bluuebunny/crossref_metadata_2025 huggingface dataset:
P1601N-glycosylation of TREK-1/hK2P2.1 two-pore-domain (K2P) potassium channels
Authors: Wiedmann F , Schlund D , Ratte A , Katus H A , Kraft M , Thomas D , Schmidt C
Published: October 2019

Background and purpose

Mechanosensitive hTREK-1 (hK2P2.1) two-pore-domain potassium channels give rise to background currents that control resting membrane potential in excitable tissue. Recently TREK-1 currents have been linked to regulation of cardiac rhythm as well as hypertrophy and fibrosis. Even though pharmacological and biophysical characteristics of hTREK-1 channels have been widely studied, less is known about its posttranslational modifications. This study aims to evaluate whether hTREK-1 channels are N-glycosylated and whether glycosylation may affect channel functionality.

Experimental approach

Following pharmacological inhibition of N glycosylation, enzymatic digestion or mutagenesis, immunoblots of Xenopus laevis oocytes and HEK-233T cell lysates were used to assess electrophoretic mobility. Two-electrode voltage clamp measurements were employed to study channel function.

Key results

TREK-1 channels subunits undergo N-glycosylation at asparagine residues 110 and 134. The presence of sugar moieties at these two sites increases channel function. Detection of glycosylation-deficient mutant channels in surface fractions and recordings of macroscopic potassium currents mediated by these subunits demonstrate that non-glycosylated hTREK-1 channels subunits are able to reach the cell surface in general, but seemingly with reduced efficiency.

Conclusion and implications

hTREK-1 are glycoproteins and N glycosylation at positions 110 and 134 is involved in channel surface trafficking. These findings extend our view on regulation of hTREK-1 currents by posttranslational modifications and provide novel insights into how glycosylation deficiency disorders may promote arrhythmogenesis.
P1623Activation of invariant natural killer T cells by alpha-galactosylceramide ameliorates doxorubicin-induced cardiotoxicity in mice
Authors: Obata Y , Ishimori N , Saito A , Kinugawa S , Nakano I , Kakutani N , Yamanashi K , Anzai T
Published: October 2019

Objective

Doxorubicin (DOX) is an effective antineoplastic agent commonly used to treat many types of cancer but its clinical use is limited because of cardiotoxicity, which might proceed to irreversible cardiac dysfunction in a dose-dependent manner. The precise mechanism of DOX-induced cardiotoxicity is still not fully elucidated but it has been reported that cardiac inflammation is involved in the cardiotoxicity. Invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens and secrete a large amount of Th1 and Th2 cytokines on activation, have been shown to play crucial roles in the regulation of immune responses. However, it remains unclear whether iNKT cells are involved in DOX-induced cardiotoxicity.

Methods and results

Male C57BL/6J mice were administered DOX (20mg/kg body weight single intraperitoneal injection; n=28) or vehicle (Vehicle; n=6). DOX-administered mice were further divided into 2 groups; α-galactosylceramide (αGC, 0.1μg/g body weight twice intraperitoneal injection; DOX-αGC; n=14), which specifically activates iNKT cells, or phosphate-buffered saline alone (PBS; DOX-PBS; n=14) 4 days before and 3 days after DOX administration. Survival rate at 14 days after DOX/Vehicle administration was significantly lower in DOX-PBS than in Vehicle (71% vs. 100%, P<0.05), and this decrease was completely attenuated in DOX-αGC (100%, P<0.05 vs. DOX-PBS). Echocardiography at 14 days after DOX/Vehicle administration revealed that left ventricular (LV) fractional shortening was significantly reduced in DOX-PBS compared to Vehicle (49.3±0.8% vs. 59.2±1.7%, P<0.05), and this decrease was completely attenuated in DOX-αGC (57.7±1.3%, P<0.05 vs. DOX-PBS) without affecting LV end-diastolic diameter. Picro-sirius red staining revealed that the ratio of fibrosis area to the cardiac tissue was markedly higher in DOX-PBS than in Vehicle (4.3±0.5% vs. 2.2±0.1%, P<0.05), and this increase was completely attenuated in DOX-αGC (2.8±0.1%, P<0.05 vs. DOX-PBS). Real-time PCR analysis revealed that mRNA expression of anti-inflammatory Th2 cytokine IL-4 was enhanced by 7.9-folds in DOX-αGC compared to DOX-PBS, though the difference did not reach statistically significance (P=0.09).

