bluuebunny/crossref_metadata_2025 huggingface dataset:
P2280Incidence and predictors of alarms in patients with wearable cardioverter defibrillator (WCD) - results of the Austrian WCD Registry
Authors: Rohrer U , Manninger M , Odeneg T , Ebner C , Moertl D , Dirninger A , Keller H , Stix G , Alber H , Steinwender C , Binder R , Stuehlinger M , Zirlik A , Scherr D
Published: October 2019

Background

The wearable cardioverter-defibrillator (WCD) is a treatment option for patients at high risk for ventricular arrhythmia, either if the risk is potentially reversible or if an implantable cardioverter defibrillator (ICD) implantation is currently not possible.

Methods

We performed a retrospective analysis of all alarms in the cohort of the Austrian WCD registry between 2010 and 2018. Type of arrhythmias was assessed by independent review of two cardiologists.

Results

25.540 automatically recorded ECGs in 605 patients (68%) were analyzed. 1125 ECGs showed sustained ventricular arrhythmias in 117 patients, 65 ECGs showed non sustained VTs.

24.415 ECGs in 488 patients showed inadequate alarms Reasons for inadequate alarms were artefacts (97%), pacemaker or t-wave oversensing (0,3%) and in 2,3% atrial fibrillation or SVTs.

5860 manually recorded ECGs in 608 patients (68%) were analyzed. 298 (5%) of these ECGs showed following arrhythmias: atrial fibrillation (34,7%), SVTs (28%), sinustachycardia (10,7%), non sustained VTs (12%) and sustained VTs or sustained slow VTs (6,7%), premature ventricular beats or bradycardia was identified in 8%. The remaining 5562 ECGs (95%) showed normal sinus rhythm.

Of the 895 patients (60±14 years, 20% female), 34 (3,8%) received a total of 65 automatically triggered shocks (median 2; range 1–5). 31/895 (3.5%) patients received 57 appropriate shocks (median 1, range 1–5) for 49 arrhythmic events, whereas 7/895 (0.8%) patients received 8 inappropriate shocks (median 1, range 1–2).

44 events were successfully terminated with the first shock (85,7%) and 4 events were terminated with the second shock. In one patient, a shock treatment for VF was not successful. The time from event onset to shock was median 60 [40; 1187] sec.

The median time from WCD prescription to a shock event was 8 days [1–151]. 23/ 34 patients (68%) received their first WCD shock within 30 days.

Seven patients (0.8%) received a total of nine inappropriate shocks due to different reasons: artefacts (2 inappropriate shocks), non-shockable rhythms (asystole, weak action, 3 shocks) and atrial fibrillation with a bundle branch block in two cases. In one patient VF terminated spontaneously before the WCD treatment was delivered.

Conclusion

The WCD is an effective treatment option in patients with a high SCD risk but it also triggers a significant amount of alarms. Although many inadequate alarms occurred, adequate alarms led to arrhythmia detection such as in VT/VF events which were successfully terminated by the WCD in 3,4% of patients.
P2431Stay on the safe side: in-silico assessment of ablation protocols to prevent steam pops during radiofrequency ablation
Authors: Petras A , Echeverria Ferrero M , Leoni M , Guerra J M , Jansson J , Gerardo-Giorda L
Published: October 2019

Background

Steam pops (SP) are among the most serious complications of radiofrequency ablation (RFA) due to its potential to cause myocardial tear or tamponade. SP occur when the tissue overheats, causing its water content to transform into steam and explode. Ablation parameters are critical in order to obtain an optimal lesion size while avoiding the occurrence of SP. However, the interaction between ablation settings and the physical parameters that predispose to SP occurrence during irrigated RFA are not fully understood.

Purpose

To characterize regularly used ablation protocols by means of a computational model, in order to achieve optimal lesion size while avoiding SP occurrence.

Methods

The in-silico evaluation is performed using our previously developed computational irrigated RFA model. Our model takes into account the blood-saline interaction as well as the mechanical deformation of the tissue due to the contact with the catheter tip. We test the effects of applied power and contact force on two catheter tip designs (spherical and cylindrical) and two substrates, simulated human atrium and ventricle, during 30 sec applications. A fixed blood flow and catheter-tip saline irrigation (0.5m/s and 17mL/min, respectively) are considered. We simulate human tissue by using the biophysical, mechanical and physiological properties found in the literature. SP occurrence is predicted when the temperature within the tissue reaches 100°C.

Results

Based on the interaction of power and contact force, four risk maps are constructed encompassing the two catheter-tip designs and the two simulated tissues. The maps allow the identification of those ablation protocols (contact force and delivered power) that can potentially result on SP. They correspond to that area of critical temperature values where the temperature within the tissue reach the established criteria for SP occurrence. We also present the lesion size dimensions of ablation protocols that avoid the formation of steam pops.

Conclusion

Our results indicate that the applied power has a strong impact in the formation of SP for a cylindrical catheter, while a combination of contact force and power is important to avoid risks in the case of the spherical catheter tip. The tissue characteristics do not affect significantly the SP occurrence, in agreement with experimental literature. However, the resulting lesion size appears to be larger in the simulated human atrium in comparison to the simulated human ventricle.

Acknowledgement/Funding

BERC 2018-2021, SEV-2017-0718
P2449Different associations of cardiovascular risk factors with markers of subclinical myocardial disease over the life course
Authors: Huynh Q , Venn A J , Magnussen C , Marwick T H
Published: October 2019

Background

Asymptomatic myocardial disease is the precursor to heart failure, but changes in myocardial markers such as global longitudinal strain (GLS), left ventricular hypertrophy (LVH), diastolic dysfunction and left atrial (LA) enlargement are not necessarily congruent. Cardiorespiratory fitness (CRF), body mass index (BMI) and mean arterial pressure (MAP) are common predictors of cardiovascular disease. This study investigated the association of markers of myocardial disease with these predictors across the life-course.

