bluuebunny/crossref_metadata_2025 huggingface dataset:
P4469Reduced myocardial perfusion reserve in type 2 diabetes is caused by increased rest perfusion as well as decreased maximal perfusion during stress
Authors: Soerensen M H , Bojer A S , Madsen P L , Gaede P
Published: October 2019

Background

Reduced myocardial perfusion reserve is a well-known complication in patients with type 2 diabetes mellitus (T2DM). Furthermore, reduced myocardial perfusion reserve has been linked to the development of diastolic dysfunction, a key characteristic in diabetic cardiomyopathy. However, it is not fully explored whether a decrease in perfusion during stress or an increase in perfusion during rest is responsible for this reduction in myocardial perfusion reserve, nor is it clear what causes these changes.

Purpose

The purpose of this study was to examine differences in myocardial perfusion in rest and during stress in patients with T2DM compared to healthy control subjects, and to identify potential predictors for changes in perfusion during rest and stress among patients with T2DM.

Methods

200 patients with T2DM and 25 healthy volunteers matched for age and sex underwent a comprehensive cardiac MRI protocol including gadolinium first-pass perfusion during rest and stress (adenosine infusion 140 mg/min–1/kg–1). Perfusion was measured on a per-segment basis based on the AHA model and averaged to calculate global perfusion index both during rest and stress. Any areas with infarctions and/or significant perfusion defects were excluded from the analysis. Backwards stepwise multiple linear regression was performed to identify predictors for perfusion changes during rest and stress in patients with T2DM. Variables with P<0.1 in a univariate analysis were included into the models.

Results

Patients with T2DM had significantly higher rest perfusion index (0.135±0.024 vs. 0.120±0.016; P=0.001) and significantly lower stress perfusion index (0.174±0.041 vs. 0.225±0.027; P<0.001) compared to healthy volunteers. In a multiple linear regression model among patients with T2DM female sex (P<0.001) was associated with increased rest perfusion. In a similar analysis for stress perfusion, diabetes duration (P=0.01), albuminuria (P<0.001) and the presence of ischaemic heart disease (P<0.001) were associated with reduced myocardial stress perfusion index in patients with T2DM.

Conclusion

In patients with T2DM reductions in myocardial perfusion reserve is caused by a combination of increased basal myocardial blood flow and a decrease in maximal blood flow during stress. Decreased stress perfusion is associated with coronary vascular disease and the diabetic complication albuminuria related to renal microvascular disease. Stress perfusion also decreased with increasing duration of T2DM. This suggest that the coronary microcirculation is gradually damaged in patients with T2DM and that the mechanism responsible is similar to that causing renal microvascular damage.

Acknowledgement/Funding

Local science committee of Region Zealand, Regional science committee of Region Zealand, The Danish Heart Association
P4485The number of lipoprotein(a) kringle IV-type 2 repeats is associated with the osteogenic profile of aortic valvular interstitial cells induced by plasma from patients with calcific aortic stenosis
Authors: Arangalage D A , Simon T S , Varret M V , Croyal M C , Arsenault B A , Cattan-Levy L C L , Sayah N S , Deschildre C D , Boutten A B , Michel J B M , Mathieu P M , Nicoletti A N , Messika-Zeitoun D M Z , Caligiuri G C , Laschet J L
Published: October 2019

Background

Considerable progresses have been made in the invasive treatment of calcific aortic stenosis (AS), but there is still no pharmacological treatment available because the exact mechanism leading to the initiation of valvular calcification remains unknown. An increasing number of evidences, including large-scale genetic studies, have linked Lipoprotein(a) (Lp(a)) to AS but its pathogenic role in the osteoblastic transition of valvular interstitial cells (VIC) has remained undeciphered.

Objective

We sought to study the mechanistic link between the transition of VICs towards an osteoblastic phenotype leading to intraleaflet calcium deposition and the type of Lp(a) isoform, defined by the number of kringle IV-type 2 (KIV 2) repeats, in the plasma of patients with AS compared with healthy controls.

Methods

VICs isolated from healthy aortic valves were cultured in the presence of plasma samples deriving from 100 patients with severe AS included in the prospective cohort GENERAC and 50 matched control patients exempt from any aortic valve disease. We evaluated the number of Lp(a) KIV 2 repeats of each plasma preparation by liquid chromatography-mass spectrometry. The phenotypic changes of VICs towards an osteoblastic phenotype were assessed by immunofluorescence microscopy (osteocalcin expression) and Alizarin red staining (calcium deposition).

Results

Incubation of VICs with the plasma of AS patients triggered their transformation towards an osteoblastic phenotype, evidenced by the production of osteocalcin, and calcium deposition. There was no association between the plasma levels of Lp(a) and the extent of calcium deposition in the study population. However, a negative and significant correlation was found between calcium deposition and the number of KIV-2 repeats in the Lp(a) of the different plasma preparations (r=−0.20, p=0.038). A direct, causal role of Lp(a) isoforms containing a low number of KIV-2 repeats (5 to 6) in the transition of VICs towards an osteoblastic phenotype was supported by experiments performed with preparations of these isoforms, isolated from the plasma of blood donors.

Conclusion

A low number of KIV–2 repeats in plasma Lp(a) triggers the acquisition of an osteoblastic phenotype by VICs. The isoform, rather than the concentration of Lp(a) may play a pathogenic role in AS. Determining the number of KIV-2 repeats in the Lp(a) of patients may allow to identify subgroups of patients with an increased risk of developing AS.

Acknowledgement/Funding

ANR-16-RHUS-0003_STOP-AS. PHRC National 2005 and 2010, and PHRC regional 2007.
P4497Serum ceramides and type 2 diabetes are mutually independent predictors of cardiovascular events in patients with peripheral artery disease
Authors: Leiherer A , Muendlein A , Saely C H , Laaksonen R , Laaperi M , Vonbank A , Larcher B , Mader A , Fraunberger P , Dopheide J F , Baumgartner I , Drexel H
Published: October 2019

Background

Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently emerged as predictors of cardiovascular outcomes in coronary artery disease patients.