Conclusions

Activation of iNKT cells by αGC ameliorates DOX-induced cardiotoxicity in mice via up-regulation of anti-inflammatory IL-4 and reducing cardiac fibrosis. iNKT cell activation may be a novel therapeutic strategy against DOX-induced cardiotoxicity.

Acknowledgement/Funding

Japan Agency for Medical Research and Development (18lm0203001j0002) and JSPS KAKENHI (18K15834)
P1626MicroRNA-21 deteriorates left ventricular reverse remodeling by promoting cardiac fibrosis in non-ischemic cardiomyopathy
Authors: Watanabe K , Narumi T , Watanabe T , Aono T , Goto J , Sugai T , Toshima T , Kato S , Tamura H , Nishiyama S , Takahashi H , Arimoto T , Shishido T , Watanabe M
Published: October 2019

Background

Left ventricular reverse remodeling (LVRR) contributes to better outcomes in patients with non-ischemic cardiomyopathy (NICM). It is reported that LVRR is associated with progression of cardiac fibrosis. MicroRNAs (miRs) have emerged as powerful regulators of post-transcriptional gene expression. We focused on miR-21, which plays a key role in pathogenesis of fibrosis in multiple organs. The aim of this study was to clarify the effect of miR-21 on cardiac fibrosis and LVRR in patients with NICM.

Methods

We measured plasma miR-21 levels in 16 patients with NICM. LVRR was defined as increased LVEF by ≥10% and decreased LV end-diastolic diameter index by ≥10% from baseline data after optimal medication treatment at 1-year of follow-up. Further, we examined miR-21 expression and its potential role in cardiac fibrosis induced by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) stimulation in neonatal rat cardiomyocytes (NRCMs).

Results

There were 12 patients without LVRR and 4 patients with LVRR. Plasma miR-21 levels were significantly higher in patients without LVRR compared with those with LVRR. In TAC mice heart, miR-21 levels were significantly increased and programmed cell death 4 (PDCD4), a main target of miR-21, was decreased. In vitro, miR-21 levels were significantly increased and its upstream transcriptional factor, activator protein 1 (AP-1), was activated by Ang II stimulation in NRCMs. After transfection of miR-21 specific inhibitor, PDCD4 levels were upregulated. Furthermore, AP-1 activity, expression of collagen type I, and α-smooth muscle actin levels were significantly decreased after miR-21 inhibition.

Conclusions

These findings suggested that miR-21/PDCD4/AP-1 feedback loop pathway was involved in LVRR in patients with NICM by promoting cardiac fibrosis. MiR-21 can be the therapeutic target in NICM.
P1631Machine-learning defined predictors of mortality in ischemic and non-ischemic heart failure patients undergoing CRT-P or CRT-D implantation
Authors: Kosztin A , Schwertner W R , Tokodi M , Toser Z S , Kovacs A , Veres B , Zima E , Geller L , Merkely B
Published: October 2019

Background

Both Cardiac Resynchronization Therapy Pacemakers (CRT-P) and CRT Defibrillators (CRT-D) improve mortality in heart failure patients with reduced ejection fraction and wide QRS complex. However, not every patient benefits equally from each type of treatment and determinants of mortality may vary across the subgroups of patients with different etiologies and devices.

Purpose

Our aim was to investigate the differences in the predictors of long-term mortality in heart failure patients with different etiologies undergoing CRT-P or CRT-D implantation using machine learning.

Methods

We created 4 separate random forest models to predict 5-year all-cause mortality (models for ischemic and non-ischemic etiology in both CRT-P and CRT-D subgroups). A registry of 1650 patients (66±10 years, 1258 [76%] males, 751 [46%] CRT-D) was used as the training cohort for the prediction models. Forty-seven pre-implant parameters including cardiovascular risk factors and clinical variables were utilized to train our models. For each clinical parameter, we calculated the mean decrease in Gini impurity (dG). Based on the extent of decline, the 10 most important features were selected for each model. To keep the data comparable between the different models, we took the union of these features and plotted the results on radar charts.

