bluuebunny/crossref_metadata_2025 huggingface dataset:
P1255Comparative safety and effectiveness of standard doses of apixaban versus dabigatran, rivaroxaban, and VKAs in non-valvular atrial fibrillation patients in France: the NAXOS study
Authors: Danchin N , Steg P G , Hanon O , Mahe I , Belhassen M , Jacoud F , Nolin M , Ginoux M , Dalon F , Lefevre C , Cotte F E , Gollety S , Falissard B , Van Ganse E
Published: October 2019

Background

Real-world data comparing all available oral anticoagulants (OAC) on a nationwide scale (i.e. in France: apixaban, rivaroxaban, dabigatran and vitamin K antagonists – VKAs) are lacking. In everyday practice, oral anticoagulants are often underdosed, which may render comparisons between agents difficult.

Purpose and methods

NAXOS is a French real-world study comparing the safety (major bleeding), effectiveness (stroke, systemic thromboembolic events (STE)) and all-cause mortality for apixaban, dabigatran, rivaroxaban, and VKAs, in adult patients with non-valvular atrial fibrillation (NVAF) initiating a given OAC between 2014 and 2016. The French national health insurance data (SNIIRAM) were used. Analyses were performed with adjustment on propensity scores. To avoid bias potentially related to underdosing, the present analysis included only patients receiving standard doses of apixaban (5mg bid), rivaroxaban (20mg od), and dabigatran (150 mg bid), or VKAs. Only OAC naïve patients were included.

Results

In the OAC-naive cohorts treated with apixaban, rivaroxaban, and dabigatran, 54,575 (62.3%), 65,208 (65.2%), and 9,000 (42.4%), respectively, had the standard dose at the index dispensation, and 112,628 patients received VKAs. After adjustment on propensity scores, apixaban 5 mg was associated with a lower risk of major bleeding, compared to VKAs (Hazard Ratio: 0.47; 95% CI: 0.43–0.51) and rivaroxaban 20mg (HR: 0.64; 0.59–0.71), but not to dabigatran 150 mg (HR: 0.97; 0.79–1.18). Apixaban was associated with a lower risk of stroke and STE, compared to VKAs (HR: 0.62; 0.56–0.69) but not to rivaroxaban (HR: 1.03; 0.92–1.16), and dabigatran (HR: 0.96; 0.76–1.21). Apixaban showed a lower risk of all-cause mortality compared to VKAs (HR: 0.44; 0.41–0.47) and rivaroxaban (HR: 0.87; 0.81–0.94) but not to dabigatran (HR: 1.10; 0.92–1.32).

Figure 1. Forest plot presenting the results of the standard dose analysis (PS adjusted).

Conclusions

The NAXOS population-based country-wide observational study shows that 42% to 65% of patients were treated with standard doses of OACs. Analyses of standard doses confirmed the superiority of apixaban compared with VKAs for the three studied outcomes and suggests better safety profile of apixaban compared to rivaroxaban but similar to dabigatran.

Acknowledgement/Funding

The Alliance Bristol-Myers Squibb/Pfizer
P1455Atrial fibrillation detection by integrated trans-telephonic ECG monitoring after cryptogenic stroke in the years 2016–2018 in the Czech and Slovak Republics
Authors: Bulkova V , Sanak D , Tomek A , Brozman M , Gandalovicova J , Kovarikova D , Pelikanova V , Mikulik R , Nevsimalova M , Monhart Z , Palanova A , Taborsky M , Linhart A , Fiala M
Published: October 2019

Background

Cryptogenic strokes can be estimated to ∼3500 patients in the Czech (CZ) and 2000 patients in Slovak (SK) republics. Systematic screening in these patients and methods of ECG monitoring are generally uneven across different hospitals and districts.

Purpose

Assessment of integrated screening for atrial fibrillation (AF) after cryptogenic stroke was launched in collaboration with Czech Society of Cardiology and stroke centers in the year 2016.

Methods

Patients with stroke of unknown source within the last 3 weeks, and without AF/atrial tachycardia (AT) detected during in-hospital ECG monitoring, were referred by stroke centers into integrated database of the MDT center, who subsequently contacted the patients and shipped the loop/continuous ECG recorder (Vitaphone, Faros, ECGPocket) with automatic data transmission over cell phone to them directly home or into aftercare unit. ECG monitoring was scheduled for 3 weeks, and the data were regularly edited and evaluated to inform the referring stroke centers in case of AF detection. Upon termination of ECG monitoring, the device was returned to the MDT center, and the final report was sent to the referring physician for eventual treatment decision.

Results

The project involved 36 stroke centers in the CZ and 11 centers in SK. A total of 3.120 patients (65±17 years, 46% females) were monitored for 21.6±5.3 days. AF was detected in 308 (9.9%) patients. Additional findings included: AV block II-III in 62 (2%), NSVT over 5 QRS complexes in 249 (8%), sinus pauses over 4 seconds in 17 (0.5%), and regular SVT over 5 minutes in 69 (2.2%) patients. Total monitoring costs amounted to 374 400 € (120 €/patient). In CZ, the counts of monitored patients in 2016, 2017, 2018 were 302, 754, and 1148, which accounted for ∼10%, 21%, and 32%, respectively, of eligible patients.

Conclusion

Systematic screening of patients after cryptogenic stroke with integrated ECG monitoring has become adopted within 3 years to cover 39% of eligible patients in CZ. Besides approximately 10% AF/AT detection, clinically significant arrhythmias were identified in another 13% of patients.
P1461Assessment of remote heart rhythm and arterial blood pressure sampling in professional drivers of public transport
Authors: Bykova A , Chashkina M I , Kopylov P H Y U , Syrkin A L
Published: October 2019

Background

Atrial fibrillation (AF) and arterial hypertension are two main causes of stroke. Therefore, screening for these diseases is essential in population and especially in people which professions is related to public safety.