Purpose

The purpose of this study was to investigate their power to predict cardiovascular events in patients with peripheral artery disease (PAD).

Methods

We measured the serum concentrations of the above mentioned ceramides in a cohort of 380 patients with sonographically proven PAD, of whom 107 had type 2 diabetes (T2DM). Prospectively, we recorded 221 cardiovascular events over a mean follow-up time of 6.3±2.3 years.

Results

Cardiovascular event risk was higher in T2DM patients than in those who did not have diabetes (69 vs. 52%, p=0.001). The ceramides Cer(18:1/16:0) and Cer(18:1/24:1) and the respective ratios Cer(18:1/16:0) / Cer(18:1/24:0) and Cer(18:1/24:1) / Cer(18:1/24:0) were significant predictors of cardiovascular events both univariately and after multivariate adjustment including the presence of T2DM (figure). Conversely, T2DM predicted cardiovascular events independently from the investigated ceramides (adjusted HR 1.76 [1.31–2.35], p<0.001).

Conclusion

We conclude that the investigated ceramides and T2DM are mutually independent predictors of cardiovascular events in PAD patients.
P4498Subcellular anti-atherosclerotic therapy: an approach to elimination of dysfunctional mithohondria by photodynamic therapy
Authors: Ryabova A V , Romanishkin I D , Skobeltsin A S , Moskalev A S , Makarov V I , Loschenov V B , Nikiforov N G , Orekhov A N , Orekhova V A , Sukhorukov V N , Sobenin I A
Published: October 2019

Photo-theranostics is a therapeutic and diagnostic approach that uses photosensibilization. This approach makes part of the medicine of the future – subcellular therapy. Photo-theranostics targets cells and tissues that are affected by pathological changes inducing apoptotic cell death. However, the approach allows targeting cellular organelles, if the photo-sensitizing agent is accumulated selectively. Such selectivity can result from the organelle's functional state, as in the case of mitochondria affected by mitochondrial genome abnormalities. For instance, some pro-atherogenic mitochondrial DNA (mtDNA) mutations can lead to mitochondrial dysfunction

Some photo-sensitizing agents accumulate selectively in mitochondria making the photodynamic targeting efficient enough. For instance, protoporfyrine IX (PpIX), which is widely used in clinical practice, is produced from a prodrug 5-aminolevulinic acid (5-ALC) in course of heme synthesis cascade in the mitochondria. Exogenous 5-ALC causes excessive formation of PpIX, which cannot be efficiently processed by ferrochelatase and accumulates in the cells. PpIX accumulation directly depends on the cell's metabolic activity.

We studied 5-ALC-induced PpIX accumulation on cybrid lines derived from thrombocytes with mutation-bearing mitochondria and THP-1 monocytes devoid of mitochondria. We used 3 cybrid lines and 2 THP-1 monocyte cultures cultured independently by different research groups. The mitochondrial functional state was assessed by fluorescence intensity of mitochondrial dye MitoTracker™ Orange CMTMRos (Thermo Fisher Scientific). Measurement of fluorescence was performed by laser scanning microscopy with spectral unmixing. MitoTracker and PpIX dyes were excited with a 561 nm laser, and fluorescence was measured at 570–750 nm wavelength. The signal was spectrally unmixed to obtain separate MitoTracker and PpIX signals. Individual cells areas were traced on microscopic images taken under identical conditions, and mean values of PpIX and MitoTracker fluorescence intensity were obtained for each cell.

We found that PpIX accumulation varied significantly from cell to cell within cell populations. Cybrid lines had increased PpIX accumulation in comparison with original THP-1 monocyte lines. A positive correlation between PpIX amount and mitochondrial membrane potential was observed (Figure 1).

Therefore, selective elimination of dysfunctional (mutated) mitochondria can be achieved by adjusting laser intensity sufficient to induce photodynamic destruction of the organelles, while normal mitochondria and the cells as a whole should be preserved at the used light intensities. This work was supported by the Russian Science Foundation (Grant #19-15-00010).

Acknowledgement/Funding

Russian Science Foundation (Grant # 19-15-00010)
P4506New indices of arterial stiffness correlates with disease severity and mid-term prognosis in acute decompensated heart failure
Authors: Zhou J T , Wang Y S , Kang Y , Feng Y Z , Chen X J , Zhang Q
Published: October 2019

Background

Arterial stiffness has been implicated in pathophysiology of heart failure (HF) since it is involved in the ventricular-vascular coupling. Recently, new indices obtained by a cuff oscillometric technique, the arterial velocity-pulse index (AVI) for the stiffness of central arteries and the arterial pressure-volume index (API) for the stiffness of peripheral arteries have been developed and validated. However, the AVI and API measurement has not been attempted in HF population.

Purpose

This study aimed to investigate the relationship between the AVI, API and clinical outcomes in HF patients.

Methods

A prospective cohort of patients with acute decompensated HF were enrolled within 6 months, who were admitted to a tertiary referral hospital in China. Measurement of the AVI and API (AVE-1500, Shisei Datum, Tokyo, Japan) was performed on the day of admission and discharge. Patients were followed up to 6 months for the composite endpoint of all-cause death and HF rehospitalization.

