherwise results in an increased risk of cardiovascular morbidity and mortality. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors, are recommended by several guidelines as first-line treatment for patients with hypertension and CKD.

Purpose

We reviewed and analysed the effect of ARB treatment on BP and renal outcomes (estimated glomerular filtration rate (eGFR), serum creatinine (SCr), creatinine clearance (CrCl) or proteinuria) in patients with hypertension and CKD with or without diabetes, including large clinical trials such as RENAAL and IDNT.

Methods

MEDLINE, EMBASE, and BIOSIS databases were searched for literature from the earliest available date to July 2017. Randomised (parallel-group) controlled trials of ≥8 weeks assessed the impact of ARBs on systolic/diastolic BP (SBP/DBP), eGFR, SCr, CrCl or proteinuria were included in the analysis. Meta-analysis (post- versus pre-treatment) and meta-regression were conducted in R-statistical software (v3.4.1) using meta- and metafor-packages. Mean difference (MD, generic inverse variance) with 95% confidence intervals (CIs) was used to pool data for an outcome in a single forest plot. The risk of bias (quality) of included studies was assessed by the six items of the Cochrane instrument.

Results

Of the 165 articles assessed for eligibility, 24 studies were included in the analysis (19 evaluated ARBs as monotherapy, 4 evaluated ARBs in combination with other antihypertensives and 1 evaluated ARBs both as mono- and combination therapy). Treatment with ARBs as monotherapy for ≥8 weeks to <1 year significantly reduced mean office SBP (MD, −12.60 mmHg; 95% CI, −18.53 to −6.67)/DBP (−6.52 mmHg; −11.27 to −1.77) (p<0.01). BP reduction was also significant (p<0.01) with ARB monotherapy for ≥1 year SBP (−14.84 mmHg; −17.82 to −11.85)/DBP (−10.27 mmHg; −12.26 to −8.27). ARBs also significantly reduced SBP/DBP when combined with other antihypertensive treatments for ≥8 weeks to <1 year as well as for ≥1 year (Figure). Moreover, ARBs induced significant reductions (p<0.01) in proteinuria (≥8 weeks to <1 year [MD, −0.6 g/L; 95% CI, −0.93 to −0.26; ≥1 year [−0.9 g/L; −1.22 to −0.59]), but no significant changes in eGFR, CrCl or SCr levels. The beneficial effect of ARBs was maintained overtime with no significant additional impact on SBP change (estimate: 0.025; 95% CI, –0.14 to 0.19) or eGFR (estimate: 0.068; 95% CI, −0.14 to 0.28; p=0.53). The overall risk of bias was judged to be low.

Effect of ARBs on blood pressure changes

Conclusion

Treatment with ARBs effectively and sustainably lowered BP and proteinuria with no significant change in eGFR in patients with hypertension and CKD with or without diabetes.
P2691Excimer laser coronary angioplasty can achieve favorable clinical outocomes for in-stent restenosis lesion with neoatherosclerosis
Authors: Matsuhiro Y , Nishino M , Nakamura H , Yasumoto K , Tanaka A , Nakamura D , Matsunaga Y , Yano M , Yamato M , Egami Y , Shutta R , Tanouti J
Published: October 2019

Background

Recent reports revealed that residual area stenosis (% AS) ≤30% after lesion preparation is a suitable predictor for target lesion revascularization (TLR) after drug-coated balloon (DCB) treatment for in-stent restenosis (ISR). Excimer laser coronary angioplasty (ELCA) can obtain larger lumen area and may be more useful for lesion preparation than plain old ballooning (POBA). On the other hands, it has been reported that in-stent neoatherosclerosis (NA) is major cause of restenosis. It is unclear the correlation between NA of ISR and the effect of ELCA. Thus, we compared the influence of NA which was evaluated by optical coherence tomography (OCT) on % AS for ISR treatment between ELCA and DCB (ELCA) group and POBA and DCB (non-ELCA) group and their clinical outcome.

Methods

We enrolled 58 consecutive ISR lesions which were treated by OCT guidance between July 2014 and July 2018 in our hospital. The lesions were divided into NA and non-NA lesions according to OCT findings. In each lesion, we compared post procedural % AS and % AS change which was calculated by the difference between pre and post procedural % AS between ELCA and non-ELCA groups. In addition, we compared 8-month major advance cardiac events (MACE) defined by composite of binary restenosis and target lesion revascularization (TLR) between ELCA and non-ELCA group in NA lesions.