Purpose

The aim of this study was to estimate the prevalence of newly cases of AF and hypertension in professional drivers of public transport working in Moscow.

Methods

From August to September 2018 480 professional drivers of public transport were enrolled in the study. All of them were screened with CardioQVARK monitor attached to iPhone to obtain 1-channel ECGs and photoplethysmograms. Blood pressure was calculated by using waveform and spectral analysis of photoplethysmograms. All ECGs were analyzed automatically and checked by experienced cardiologist. Outpatient counseling was provided to drivers with detected atrial fibrillation or hypertension. During this visit ECG and blood pressure were measured to confirm the remote monitoring results.

Results

Among 480 professional drivers 97,9% (n=470) were male and 2,1% (n=10) female, mean age was 47 years (min – 20, max – 67). 44,6% (n=214) were active smokers and 29,8% (n=143) were obese.

We diagnosed 5 new cases of atrial fibrillation (1%) and 187 (39%) new cases of hypertension. Patients with newly diagnosed AF were male, three of them had newly diagnosed hypertension and CHA2DS2-VASc score – 1. So, in three cases oral anticoagulants therapy was started. The prevalence of hypertension in patients with newly AF was higher (p<0,0001).

In patients with newly diagnosed hypertension 29,2% (n=140) were in grade 1, 8,3% (n=40) – in grade 2 and 1,5% (n=7) – in grade 3 respectively. These patients were significantly older (p<0,0001) and obese (p<0,0001). Antihypertensive therapy was started in all cases.

Conclusion

Although the professional drivers of public transport in Moscow had annually and every day medical check-up, it had been possible to evaluate new cases of AF and hypertension by using remote heart rate and photoplethysmogram monitoring. Remote monitoring of ECG and blood pressure (BP) is useful tool for screening AF and hypertension especially in people which work activities is concerned with public safety. The remote monitoring of ECG and BP in this category had great social and economic outcomes.
P1470Myocardial dysfunction index: a novel myocardial strain parameter for diagnosing myocardial ischemia
Authors: Tanekda S , Asanuma T , Masuda K , Kozuma A , Minami S , Nakayama T , Nakatani S
Published: October 2019

Background and purpose

Peak systolic strain (ε-sys) derived from speckle tracking echocardiography (STE) is a useful parameter for assessing regional contractile dysfunction during acute ischemia. However, low ε-sys does not always indicate myocardial ischemia because of its relatively large variation in segmental normal ranges and intervendor differences. Therefore, comparison of strain before and after an ischemic event and demonstration of a decrease in ε-sys should be necessary to confirm myocardial ischemia, which is not always possible in clinical situations. It is well known that early systolic lengthening (ESL) and post-systolic shortening (PSS) occur during acute ischemia. We hypothesized that ESL and PSS would correlate with the decrease in ε-sys and integrated analysis of ESL and PSS could be useful to diagnose the presence of myocardial ischemia.

Methods

2D short-axis or 3D full-volume images were acquired by Artida at baseline, during flow-limiting stenosis (mean 50±20% flow reduction), and during complete occlusion of the left circumflex coronary artery in 22 dogs (2D-STE = 12, 3D-STE = 10).Circumferential strain was analyzed in the center of risk area, and the absolute value of peak systolic strain (ε-sys), post-systolic strain index (PSI) as a parameter of PSS, and early systolic strain index (ESI) as a parameter of ESL were measured. A new parameter, myocardial dysfunction index (MDI), which was calculated as follows: (ESL amplitude + PSS amplitude)/maximal strain amplitude during the cardiac cycle, was also calculated. The difference in ε-sys between at baseline and during ischemia (Δε-sys) was measured and the diagnostic accuracy for estimating Δε-sys < −3% was assessed by the receiver operating characteristics (ROC) curve analysis.

Results

During ischemia, ε-sys decreased from 19±3 to 12±6% and MDI increased from 2±4 to 27±30%. MDI was significantly correlated with Δε-sys (2D-STE: r=−0.80, 3D-STE: r=−0.83, p<0.01, respectively) (Figure). The area under the curve (AUC) of MDI for estimating Δε-sys < −3% tended to be larger than those of ESI and PSI (MDI: 0.9, ESI: 0.73, PSI: 0.85).

Figure 1

Conclusions

The novel parameter, MDI was correlated with the decrease in ε-sys during acute ischemia. Integrated analysis of ESL and PSS may be useful for diagnosing the presence of myocardial ischemia.
P1490Exercise lung ultrasound in patients with exertional dyspnea: pilot study
Authors: Malek J , Vecera J , Kubrycht M , Matejka J , Vojtisek P
Published: October 2019

Purpose

The aim of the present study was to test the correlation of the exercise lung ultrasound (LUS) and B-lines count with clinical, laboratory and echocardiographic parameters among patients with preserved left ventricle ejection fraction and without signs of congestion reffered for cardiopulmonary exercise test (CPET) for exertional dyspnea.

Methods

The study population consisted of 39 patients (age 63.0±9.3 years; 62% females) with preserved ejection fraction (≥50%) and without signs of congestion reffered for exercise testing. Pulmonary disease and coronary artery disease was ruled out. CPET, rest and stress echocardiography and B-lines count assessed by 8 zone LUS were performed.

Results

Exercise B-lines count was significantly higher than rest B-lines count (3.1±0.5 vs. 1.1±0.2; p<0.001). No correlation was found between B-lines count and peakVO2, workload, NT-proBNP. Among echocardiographic parameters only left atrium diameter correlated weakly (r=0.35; p=0.027) with exercise B-lines count. Difference between rest and exercise B-lines count correlated weakly with VE/VCO2 (r=0.41; p=0.015).