Results

A Total of 127 patients were recruited for analysis (60±15 years, 70% male). 80% of the patients were in New York Heart Association (NYHA) Class III or above at admission, who presented a mean left ventricular ejection fraction (LVEF) of 34±9%. During hospitalization, all patients received guideline directed medical therapy if not contraindicated. The AVI (27.3±5.2 vs. 28.6±6.7, p=0.002) and API (24.9±4.9 vs. 26.0±6.5, p=0.05) were lower at discharge than at admission. By dividing the patients into tertiles according to the amino-terminal pro-brain natriuretic peptide (NT-proBNP), LVEF, transmitral E velocity over mitral annular e' velocity (E/e' ratio) and systolic blood pressure (SBP) at admission, it was observed that the AVI increased with a higher level of NT-proBNP (p for trend <0.001), a larger E/e' (p<0.001) and a lower LVEF (p=0.001), while the API increased as the SBP became higher (p=0.005).The improvement in AVI at discharge was correlated with that in LVEF (R=-0.3024, p<0.05) and NT-proBNP (R=0.3118, p<0.05), while the change in API was positively correlated with that in SBP (R=0.3897, p<0.001). In 6 months after discharge, there were 52 predefined events including 15 deaths and 44 HF rehospitalization. Apart from the level of NT-proBNP, the AVI at discharge of ≥26 showed a trend of being associated with the composite outcome (2.747, 1.411–5.349, p<0.001 for univariate analysis; 1.8648, 0.8928–3.8949, p=0.0973 for multivariate analysis).

Conclusions

New noninvasive arterial stiffness indices as the AVI and API reflected severity of illness and mid-term prognosis in admitted HF patients. Further studies are warranted for understanding its mechanisms and developing clinical applications.
P4528Feasibility and safety of left bundle branch area pacing by transvenous approach through the interventricular septum in patients with left bundle branch block
Authors: Huang W J , Wu S J , Su L , Chen X Y , Cai B N , Zhou J G , Lan R F , Fu G S , Xu L , Xiao F Y , Wang S J , Mao G Y , Vijayaraman P , Ellenbogen K
Published: October 2019

Background

His bundle pacing (HBP) has been shown to correct left bundle branch block (LBBB), however it often requires high pacing output and the success rate is variable.

Objective

To assess the feasibility and safety of left bundle branch area pacing (LBBAP) in patients with LBBB.

Methods

From Apr 2014 to Aug 2018, patients with LBBB from multicenters indicated for CRT or pacing therapy were included. LBBAP was performed by advancing the MDT 3830 lead deep into the septum about 1 cm distal to the His bundle region (Figure 1F). Pacing characteristics, success rate, threshold and R-wave amplitude were assessed.

Results

A total of 94 patients aged 68.3±10.7 y with the native QRS duration of 167.2±17.2 ms were included. In 92 patients, LBBAP was successfully achieved and demonstrated RBBB pattern during unipolar tip pacing (UTP), with the paced QRS duration of 116.4±12.6ms (Figure 1C). Fusion of LBBAP and native conduction via the RBB eliminated RBBB and resulted in an average QRS duration of 103.2±10.1 ms (Figure 1D). LBB potential could be recorded from the LBB lead during correction of LBBB by HBP in 21 patients who used two leads method (His lead and LBB lead, Figure 1B). Output dependent selective and non-selective LBBAP were demonstrated in 48 patients (Figure 1C, D). The LBB capture threshold by UTP was 0.53±0.18V/0.5ms at acute and 0.62±0.17V/0.5ms at 6 months and 0.65±0.2V/0.5ms at 1 year. The R-wave amplitude were 11.4±5.2mV, 12.4±5.8mV and 12.0±5.8mV at acute, 6 month and 1 year. During follow-up, only one patient had an increase in LBB capture threshold to 2.5V/0.5ms at 3 months and there were no other complications such as dislodgment, infections, embolism or stroke associated with the implantation.

Conclusion

Permanent LBBAP is feasible and safe in patients with LBBB.
P4535Discharge treatment with ACE inhibitor/ARB after a heart failure hospitalization is associated with a better prognosis irrespectively of left ventricular ejection fraction
Authors: Vicent Alaminos L , Cinca J , Vazquez-Garcia R , Gonzalez-Juanatey J R , Rivera M , Segovia J R , Pascual-Figal D , Bover R , Worner F , Delgado-Jimenez J , Fernandez-Aviles F , Martinez-Selles M
Published: October 2019

Background

Medical therapy could improve the prognosis of real-life patients discharged after a heart failure (HF) hospitalization.

Purpose

We aimed to determine the impact of discharge HF treatment on mortality and readmissions in different left ventricular ejection fraction (LVEF) groups.

Methods

Multicentre prospective registry in 20 Spanish hospitals. Patients were enrolled after a HF hospitalization.

Results

A total of 1831 patients were included (583 [31.8%] HF with reduced ejection fraction [HFrEF]; 227 [12.4%] HF with midrange ejection fraction [HFmrEF]; 610 [33.3%] HF with preserved ejection fraction [HFpEF], and 411 [22.4%] with unknown LVEF. Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin II receptor blockers (ARB) at discharge were independently associated with a reduction in: i) all-cause mortality: hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.41–0.74, P<0.001, with a similar effect in the four groups; ii) mortality due to refractory HF HR 0.45, 95% CI 0.29–0.64, P<0.001, with a similar effect in the three groups with known LVEF; iii) mortality/HF admissions (HR 0.61; 95% CI: 0.50–0.74), more evident in HFrEF (HR 0.54; 95% CI: 0.38–0.78) compared to HRmEF (HR 0.64; 95% CI 0.40–1.02), orHFpEF (HR 0.70; 95% CI 0.53–0.92).Inpatients with HFrEFtriple therapy (ACE inhibitor/ARB+ betablocker+ mineralocorticoid receptor antagonist) was associated with the lowest mortality risk (HR 0.21; 95% CI: 0.08–0.57, P=0.002) compared to patients that received none of these drugs.