Results

There were 879 (53%) deaths during the follow-up period. The mortality benefit of adding an Implantable Cardioverter Defibrillator could be observed only in ischemic patients (Hazard Ratio = 0.83, 95% Confidence Interval: 0.72–0.97, p<0.005), but not in the entire cohort or in patients with non-ischemic etiology. In patients with non-ischemic etiology, the pattern of mortality predictors were almost similar: in CRT-P patients the most important predictors were age, serum urea levels and left ventricular ejection fraction (LVEF) (dG: 0.114, 0.054 and 0.053, respectively) whereas in the CRT-D subgroup these factors were age, LVEF and serum sodium (dG: 0.116, 0.060 and 0.052, respectively). In CRT-P patients with non-ischemic etiology, the most relevant variables were age serum urea and LVEF in decreasing order (dG: 0.085, 0.060 and 0.050, respectively). The strongest predictors of mortality were age, hemoglobin and serum creatinine in ischemic patients with CRT-D (dG: 0.088, 0.060 and 0.052, respectively).

CRT-P vs. CRT-D by ischemic etiology

Conclusions

In patients with ischemic heart failure, CRT-D was associated with a mortality benefit compared to CRT-P. Our results also suggest that machine-learning may identify distinct patterns in clinical characteristics for a better mortality prediction. Taking these factors into consideration during the management of heart failure patients with CRT, risk stratification and outcomes could be improved.
P1642High-sensitivity cardiac troponin I and NT-proBNP and their relationship to heart failure in the European BiomarCaRE population
Authors: Yan I , Boerschel C , Neumann J , Spruenker N , Kontto J , Kuulasmaa K , Salomaa V , Iacoviello L , Di Castelnuovo A , Costanzo S , Linneberg A , Soederberg S , Zeller T , Blankenberg S , Westermann D
Published: October 2019

Aims

Heart failure (HF) is an increasingly important contributor to the overall burden of cardiovascular disease in the population. We aimed to determine the distribution of the cardiac biomarkers high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations across the European population to characterize the association with incident HF.

Methods and results

Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 48,455 individuals from four prospective population-based cohort studies (DanMONICA, FINRISK, Moli-Sani, Northern Sweden MONICA study) across Europe with a maximum follow-up of 27 years. The median age of the participants was 50.7 years (25th percentile: 40.0 years, 75th percentile: 61.7 years) and 49.1% (25,146) were men. Considered endpoints were incident HF and all-cause mortality. The median follow-up time for occurrence of HF was 6.61 (6.55; 6.66) years. We found that cardiovascular risk factors (CVRFs), especially diabetes with HR of 2.11 (95% CI 1.8, 2.5) and smoking status with HR of 1.79 (95% CI 1.59, 2.1) (Figure 1) were associated with incident HF. Furthermore, beyond the CVRFs, elevated hs-cTnI and NT-proBNP concentrations contributed to risk of HF in the general population with HR of 1.49 (95% CI 1.21, 1.9) and HR of 2.37 (95% CI 1.97, 3.0) respectively. As a cut-off value to select individuals, who would benefit most from preventive strategies, a hs-cTnI concentration of 2.8 ng/L was calculated using the optimal cut-off methodology by Contal and O'Quigley in CSDA 1999.

Hazard ratio for incident HF

Conclusion

In our large population-based cohort, hs-cTnI and NT-proBNP were independently associated with incident HF. Use of biomarkers for HF screening thus may help to select those individuals in the general population who would benefit most from preventive strategies. Based on the cut-off value future studies are needed to evaluate therapeutic options.
P1643An exploratory analysis for the optimal monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure
Authors: Dai Z , Asano T , Ohde S , Komiyama N
Published: October 2019

Background

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potential biomarker for monitoring the status of heart failure. However, the optimal monitoring interval is unknown. This study aims to investigate minimal informative monitoring interval of NT-proBNP in patients with stable chronic heart failure.

Methods

In this retrospective open cohort study, adult patients followed up at a tertiary hospital for chronic heart failure with NT-proBNP measurements were included if they had been previously admitted due to acute heart failure and were free from readmission over 6 months after discharge. We analyzed NT-proBNP measured between 6 months after discharge and the timepoint of an alteration of medication regimen or readmission due to worsening of heart failure. To distinguish actual progression of the disease from biological variability and measurement error, the signal-to-noise ratio method was applied with a random-effects model. Stratified analysis was performed according to underlying risks.