Characteristics of study population <3 B-lines (n=22) ≥3 B-lines (n=17) p Age (years) 62.2±6.2 64.1±12.1 NS Females (n; %) 16 (72.7%) 8 (47.1%) NS DM (n; %) 3 (14%) 1 (6%) NS Arterial hypertension (n; %) 15 (68%) 14 (82%) NS BMI (kg/m2) 29.4±5.7 31.3±3.3 NS NYHA class 1.9±0.5 2.0±0.4 NS HFpEF (n; %) 8 (57.1%) 8 (42.1%) NS NT-proBNP (pg/ml) 240.0±472.8 275.4±323.1 NS E/e' 9.8±2.7 10.4±2.2 NS Left atrial diameter (mm) 36.4±4.7 39.4±4.6 p=0.039 LVEF (%) 62.9±5.6 60.6±4.7 NS PeakVO2 (ml/kg/min) 20.2±5.7 19.5±3.6 NS VE/VCO2 32.3±5.7 35.9±6.2 NS WR (W/kg) 1.7±0.5 1.5±0.3 NS DM = diabetes mellitus; LVEF = left ventricle ejection fraction; WR = workload.

Rest and peak exercise B-lines count

Conclusion

We observed weak but significant correlation between exercise B-lines count and left atrium diameter. However we didn't observe significant difference between HFpEF patients and rest of study population in B-lines count. Limitation of our observation is small study population.
P1514Evaluation of endothelial progenitor cells as cardiovascular prognostic biomarkers in hemodialysis patients
Authors: Infante T , Bruzzese G , Schiano C , Lucchese R , Alfano R , Faenza M , Nicoletti G F , Napoli C
Published: October 2019

Background

Endothelial cells arise from endothelial progenitor cells (EPCs), which reside in bone marrow vascular niches, and are classified according to specific functional differences. Oxidative stress and inflammation lead to endothelial dysfunction that is a critical event in the initiation and progression of atherosclerotic plaques. Patients with chronic renal failure frequently show endothelial dysfunction and are at a greatly increased risk of developing atherosclerosis. Owing to their ability to partially restore vascular damage, both the number and functional changes in EPCs may be considered as useful prognostic biomarkers of cardiovascular events in hemodialysis (HD) patients.

Purpose

This study investigated EPC features and several biomarkers of systemic vascular inflammation and carotid atherogenesis in hemodialysis (HD) patients.

Methods

We studied 104 HD patients (males=55 and females 49, mean age: 51±12 years) and 40 healthy controls (males=20/females=20; mean age: 52±11 years). Isolated EPCs were cultured in the fibronectin-covered culture dishes and counted. EPC markers were studied by flow cytometry (FACS) by using anti-CD34, anti-CD133 and anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibodies. Serum levels of intercellular cell adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), IL-6, TNF-α, and asymmetric dimethyl-arginine (ADMA) were measured by ELISA method. Carotid intima-media thickness (CIMT) and ratio (CIMR) were also evaluated.

Results

In our experimental conditions, EPC number was decreased in HD patients when compared to controls (p<0.01). Expression of CD34 was significantly lower in the HD group (p<0.01). Interestingly, EPCs were significantly inversely correlated with serum TNF-α levels in HD patients (r=−0.388, p<0.01) but not in the control group (r=−0.133, p=NS). Furthermore, there was an inverse association between VEGFR-2 positive cells and serum TNF α levels (r=−0.401, p=0.002) in HD patients. In HD patients, there was a positive correlation between ICAM levels with CIMT (r=0.405, p=0.03) and CIMR was positively correlated with VCAM levels (r=0.377, p=0.01) and ADMA (r=0.233, p<0.05).

Conclusions

Our study shows that EPC number was decreased in HD patients and it was associated with systemic inflammation. TNF-α could activate inhibitory actions on EPC in HD patients. A significant relationship was present between ICAM/VCAM and carotid atherosclerosis, while this was not evident with EPC number. These pathogenic mechanisms can contribute to the high incidence of cardiovascular diseases in HD patients. However, further larger studies should investigate this working hypothesis.
P1515Female sex is an independent predictor of mortality in patients with STEMI in Spain: a study in 325,017 episodes over 11 years (2005–2015)
Authors: Anguita M , Sambola Ayala A , Elola J , Bernal J L , Fernandez C , Ferreiro J L , Bueno H , Marin F , Bonilla J L , Nunez-Villota J , Sanmartin M , Raposeiras S , Jimenez-Navarro M F , Filgueiras D , Ruiz-Ortiz M
Published: October 2019

Background

Recent studies reported a decrease in the mortality of ST-elevation myocardial infarction (STEMI) patients. This favorable evolution could not extend to women. The interaction between gender and mortality in STEMI remains controversial.

Purpose

To assess the impact of female sex on mortality of patients with STEMI through of period of 11 years.

Methods

We conducted a retrospective longitudinal study using information provided by the minimal database system of the Spanish National Health System to identify all hospitalizations in patients aged 35–94 years with the principal diagnosis of STEMI from 2005–2015.

Results

A total of 325,017 STEMI were identified. Of them, 273,182 were included, and 106,277 (38.8%) were women. Women were older than men and had more comorbidities. Through the study period 53% men vs 37.2% underwent PTCA; women presented more frequently heart failure, shock and stroke than men (p<0.001, respectively). The mean crude in-hospital mortality rate for the whole study period was higher in women (OR: 2.18; 95% CI: 2.12.-2.23, p<0.0001). Female sex was independently associated with higher in-hospital mortality (adjusted OR: 1.18; 95% CI: 1.14–1.22, p<0.001) (Table 1). The risk was maintained through the whole study period (lower OR: 1.14 in 2014; higher OR: 1.28 in 2006).