Results

There were 19 NA (33.3%) and 39 non-NA lesions. In NA lesions, ELCA group can obtain significantly lower % AS (p=0.02) and significantly larger % AS change (p<0.01) than non-ELCA group, but in non-NA lesions, % AS and %AS change were similar between ELCA and non-ELCA groups (table). In 8-month clinical outcome, non-ELCA group experienced MACE twice as much as ELCA group did. (31% vs 17%)

Results of %AS NA lesions (n=19) P value non-NA lesions (n=39) P value ELCA group (n=6) non-ELCA group (n=13) ELCA group (n=17) non-ELCA group (n=22) Post %AS (%) 2±21 26±25 0.02 7±29 23±19 0.07 %AS change (%) 71±15 38±19 <0.01 56±29 44±17 0.11

Conclusion

Although neoatherosclerosis is correlated with refractory restenosis, ELCA can improve residual area stenosis in neoatherosclerosis lesions and can achieve better clinical outcomes for in-stent neoatherosclerosis.
P2695ABSORB bioresorbable scaffold versus Xience metallic stent in acute coronary syndromes with treated with percutaneous coronary intervention. A subanalysis of the COMPARE-ABSORB trial
Authors: Van Geuns R J , Smits P C , Chang C C , Wlodarczyk A , Chevalier B , West N , Gori T , Barbato E , Tarantini G , Kocka V , Achenbach S , Dudek D , Escaned J , Tijssen J , Onuma Y
Published: October 2019

Background

The safety and efficacy of the ABSORB scaffold in ACS patients remain unclear. The COMPARE-ABSORB trial compares the ABSORB to the Xience stent in lesions and patients at high risk for restenosis Patients with STEMI and urgent PCI for non-STEMI were not excluded.

Methods

Patients included in the COMPARE-ABSORB trial undergoing PCI for ACS were eligible. Predefined implantation techniques for ABSORB was mandatory. Primary endpoint is target lesion failure (TLF) at 1 year, defined as a composite of cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularization.

Results

Of 1670 patients, 842 were treated for ACS. At 1-year, TLF occurred in 22 patients (5.0%) of the ABSORB group and in 14 patients (3.5%) of the Xience group (HR 1.44%; 95% CI 0.74%-2.82%, P=0.284). Definite device thrombosis occurred in 9 patients (2.0%) of the ABSORB group and in 2 patients (0.5%) of the Xience group (HR 4.10%; 95% CI 0.89%-18.9%, P=0.071).

Baseline characteristics ABSORB (n=442) XIENCE (n=400) Age, years (SD) 60.7 (9.6) 61.3 (9.1) Male 350/442 (79.2%) 313/400 (78.3%) Current smoker 159/439 (36.2%) 126/397 (31.7%) Diabetes mellitus 152/440 (34.5%) 138/399 (34.6%) Hypertension 298/442 (67.4%) 266/400 (66.5%) Hypercholesterolemia 255/442 (57.7%) 232/400 (58.0%) Family history of coronary artery disease 147/442 (33.3%) 103/400 (25.8%) Previous MI 61/442 (13.8%) 67/400 (16.8%) Established Peripheral Vascular Disease 27/442 (6.1%) 15/400 (3.8%) Previous PCI 83/442 (18.8%) 86/400 (21.5%) Previous CABG 1/442 (0.2%) 4/400 (1.0%) Previous stroke 15/442 (3.4%) 21/400 (5.3%) Renal Insufficiency 9/442 (2.0%) 13/400 (3.3%) Clinical presentation   Unstable angina 149/442 (33.7%) 141/400 (35.3%)   Non-ST elevation myocardial infarction 183/442 (41.4%) 156/400 (39.0%)   ST elevation myocardial infarction 110/442 (24.9%) 103/400 (25.7%)

KM plot for target lesion failure

Conclusion

The COMPARE-ABSORB trial showed no difference in the primary endpoint at one year for the ACS subgroup. The signal for increased thrombosis remained, even with the optimized implantation protocol

Acknowledgement/Funding

Maasstad Hospital, Rotterdam, the Netherlands
P2717Type-II MI and chronic myocardial injury rates, invasive management and 4 year mortality among consecutive patients undergoing high sensitivity troponin T testing in the emergency department
Authors: Etaher A , Gibbs O , Saad Y M , Frost S , Nguyen T , Ferguson I , Juergens C , Chew D , French J K
Published: October 2019

Background

In emergency departments (EDs), assessment of patients with suspected acute coronary syndromes (ACS) represents a major workload and high sensitivity troponin (HsTn) T and I levels are frequently measured. A minority of patients have final diagnosis of myocardial infarction (MI).