Methods

This study followed 562 participants from childhood (aged 7–15 years in 1985) who were followed-up into adulthood at aged 26–36 years during 2004-06 and 39–49 years during 2017-19. CRF, BMI and blood pressure were measured at baseline and follow-up. Echocardiogram was used to identify asymptomatic myocardial disease at the latest follow-up, including abnormal GLS (GLS greater than −18% in 102/562 participants), LVH (55/562), dilated LA (LA volume index >34 in 268/562) and increased LV filling pressure (E/e' >8 in 32/562).

Results

Current physical measurements were generally stronger than previous measurements in predicting myocardial function and structure. Abnormal GLS was associated with childhood CRF (OR=0.77 [95% CI: 0.62, 0.96]) independently of adult CRF. While the association of abnormal GLS with BMI was influenced primarily by the most current BMI, its association with MAP appeared to be similar over the life-course. Dilated LA was associated with childhood CRF (OR=1.32 [95% CI: 1.08, 1.60]) independently of adult CRF, and was not associated with BMI or MAP in either childhood or adulthood. The associations of LVH with CRF, BMI and MAP were primarily dependent on current rather than earlier CRF, BMI and MAP. LV filling pressure was not associated with any childhood measurements but was associated with current BMI and MAP.

Conclusions

Different aspects of myocardial physiology appear to have different associations over the lifecycle, supporting the concept of different phenotypes of asymptomatic myocardial disease.
P2454Left atrial strain and recurrence of atrial fibrillation after thoracoscopic atrial fibrillation surgery
Authors: Baalman S W E , Van Den Berg N W E , Neefs J , Berger W R , Meulendijks E R , De Bruin-Bon R.H.A.C.M , Van Boven W J P , Driessen A H G , De Groot J R
Published: October 2019

Background

Left atrial (LA) strain has a prognostic value for atrial fibrillation (AF) recurrence after AF ablation. The value of LA strain as a predictor of AF recurrence after thoracoscopic AF surgery in patients in sinus rhythm (SR) or AF during echocardiography is unknown.

Purpose

To assess the association between LA strain and AF recurrence after thoracoscopic surgery for AF in both patients in SR and AF during baseline echocardiography.

Methods

Patients participating in the AFACT trial (n=240) with baseline transthoracic echocardiography (TTE) suitable for LA strain analysis were included in this subanalyses. All patients underwent thoracoscopic pulmonary vein isolation (PVI) with left atrial appendage (LAA) exclusion, and were randomized to ganglion plexus (GP) or no GP ablation. LA strain and mechanical dispersion (MD) of the LA reservoir, conduit and contraction phase were determined retrospectively from TTE images of both patients in AF and SR before thoracoscopic AF surgery. AF recurrence was defined as any recorded atrial tachyarrhythmia lasting >30 sec during a one year FU period.

Results

A total of 204 patients (58.6±7.8 years, 73% male, 57% persistent AF) were included. Of the 204 patients 121 (59%) were in SR and 83 (41%) were in AF during baseline TTE. Patients in SR during TTE had higher LA strain values and lower MD compared to patients in AF. Of all patients, those with AF recurrence had lower LA strain of the reservoir phase (13.0% vs. 16.6%; p=0.003) and contraction phase (7.4% vs. 11.5%; p=0.012). MD of the contraction phase was increased in patients with AF recurrence (65.1msec vs. 19.2 msec; p=0.003). Multivariable cox regression analysis showed an association between LA strain, MD and AF recurrence (figure).

Conclusions

Left atrial strain and mechanical dispersion prior to thoracoscopic AF surgery are associated with recurrence of AF. LA strain showed to be a valuable tool to add in the decision making for thoracoscopic AF surgery regardless rhythm during baseline echocardiography.
P2474Noninvasive estimation of pulmonary capillary wedge pressure by novel 3D speckle tracking echocardiography and validation study by cardiac catheterization
Authors: Yoshizane T , Tanaka R , Kawasaki M , Otsuka M , Shoji T , Nagaya M , Hattori K , Murayama M , Yagasaki H , Minatoguchi S , Ono K , Tanihata S , Arai M , Noda T , Okura H
Published: October 2019

Background

We previously reported that pulmonary capillary wedge pressure (PCWP) was noninvasively evaluated by 2D speckle tracking echocardiography (STE). Recently, novel software was introduced to examine volume and function of left ventricular and left atrium (LA) by 3D-STE automatically.

Purpose

We sought to compare the PCWP estimated by conventional 2D-STE (2D-ePCWP) and by novel 3D-STE (3D-ePCWP), and validate those values by cardiac catheterization.

Methods

Echocardiography and catheterization were performed in 29 patients (age 72±2) (7 ischemic heart disease, 2 hypertensive heart disease, 5 dilated cardiomyopathy, 12 valvular heart disease and 3 primary pulmonary hypertension).The ePCWP (mmHg) is noninvasively obtained as 10.8 − 12.4 x Log (left atrial active emptying function/minimum volume) as we previously reported. Echocardiography was performed just before the catheterization and we analyzed the 2D and 3D data by novel off-line software. 3D data was automatically analyzed and the border settings were fixed at default (ES60, ED30) (Figure).

Results

2D-ePCWP and 3D-ePCWP had a good correlation with PCWP invasively obtained by catheterization (r=0.87 and 0.83, respectively, both p<0.001). There was an excellent correlation between 2D-ePCWP and 3D-ePCWP (r=0.94, p<0.001) and there was a good correlation between 2D-LA volume index and 3D- LA volume index (r=0.80, p<0.001). Bland-Altman analysis revealed a good agreement between 2D-ePCWP and 3D-ePCWP, and between 2D-ePCWP and 3D-ePCWP without fixed and proportional bias.