Table 1. Variables independently associated with in-hospital mortality adjusted by risk in a multilevel logistic regression model, 2005–2015 STEMI In-hospital mortality Odds Ratio P 95% CI Woman 1.18 <0.001 1.14 1.22 Age 1.06 <0.001 1.06 1.06 History of PTCA 1.58 <0.001 1.40 1.77 Congestive heart failure 1.26 <0.001 1.22 1.30 Acute Myocardial Infarction 1.84 <0.001 1.54 2.20 Anterior myocardial infarction 1.47 <0.001 1.23 1.76 Cardio-respiratory failure or shock 15.25 <0.001 14.78 15.75 Hypertension 0.81 <0.001 0.79 0.84 Stroke 5.76 <0.001 5.18 6.42 Cerebrovascular disease 0.86 <0.001 0.79 0.93 Renal failure 1.95 <0.001 1.88 2.02 Vascular disease and complications 7.03 <0.001 5.72 8.63 CI, Confidence Interval.

Conclusions

Female sex is an independent predictor of mortality in patients with STEMI in Spain, maintaining through a period of the 11 years.
P1519IL6 trans-signalling affects risk of cardiovascular events pre-eminently in men
Authors: Ziegler L , Frumento P , Wallen H , De Faire U , Gigante B
Published: October 2019

Background

Interleukin 6 (IL6) is a known cardiovascular risk marker. The pro-atherogenic effects of IL6 are mediated by the IL6 trans-signalling pathway via a binary complex of IL6 and the soluble IL6 receptor (IL6:sIL6R). The binary complex is however neutralised by the natural inhibitor, sgp130 when forming the ternary complex (IL6:sIL6R:sgp130). To assess the risk of cardiovascular events (CVE) with IL6 trans-signalling, a ratio between the active binary complex and the neutralised ternary complex was calculated. We recently demonstrated that high levels of the binary/ternary complex ratio (b/t ratio > the median) representing an excess of the active binary complex, was independently associated with a 44% increased risk of future CVE in subjects free of prevalent cardiovascular disease.

Purpose

In this study we aimed to analyse the risk of CVE and time to event associated with the b/t ratio in men and women separately.

Methods

In a cohort of 60 year old men and women from Stockholm, the molar concentrations of the binary and ternary IL6 complex were estimated at baseline. Subjects free of prevalent cardiovascular disease were followed through national registers to assess future CVE (myocardial infarction, hospitalised angina pectoris and ischemic stroke). During a 16 year follow-up, 525 first time CVEs were registered. The risk for CVE and time to CVE was calculated for men and women, separately. To evaluate the risk associated with IL6 trans-signalling, the b/t ratio dichotomised at the median was modelled in a Cox regression model and risk was expressed as hazard ratios (HR) with 95% confidence intervals (CI). In addition, analysis was performed using censored quantile regression that allows measuring the effect of covariates on different quantiles of the time to CVE.

Results

Approximately half of the population were men and 64% of the CVE occurred in men. The risk of CVE during follow-up was significantly higher in men with b/t ratio > median (HR 1.70; 95% CI 1.35–2.15), while no significant difference was found in women (HR 1.12; 95% CI 0.84–1.50). Consistently, quantile regression showed that, men with a b/t ratio > median suffered their CVEs at an earlier time point. The time at which 15% of the male population was observed to have experienced CVE was 5.6 years shorter (95% CI: 4.0–7.2) in the high b/t ratio group. In women there was no significant difference in time to CVE.

Conclusion

The risk of CVE and early events associated with IL6 trans-signalling estimated by a b/t ratio >median is significantly increased in men.

Acknowledgement/Funding

The Stockholm County Council ALF project, Strategic research in Epidemiology
P1520Management and outcome of women with NSTEMI. Have there been any changes in recent years?
Authors: Cacho C , Gonzalez Ferrero T , Torrelles Fortuny A , Perez Dominguez M , Abbou Johk C , Antunez Muinos P J , Alvarez Alvarez B , Agra Bermejo R , Rigueiro Veloso P , Garcia Acuna J M , Gonzalez Juanatey J R
Published: October 2019

Introduction

Women have been less represented in every NSTEMI clinical trial. Moreover, it has been observed that this group of patients have usually received less revascularization and evidence based treatment, therefore presenting with a greater long and short-term mortality.

Purpose

The purpose of our study is to analyze the presence of differences in baseline characteristics, management and outcome of women with NSTEMI during the last decade.

Methods and results

Retrospective study including 861 women admitted for NSTEMI between 2003 and 2015 in our center. We divided 2 groups according to hospitalization period (2003–2008 and 2009–2015) with a medium follow up of 4.5±2.9 years. Baseline characteristics and treatment at discharge are described on table 1. We noticed a greater use of statins and ACEI/ARB on the second period as well as a greater percentage of patients receiving early revascularization. It is remarkable on women a non-significant reduction of heart failure hospitalization at follow up (6.8% vs 4.5%; p=0.091), neither differences on 30-day mortality (1.3% vs 0,4%) or 1-year mortality (7.1% vs 5.8%). However, long-term mortality for the second group is reduced (HR 0.69; CI 95% 0.52–0.89), even after performing a multivariate analysis (HR 0.64; CI 95% 0.48–0.85).