Methods and results

Among 2738 consecutive patients with suspected ACS presenting to ED at Liverpool Hospital, Australia, between March and June 2014, we determined the relative frequencies of 3 patient groups: type-I MI, type-II MI including chronic myocardial injury (CMI), and assessed the use of invasive and pharmacological therapies and 4-year outcomes. Adjudication of MI was according to the 4th universal definition of MI as follows: 1) type-I MI; 2) type-II MI (including acute myocardial injury), and 3) CMI. Of 995 patients (36%) median age 76 years [IQR 65–83]), with at least 2 HsTnT measurements and one >14ng/l, 727 (73%) had chronic myocardial injury, 171 (17%) had type-II MI; and 97 (9.7%) had type-I MI. Patients with type-I MI (mean age 63 years) were younger than those with type-II MI or chronic myocardial injury by 12 and 14 years respectively. The main triggering factors for type-II MI/acute injury included: sepsis (21.1%), acute heart failure (18.3%), tachyarrhythmia (16.9%), anaemia (8.6%) and a combination of factors (16%). In-hospital angiography (62% had PCI) rates were 95% for patients with type-I MI, 24% (7% PCI) for those with type-II MI and 3.4% for CMI. Mortality at 4 years was 55% for type-II MI, 44% for CMI and 18% for type-1 MI (P<0.001; Figure), though after Cox modelling adjusting for age, gender, renal function and COPD, compared to type 1 MI, type-II MI (hazard ratio 1.61 [95% CIs 0.90–2.86]; p=0.106) and CMI (hazard ratio 1.01 [95% CIs 0.59–1.74]; p=0.963) were not independently associated with increased late mortality, largely because patients with type 1 MI were a decade younger.

Conclusion

Among unselected patients undergoing HsTnT testing in EDs, type-II MI including acute myocardial injury was more common than type-I MI. Chronic myocardial injury, which occurred in 3 of 4 patients. While patients with type-II MI acute myocardial injury had higher late mortality rates than type-I MI, though after multivariable analyses mortality rates were not different.
P2726Extremely boosted prediction of cardiac amyloidosis by routine laboratory paramaters
Authors: Agibetov A , Seirer B , Aschauer S , Dalos D , Rettl R , Duca F , Agis H , Kain R , Binder C , Mascherbauer J , Hengstenberg C , Samwald M , Dorffner G , Bonderman D
Published: October 2019

Background/Introduction

Cardiac amyloidosis (CA) is a rare and complex condition with poor prognosis. Novel therapies have been shown to improve outcome, however, most of the affected individuals remain undiagnosed, mainly due to a lack in awareness among clinicians. One approach to overcome this issue is to use automated diagnostic algorithms that act based on routinely available laboratory results.

Purpose

We tested the performance of flexible machine learning and traditional statistical prediction models for non-invasive CA diagnosis based on routinely collected laboratory parameters. Since laboratory routines vary between hospitals or other health care providers, special attention has been taken to adaptive and dynamic parameter selection, and to dealing with the frequent occurrence of missing values.

Methods

Our cohort consisted of 376 clinically accepted patients with various types of heart failure. Of these, 69 were diagnosed with CA via endomyocardial biopsy (positives), and 307 had unrelated cardiac disorders (negatives). A total of 63 routine laboratory parameters were collected from these patients, with a high incidence of missing values (on average 60% of patients for each parameter). We tested the performance of two prediction models: logistic regression, and extreme gradient boosting with regression trees. To deal with missing values we adopted two strategies: a) finding an optimal overlap of parameters and deleting all patients with missing values (reduction of parameters and samples), and b) retaining all features and imputing missing values with parameter-wise means. To fairly assess the performance of prediction models we employed a 10-fold cross validation (stratified to preserve sample class ratio). Finally, area under curve for receiver-operator characteristic (ROC AUC) was used as our final performance measure.