Conclusion

This study demonstrated that PCWP might be noninvasively assessed by not only 2D-STE but also 3D-STE with reasonable accuracy and 3D-STE might have utility and value in the routine clinical practice.
P2478Prognostic impact and severity assessment of combinational elastography in heart failure patients
Authors: Sakamoto T , Ito S , Uchida K , Kuroda H , Minoji T , Endo A , Yoshitomi H , Tanabe K
Published: October 2019

Background

Heart failure (HF) causes liver congestion, which is thought to increase liver stiffness. Elastography is a noninvasive method of measuring organ stiffness that was originally developed to evaluate fibrosis caused by liver diseases such as cirrhosis. There are two main techniques of elastography: shear wave imaging and strain imaging. Shear wave imaging varies significantly due to the influence of not only fibrosis but also congestion, inflammation, and jaundice. In contrast, strain imaging in chronic liver disease reflects only the progression of liver fibrosis. We previously presented a method that is measuring both shear wave and strain imaging (combinational elastography) for assessing liver congestion. This study demonstrates the prognostic impact and severity assessment of combinational elastography in HF patients.

Methods

This study included 144 HF patients (age 76.4±12.3, men 67). The velocity of shear wave (Vs) values was measured with shear wave imaging. Fibrosis index (F Index) was calculated by measuring both shear wave and strain imaging.

Results

During a median follow-up of 161 days, 14 deaths or hospitalization for HF was observed. A multivariable cox regression analysis demonstrated that high vs values was dependently correlated with higher mortality rate and HF hospitalization (hazard ratio: 2.31; 95% confidence interval: 1.09–4.89; p=0.029). The Kaplan-Meier analysis demonstrated that high vs (>1.87 m/s) was associated with higher hospitalization rates for HF compared with low vs (≤1.87 m/s, log rank test, p<0.001). F index showed graded elevation as stage of HF progressed (stage A or B, C, D: 1.19±0.43, 1.38±0.56, 2.8±1.32; p<0.001).

Conclusion

Combinational elastography can predict the severity of HF.
P2483Differential effects of novel antidiabetics on arterial stiffness in patients with type 2 diabetes mellitus
Authors: Bletsa E , Antonopoulos A , Siasos G , Stampouloglou P K , Batzias K , Paschou S A , Oikonomou E , Gouliopoulos N , Tsigkou V , Kassi E , Thanopoulou A , Vryonidou A , Tentolouris N , Pallantza Z , Tousoulis D
Published: October 2019

Background

Arterial stiffness flags increased cardiovascular disease risk in type 2 diabetes mellitus (T2DM) patients. There is limited data on how novel anti-diabetic agents affect arterial stiffness.

Purpose

To investigate the effects of novel anti-diabetic agents on arterial stiffness in T2DM patients.

Patients and methods

We enrolled 64 consecutive patients under stable antidiabetic therapy who did not achieve therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; dipeptidyl peptidase-4 inhibitor (DPP4i, n=14), glucagon like peptide-1 receptor agonist (GLP1RA, n=21), sodium/glucose cotransporter-2 inhibitor (SGLT2i, n=21) or long-acting insulin (n=8). Glycosylated hemoglobin (HbA1c) as well as carotid-femoral pulse wave velocity (PWV) and augmentation index (Alx) were measured (as indices of arterial stiffness) were measured at baseline and 3 months after treatment intensification.

Results

There were no differences between the study groups in traditional risk factors, or baseline HbA1c, PWV and Alx levels (p=NS for all). All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up (for DPP4i: 7.4±0.2% vs 6.7±0.2%, for GLP1RA: 8.3±0.2% vs 6.9±0.1%, for SGLT2i: 7.5±0.1% vs 6.7±0.1% and for insulin 9.8±0.5% vs 7.7±0.4%, p<0.001 for all). PWV decreased from 10.0±0.84 to 9.1±0.43 m/sec (p=0.092) in the DPP4i group, from 11.7±0.72 to 10.2±0.74 m/sec (p<0.001) in the GLP1RA group, from 1.3±0.54 to 9.6±0.59 m/sec (p=0.001) in the SGLT2i group and from 11.6±1.04 to 11.1±1.02 m/sec (p=0.219) in the insulin group. Alx was also decreased from 34.2±1.89 to 31.5±2.17% (p=0.023) in the DPP4i group, from 29.1±1.52 to 25.6±2.09% (p<0.001) in the GLP1RA group, from 29.9±1.44 to 24.2±1.48% (p<0.001) in SGLT2i group, and from 28.2±2.33 to 26.2±1.64% (p=0.153) in insulin group.

Conclusions

These preliminary data provide evidence that treatment intensification -particularly with GLP1RA, and SGLT2i- benefits vascular properties, a finding which could partly explain the positive findings of recent randomized clinical trails in this field.

Acknowledgement/Funding

None
P2493Change in cardiovascular health and incident type 2 diabetes and prediabetes: The Whitehall II Study
Authors: Climie R , Van Sloten T T , Perier M C , Tafflet M , Fayosse A , Dugravot A , Singh-Manoux A , Empana J P
Published: October 2019

Background

Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) used a single measure of CVH and none investigated the association with incident prediabetes. This study aimed to examine whether changes in CVH are associated with incident T2D and prediabetes.

Methods

Within the prospective Whitehall II study, CVH was examined serially every 5 years from 1991/93 until 2015/16. Subjects with 0–2, 3–4 and 5–6 ideal metrics of CVH from the American Heart Association (non-smoking, and ideal levels of body mass index, physical activity, diet, blood pressure, and total cholesterol, fasting glycaemia was not considered),were categorized as having low, moderate or high CVH.