Results

In this analysis, 368 patients were included with NT-proBNP measured between July 2009 and December 2017. The patients had 6.0 times of NT-proBNP measurements in median (interquartile range [IQR] 4.0–10.0) during the follow-up period (median 12.0 months [IQR 6.0–27.0]). In the estimates of the random-effects model, signal (i.e. actual progression of the disease) exceeded noise (i.e. biological variability and measurement error) at 8.1 months (95% confidence interval [CI]: 5.7–10.1) after the index measurement. In a subgroup analysis according to the AHEAD risk score, the minimal informative monitoring interval was shortened as the risk score increased (0–1 point: 12.3 months [95% CI: 10.3–14.5]; 2–3 points: 8.0 months [95% CI: 6.8–9.7]; 4–5 points: 3.3 months [95% CI: 3.0–3.8]; Figure).

Informative intervals stratified by risk

Conclusion

In patients with stable chronic heart failure, the overall minimal informative monitoring interval of NT-proBNP measurement was 8.1 months, which varies by underlying risk. The optimal monitoring interval could be lengthened especially for patients at lower risk.
P1651Pulmonary artery pressure could predict closed aortic valve in patients managed by veno-arterial extracorporeal membrane oxygenation
Authors: Yamaguchi S , Sawamura A , Arao Y , Ooishi H , Kato H , Kuwayama T , Haga T , Hiraiwa H , Yokoi T , Kondo T , Morimoto R , Okumura T , Murohara T
Published: October 2019

Background

Although veno-arterial extracorporeal oxygenation (VA-ECMO) is widely used as mechanical circulatory support, it reduces native left ventricular (LV) stroke volume through the cardiac preload decrease and afterload increase. Therefore some patients with severe cardiac dysfunction present persistently closed aortic valve (AV). The closed AV is considered to increase the risk of pulmonary edema or intracardiac thrombosis. However, little is known about the variables that contribute to persistently closed AV under the management of VA-ECMO.

Purpose

We investigated the factors that could predict persistently closed AV at the time of VA-ECMO initiation.

Methods

This was a retrospective chart review. We investigated the patients who received the management of VA-ECMO due to cardiogenic shock from April 2011 to December 2018, and analyzed 18 patients (43±16 years, 50% female) who presented closed AV immediately after the introduction of VA-ECMO. We obtained the hemodynamic data at the time of VA-ECMO initiation (baseline) and 24h after. The patients who presented persistently closed AV during 24h were defined as Close-group (n=8). The patients whose AV was opened within 24h were defined as Open-group (n=10). The status of AV was investigated by the echocardiogram.

Results

All patients were managed by concomitant use of intra-aortic balloon pumping. The etiologies were myocarditis (56%), cardiomyopathy (33%), and acute myocardial infarction (11%). Nine patients experienced in-hospital death (6 were Close-group and 3 were Open-group, p=0.15). At baseline, there were no significant differences between mean arterial blood pressure (mABP) (p=0.07), central venous pressure (CVP) (p=0.71), and left ventricular ejection fraction (p=0.44). However, Close-group had significantly lower mean pulmonary artery pressure (MPAP) and pulmonary artery pulse pressure (PAPP) than Open-group (Close-group versus Open-group; MPAP, 15±6 mmHg versus 27±11 mmHg, p=0.01; PAPP, 3±2 mmHg versus 8±3 mmHg, p=0.01). Logistic regression analyses revealed the lower MPAP and PAPP had the predictive value of closed AV within 24-h after VA-ECMO initiation [MPAP: odds ratio (OR) 0.78, 95% confidence interval (95% CI) 0.62–0.99, P=0.003; PAPP: OR 0.18, 95% CI 0.02–1.13, P<0.001]. In the following 24h, no significant change was found in MPAP and PAPP.

Conclusion

At the time of VA-ECMO initiation, lower MPAP and PAPP had the predictive value for persistently closed AV. LV preload derived from right heart function would have major impact on AV status.
P1704The impact of electrocardiographic changes upon resuscitation from out-of-hospital cardiac arrest on mortality
Authors: Iiya M , Kimura S , Shimizu M , Fujii H , Suzuki M
Published: October 2019

Background

The serial electrocardiographic changes in patients following out-of-hospital cardiac arrest (OHCA) are unclear.

Purpose

To evaluate serial electrocardiographic changes and to predict all-cause mortality in patients following OHCA.

Methods

We retrospectively studied 101 OHCA patients (70±16 years, 49 male) who achieved a return of spontaneous circulation (ROSC) and survived for ≥3hours. Twelve-lead electrocardiograms (ECGs) were evaluated twice in each patient: initial-ECG, after achieving ROSC; and 2nd-ECG, after receiving the initial evaluation in the emergency room. Patients were divided into two groups: S-group, those surviving for 28 days, and D-group, those dying within 28 days. Multivariate Cox regression analyses were performed to predict the 28-day survival following OHCA. A Kaplan-Meier curve analysis for the 28 day mortality stratified by the QRS morphology and rhythm of initial-ECG was performed.