Events according to the number of drugs – HFrEF (n=583) 0 (n=14) 1 (n=98) 2 (n=160) 3 (n=294) P Death or heart failure readmissions 10 (71.4) 58 (59.2) 66 (41.3) 106 (36.1) <0.001 All-cause mortality 9 (64.3) 28 (28.6) 31 (19.4) 36 (12.2) <0.001 Mortality due to refractory heart failure 7 (50.0) 14 (14.3) 17 (10.6) 17 (5.8) <0.001 – HFmrEF (n=227) 0 (n=18) 1 (n=57) 2 (n=81) 3 (n=65) P Death or heart failure readmissions 9 (50.0) 35 (61.4) 34 (42.0) 25 (38.5) 0.057 All-cause mortality 5 (27.8) 18 (31.6) 15 (18.5) 11 (16.9) 0.191 Mortality due to refractory heart failure 3 (16.7) 7 (12.3) 7 (8.6) 4 (6.2) 0.475 – HFpEF (n=610) 0 (n=61) 1 (n=242) 2 (n=219) 3 (n=69) P Death or heart failure readmissions 32 (52.5) 97 (40.1) 89 (40.6) 20 (29.0) 0.057 All-cause mortality 20 (32.8) 41 (16.9) 32 (14.6) 10 (14.5) 0.017 Mortality due to refractory heart failure 11 (18.0) 18 (7.4) 13 (5.9) 4 (5.8) 0.041 Outcomes according to the number of medications at discharge.

Kaplan-Meier Curves for study outcomes

Conclusions

Discharge treatment with ACE inhibitor/ARB after a HF hospitalization is associated with a reduction in all-cause and refractory HF mortality, irrespectively of LVEF.
P4540Obesity in patients with heart failure and without diabetes mellitus is associated with longer event-free survival only among those with high dietary sodium intake
Authors: Saleh Z , Lennie T , Moser D
Published: October 2019

Background

Obesity is paradoxically associated with better short- and long-term outcomes in patients with heart failure (HF) and without diabetes mellitus (DM). While excessive dietary sodium intake is common among obese persons, its impact on the association between obesity and outcomes has not been considered.

Aim

To determine whether dietary sodium intake levels would affect the association between obesity and better outcomes in patients with HF and without DM.

Method

A sample of 129 patients (age 60±12.4 years; 30% female) provided a single 24-hour urine collection sample to estimate dietary sodium intake. Patients were divided into 4 groups based on body mass index (BMI) and the sodium intake recommendation for HF of 3g/day (obese with high sodium intake [n=41; 32%], obese with low sodium intake [n=16; 12%], non-obese with high sodium intake [n=35; 27%], and non-obese with low sodium intake [n=37; 29%]). Patients were followed-up during an average period of 395 days to determine time to first event of all-cause hospitalization or death. Cox regression was used to determine the association between obesity and outcomes in the context of sodium intake after controlling for age, gender, NYHA class (I II vs. III IV) and LVEF.

Results

There were 41 patients (31.8%) who had an event of all-cause hospitalization or death. Obese patients with high sodium intake had 61% lower risk for events than those non-obese with low dietary sodium intake (figure). There were no differences in the event-free survival among other groups.

Conclusion

These data suggest that dietary sodium intake may be particularly important for obese patients with HF and without DM.
P4550Growth differentiation factor 15 as an integrative biomarker of heart failure in patients with acute myocardial infarction
Authors: Meloux A , Rochette L , Maza M , Bichat F , Chague F , Cottin Y , Zeller M , Vergely C
Published: October 2019

Background

Growth differentiation factor 15 (GDF15), a stress-responsive cytokine member of the transforming growth factor-β family, is an emerging biomarker in cardiovascular (CV) diseases. GDF15 is weakly expressed in normal condition but increased in pathological situations such as inflammation, oxidative stress, and left ventricular remodeling. Recent data suggest GDF15 as a marker in heart failure (HF).

Purpose

We aimed to identify the determinants of GDF15 circulating levels in patients admitted for an acute myocardial infarction (AMI).

Methods

In our prospective study, all consecutive patients admitted from June 2016 to February 2018 for type 1 AMI in the Coronary Care unit from our University Hospital were included. Chronic HF patients were excluded. In-hospital severe HF was defined as killip class>2. Blood samples were taken on admission and serum levels of GDF15 were measured using a commercially available ELISA kit.

Results

Among the 284 AMI patients, median age was at 67 (57–78) y, 27% were women, 23% had diabetes and 59% were hypertensive. GDF15 levels (median = 1,144 (775–1,891) ng/L were strongly correlated with age (r=0.493, p<0.001), and elevated with most CV risk factors (i.e. hypertension, diabetes), prior CAD, chronic kidney disease (p<0.001 for all) and in patients with CRP >3 mg/L (p<0.001). When compared with patients who didn't develop severe HF (274/284), patients experiencing HF (10/284), GDF15 was more than twice higher (figure). By Receiving Operating Curve analysis, GDF15 was associated with HF (AUC (95% CI) = 0.716 (0.52–0.91), p=0.021). Moreover, GDF15 levels were negatively correlated with Left Ventricular Ejection Fraction (LVEF) (r=−0.193, p=0.001). Multivariate logistic regression analysis showed that GDF15 >5,000 ng/L [OR: 8.43; 95% CI (1.57–45.32)] is as independent estimate of HF, beyond age and other confounding (i.e. admission systolic blood pressure, LVEF and Log N-terminal pro-Brain Natriuretic Peptide).

GDF15 levels according to HF development

Conclusions

These preliminary results suggest that GDF15 could be an integrative biomarker of severe HF in patient with AMI. Further studies are needed to elucidate the underlying mechanisms linking the cytokine with the development of HF.
P4561Patients adherence with fixed dose combinations of renin-angiotensin-aldosterone system inhibitors in hypertension
Authors: Simonyi G A , Ferenci T , Finta E , Balogh S , Medvegy M
Published: October 2019

Introduction

The latest ESC/ESH guidelines recommended fixed dose combinations (FDC) for first therapy in hypertension. Preferred two-drug combinations are a RAS (renin–angiotensin system) blocker with a CCBs (calcium channel blockers) or a diuretic. There are no available data about these FDCs adherence in hypertension.