Results

There were 6234 participants without prior cardiovascular disease and T2D (mean age 49.8±6.0 years, 70% male) including 5015 who were additionally free of prediabetes (49.6±6.0 years, 67% male) at baseline. Over a median follow-up of 24.8 (IQR 24.0 to 25.2) years, 895 and 1703 incident cases of T2D and prediabetes occurred respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4470 participants without CVD and T2D in the interval, and among 2798 participants additionally free of prediabetes. In multivariate analysis, compared to those with stable low CVH, risk of T2D was lower in those with initially high CVH (HR=0.23; 0.09, 0.56), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR=0.42; 0.33, 0.54), low-moderate/high (HR=0.50; 0.36, 0.69) and moderate-low (HR=0.63; 0.48, 0.83). Results were similar for prediabetes, but effect sizes were smaller.

Conclusions

Among participants without previous CVD, T2D or prediabetes, change in CVH was related to the risk of incident T2D and prediabetes.
P2504Chronotropic incompetence and exercise capacity in patients treated with beta-blockers
Authors: Smarz K , Jaxa-Chamiec T , Zaborska B , Budaj A
Published: October 2019

Background

Chronotropic incompetence (CI) in patients treated with beta-blockers correlates with worse prognosis but influence of CI on exercise capacity (EC) is unclear.

Aim

To assess relationship between CI and EC in patients treated with beta-blockers.

Methods

We have analysed retrospectively data from consecutive cardiopulmonary exercise tests performed between 2008 and 2016 in our department. The inclusion criteria were: treatment with beta-blockers started at least 4 weeks before and continued on the day of the test, sinus rhythm during the test, respiratory exchange ratio ≥1.05 at peak exercise, absence of haemodynamically important valve dysfunction, pulmonary hypertension, exercise induced ischemia, pulmonary or peripheral limitations of exercise. CI was defined as chronotropic index ≤62%. Beta-blocker dose was calculated as bisoprolol equivalent dose. Included patients were divided, according to CI, in two groups: with CI and without CI. EC was assessed as percent of maximal predicted oxygen uptake achieved at peak exercise (%peakVO2).

Results

One hundred forty two patients (age 61±10 years, 73% males, hypertension 63%, ischemic heart disease 79%, chronic heart failure 12%, diabetes mellitus 20%, paroxysmal atrial fibrillation 10%) fulfilled the inclusion criteria. The group with CI comprised 115 and the group without CI 27 patients. Diabetes mellitus was more frequent and beta-blockers daily dose was higher in the CI group. There were no differences in other clinical parameters between groups. The group with CI had worse EC than the group without CI (69±18% vs 89±18%, p=0.ehz748.083301). In multivariate regression analysis, chronotropic index was independently related to EC (Table).

Table 1. Relationship of variables to exercise capacity in multivariate regression analysis Variable Coefficient β 95% Confidence interval p Age (years) 0.242 −0.049 to 0.533 NS Sex (male vs female) 5.260 −1.344 to 11.865 NS Body mass index (kg/m2) −0.786 −1.476 to −0.095 0.05 Left ventricular ejection fraction (%) 0.353 0.116 to 0.590 0.01 Beta-blocker daily dose (mg) 0.150 −0.962 to 1.262 NS Diabetes mellitus 0.070 −7.103 to 7.243 NS Heart rate at rest (bpm) −0.238 −0.440 to −0.035 0.05 Chronotropic index 0.496 0.327 to 0.665 0.ehz748.083301

Conclusions

In patients treated with beta-blockers CI was revealed as an independent factor related to worse EC.
P2508Physical exercise improves diastolic function and attenuates type III collagen myocardial accumulation in aged rats
Authors: Guirado G N , Cezar M D M , Pagan L U , Lima A R R , Damatto R L , Campos D H S , Bonomo C , Rosa C M , Gimenes C , Okoshi K , Okoshi M P
Published: October 2019

Background

Interstitial collagen matrix increase and left ventricular (LV) diastolic dysfunction are the most frequent cardiac alterations during aging. Whether changes are part of the aging process or induced by a sedentary life style is not clear.

Purpose

To evaluate the effects of aerobic exercise on functional capacity, cardiac and myocardial function, and interstitial collagen matrix of aging rats.

Methods

Male Wistar rats were assigned into three groups: 1) sedentary six-month-old rats (W6, n=24); 2) sedentary 21-month-old rats (W21-Sed, n=25); and 3) exercised 21-month-old rats (W21-Ex, n=20). Physical exercise was by treadmill for 12 weeks. In vivo cardiac evaluation was performed by Doppler echocardiography. Myocardial function was assessed in LV papillary muscle preparation. Total and soluble myocardial collagen concentrations were evaluated by spectrophotometry. Protein expression was analyzed by Western blot. Statistical analysis: ANOVA and Bonferroni or Kruskal-Wallis and Dunn.

Results

Body weight was greater in W21-Sed and W21-Ex than W6. Before exercise, functional capacity did not differ between aged groups. After training, W21-Ex group ran farther and longer in treadmill than W21-Sed e W6, and W21-Sed presented worse physical capacity than W6. LV diastolic posterior wall, interventricular septum, and relative wall thicknesses were greater in W21-Sed and W21-Ex than W6, and did not differ between aged groups. E wave was lower in both aged groups than W6. E/E' ratio was lower in W21-Ex than W21-Sed. Isolated papillary muscle developed tension was higher in W21-Sed than W6; W21-Ex values did not differ from both W6 and W21-Sed groups. Time to peak tension was higher in W21-Sed and W21-Ex than W6 and did not differ between aged groups. The same results were observed after positive inotropic stimulation. Total collagen concentration was higher in W21-Sed and W21-Ex than W6 and did not differ between aged groups. Soluble collagen did not differ between groups. Type III collagen expression was higher in W21-Sed than W6; the W21-Ex group presented intermediary values that did not differ from W21-Sed or W6 groups. Type I collagen was similar between groups.