Characteristic Population (n=861) 2003–2008 (n=395) 2009–2015 (n=466) p-value Age (years) 73±12 73±12 72±12 0.316 Hypertension 629 (73.1%) 285 (72.2%) 344 (73.8%) 0.318 Hypercholesterolemia 414 (48.1%) 190 (48.1%) 224 (48.1%) 0.523 Killip class 0.292   I 664 (77.1%) 299 (75.7%) 365 (78.3%)   II 143 (16.6%) 74 (18.7%) 69 (14.8%)   III 47 (5.5%) 20 (5.1%) 27 (5.8%)   IV 4 (0.5%) 2 (0.5%) 2 (0.4) GRACE score 129±32 130±37 128±33 0.897 Early PCI 249 (29.3%) 76 (19.2%) 173 (38.0%) <0.005 Treatment at discharge   AAS 698 (81.1%) 313 (79.2%) 385 (82.6%) 0.120   Clopidogrel 465 (54.0%) 221 (55.9%) 244 (52.4%) 0.162   ACEI/ARB 466 (54.1%) 191 (48.4%) 275 (59.0%) 0.001   Beta-blocker 509 (59.1%) 238 (60.3%) 271 (58.2%) 0.290   Statins 643 (74.7%) 275 (69.6%) 368 (79.0%) 0.001

Conclusions

In recent years, early interventionist management and greater use of evidence-based therapies have been observed in women with NSTEMI. This has been associated with a lesser long-term mortality, although short-term events have remained the same.
P1528The added value of cardiac magnetic resonance to the diagnosis of patients after aborted sudden cardiac death
Authors: Szabo L , Czimbalmos C S , Dohy Z , Csecs I , Toth A , Suhai F , Becker D , Geller L , Merkely B , Vago H
Published: October 2019

Introduction

An estimated 25% of all cardiovascular deaths are due to sudden cardiac death (SCD). The primary cause of SCD is coronary artery disease, however cardiac diseases accounted for SCD differ in young vs. older individuals. In patients with normal coronary angiography (NCA) the differential diagnosis is still challenging, due to the broad spectrum of underlying cardiovascular abnormalities. Cardiac magnetic resonance (CMR) provides accurate tissue specific and functional information of the heart.

Purpose

We aimed to investigate patients after aborted sudden cardiac death but NCA using cardiac magnetic resonance imaging (CMR). Our goal was to evaluate left and right ventricular parameters, presence of late gadolinium enhancement (LGE) and to assess the diagnostic value of CMR.

Methods

We enrolled 84 consecutive patients (39±13 y; 51% male) after aborted SCD with NCA and without CMR contraindication. CMR examination including long- and short-axis cine, T2-weighted and LGE images were performed. Left and right ventricular parameters were evaluated. Presence and pattern of the oedema and LGE were also assessed.

Results

Structural myocardial abnormality was present in 57% of pts: dilated (n=13), arrhythmogenic right ventricular (n=6) and hypertrophic (n=4) cardiomyopathy (CMP), moreover acute (n=2) and chronic (n=3) myocardial infarction, acute (n=2) and chronic (n=2) myocarditis, Tako-Tsubo CMP (n=1), noncompaction CMP (n=1), endomyocardial fibrosis (n=1). In 13 cases aspecific structural alterations were detected with (n=7) and without (n=6) LGE. Only 13% of the patients showed ejection fraction lower than 35% (LVEF=52±9%), 54% showed LV dilation (LVEDVi>100 ml/m2 in males and >90 ml/m2 in females; LVEDVi=104±22 ml/m2). LGE was present in 36%, showing ischemic pattern in five cases and nonischaemic pattern in 25 cases. Eleven patients were elite athletes (28±10y, 91% male, training hours: >10 hours/week). Three of them showed ARVC based on the current Task Force criteria, another three athletes showed aspecific structural alteration with nonischaemic LGE.

The CMR examination confirmed the referral diagnosis in 22%, excluded the presence of structural myocardial alteration in 43% and changed the clinical diagnosis in 35% of the patients.

Conclusion

CMR has an important diagnostic value in patients after reanimation but NCA. More than half of these patients showed structural alteration and CMR provided a diagnosis in 42%.

Acknowledgement/Funding

Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary
P1530Vasorelaxation as a mechanism of procyanidin B2 cardioprotective effect
Authors: Marinko M , Jankovic G , Milojevic P , Stojanovic I , Nenezic D , Kanjuh V , Yang Q , He G W , Novakovic A
Published: October 2019

Introduction

Findings from epidemiological studies indicate that polyphenols, widespread in human diet and with numerous biological activities, act cardioprotectively. Procyanidins are subclass of polyphenols with high content in commonly consumed foods and beverages, such as grapes, tea, chocolate, nuts and apples. Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties.

Purpose

Because the exact mechanisms by which procyanidin B2 causes vasorelaxation are unclear, we aimed to investigate relaxant effect of procyanidin B2 on the isolated human internal mammary artery (HIMA) and its underlying mechanisms.

Methods

The HIMA segments were collected from patients suffering from coronary artery disease who were undergoing coronary artery bypass surgery and studied in organ bath.

Results

Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K+ (KATP) channel blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K+ (KV) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+-activated K+ (IKCa) channels, slightly reduced maximal relaxation of HIMA.

Conclusion

Our results demonstrate that, in HIMA, procyanidin B2 produces strong endothelium-dependent vasorelaxant effect. It seems that this relaxation is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BKCa and KATP, as well as KV and IKCa channels in high concentrations of procyanidin B2.

Acknowledgement/Funding

The study was supported by a Scientific Research Grant (P175088) from Ministry of Science and Technology Serbia.
P1537Cardiotoxicity induced by the combinatorial treatment based on the immune checkpoint inhibitor pembrolizumab associated to trastuzumab
Authors: Maurea N , Quagliariello V , Passariello M , Coppola C , Rea D , Barbieri A , Arra C , Scherillo M , Iaffaioli R V , Botti G , De Lorenzo C
Published: October 2019

Background

The immunotherapy has revolutionized the world of oncology in the last decades with considerable advantages in terms of overall survival in cancer patients. A combination therapy based on the co-administration of Pembrolizumab (an antibody against PD-1) and Trastuzumab (the humanized anti-Her2 mAb) was recently proposed in clinical trials for the treatment of Trastuzumab-resistant advanced HER2-positive breast cancer. Although immunotherapies are frequently associated with a wide spectrum of immune-related adverse events, the cardiac toxicity has not been properly studied.