Aim

To assess one year persistence of recommended FDCs (RAS-inhibitors/CCBs or diuretics) in hypertensive patients.

Method

Prescriptions database of National Health Insurance Found in Hungary on pharmacy-claims were analysed between October 1, 2012 and September 30, 2013. We identified patients who filled prescriptions for FDCs of RAS-inhibitors/CCBs or diuretics prescribed for the first time in hypertensive patients who have not received similar drugs during one year before. To model the persistence, the apparatus of survival analysis was used, where “survival” was the time to abandon the medication.

Results

443,149 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinuation (reference was ACEi/indapamide FDC) in patients with ACEi/CCB FDCs (n=124,154) was 44,95% (HR=0.69, [CI: 0.68–0.69], p<0.0001), ARB/HCT FDCs (n=109,707) was 42,52% (HR=0.80, [CI: 0.81–0.83], p<0.0001), ACEi/indapamide FDC (n=127,757) was 37,27% (HR=1.00, reference), ARB/CCB FDCs (n=13,542) was 29.04% (HR=1.19, [CI: 1.17–1.22], p<0.0001) and ACEi/HCT FDCs (n=67,989) was 27.47% (HR=1.17, [CI: 1.15–1.18], p<0.0001).

One year peristence of FDCs

Conclusions

We have found significant difference between FDC s of RAS-inhibitors in hypertensive in relation of patients adherence. Our result demonstrated that ACEi/CCBs FDC therapy has the best one year persistence rate.
P4575UA and NSTEMI in the era of high-sensitivity Troponin: impact on patient risk profile and management
Authors: Carvalheira Dos Santos R , Raposo L , Madeira S , Brito J , Goncalves M , Brizido C , Vale N , Leal S , Sousa P , Araujo Goncalves P , Mesquita Gabriel H , Campante Teles R , Almeida M , Mendes M
Published: October 2019

Aim

High-sensitivity troponin assays (HST) entered the clinical arena to facilitate exclusion of ACS in the emergency department (ER) in patients presenting with chest pain. Due to its higher sensitivity there is the potential for an overestimation of the diagnosis of NSTEMI, and possibly ACS overall. We assessed the impact of HST in the classification of ACS (NSTEMI vs UA) and its ability to predict obstructive coronary disease (CAD), in a population of pts referred to coronary angiography (ICA).

Methods

Retrospective analysis of 1844 pts with suspected NSTEMI or UA referred for ICA from a single ER between Feb 2013 and Nov 2018. Standard Troponin-I was used until Feb 2016 and HST thereafter. The characteristics of UA and NSTEMI pts before and after the introduction of HST were compared. Multivariate binary logistic regression models were used to access the association of different troponin assays with CAD (>50% for LM and >70% for the remaining). Sensitivity, specificity, NPV and PPV for angiographic CAD were also determined.

Results

The relative proportion of patients with UA and NSTEMI was similar between study periods: 31% vs 29% and 69% vs 71%, respectively (p=0.3). Clinical and angiographic characteristics did not differ in UA pts before and after the use of HST. NSTEMI patients in the HST era were less frequently women (39% vs 32%, p=0.026), had higher creatinine (0.93 IQR 0.75–1.3 vs 1.0 IQR 0.82–1.38), higher number of lesions (2 IQR 1–4 vs 3 IQR 1–4) and a lower rate of normal coronary arteries (10.5% vs 3.9%, p<0.001). The prevalence of significant CAD in this population, before and after HST, was 65% and 73%, respectively (p=0.001). However, when clinically relevant characteristics and judgement were accounted for, both standard troponin (OR 0.99, 95% CI 0.99–1.01) and HST (1.0, 95% CI 1.0–1.0) were poor predictors of significant CAD. Sensitivity was 69% vs 72%, specificity 30% vs 30%, PPV 65% vs 73% and NNP 34% vs 28%, respectively. Finally, rates of percutaneous intervention did not differ between the two periods (30% vs 33.5%, p=0.157), nor between ACS types within each period.

CAD/PCI in ACS within each period

Conclusion

The introduction of HST did not result in an increase of the diagnosis of NSTEM vs UA, suggesting that clinical judgment remains an important determinant of the diagnosis of ACS. Also there was no evidence of an increase in PCI rates, despite worse CAD severity in NSTEMI patients.
P4593Effectiveness of using the Syntax Score II calculator for the patients with multi-vessel coronary arteries lesion
Authors: Alekyan B , Karapetyan N , Kishmiryan D
Published: October 2019

Introduction

The most significant disadvantage of the SYNTAX score is the lack of an individualized approach due to the absence of the clinical parameters. The Syntax Score II calculator which includes 6 clinical indicators is more accurate decision-making tool that should help the “heart team” to choose a strategy for myocardial revascularization.

The purpose of the study was to examine the effectiveness of using Syntax Score II for patients with multi-vessel coronary artery lesions who was dedicated to PCI.

Material and methods

From 01/2018 to 12/2018, 760 patients were included in the research, who was dedicated to PCI by the decision of the local “heart team”. In present analysis were included 116 (15%) of these patients with the multi-vessel coronary lesion and with a left main coronary artery lesion of different complexity. Patients who had previously undergone myocardial revascularization were excluded from analysis. The age of patients ranged from 41 to 86 years (mean age 67 + 9 years). There were males - 67.2%. Diabetes mellitus was present in 34.5% of the patients. 42.2% of the patients had angina pectoris (NYHA 3–4), and 60.3% had II class chronic heart failure.

Results

The average Syntax Score of the 116 patients was 23.1 + 7.8 (from 11 to 59). Syntax Score of the 52 (44.8%) patients was more than 23, and less than 23 in 64 (55.2%) of the cases.