Results

Among variables of initial-ECG, there were significant differences between the group-S and group-D (table). Multivariate analysis with a step-wise regression demonstrated that age, lactate, and QRS duration of the initial-ECG were significant predictors of all-cause mortality (Odds ratio (OR): 1.04, 1.21, 1.02, p: 0.002, 0.001, 0.001, respectively). Kaplan-Meier analysis revealed that a complete right bundle branch block (CRBBB) of initial-ECG and presence of atrial fibrillation were associated with an increased risk of all-cause mortality (Picture).

Serial change of ECG variables Initial-ECG 2nd-ECG Group S Group D p Group S Group D p Heart Rate [/min] 109±23 105±31 0.527 88±21 94±23 0.341 Af [N,%] 10 (25%) 27 (52%) 0.018* 3 (9%) 6 (26%) 0.134 QRS duration [ms] 111±18 139±33 0.001* 107±29 111±30 0.623 Morphology 0.001* 0.284 – Normal [N,%] 30 (75%) 10 (19%) 29 (81%) 14 (61%) – CRBBB [N,%] 5 (13%) 30 (57%) 5 (14%) 5 (22%) – CLBBB [N,%] 1 (2%) 0 0 1 (4%) – IVCD [N,%] 4 (10%) 13 (24%) 2 (6%) 3 (13%) Comparing variables between group S and group D stratified by initial ECG and delayed ECG. QRS morphology were examined, normal, complete right bundle branch block (CRBBB), complete left bundle branch block (CLBBB), and unspecific interventricular conduction delay (IVCD).

Study flow diagram, KM curve analysis

Conclusions

The QRS duration and morphology upon resuscitation were associated with an increased risk of all-cause mortality following OHCA.
P1707Non-business hours and cold exposure independently worsen neurological outcome after out-of-hospital cardiac arrest
Authors: Uechi T , Shibata S , Suda T , Hata N , Hirabuki K , Tsukada T , Hirasawa A , Matsuda T
Published: October 2019

Background

It has been known that survival rates after out-of-hospital cardiac arrest (OHCA) are lower at night than during the day. It may be explained by diurnal temperature changes.

Purpose

The purpose of the present study was to test our hypothesis that diurnal variation of the prognosis after OHCA would be independent from the ambient temperature changes.

Methods

We used the All-Japan Utstein Registry (2005–2010) combined with atmospheric temperature from the Automated Meteorological Data Acquisition System, and enrolled adult OHCA patients who had suffered from a witnessed cardiac arrest and who had been resuscitated.

The primary outcome was a favorable neurological outcome one month after OHCA and the secondary outcome was the presence of return of spontaneous circulation (ROSC) before hospital admission. Effects of business vs. non-business hours and ambient temperature on the primary and secondary outcomes were assessed with adjustment for factors that are known to potentially affect OHCA outcomes. Sub-group analysis based on the initial cardiac rhythm (VT/Vf, PEA and Asystole) was also performed.

Results

Among the 263,750 witnessed OHCA patients, neurological survival and ROSC rates were significantly increased with an adjusted odds ratio (OR) of 1.13 (95% CI 1.08–1.18) and hazard ratio (HR) of 1.06 (95% CI 1.04–1.09) for non-business hours, and OR of 1.11 (95% CI 1.05–1.17) and HR of 1.05 (95% CI 1.02–1.08) for each 20°C increase in temperature. The effects were different between business vs. non-business hours and ambient temperature dependent on the initial cardiac rhythm.

Conclusions

These findings suggest that both the outdoor temperature and business hours are independent factors for predicting neurological outcomes after OHCA with different characteristics based on the initial cardiac rhythms. Diurnal variability of prognosis after OHCA is likely to be attributable to diurnal variation of medical resources.
P1726A gender perspective on incidence, management, short- and long term outcome of cardiogenic shock complicating ST-elevation myocardial infarction - A report from the SWEDEHEART register
Authors: Sederholm Lawesson S , Venetsanos D , Fredriksson M , Jernberg T , Johnston N , Ravn-Fischer A , Alfredsson J
Published: October 2019

Background

Cardiogenic shock [CS] is a severe complication of ST-elevation myocardial infarction [STEMI]. An increased use of primary percutaneous coronary intervention [PPCI] has been associated with a decline in CS incidence, and a better prognosis. Female gender has been associated with a worse prognosis in STEMI, but whether there is a gender difference in incidence and outcome of CS complicating STEMI is not known.