Conclusion

Regular physical aerobic training improves functional capacity and left ventricular diastolic function and attenuates type III collagen myocardial accumulation in aged rats.

Acknowledgement/Funding

Fapesp, CNPq, Capes, and UNESP
P2510Cardiorespiratory optimal point as a predictor of outcomes in patients enrolled in a cardiac rehabilitation program
Authors: Castelo A , Rio P , Silva A S , Alves S , Bras P , Mano T , Ferreira V , Ferreira R
Published: October 2019

Introduction

The cardiopulmonary exercise test (CEPT) allows the evaluation of peak and sub-maximal tolerance to the effort, giving us relevant information for clinical decisions. Evidence has emerged that Cardiorespiratory Optimal Point (COP)>30, calculated as the minimum ratio between ventilation and oxygen (VE/VO2) may be a good predictor of events.

Purpose

The aim was to characterize the population of the cardiac rehabilitation (CR) appointment that performed CEPT, evaluate COP as a predictor of events and determine the best cut off for our population.

Methods

Retrospective analysis of CR appointment patients who performed CEPT between 2014 and 2017 in a single center. We compared the mortality and hospitalizations according to COP and COP>30. We established the appropriate Cut Off for our population and compared the same with the occurrence of events.

Results

207Patients (P) (83.6% men) were included, with a mean age of 57 years. The mean COP was 23.6±5.8 (IC [24.06–25.66]). 15.9% P had COP >30 and 33.8% had COP<22. The majority (96.6%) had a cardiovascular disease or risk factors and 99% were medicated. The majority (87.9%) was referred for CR with isquemic cardiopathy (AMI or stable or unstable coronary disease), 9.2% with heart failure (HF) and 9.2% with valvulopathy. 6.9% P died from any cause, 33.8% had an hospitalization (78.6% from a cardiovascular reason). Higher COP values correlated with higher number of all causes hospitalizations (H) (CC = 0.123, p=0.032), cardiovascular H (CC = 0.123, p=0.032), heart failure H (CC = 0.189, p=0.001) and device placement H (CC = 0.173, p=0.003). COP did not correlate with mortality (p=0.453). The cut off of 30 only correlated with HF hospitalization in this population (OR = 5, IC [1.429–17.494] p=0.006). In our population, COP was a good predictor for all cause H and heart failure H (AUC = 0.8 in both). A cut off of 25 had a sensitivity (S) of 78% with a specificity (E) of 70% for all cause hospitalization and S 73% and E 68% for heart failure H. Values above this cut off correlate with more all cause H (OR = 1,928, IC [1.06–3.507], p=0.031) and heart failure H (OR = 5.63, IC [1,44–21.94]), p=0.006). COP was an independent predictor of all-cause H (p=0.018) and heart failure H (p<0.0001). Other independent predictors of HF hospitalization are BNP (p=0.0011) and ejection fraction (p<0.0001).

Conclusion

COP was a good independent predictor of all-cause hospitalizations and HF hospitalization. In our population the cut off 25 for COP had the greatest S and E for predicting events. In our population this factor was not a good predictor of mortality.
P2525Relationship of Charlson Comorbidity Index with adverse events in elderly patients with Acute Coronary Syndromes: an analysis from LONGEVO-SCA Registry
Authors: Esteve Pastor M A , Martin E , Alegre O , Castillo Dominguez J C , Formiga F , Martinez-Selles M , Diez-Villanueva P , Sanchis J , Ariza-Sole A , Marin F
Published: October 2019

Background

Elderly patients with Acute Coronary Syndromes (ACS) are under-represented in clinical trials and they have higher risk of new due their comorbidities. Charlson Comorbidity Index (CCI) is an established tool for evaluating the burden of comorbidity status and a high score of CCI is related with an increased risk of death.

Purpose

The aim of this study was to analyze the relationship of CCI in adverse outcomes at short-term follow-up in elderly patients admitted by an ACS.

Methods

The prospective multicenter LONGEVO-SCA included unselected elderly patients (≥80 years old) hospitalized after non-STACS. In this substudy, we analyze the influence of comorbidities, comparing the relationship between quartiles of CCI and adverse events at 6 months follow-up of CCI.

Results

We analyzed 520 patients (mean age 84.4±3.6 years; 320 (61.5%) male). 196 (37.6%) were classified into Q1, 105 (20.2%) into Q2, 93 (17.9%) into Q3 and 126 (24.2%) into Q4. No differences were observed in treatment at discharge across different quartiles for aspirin (p=0.648), beta-blockers (p=0.908) or statins (p=0.756). We observed a significant increase for all-cause mortality [9 (4.8%) vs 10 (10.2%) vs 11 (12.0%) vs 32 (26.0%); p<0.001] and readmissions [36 (18.4%) vs 21 (20%) vs 33 (35.5%) vs 48 (38.1%); p<0.001] respectively from Q1 to Q4. After Cox multivariate regression analysis, CCI was independently associated with mortality or readmissions [HR 1.15, 95% CI (1.06–1.26); p=0.001] and patients into high quartile had 6-fold risk of mortality [HR 6.19, 95% CI (2.95–12.99); p<0.001]. Kaplan Meier analysis showed that patients in the highest quartiles had significantly worse prognosis during the follow-up with high risk of all-cause mortality and readmissions (both p<0.001).