The Syntax Score II for the same patients recommended only CABG in 13 (11.2%), only PCI - in 6 (5.2%) and equality between methods - in 97 (83.6%) cases. Only in 6 (5.2%) patients, there was complete agreement between the risk scales, and for 53 (45.7%) of them, the methods were equal. For 44 (37.9%) patients, the Syntax score recommended CABG (Syntax score more than 23), and Syntax Score II indicated equality of methods. In 2 (1.7%) patients with a SYNTAX score of more than 23 the Syntax Score II nevertheless recommended PCI. The “heart team” decision and the Syntax Score II recommendation were in agreement in 103 (88.8%) of the cases, while the “heart team” decision and the SYNTAX recommendation were in agreement only in 64 (55.2%) of the cases.

At the hospital stage, there were 2 (1.7%) cases of stent thrombosis with a fatal outcome, both in patients with SYNTAX score 42 and 28.

To determine the degree of consistency between the risk scales, the Kappa Cohen coefficient was calculated, which was 0.06 (p=0.93), which indicates lack of consistency between SYNTAX and Syntax Score II in recommendations.

Conclusion

The Syntax Score II risk scale is an effective tool for making “heart team” decisions about myocardial revascularization method and expands indications for performing PCI, and in 88.8% of cases with multi-vessel coronary arteries lesion, it is possible to get equal predictions between the methods of revascularization. In 40% of cases in patients with a SYNTAX of more than 23 Syntax Score II determines an equiprobable prognosis for performing PCI and CABG.
P4596Long-term outcomes of culprit lesion only versus multi-vessel one-stage intervention in non-ST elevation acute coronary syndrome patients undergoing percutaneous coronary interventioo
Authors: Jia S , Liu Y , Yao Y , Yang Y J , Gao R L , Xu B , Yuan J Q
Published: October 2019

Background

It is recommended to base revascularization strategy on the clinical status, comorbidities and lesion characteristics in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). However, the risk and benefit of Culprit Lesion Only (CVO) versus Multi-vessel One-stage Intervention (MVOI) is unclear. We aim to compare the long-term prognosis of NSTE-ACS undergoing CVO and MVOI PCI strategy.

Method

A total of 4768 consecutive patients with NSTE-ACS who underwent PCI in our hospital in 2013 were enrolled in this study. Patients were divided into CVO group and MVOI group according to whether the culprit vessel was the only target vessel. Prognosis impact on 2-year major adverse cardiovascular and cerebrovascular events (MACCE) is analyzed across 2 groups, including death, cardiac death, myocardial infarction, unplanned revascularization, in-stent thrombosis, stroke and bleeding.

Results

Compared with CVO group, MVOI patients had generally worse clinical baseline characteristics and angiographic findings, including higher BMI, SYNTAX score, higher proportion of diabetes, hypertension, NSTEMI, tri-vessel disease, total occlusion, etc. Two-year follow-up revealed that MVOI patients have significantly higher rate of unplanned revascularization (10.1% vs. 7.9%, p=0.018), stroke (2.2% vs. 1.3%, p=0.042) and MACCE (14.0% vs. 11.3%, p=0.012). Kaplan-Meier survival analysis yielded similar results. After adjusting for confounding factors by Cox regression analysis, MVOI was shown to be independently associated with higher rate of 2-year in-stent thrombosis (HR = 3.718, 95% CI: 1.125 - 12.293).

Two-year Clinical Outcomes CVO (n=3634) MVOI (n=1134) P value All-cause Death 39 (1.1) 13 (1.1) 0.836 Cardiac Death 18 (0.5) 8 (0.7) 0.402 Myocardial Infarction 64 (1.8) 22 (1.9) 0.693 Unplanned Revascularization 287 (7.9) 115 (10.1) 0.018 In-stent Thrombosis 26 (0.7) 12 (1.1) 0.257 Stroke 49 (1.3) 25 (2.2) 0.042 Bleeding 253 (7.0) 67 (5.9) 0.216 MACCE 409 (11.3) 159 (14.0) 0.012 CVO = Culprit Vessel Only; MVOI = Multivessel One-stage Intervention; MACCE = Major Adverse Cardiac and Cerebrovascular Events.

Cox Regression Analysis on CVO/MVOI

Conclusion

In our large cohort of Chinese patients, MVOI strategy for NSTE-ACS patient undergoing PCI was associated with worse 2-year prognosis compared with CVO strategy. MVOI is an independent risk factor for 2-year in-stent thrombosis.

Acknowledgement/Funding

Ministry of Science and Technology of the People's Republic of China (2016YFC1301301) and National Natural Science Foundation of China (81470486)
P4597Impact of operator experience with radial approach for clinical outcome on percutaneous coronary intervention in acute coronary syndrome performed with femoral artery access site
Authors: Tokarek T , Dziewierz A , Plens K , Rakowski T , Zabojszcz M , Dudek D , Siudak Z
Published: October 2019

Introduction

Radial approach (RA) for percutaneous coronary intervention (PCI) is associated with reduced mortality and access site complications. The routine use of the RA in patients should be strongly considered, keeping in mind the learning curve associated with the technique. However, promotion of RA may interfere with the equally important goal of maintaining proficiency in the femoral approach (FA), which is essential in a variety of procedures as well as when RA fails. There is possible risk of higher rate of complications in PCI with FA performed by operators mainly using radial artery as access site.

Purpose

The aim of this study was to evaluate impact of experience and proficiency with RA for clinical outcomes on PCI via FA in “real-world” patients with acute coronary syndrome (ACS).

Methods

A total of 539 invasive cardiologists performing PCI in 151 invasive cardiology centers on the Polish territory between 2014 and 2017 were included in study analysis. Proficiency threshold has been set at >400 procedures during four consecutive years per individual operator. They were categorized to quartiles according to total volume of radial artery utilization during all PCIs. Procedures performed on patients with Killip-Kimball class IV on admission to catheterisation laboratory were excluded from analysis.