Results

A complex machine learning model based on forests of regression trees proved to be the most performant (ROC AUC 0.94±4%) and robust to missing values. The best regression model was obtained with the 25 most frequent variables and patient deletion in case of missing values (ROC AUC 0.82±0.8%). While progressive inclusion of predictor variables worsened the performance of the logistic regression, it increased that of the machine learning approach.

Conclusions

Extreme gradient boosting of regression trees by routine laboratory parameters achieved staggering accuracy results for the automated diagnosis of CA. Our data suggest that implementations of such algorithms as independent interpreters of routine laboratory results may help to establish or suggest the diagnosis of CA in patients with heart failure symptoms, even in the absence of specialized experts.
P2731Genetic ancestry analysis of the Italian founder population carrying the cardiac amyloidosis-causing variant Val122Ile in the transthyretin gene
Authors: Cappelli F , Mazzarotto F , Frusconi S , Contini E , Polimanti R , Buxbaum J , Martone R , Morini S , Taborchi G , Bartolini S , Olivotto I , Pelo E , Di Mario C , Perfetto F
Published: October 2019

Background

Transthyretin amyloidosis is a life-threatening disorder caused by the deposition of TTR amyloid in various tissues and organs. The most common worldwide pathogenic variant with almost exclusive cardiac involvement is Val122Ile (rs76992529), with an allele frequency of 3.5% in the U.S. African-American population, but rare in Caucasians. Unexpectedly, we identified 23 Caucasian individuals with Val122Ile in our amyloidosis referral center (9 affected patients, 14 carriers), belonging to 9 unrelated families.

Purpose

To determine the ancestral origin of the Tuscan founder population of TTR Val122Ile carriers.

Methods

A total of 24 individuals were included in the analysis (our 23 probands and relatives from Val122Ile families and the Caucasian reference sample NA10851 (CEU – Utah resident with European ancestry). All samples were genotyped using the EUROFORGEN Global AIM-SNP array1, inclusive of 127 highly informative SNPs to infer genetic ancestry. We have performed a principal component analysis (PCA) of the 9 unrelated probands and NA10851, compared with the Phase 3 of the 1000 Genomes Project data, comprising 2504 unrelated individuals from >20 distinct populations.(Figure 1).

Results

As shown in Figure 1, all our samples but one (from Argentina) cluster very close to the super-cluster of European populations, and distant from the populations of African ancestry. The proband from Argentina and the Caucasian reference sample NA10851 cluster close to Mexicans and Peruvians, and the super-cluster of European populations, respectively, confirming the robustness of the analysis.

Conclusion

Based on this result, we can confidently conclude that our samples from Tuscan families in which the TTR Val122Ile variant segregates are of ancestral European origin, with no mixed African ancestry, implying that the same variant originated in Africans and Europeans independently and not as result of genetic admixture. These findings suggest the presence of a mutational hot spots in TTR, with potential impact on the epidemiology of amyloidosis worldwide.

Acknowledgement/Funding

The present study was supported by an Investigator-Initiated Research to Azienda Ospedaliero Universitaria Careggi from Pfizer Srl.
P2732Prevalence of electrocardiographic abnormalities in patients with cardiac amyloidosis
Authors: Martone R , Taborchi G , Bartolini S , Morini S , Lossi A , Perlini S , Mussinelli R , Sabena A , Palladini G , Gabriele M , Vignini E , Di Mario C , Olivotto I , Perfetto F , Cappelli F
Published: October 2019

Background

Electrocardiographic (ECG) abnormalities are common in patients presenting with Light-Chain (AL) or Transthyretin (ATTR) related Cardiac Amyloidosis (CA). Type of amyloid may differently affect electrical properties of the heart being responsible for variable patterns of ECG anomalies at presentation.

Purpose

In this retrospective, observational study we sought to compare prevalence of ECG abnormalities between AL and ATTR patients with CA.

Methods

Clinical files from two Referral Centres were reviewed; ECG recordings were analysed by trained cardiologists and relevant findings were reported about rhythm (sinus vs atrial fibrillation [AF]), grade I or grade II atrio-ventricular (AV) delays, intra-ventricular (IV) conduction abnormalities, low-voltage QRS and pseudo-necrosis pattern. Presence of pace-maker (PM) and stimulated QRS were regarded to as clinical equivalents for AV block, after review of indications to implantation.