Event Free Survival according Charlson

Conclusions

In LONGEVO-SCA registry, we validated for the first time CCI as an independent factor related with adverse events. Patients into high quartiles of CCI had significantly worse prognosis during the follow-up and elderly patients into Q4 had 6-fold risk of mortality compared to Q1 patients.
P2529Efficacy and safety of oral anticoagulation in nonagenarian patients with atrial fibrillation
Authors: Dominguez Rodriguez L , Raposeiras Roubin S , Alonso Rodriguez D , Camacho Freire S J , Abuassi E , Cubelos Fernandez N , Lopez-Masjuan Rios A , Rodriguez Albarran A , Muniz Pousa I , Cespon Fernandez M , Dominguez Erquicia P , Diaz Fernandez J F , Fernandez Vazquez F , Iniguez Romo A
Published: October 2019

Introduction

Embolic prevention with oral anticoagulation is the cornerstone for the management of patients with atrial fibrillation (AF). However, data about the efficacy and safety of oral anticoagulation in nonagenarian patients are limited. We aimed to analyze the impact of oral anticoagulation in mortality, embolic and hemorrhagic events, in patients ≥90 years with non-valvular AF.

Methods

We used data from a multicentric registry of 1,750 consecutive nonagenarian patients diagnosed of AF between 2013 and 2018. A propensity-matched analysis was performed to match the baseline characteristics of patients treated or not with oral anticoagulants, and for those treated with vitamin K antagonists (VKAs) vs direct oral anticoagulants (DOACs). The impact of oral anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For embolic risk, we have considered a stroke, pulmonary or peripheral embolism. For bleeding risk, we have considered any bleeding requiring hospital admission.

Results

The mean of CHA2DS2-VASC and HASBLED scores was 4.5±1.3 and 2.8±1.0 points, respectively. Most of patients were anticoagulated (70.1%; n=1,256). DOACs were used in 709 patients, and VKAs in 517 patients. During a median follow-up of 25.2 months (IQR 12.2–44.3 months), 988 patients died (56.5%), 180 presented embolic events (10.3%), 186 had bleeding events (10.6%), and 29 had intracranial hemorrhage (ICH, 1.7%). After propensity-score matching, anticoagulation (versus non anticoagulation) was associated with lower mortality rate (HR 0.73, 95% CI 0.60–0.89; p=0.002), less mortality and embolic events (HR 0.77, 95% CI 0.64–0.92; p=0.005), but more bleeding events (HR 2.05, 95% CI 1.25–3.35; p=0.004). In comparison with VKAs, DOACs showed similar risk of mortality and embolic events (HR 1.14, 95% CI 0.88–1.47; p=0.337), and similar risk of bleeding events (HR 0.75, 95% CI 0.43–1.28; p=0.287), although a trend to lower risk of ICH was found (HR 0.17, 95% CI 0.02–1.39; p=0.097).

Conclusions

Among nonagenarian patients with AF, oral anticoagulation was associated with lower all-cause mortality. Although survival free of embolic events was significantly higher in patients with anticoagulation, the risk of major bleeding was twice than in non-anticoagulated patients. There was not differences between VKAs and DOACs in terms of embolic events and total major bleeding. However, compared with VKAs, DOACs were showed a trend to lower risk of ICH.
P2536Protective effects of ultra-low-dose menopausal hormonal therapy on endothelium function in postmenopausal women
Authors: Tolstov S N , Salov I A , Rebrov A P
Published: October 2019

Introduction

This is the first pilot study to assess the functional state of the vascular wall in postmenopausal women on the background of ultra low-dose menopausal hormone therapy (MHT).

Purpose

To evaluate the protective effects on endothelial function of ultra-low-dose MHT 0.5 mg of 17β-estradiol (E2) and 0.25 mg of drospirenone (DRSP) in postmenopausal women.

Methods

The study included 115 previously examined postmenopausal women. Group 1 (n=25) included patients who started receiving MGT with DRSP during the menopausal transition; in the 2nd group (n=31), women who started receiving MGT with DRSP in the early postmenopausal period. Women of the 1st and 2nd groups made the transition to a combination of 0.5 mg E2/0.25 mg DRSP. The control group (n=59) of women not taking MGT. The duration of therapy is 1.0 (0.9; 1.2) years. The age of women was 56.8±1.6 years, 57.1±2.8 years and 57.3±1.7 years (p>0.05). Endothelium-dependent vasodilation (EDV) of the brachial artery, levels of endothelin-1 (ET-1), metabolites of nitric oxide (NO), asymmetric dimethylarginine (ADMA), von Willebrand factor antigen (vWF: Ag) in plasma were evaluated.

Results

In the control group EDV 8.6±5.1% of the original and 7.4±4.5% by the end of the study (p=0.08); in women of the 1st group 12.5±3.8% and 12.2±4.4; in women of the 2nd group11.1±8.5% and 10.5±0.2% (p=0.07 between women of the 1st and 2nd groups by the end of the study).

The level of NO metabolites in women of the 1st group 43.4 (28.6; 45.9) at baseline and 40.7 (34.4; 41.5) μmol/l by the end of the study, in women of the 2nd group 38.8 (36.5; 44.9) and 35.2 (32.8; 38.9) μmol/l (p=0.04 between the women of the 1st and 2nd groups). In the control group 34.6 (30.4; 38.2) and 27.8 (24.5; 34.9) μmol/l (p<0.001 for women of the 1st and 2nd groups).

In women of the 1st group a significant increase in ET-1 was detected from 1.02±0.26 initially to 1.18±0.24 fMol/ml by the end of the study; levels of vWF:Ag with 0.839 (0.695; 0.940) and 0.900 (0.782; 0.925) U/ml. The level of ADMA did not change significantly 0.43±0.10 and 0.45±0.10 μmol/L.

In women of the 2nd group a significant increase ET-1 was detected from 1.08±0.42 to 1.29±0.59 fMol ml; vWF:Ag from 0.841 (0.718; 0.960) to 0.829 (0.811; 0.984) U/ml and ADMA from 0.43±0.10 to 0.48±0.15 μmol/l (p>0.05).