Purpose

We studied, for the first time, the putative cardiotoxic effects of Pembrolizumab associated to Trastuzumab turning the light on the pro-inflammatory effects of this novel combined therapy

Methods

Cell viability, intracellular calcium quantification and pro-inflammatory assays (analyzing the production of Interleukin 1β, 6 and 8 as well as the expression of p65/NFkB and Leukotriene B4) were performed in human fetal cardiomyocytes in vitro. Preclinical studies were also performed in vivo on C57BL6 mice untreated (Sham) or treated with Pembrolizumab and Trastuzumab alone or in combination by analyzing (in cardiac tissue extracts) the same markers of inflammation used in cellular studies.

Results

Combination therapy leads to an increase of the intracellular calcium overload (more than 3 times compared to untreated cells) and to a reduction of the cardiomyocytes viability (of more than 65 and 20–25%, compared to untreated and Pembrolizumab or Trastuzumab treated cells, respectively) thus indicating cardiotoxic effects. Notably, combination therapy increases the inflammation of cardiomyocytes enhancing significantly the production of p65/NFkB and Interleukins. Moreover, in in vivo studies on mice, the association of Pembrolizumab and Trastuzumab shows pro-inflammatory effects in cardiac tissue by stimulating the Interleukin 1β, 8 and 6 expression of 40–50% more than the single treatments; the expression of p65/NFkB and Leukotriene B4 was also increased indicating pro-inflammatory effects.

Conclusion

Combination therapy based on Pembrolizumab associated to Trastuzumab leads to significant cardiac pro-inflammatory effects mediated by overexpression of NFkB/p65 and Leukotriene B4 related pathways
P1541The relation between right ventricular-pulmonary circulation coupling and aging in healthy population
Authors: Vriz O V , Ferrara F F , Galzerano D G , Adams M A , Shisamma E S , Naeije R N , Bossone E B
Published: October 2019

Purpose

The aim of the study was to evaluate the right ventricular (RV) structure and functional adaptation to age, in particular the RV pulmonary circulation (PC) coupling and physiologic correlates.

Methods

1177 healthy subjects aged 16–100 years were enrolled. They underwent general medical evaluation and a comprehensive TTE included RV systolic such as tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP) derived from the tricuspid regurgitation (TR), the derived RV-pulmonary circulation (PC) coupling or TAPSE/PASP, pulmonary vascular resistances (PVR) derived from TR/RV outflow tract velocity (RVOT VTI) and diastolic function parameters. The cohort was divided in 4 groups of age: group 1: 300 subjects from 18 to 35 years; group 2: 383 subjects from 36 to 50; group 3: 451 from 50 to 79 years and group 4: 43 subjects > than 80 years of age The oldest subjects were completely independent in daily living activities. The groups were compared by ANOVA and the difference was adjusted by gender, BMI and mean arterial pressure. For each group the difference between genders was tested by T-Test. Multivariate analysis was used to evaluate the relationship between RV function and structure indexes and covariates selected according to pathologic relevance.

Results

There was a progressive increase in blood pressure (BP) according to age. The RV longitudinal diameter, right E/A ratio, right ventricular outflow tract acceleration time and TAPSE/PASP decreased according to age increase (p<0.0001). The right atrial volume indexed by BSA, PASP, PVR increase with age (p<0.0001). Either TAPSE or Sm were unaffected by age. Women had constantly smaller RV longitudinal diameters, right atrium volume index, TAPSE and TAPSE/PASP (p<0.001). In the multiple regression analysis, though the proportion of variance of the dependent variables predicted by the independent ones was very small, age, BSA, gender, E/Em and the longitudinal diameter of the RV were independent predictors of TAPSE/PASP. Heart rate, left ventricular (LV) diastolic function, stroke volume (SV) and TR were independently related to Sm, while age, BSA, LV diastolic function and SV were independently related to TAPSE.

Conclusion

With ageing there is a progressive involvement not only of the LV in terms of adaptation to increase afterload related to arterial stiffness but also of the RV. With age PVR and PASP increase while RV contractility is still unchanged. While the RV adapts very well to volume overload, even the physiologic increase in PASP with age, causes a RV-PC coupling impairment.
P1555Agreement of coronary calcium scoring on chest CT and ECG triggered cardiac CT: a population-based study
Authors: Xia C , Alsurayhi A , Pelgrim G J , Rook M , Vonder M , Oudkerk M , Vliegenthart R
Published: October 2019

Background

Low-dose chest computed tomography (CT) is increasingly used in lung cancer screening. The heart is inherently visualized on chest CT. Coronary artery calcium (CAC) identified on chest scans has predictive value for risk of cardiovascular disease. There is discussion whether non-ECG-triggered chest CT is reliable for CAC scoring.

Purpose

To investigate the agreement between chest CT and ECG-triggered cardiac CT in CAC identification and risk classification.

Methods

We included 1000 ImaLife participants who underwent a cardiac scan immediately followed by a non-ECG triggered chest scan. Third-generation dual-source CT and dedicated software were used for scan acquisition and CAC measurement. Chest scans were analyzed after cardiac scans with an interval of at least a month and in a different order. To ensure a comparable prevalence of CAC with previous studies and adequate samples in CAC strata, after the inclusion of the 500th consecutive participants with zero CAC, only participants with >0 CAC based on dedicated cardiac CT were included. CAC scores were divided into four risk strata: 0, 1–99, 100–399, 400. Kappa was used to assess agreement in CAC identification (0 versus >0) and risk classification.

Results

The mean age was 54 years (range 45–77), 42.5% were women, average body mass index (BMI) was 26.1kg/m2. Compared with dedicated cardiac CT, non-ECG triggered chest CT had an accuracy of 0.97, sensitivity of 0.96 and specificity of 0.99 for identifying CAC, and agreement between scans was very high (kappa 0.95) for CAC presence. In terms of CAC risk strata, chest CT had a very high agreement with cardiac CT (kappa 0.95). Total misclassification rate of CAC strata was 6.5%, with most misclassified cases shifting one risk category downward (55/65, 85%). BMI of discordant pairs was significantly higher than concordant pairs, while no difference in heart rate was found.