Results

Two hundred and fifty-one patients were identified (127 ATTR vs 124 AL; among ATTR, 27 patients had mutation in TTR gene: 10 Val142Ile, 11 Ile88Leu, 6 other). As expected, most ATTR patients were male (89% vs 56% in AL, p: <0.001), and AL patients were younger (mean age 64 [53–70] vs 79 [73–83]; p: <0.001).

Pathological ECG findings were common in both subgroups, involving more than three-quarters of the overall population (82% in ATTR, vs 72% in AL, p: 0.06). Atrial fibrillation was more common in ATTR, prevailing in 39% vs 5.6% (p: <0.001). ATTR had a higher burden of AV block (53% vs 13%, p: <0.001) and IV conduction delays (43% vs 21%, p: <0.001), and consistently presented a higher prevalence of PMs (24 patients vs 1). Low-voltage QRS was more prevalent in AL patients (52% vs 28%, p: <0.001), while no significant difference was found in prevalence of pseudo-necrosis patterns (ATTR: 29%, AL: 40%; p: ns).

Due to imbalance in age and gender and relative possible confounding effect on rhythm disturbances, adjusted odds ratios (OR) were calculated. It resulted that ATTR was independently associated with a higher prevalence of AF and AV conduction delays when compared to AL (adjusted OR: 4 [95% CI: 1.4–11.2], p: 0.008, and 6.2 [95% CI: 2.6–14.9], p: <0.001; respectively), while being inversely associated with low-voltage QRS (adjusted OR: 0.4 [95% CI: 0.2–0.9], p: 0.026).

Conclusions

ECG abnormalities are common in CA. Rhythm disturbances are more prevalent in ATTR, while AL more often results in low-voltage QRS. Such differences remain relevant after adjustment for age and gender imbalance, thus suggesting an aetiology-specific link.
P2733Prognostic value of cardiac dysautonomia in AL amyloidosis
Authors: Nicol M , Cescau A , Baudet M , Harel S , Royer B , Sarda L , Cohen Solal A , Arnulf B , Logeart D
Published: October 2019

Introduction

Cardiac involvement is the major prognostic factor in patients with light chain amyloidosis (AL). Cardiac dysautonomia can occur early in amyloidosis and can be assess by Iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Its prognostic value has been shown in TTR amyloidosis but is unknown in AL amyloidosis. We aimed to evaluate the prognosis impact of cardiac dysautonomia in patients with AL amyloidosis.

Methods

We carried out a prospective study in consecutive patients with biopsy-proven AL amyloidosis. All patients underwent clinical examination, EKG, echocardiography, cardiac MRI and biological tests. The 2012 Mayo clinic prognostic classification was calculated by using blood levels of NT-proBNP, cardiac T troponin and the differential of free light chains as recommended. The sympathetic cardiac innervation was assessed by using 123I-MIBGscintigraphy and measurement of the heart-to-mediastinum uptake ratio (late H/M) in the anterior view of the chest. A cardiac denervation was defined by late H/M <1.8 4h after injection of 3 MBq/kg of 123I-MIBG. The primary end-point was all-cause mortality during follow-up.

Results

Fifty consecutive patients with AL amyloidosis were included. The median age was 68 years old [58–73]. By using both echocardiography and MRI, cardiac involvement was diagnosed in 33 patients (66%) and thirteen of these patients were NYHA class III or IV. By using Mayo clinic classification, patients were I, II, III and IV classes in 9 (18%), 14 (28%), 16 (32%) and 11 (22%) cases respectively. According to echocardiographic data, the median wall thickness of left ventricle was 13 mm [12–15]. The late H/M was 1.51 [1.33–1.67]. Cardiac denervation was found in 44 patients (88%). The 6 patients (12%) with a normal late H/M had no cardiac amyloidosis involvement.

During a median follow-up of 24 months, 9 patients (18%) died. The area under the ROC curve of late H/M for predicting death was 0.74 (CI 95% 0.58–0.86). According to this curve, the best threshold was 1.44 and 7 of the 9 patients who died had late H/M ≤1.44. The figure shows the 2 year-survival according to late H/M. Late H/M ≤1.44 predicted all-cause death irrespective of the Mayo clinic classification: HR 8.0 (CI 95% 2.1–63) after adjustment on the Mayo clinic score (p=0.005). In addition, unplanned hospitalization for heart failure occurred in 8 patients with late H/M ≤1.44 versus 3 patients with late H/M >1.44 (p=0.03).