In the the control group a significant increase in the level of ET-1 was observed from 1.40±0.43 to 1.74±0.34 fMol/ml by the end of the study; vWF levels:Ag 0.860 (0.743; 0.941) and 0.960 (0.850; 1.025) U/ml, ADMA 0.48±0.16 and 0.60±0.18 μmol/l (p<0.01 compared with women of the 1st and 2nd groups).

Conclusions

Revealed protective effects on endothelial function of ultra low-dose MHT in postmenopausal women. Early and prolonged MHT has an additional positive effect on the functional state of the vascular wall.

Acknowledgement/Funding

None
P2538Arterial stiffness and remodeling from large to small arteries in patients with spontaneous coronary artery dissection: evidence for a systemic subclinical involvement
Authors: Bruno R M , Di Lascio N , Al Hussaini A , Vitali S , Rossi P , Caramella D , Regazzoli D , Cortese B , Lettieri C , Spontoni P , Emdin M , Faita F , Ghiadoni L , Taddei S , Adlam D
Published: October 2019

Background and aim

Spontaneous coronary artery dissection (SCAD) is a major cause of acute coronary syndrome in women aged 50 years or less (22–43%). Its etiology is still unknown, though an association with systemic diseases such as fibromuscular dysplasia and collagenopathies has been found. This study is aimed at investigating the presence of subclinical structural and functional alterations in extracoronary districts in SCAD patients.

Methods

The design was a case-control study. Carotid, radial and digital arteries were scanned by standard or ultrahigh frequency ultrasound; clips were analyzed by automated image analysis software for diameter, intima-media thickness (IMT) and local distensibility. Applanation tonometry was used to obtain carotid-femoral pulse wave velocity, a measure of regional, aortic stiffness, and carotid pressure waveform.

Results

30 patients previously diagnosed with SCAD (27 women, age 51±10 years, 8 treated hypertensives, 4 smokers, mean BP 83±11mmHg, BMI 25±5kg/mq) and 30 controls, matched for age, sex and CV risk factors by propensity score, were enrolled. 18 SCAD patients underwent PTCA and 6 had a diagnosis of extracoronary fibromuscular dysplasia. In the left radial artery, wall thickness, cross-sectional area (2.96±1.07 vs 1.79±1.41mm2, p=0.008), and wall inhomogeneity were increased, especially in the outer layer, whereas diameter, wall/lumen ratio and distensibility were comparable to controls. In the left common carotid artery, an increased carotid stiffness was shown in SCAD (5.99±0.89 m/s vs 5.6±0.85, 0.03), while IMT tended to be increased bilaterally (0.63±0.12 vs 0.59±0.10mm, p=0.08). Aortic stiffness was similar in the two groups (7.0±1.9 vs 6.7±1.7m/s, p=0.60). Carotid (20.4±14.2 vs 11.9±15.0%, p=0.03), but not aortic augmentation index, was increased bilaterally.

Conclusions

SCAD patients showed a peculiar pattern of alterations in vascular remodeling and stiffness in extracoronary arterial segments such as the carotid and radial arteries, supporting the hypothesis that a systemic susceptibility is present even in the absence of systemic diseases.
P2552Triple vs. double antithrombotic therapy in patients needing oral anticoagulation undergoing percutaneous coronary intervention: a meta-analysis
Authors: Errigo D , Saglietto A , Angelini F , Lip G Y H , Lopes R D , Conrotto F , Omede P G , Montefusco A , Manzano-Fernandez S , Raposeiras-Rubin S , Varbella F , D'Amico M , D'Ascenzo F , Rinaldi M , Giustetto C
Published: October 2019

Background

The optimal antithrombotic therapy strategy in patients undergoing PCI who need OAC is currently debated.

Purpose

To determine the best regimen in terms of safety and efficacy.

Methods

We performed a meta-analysis of RCT and adjusted results reporting outcomes of patients who underwent PCI and were on TT or DAPT or DT. All-cause death was the primary end point, while MACE was the secondary outcome, along with its individual components, and major bleedings.

Results

15 studies encompassing 27070 patients were included. After a follow up of 12 (11–14) months, TT reduced all-cause death compared to DAPT (OR 0.52, 0.35–0.78), mainly driven by a lower incidence of MI (OR 0.81, 0.69–0.85) and stroke (OR 0.76, 0.56–1.03) despite higher rates of major bleedings (OR 2.81, 1.54–5.12). Comparing TT vs. DT with warfarin, all-cause death was non-significantly different (OR 1.23, 0.60–2.53), nor MI (OR 0.77, 0.23–2.59) and stroke (OR 4.01, 0.80–20.07), while major bleeding was increased with TT (OR 2.40, 1.34–4.38). When compared to DT with NOACs, TT did not reduce risk of MI (OR 0.96, 0.67–1.36) or stroke (OR 0.82, 0.55–1.24), but increased major bleedings (OR 1.98, 1.43–2.73). The non-randomized comparison between DT with warfarin and DT with NOACs showed a neutral effect on death and major bleedings, with similar rates also of MI (OR 0.47, 0.20–1.11, all CI 95%).

Conclusion

Double therapy with warfarin or with NOAC plus a single antiplatelet agent reduces the risk of major bleeding compared to triple therapy, with a neutral impact of subsequent ischemic events.
P2570Synergistic activation of the cardiac enhancer landscape during reprogramming
Authors: Hashimoto H , Wang Z , Garry G , Zhou H , Bassel-Duby R , Olson E N
Published: October 2019

Introduction

Cardiogenic transcription factors (TFs), Gata4, Mef2c, and Tbx5, can directly reprogram fibroblasts to a cardiac fate and their cardiogenic activity is enhanced by the Hand2 TF and the Akt1 kinase. Although these cardiac reprogramming factors are key regulators of heart development, their expression and biological functions are not limited to the heart, and the mechanism by which these cardiac factors orchestrate reprogramming remains unclear.