Results

The most of the operators performed >75% of all procedures via radial artery (326 (60.5%)), 112 (20.8%) used RA in 50–75% of cases, 67 (12.4%) in 25–50% of all PCIs and only 34 (6.3%) invasive cardiologist were using RA in less than 25% of all procedures. Mortality during PCI via FA was higher in group of invasive cardiologist with >75% of all procedures performed with radial access (>75% vs. 50–75% vs. 25–50% vs. <25%: 1.63% (±2.52%) vs. 0.93% (±1.05%) vs. 0.68% (±0.73%) vs. 0.31% (±0.40%); p=0.01). A trend towards higher rate of bleeding at the puncture site during PCI procedures with femoral artery were reported in groups of operators with higher expertise in RA (>75% vs. 50–75% vs. 25–50% vs. <25%: 0.43% (±1.09%) vs. 0.14% (±0.36%) vs. 0.21% (±0.45%) vs. 0.14% (±0.37%); p=0.09).

Conclusions

Higher experience in radial access might be linked to worse outcome in PCI via FA in ACS settings. Femoral artery is important vascular approach and should not be abandoned while learning procedures with radial artery utilization.

Acknowledgement/Funding

None
P4610Gut microbiome and atherosclerotic plaque instability: does choline consumption in red meat influence plaque stability?
Authors: Chen Y.-C , Doma V , Reimark R , Ying Y.-L , Peter K
Published: October 2019

Background

Myocardial infarction is the major cause of deaths worldwide. Gut bacteria can process choline as abundant in red meat and subsequently converted by flavin containing monooxygenase in the liver to trimethylamin-N-oxide (TMAO) metabolite, which is strongly associated with cardiovascular events.

Aim

To investigate the gut microbiome and its association with atherosclerotic plaque instability.

Methods

Forty-eight Apolipoprotein E deficient mice were randomly divided into two groups and two time points, fed with a high fat diet (containing either 0.4% choline or 3% choline) at 12 weeks of age, for 7 weeks or for 14 weeks. All mice underwent Tandem Stenosis (TS) surgery to induce the development of unstable plaques. Stool samples were collected directly from the colon. Measurements of gut microbes were performed by AGRF diversity profiling. After bacterial genomic DNA isolation, 16S rRNA were sequenced by targeting 27F-519R (V1-V3) and 341F-806R (V3-V4) on the Illumina MiSeq platform. Vessel segments of TS were histologically processed and plaque composition of lipid, collagen, and intraplaque hemorrhage (marker of unstable plaques) were performed by a series of chemical staining and immunohistochemistry.

Results

Monocytes and granulocytes in mouse blood were significantly increased in the high choline group (p<0.05, unpaired t-test) after 7 weeks of high fat diet (21% fat, 0.15% Cholesterol, 3% Choline). Profiling of gut microbiota showed that Fimicutes were down regulated in the high choline group (p<0.05, unpaired t-test). Within Phylum Fimicutes, only Clostridia (class) Clostridiales (order) were significantly downregulated. Interestingly, histological analysis of TS segments showed that TER-119 (intraplaque haemorrhage marker) and CD42c (platelet marker) were significantly increased in the high choline group, indicating atherosclerotic plaques are more unstable and prone to rupture (p<0.05, unpaired t-test). Nevertheless, CD68 (Foam cells) in plaques, and total atherosclerotic plaque burden in the aortic sinus and aortic arch were not affected by the elevated levels of choline consumption.

Conclusion

Choline intake increases circulating monocytes and granulocyte numbers in the blood but not in the atherosclerotic plaque itself. Whereas the total plaque burden is not changed by an increased choline intake, the reduction of Fimicutes, Clostridia and Clostridiales seems to contribute to atherosclerotic plaque instability.

Acknowledgement/Funding

Heart Foundation 2018 Future Leader Fellowship (2018 FLF) ID: 102068 Chen
P4624Predictive performance of CRUSADE bleeding score in non ST elevation acute coronary syndrome patients treated with ticagrelor versus clopidogrel
Authors: Graca Santos L , Montenegro Sa F , Ruivo C , Ribeiro Carvalho R , Correia J , Pernencar S , Soares F , Morais J
Published: October 2019

Introduction

CRUSADE score is commonly used for bleeding risk stratification in the context of acute coronary syndrome (ACS). However, the study validating it was performed before ticagrelor was available.

Purpose

To compare the predictive performance of CRUSADE score in two groups of non-ST elevation ACS (NSTEACS) patients, one treated with ticagrelor and another with clopidogrel.

Methods

Retrospective study of 2077 NSTEACS patients admitted between January 2014 and September 2017 and included in a multicentre national registry. Group 1 was composed by patients medicated with ticagrelor, and Group 2 with clopidogrel. Patients with bleeding history were excluded. The primary endpoint (PE) results from a composite which includes: in-hospital major bleeding (MB) according to the Registry criteria, need for red blood cell transfusion (RBCT), or haemoglobin drop ≥2g/dL (HbD). The groups were compared according to their demographic, clinical and laboratory characteristics. The occurrence of the PE (and its components) across CRUSADE risk categories was assessed by Chi-square for linear trend. The performance of CRUSADE score for PE prediction in each cohort was assessed by Receiver Operator Characteristics (ROC) curves.

Results

Group 1 included 662 (31.9%) and Group 2 1415 (68.1%) patients. Mean CRUSADE score was higher in Group 2 (23.1±14.7 versus (vs) 26.7±16.3, p=0.001). No difference was observed regarding the PE (14.8% vs 17.0%, p=0.200) and its components. With the exception of MB in Group 1 (p-trend=0.425), the relative occurrence of the PE and its components increased across CRUSADE risk categories [Figure 1. panel A]. In-hospital mortality was numerically superior in Group 2, but did not reach statistical significance (1.1% vs 1.6%, p=0.368). In both groups, the performance of CRUSADE score in predicting the PE was modest (Group 1 AUC=0.59 and p=0.006, Group 2 AUC=0.62 and p<0.001), and no difference was observed when comparing the two groups (P value for ROC curves comparison = 0.899) [Figure 1. panel B and C respectively].