Survival according to late H/M

Conclusion

Late H/M ≤1.44 is predictive of adverse outcomes in patients with AL amyloidosis, independently of the Mayo Clinic prognostic classification.
P2748Lipoprotein(a) and autotaxin in patients with stenotic atherosclerosis of coronary arteries and aortic valve stenosis
Authors: Afanasieva O , Tmoyan N , Razova O , Klesareva E , Afanasieva M , Burdeynaya A , Ezhov M , Pokrovsky S
Published: October 2019

Background

Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). It has been recently shown that autotaxin (ATX), which breaks down lysophosphatidylcholine, derived from oxidized phospholipids, to lysophosphatidic acid, was strongly associated with CAVS.

Purpose

The aim of the study was to investigate the role of Lp(a) and ATX in CHD patients with and without CAVS.

Methods

The study included 438 patients (average age 66±11 years, men 310), 332 had CHD with ≥50% stenosis in at least one coronary artery according to angiography. CAVS was diagnosed with ultrasound. The control group consisted of 106 patients without CHD and CAVS. The concentrations of Lp(a), ATX, lipids and blood cells were measured for all the patients.

Results

CHD without CAVS (group I) was diagnosed in 287 patients, 45 patients had CHD and CAVS (group II). Patients in both groups were older than patients in the control group (75±8, 66±10 and 61±13 years respectively). ATX level was lower in group I (median [25; 75%]: 493 [406; 583] ng/ml) than in control group (544 [412; 655] ng/ml, p=0.02) or group II (553 [475; 609] ng/ml, p=0.003). Lp(a) was lower in control group (14.5 [5.5; 36.0] mg/dl) than in group I (25.6 [9.7; 58.5] mg/dl, p=0.0004) and group II (23.8 [9.9; 79.1] mg/dl, p=0.02). Elevated level of ATX was positively associated with CAVS in CHD patients, but negatively with CHD in patients without CAVS. We have shown that age, glucose level and neutrophil-lymphocytes index (NLI) could be predictors of CAVS in patients with CHD according to results of logistic regression analysis.

Odds ratio of high (QIV) vs. low (QI) Odds ratio (95% confidence interval) Groups Autotaxin Lipoprotein(a) Neutrophil-lymphocytes index I vs. control 0.5 (0.3–0.9)* 2.7 (1.3–5.2)** 2.4 (1.3–4.6)* II vs. control 8.6 (1.1–70.1)* 3.4 (1.2–9.4)* 6.2 (2.2–16.9)** II vs. I 16.6 (2.1–131.1)** 1.3 (0.5–3.2) 2.5 (1.0–6.37)* *p<0.05, **p<0.005.

Conclusion

Elevated Lp(a) level is a predictor of CHD regardless of calcific aortic valve stenosis, whereas elevated concentration of autotoxin in CHD patients was associated with calcific aortic valve stenosis.
P2753Anticoagulation control and all-cause death in patients with operated valvular heart disease with and without atrial fibrillation receiving vitamin K antagonists
Authors: Zulkifly H , Pastori D , Lip G Y H , Lane D
Published: October 2019

Introduction

Good quality of anticoagulation in patients with valvular heart disease (VHD) is needed to reduce ischaemic complications. There is limited evidence on factors affecting anticoagulation control in patients implanted with mechanical or tissue prosthetic valve(s).

Objective

To examine quality, factors affecting anticoagulation control and all-cause death in VHD patients with and without atrial fibrillation (AF) receiving a vitamin K antagonist (VKA) oral anticoagulant. The relationship between INR control with all-cause death and ≥1 adverse clinical events (ACE) [thromboembolism, bleeding, cardiovascular hospitalisation and all-cause death] were explored.

Methods

Anticoagulation control of 456 VHD patients [164 (36%) with AF and 290 (64%) without AF] referred to a hospital-based anticoagulation clinic were assessed retrospectively by time in therapeutic range (TTR) (Rosendaal) and percentage of INRs in range (PINRR) for a median of (IQR) 6.2 years (3.3–8.5). VHD was defined by the presence of mechanical or tissue prosthetic valve at either the mitral or aortic site or both.