Purpose

We sought to study the molecular mechanisms by which cardiac reprogramming factors contribute to cell fate conversion using a genome-wide approach.

Methods

Here, we used chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) to explore the genomic binding sites of reprogramming TFs and the landscape of active enhancers, annotated by H3K27ac histone modification, during cardiac reprogramming.

Results

We found that reprogramming TFs rapidly silence fibroblast enhancers and synergistically activate cardiac enhancers which were predominantly enriched with Mef2 motifs. Addition of Hand2 and Akt1 to GMT expands TF co-occupancy and thereby activates additional cardiac enhancers, which further augments cardiac gene expression. Moreover, additional cardiac enhancers were sequentially activated during the reprogramming process, in accordance with the temporal acquisition of functional phenotypes in induced cardiac-like myocytes. We discovered that subsets of reprogramming enhancers are conserved among other cardiogenic processes, and a collection of reprogramming enhancers displayed unique spatial expression patterns in the developing heart in transgenic mouse embryos.

Conclusion

Our study describes the epigenomic dynamics that underlie cardiac reprogramming which is cooperatively orchestrated by reprogramming factors to convert fibroblasts toward a cardiac lineage.

Acknowledgement/Funding

NIH (AR-067294, HL-130253, HL-138426, HD-087351), Fondation Leducq Transatlantic Networks of Excellence in Cardiovascular Research
P2581Unique molecular profile of exosomes from epicardial fat of patients with atrial fibrillation
Authors: Shaihov - Teper O , Ram E , Levin - Kotler L , Naftali - Shani N , Leor J
Published: October 2019

Background and aim

Exosome, the smallest vesicles that originate from intracellular compartments, contains and delivers specific bioactive proteins, lipids, mRNA, and miRNA to facilitate intercellular signaling. However, the role and mechanism of exosomes in atrial remodeling and fibrillation (AF) has not been determined. While epicardial fat (eFat) and inflammation have been linked to atrial remodeling and fibrillation (AF), the role of eFat exosomes in the pathogenesis of AF remains unknown. Thus, we aimed to determine whether eFat exosomes play a role in the initiation and progression of AF.

Methods and results

We collected eFat specimens from patients with and without chronic or paroxysmal AF undergoing heart surgery. Isolated fat specimens were cut into small pieces and incubated as organ cultures. We isolated exosomes from the medium of the explant by differential ultra-centrifugation and characterized the vesicle size distributions, morphology, specific markers, and molecular cargo. Immunoblotting of CD63, CD81 and TSG101 confirmed the presence of exosomes (Fig.1 B). Significantly, eFat from patients with AF secreted higher amounts of exosomes compared with controls (p<0.001), which confirmed by Nanoparticle Tracking Analysis (NTA) (Fig.1 A). The levels of exosomal pro-inflammatory and pro-fibrotic cytokines were higher in exosomes from patients with, compared with those without, AF (Fig.1 C, D). Measurements of micro RNA (miRNA) by real-time PCR showed lower levels of anti-fibrotic miRNA-133a (p=0.2), and higher levels of pro-fibrotic miRNA-146b (p=0.2) in exosomes from patients with, compared with those without, AF (Fig.1 E, F)

Conclusion

We show, for the first time, that exosomes from eFat of patients with AF have a unique pro-inflammatory and pro-fibrotic profile. We suggest a novel mechanism that links eFat to AF and eFat exosomes as novel biomarkers and potential therapeutic targets for AF.
P2590A liver-derived secretory protein, selenoprotein P causes pressure overload-induced cardiac hypertrophys
Authors: Usui S , Takashima S , Inoue O , Goten C , Takeda Y , Yamaguchi K , Murai H , Kaneko S , Takamura M
Published: October 2019

Background

Hepatokine selenoprotein P (SeP) contributes to insulin resistance and hyperglycemia in patients with type 2 diabetes. Inhibition of SeP protects the heart from ischemia reperfusion injury and serum levels of SeP are elevated in patients with heart failure with reduced ejection fraction.

Objective

We investigated the role of SeP in the regulation of cardiac remodeling in response to pressure overload.

Methods and results

To examine the role of SeP in cardiac remodeling, transverse aortic constriction (TAC) was subjected to SeP knockout (KO) and wild-type (WT) mice for 2 weeks. Hepatic expression of SeP in WT was significantly increased by TAC. LV weight/tibial length (TL) was significantly smaller in SeP KO mice than in WT mice (6.75±0.24 vs 8.33±0.32, p<0.01). Lung weight/TL was significantly smaller in SeP KO than in WT mice (10.46±0.44 vs 16.38±1.12, p<0.05). TAC-induced cardiac upregulation of the fetal type genes, including atrial and brain natriuretic factors, was significantly attenuated in SeP KO compared to WT. Furthermore, azan staining revealed that there was significantly less interstitial fibrosis in hearts after TAC in SeP KO than in WT mice. To determine whether hepatic overexpression of SeP affects TAC-induced cardiac hypertrophy, a hydrodynamic injection method was used to generate mice that overexpress SeP mRNA in the liver. Hepatic overexpression of SeP in SeP KO mice lead to a significant increase in LV weight/TL and Lung weight/TL after TAC compared to that in other SeP KO mice.

Conclusions

These results suggest that cardiac pressure overload induced hepatic expression of SeP and the absence of endogenous SeP attenuated cardiac hypertrophy, dysfunction and fibrosis in response to pressure overload in mice. SeP possibly plays a maladaptive role against progression of heart failure through the liver-heart axis.