Figure 1

Conclusion

In this study based on a national registry of NSTEACS patients, the use of ticagrelor did not influence the occurrence of bleeding related events and it did not change the predictive performance of the CRUSADE score. According to this analysis, CRUSADE score may be applied without limitation to NSTEACS patients managed with ticagrelor.
P4645Prevalence of interatrial communications in 7,000 newborns from a large, prospective population study
Authors: Blixenkrone-Moeller E , Dannesbo S , Pihl C , Sillesen A.-S , Voegg O , Axelsson Raja A , Colan S , Mertens L , Vejlstrup N , Bundgaard H , Iversen K
Published: October 2019

Introduction

The prevalence of any interatrial communication (IAC) (patent foramen ovale (PFO) or atrial septal defect (ASD)) in newborns has previously been reported to be between 24% and 92%. However, previous studies were relatively small, and no universal classification of IACs exists. We proposed a new echocardiographic diagnostic algorithm developed in collaboration with a group of international experts to classify IACs based on echocardiographic findings on subxiphoid transthoracic echocardiographic (TTE) images of the atrial septum in unselected newborns.

Purpose

To determine the prevalence of IACs (PFO and ASD) in newborns based on the new diagnostic algorithm.

Method

Echocardiograms of newborns (age 0–30 days) consecutively included in a large, prospective population study (n=25,000) were analyzed using the new algorithm. The algorithm classifies IACs into PFO and ASD based on transthoracic echocardiographic (TTE) findings including size and number of the communication(s) as well as the morphology and structure of the atrial septum, taking the normal fetal development into consideration. An IAC was classified as a PFO when either there was only one communication located in the upper 2/3 of the atrial septum with a visible communication having a diameter of ≤3.4 mm or a channel-like structure; or there was no visible communication on 2D but acceleration of colour Doppler flow crossing the septum was documented. An IAC was classified as an ASD if the diameter of a visible communication was >3.4 mm, or the communication was located in the lower 1/3 part of the atrial septum, or more than one communication was present. No visible communication on 2D and no flow acceleration despite possible colour Doppler flow crossing the atrial septum was classified as an absence of IAC.

Preliminary results

As of 3 February 2019, 9,028 echocardiograms have been analyzed. A total of 2,026 (22.4%) were excluded due to poor image quality of the atrial septum. Of the 7,002 included echocardiograms, an IAC was detected on the TTE images in 85.9% of the newborns (median age 12 days [IQR 8; 15], 47.9% females). According to the algorithm 78.7% of the newborns were classified as having a PFO (see Table 1) whereas 7.2% were classified as having an ASD.

Table 1. Prevalence of interatrial communications in newborns aged 0–30 days Type of interatrial communication: Prevalence (n=7,002): Patent foramen ovale 78.7% Atrial septal defect 7.2% No interatrial communication 14.1%

Conclusion

An IAC was present in the vast majority of newborns aged 0–30 days. PFOs were 11 times more frequent than ASDs.

Acknowledgement/Funding

Danish Heart Association, Danish Children's Heart Foundation, Candy's Found., Toyota Found., Herlev-Gentofte Hospital Research Found., Gangsted Found.
P4671A well-defined subgroup of chronic thromboembolic pulmonary hypertension patients are positive for antiphospholipid antibodies
Authors: Denas G , Chen C , Du Y , Jiang X , Zhou Y , Wu T , Zhang Y , Han Z , Pengo V , Jing Z
Published: October 2019

Introduction

Recurrent thromboembolism is a major risk factor for chronic thromboembolic pulmonary hypertension (CTEPH). Antiphospholipid antibodies (aPL) are a recognized risk factor for recurrent thromboembolism, however, their contribution to the development of CTEPH is currently unknown.

Purpose

The aim of this study was to evaluate the prevalence of antiphospholipid autoantibodies in a large cohort of consecutive patients with CTEPH.

Methods

Starting May 2013 to December 2018, 297 CTEPHpatients were consecutively enrolled. Diagnosis was confirmed with standardized right heart catheterization, 2D or/and 3D pulmonary angiography in all patients.All patients were also screened for thrombophilia including lupus anticoagulant IgG/IgM anticardiolipin antibodies and IgG/IgM aβ2GPI antibodies. Clinical and demographic characteristics, laboratory profile and hemodynamic data were compared between patients with aPL positive and aPL negative laboratory profiles.

Results

Overall, 297 consecutive patients with CTEPH were assessed for aPLs. Of these, 23 patients (7.7%) resulted positive for laboratory tests exploring aPL. Among patients with positive aPL, profile 17 (74%) were positive for all three test exploring aPL (LA+, aCL+, aB2GPI+). When compared to CTEPH patients without aPL test positivity, those positive for aPL were significantly younger (30.0 vs 55.6 years, p<0.0001), had a positive history of pulmonary embolism (95.6% vs 65.7%, p=0.003), deep venous thrombosis (78.3% vs 41.9%, p=0.0008) and were more frequently affected by other autoimmune diseases (43.5% vs 2.9%, p<0.0001). Moreover, positive aPL patients showed better hemodynamics on right heart catheterization, had more proximal lesions, and had more frequently level I and II surgical classification (82.6% vs 40.5%, p=0.0002) on pulmonary angiography.

Conclusions

These findings suggest that young patients with pulmonary embolism should be assessed for aPLs to guide anticoagulation therapy and prevent recurrences. Additionally, younger age, more proximal lesions and less severe hemodynamic profiles make majority patients with APS good candidates for PEA surgery.