Conclusion

Non-ECG triggered chest CT may be reliably used for CAC identification and risk classification since chest CT has very high agreement with dedicated cardiac CT results.
P1559Frailty is an independent predictor of one-year mortality in patients with ST-segment elevation myocardial infarction, regardless of age, clinical severity and left ventricular function
Authors: Arroyo Espliguero R , Silva-Obregon A , Viana-Llamas M C , Estrella-Alonso A , Saboya-Sanchez S , Uribe-Heredia G , Eguileor-Marin Z , Castillo-Sandoval A , Arriero-Fernandez N , Garcia-Magallon B , Toran-Martinez C , Marian-Crespo C
Published: October 2019

Background

Frailty is characterized by decline in physiologic reserve and function leading to increased vulnerability. Sarcopenia, one of its features, has been associated with cardiac dysfunction.

Purpose

Assess frailty-based mortality in ST-segment elevation myocardial infarction (STEMI) patients following primary angioplasty.

Methods

Retrospective cohort of 427 consecutive STEMI patients (64 years [55–75]; 78% men) admitted to a general ICU between November-2013 and February-2017. We assessed frailty with the Clinical Frailty Scale (CFS). We used Kaplan-Meier and Cox regression models for survival analysis, stratified by CFS score categories (Figure). For clinical relevance, patients were dichotomized in robust (CFS 1–3) and vulnerable (CFS ≥4).

Results

Vulnerable patients were older, had more comorbidities and a higher GRACE 2.0. They had lower CK and albumin levels and higher BNP levels, despite the lack of frailty-based differences in LVEF and MI size and location. One-year mortality rate was higher in vulnerable patients (Table). After Cox regression analysis, vulnerable patients (CFS ≥4) showed a 3.37-fold higher risk of one-year mortality than robust ones (95% CI, 1.59–7.15; P=0.002), independently of age, gender, GRACE 2.0 or LVEF.

Baseline characteristics Vulnerable (CFS ≥4) Robust (CFS 1–3) P value (n=60) (n=367) One-year mortality, n (%) 15 (25) 14 (4.1) <0.001 Age (years) 78 [67–85] 61 [54–72] <0.001 Gender (women), n (%) 28 (46.7) 65 (17.7) <0.001 Hypertension, n (%) 47 (78.3) 156 (42.5) <0.001 Diabetes mellitus, n (%) 31 (51.7) 79 (21.5) <0.001 GRACE 2.0 150 [129–170.8] 112 [93–136] <0.001 Left ventricular ejection fraction (%) 52 [40–60] 55 [45–60] 0.151 MI location (anterior), n (%) 26 (43.3) 168 (45.8) 0.781 Creatin-phosphokinase (UI/L) 921 [286.8–2072] 1496 [607–2786] 0.011 High-sensitivity troponin I (pg/mL) 3699.5 [38–47968.1] 8789.8 [65.8–61970] 0.537 B-natriuretic peptide (pg/mL) 267.9 [117.3–901.6] 104.3 [29.5–268.7] <0.001 Albumin (g/L) 34.9 [32.8–37.4] 38.4 [35.7–40.4] <0.001

Kaplan-Meier and Cox survival curves.

Conclusions

Frailty is an independent predictor of one-year mortality in STEMI patients, independently of age, clinical severity and ventricular function. Frailty assessment should be routinely included in the clinical examination and decision-making process of STEMI patients.
P1572Cardiovascular and inflammatory biomarkers in cancer patients and their impact on mortality
Authors: Lueck L C , Lena A , Hadzibegovic S , Weinlaender P , Letsch A , Karakas M , Landmesser U , Anker S D , Anker M S , Von Haehling S
Published: October 2019

Background

Cardiovascular (CV) blood biomarkers are considered prognostic markers of CV dysfunction during anti-cancer treatment. It is largely unknown, whether they are also prognostic markers for mortality.

Purpose

To investigate the prognostic impact of CV and inflammatory biomarker levels in cancer patients without significant CV disease at baseline on all-cause mortality.

Methods

We enrolled 138 unselected cancer patients without significant CV disease from November 2017 until December 2018 (age 63±14yrs, 45%male, body mass index (BMI) 25.5±7.7kg/m2) and 25 healthy controls (age 57±10yrs, 36% male, BMI 25.1±3.4kg/m2). The cancer group consisted of 85 lymphoma (62%), 25 breast cancer (18%), 10 colorectal cancer (7%), 11 non-small cell lung cancer (8%) and 7 other types of cancer (5%) patients. All cancer stages were represented (25% I/II, 76% III/IV). For biomarker analyses, blood samples were taken from an antecubital vein.

Results

N-terminal pro brain natriuretic peptide (NT-proBNP), high-sensitive Troponin T (hsTnT) and C-reactive protein (CRP) were significantly increased in cancer patients vs. healthy controls (90 ng/L [85–94] vs. 40 ng/L [35–45], p<0.0001; 89 ng/L [IQR 85–93] vs. 44 ng/L [39–48], p<0.0001; 84.3 mg/L [78.8–89.7] vs. 27.9 mg/L [22.5–33.4], p<0.0001). 29 cancer patients (21%) died during a mean follow-up time of 172 days (range 1–405) (6-month mortality 23% [95% CI 15–32]). In univariable Cox analyses all biomarkers predicted survival: NT-proBNP (per 100ng/L, HR 1.049 [1.013–1.085], p=0.0082), hsTnT (per 1ng/L, HR 1.017 [95% CI 1.006–1.029], p=0.0017) and CRP (per 1mg/L, HR 1.019 [1.009–1.030], p<0.0001). Including the two CV biomarkers and the inflammatory biomarker, cancer entity, cancer stage and other clinical variables in multivariable Cox analysis, all three biomarkers remained significant prognostic markers of mortality (NT-proBNP per 100ng/L, HR 1.044 [1.007–1.082], p=0.021; hsTnT per 1ng/L, HR 1.017 [1.005–1.030], p=0.0067; CRP per 1ng/L, HR 1.017 [1.005–1.029], p=0.0047). To predict survival, the best cut-offs for the highest product of specificity and sensitivity were 260ng/L for NT-proBNP, 12ng/L for hsTnT and 9mg/L for CRP.