Results

Mean (SD) age 51 (14.7), 64.5% male, mean (SD) CHA2DS2-VASc score 2.0 (1.4), 96.1% mechanical prosthesis and 64% aortic valve replacement. VHD patients with AF had lower mean TTR and PINRR, lower proportion of optimal TTR (i.e.≥70%) despite similar number of INR tests compared to VHD patients without AF [Table 1]. Predictors of poor TTR on multivariate logistic regression analysis were female sex, AF and anaemia/bleeding history. Significantly higher proportions of VHD patients with AF died [Table 1]. More deaths (13.1% vs. 4.1%; p=0.011) and ≥1 ACE (42.7% vs. 27.6%; p=0.006) were seen in VHD patients with TTR <70% vs. TTR≥70%, respectively.

Table 1 N (%) Total (N=456) AF (N=164) No AF (N=290) p-value Mean (SD) TTR 58.5 (14.6) 55.7 (14.2) 60.1 (14.6) 0.002 TTR ≥70% 98 (21.5) 23 (14.0) 75 (25.7) 0.004 Mean (SD) PINRR 50.1 (13.8) 47.4 (13.5) 51.6 (13.7) 0.002 Mean (SD) INR tests 96.2 (55.3) 100.7 (58.8) 93.7 (53.1) 0.19 All-cause death 51 (11.2) 34 (20.7) 17 (5.8) <0.001 AF: Atrial fibrillation; IQR: interquartile range; PINRR: percentage of INRs in range; SD: standard deviation; TTR: Time in therapeutic range.

Conclusion

The quality of anticoagulation in VHD patients with AF was low. The presence of AF, anaemia/bleeding history and female sex independently predicted poor TTR. All-cause death was more common in VHD patients with AF and poor TTR. Closer INR monitoring is needed especially in VHD patients with AF to improve anticoagulation control and prevent adverse clinical outcomes.

Acknowledgement/Funding

Kementerian Pendidikan Malaysia and Universiti Teknologi MARA for PhD study but not directly for work under consideration
P2755Acute kidney injury risk calculator in patients with infective endocarditis
Authors: Pisaryuk A , Povalyaev N , Sorokina M , Teterina M , Kotova E , Goreva L , Balatskiy A , Karaulova Y , Efremovtseva M , Milto A , Kobalava Z
Published: October 2019

Background

Kidney involvement in IE has a huge contribution in failure of the treatment. Frequency of kidney lesions is still high. There are several risk calculators for prognosing embolic events, perioperational mortality, 6-month mortality, but there is none for prognosing kidney events in IE.

Materials/Methods

209 patients with verified IE (DUKE 2009, 2015), hospitalized from 2010 to 2018, were included in the study. Kidney function was assessed using CKD-EPI formula. AKI was diagnosed according to current guidelines (KDIGO 2012). Clinical, hematological and echocardiographic features were analysed to look for predictors of AKI. To create a simple risk calculator independent predictors obtained from log-regression analysis were used. The risk formula was derived using the coefficients: Pr(Y) = 1/[1 + exp(−XB)] where Pr(Y) = prognosed risk of AKI, XB = coef1*predictor1 + ... + logit-regression constant.

Results

AKI was presented in 66% cases and mainly was I (41%) and III (37%) stages. Predictors for AKI were established: MRSA OR 8.0 (95% CI 1.01–68.48; p=0.054), emergence or worsening of the HF sympthoms OR 2.83 (95% CI 1.27–6.32; p=0.011), gentamycin OR 2.71 (95% CI 1.33–5.53, p=0.006), history of CAD OR 2.35 (95% CI 1.05–5.27) p=0.038, WBC at admission >11.5x109/l OR 1.07 (95% CI 1.01–1.13), duration of hospitalization >20.7 days OR 1.03 (95% CI 1.01–1.05) p=0.005, C-reactive protein >90 mg/l OR 1.01 (95% CI 1.01–1.02) p=0.001.

Simple risk calculator Coef OR Indicator MRSA 2.0755 8 0 Emergence or worsening of the heart failure sympthoms 1.04041 2.83 0 Gentamycin 0.3640833 2.71 1 History of coronary artery disease 0.8542633 2.35 1 White blood count at admission 0.0691979 1.07 13 Duration of hospitalization 0.0308953 1.03 2 C-reactive protein 0.0075288 1.01 180 Constant −3.275098 0.0378132 Logit 0.259795900 P 0.564586119 Scaling parameter 100 Points 56 Result 56

Conclusions

A simple risk calculator for AKI is developed for patients with IE.