Conclusion

In cancer patients without significant CV disease, plasma levels of the CV biomarkers NT-proBNP, hsTnT and the inflammatory biomarker CRP are elevated compared to healthy controls. All three blood biomarkers are independent prognostic markers of short-term mortality.
P1585Increased circulating galectin 1 level is associated with progression of kidney function decline in patients with suspected coronary artery disease, independent of diabetes
Authors: Kuo C S , Chou R H , Lu Y W , Lin S J , Huang P H
Published: October 2019

Background

Galectin-1 modulates acute and chronic inflammation, and is associated with glucose homeostasis and chronic renal disease. Whether serum Galectin-1 levels could predict the short-term and long-term renal outcomes after contrast exposure in patients with suspected coronary artery disease remains uncertain.

Purpose

This study aimed to evaluate the relationship between serum Galectin-1 levels and the incidence of contrast-induced nephropathy and to investigate the predictive role of circulating galectin-1 levels in renal function decline in patients undergoing coronary angiography.

Methods

In total, 798 patients who had received coronary angiography were enrolled. Serum galectin-1 levels were determined before administration of contrast media. Contrast-induced nephropathy was defined as a rise in serum creatinine of 0.5 mg/dL or a 25% increase from baseline within 48 h after the procedure. Progressive renal function decline was defined as >30% decrease in estimated glomerular filtration rate after discharge. All patients were followed up for at least one year or until the occurrence of death after coronary angiography.

Results

Overall, contrast-induced nephropathy occurred in 41 (5.1%) patients. During a median follow-up of 1.4±1.1 years, 80 (10.0%) cases had subsequent decline in renal function. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, higher galectin-1 level was found to be independently associated with a higher risk for mortality and renal function decline (tertile 2, HR=3.12 95% CI,1.25–7.78; tertile 3, HR=3.25, 95% CI,1.42–7.41) but not for contrast-induced nephropathy, regardless of the presence of diabetes.

Conclusions

Higher baseline serum galectin-1 levels were associated with a higher risk of mortality and renal function decline in patients undergoing coronary angiography. Galectin-1 may play a pivotal role in progressive renal dysfunction, but further studies are needed to verify these results.

Acknowledgement/Funding

Ministry of Science and Technology of Taiwan (MOST 104-2314-B-075-047), Taipei Veterans General Hospital (V105C-0207, V106C-045, V108C-195)
P1597Two novel mutations in SCN5A gene cause enhanced inactivation and lead to Brugada syndrome
Authors: Zaytseva A , Karpushev A V , Karpushev A V , Fomicheva Y , Fomicheva Y , Vasichkina E S , Vasichkina E S , Michaylov E N , Michaylov E N , Kostareva A A , Kostareva A A , Zhorov B Z , Zhorov B Z
Published: October 2019

Background

Mutations in gene SCN5A, encoding cardiac potential-dependent sodium channel Nav1.5, are associated with various arrhythmogenic disorders among which the Brugada syndrome (BrS) and the Long QT syndrome (LQT) are the best characterized. BrS1 is associated with sodium channel dysfunction, which can be reflected by decreased current, impaired activation and enhanced inactivation. We found two novel mutations in our patients with BrS and explored their effect on fast and slow inactivation of cardiac sodium channel.

Purpose

The aim of this study was to investigate the effect of BrS (Y739D, L1582P) mutations on different inactivation processes in in vitro model.

Methods

Y739D and L1582P substitutions were introduced in SCN5A cDNA using site-directed mutagenesis. Sodium currents were recorded at room temperature in transfected HEK293-T cells using patch-clamp technique with holding potential −100 mV. In order to access the fast steady-state inactivation curve we used double-pulse protocol with 10 ms prepulses. To analyze voltage-dependence of slow inactivation we used two-pulse protocol with 10s prepulse, 20ms test pulse and 25ms interpulse at −100mV to allow recovery from fast inactivation. Electrophysiological measurements are presented as mean ±SEM.

Results

Y739D mutation affects highly conserved tyrosine 739 among voltage-gated sodium and calcium channels in the segment IIS2. Mutation L1582P located in the loop IVS4-S5, and leucine in this position is not conserved among voltage-gated channels superfamily. We have shown that Y739D leads to significant changes in both fast and slow inactivation, whereas L1582P enhanced slow inactivation only. Steady-state fast inactivation for Y739D was shifted on 8.9 mV towards more negative potentials compare with that for WT, while L1582P did not enhanced fast inactivation (V1/2 WT: −62.8±1.7 mV; Y739D: −71.7±2.3 mV; L1582P: −58.7±1.4 mV). Slow inactivation was increased for both substitutions (INa (+20mV)/INa (−100mV) WT: 0.45±0.03; Y739D: 0,34±0.09: L1582P: 0.38±0.04).

Steady-state fast inactivation

Conclusions

Both mutations, observed in patients with Brugada syndrome, influence on the slow inactivation process. Enhanced fast inactivation was shown only for Y739D mutant. The more dramatic alterations in sodium channel biophysical characteristics are likely linked with mutated residue conservativity.

Acknowledgement/Funding

RSF #17-15-01292