Purpose

The objectives of this study were to compare the genders regarding incidence, management, and prognosis of CS complicating STEMI.

Methods

Patients with STEMI and CS were identified in SWEDEHEART 2005–2014. Cardiogenic shock was defined as any of; 1) systolic blood pressure [BP] <90 mm Hg ≥30 min, 2) signs of tissue hypoperfusion, 3) cardiac index <1,8 l/min/m2, 4) ionotropic drugs and/or need of intra-aortic balloon pump. Multiple logistic and cox regression analyses were done with reperfusion therapy, in-hospital and 1-year mortality as dependent variables.

Results

Among 56072 STEMI patients 3134 CS cases were identified. Women more often than men developed CS (6.3 vs 5.2%, p<0.001). The age-adjusted incidence of CS did not change in women, whereas in men the incidence increased by 2.7% yearly. Women had a less chance of receiving reperfusion therapy, OR 0.77 (95% CI 0.65–0.92), but had neither higher in-hospital mortality (OR 1.01, 95% CI 0.85–1.19), nor higher 1-year mortality (OR 0.97, 95% CI 0.70–1.33). Upon age stratification the gender difference in reperfusion was only evident among the oldest (>80 years).

Conclusion

Women had higher risk of CS than men when stricken by STEMI, but whereas CS incidence increased in men it was stable in women. Although women had less likelihood of receiving reperfusion therapy, adjusted in-hospital, and 1-year mortality was without any gender difference. The rate of reperfusion was especially low in elderly women, where there seems to be room for improvement.
P1743Assessment of quality of care of patients with ST-segment elevation myocardial infarction in Poland
Authors: Hudzik B , Budaj A , Gierlotka M , Witkowski A , Wojakowski W , Zdrojewski T , Gil R , Legutko J , Bartus S , Buszman P , Dudek D , Gasior M
Published: October 2019

Introduction

2017 ESC Guidelines for the management of ST-elevation myocardial infarction (STEMI) patients have called for the assessment of the quality of care to establish measurable quality indicators in order to ensure that every patient with STEMI receives the best possible care. We investigated the quality indicators of health care services in Poland provided to STEMI patients.

Methods

The Polish Registry of Acute Coronary Syndromes (PL-ACS) is an ongoing, nationwide, multicenter, prospective, observational study of consecutively hospitalized patients with the whole spectrum of ACS in Poland. For the purpose of assessing quality indicators, we included 8,279 patients from the PL-ACS Registry hospitalized with STEMI between January 1 and December 31, 2018.

Results

All emergency medical services (EMS) are equipped with ECG/defibrillators. 408 of 8,279 patients (4.9%) arrived at PCI center by self-transport, 4,791 patients (57.9%) patients arrived at PCI center by direct EMS transport, and 2,900 patients (37.2%) were transferred from non-PCI facilities. Whilst 95.1% of STEMI patients arriving in the first 12 hours received reperfusion therapy, the rates of timely reperfusion were much lower (ranging from 39.4% to 55.0% for various STEMI pathways). 7,807 patients (94.3%) underwent PCI as a mode of primary reperfusion strategy. The median left ventricular ejection fraction (LVEF) was 46% and was assessed before discharge in 86.0% of patients. 489 of 8,279 patients (5.9%) died during hospital stay. Optimal medical therapy is prescribed in 50–85% of patients depending on various clinical settings. Only one in two STEMI patient is enrolled in a cardiac rehabilitation program at discharge. No patient-reported outcomes were recorded in the PL-ACS Registry.

Figure 1

Conclusions

The results of this study identified areas of healthcare systems that require solid improvement. These include prehospital ECG decision strategy, direct transport to PCI center, timely reperfusion, guidelines-based medical therapy (in particular in patients with heart failure), referral to cardiac rehabilitation/secondary prevention programs. More importantly, we recognized an urgent need for the initiation of recording quality indicators associated with patient-reported outcomes.
P1757GLP-1 levels predict cardiovascular risk in patients with acute myocardial infarction
Authors: Kahles F , Rueckbeil M V , Mertens R W , Foldenauer A C , Arrivas M C , Moellmann J , Lebherz C , Biener M C , Giannitsis E , Katus H , Marx N , Lehrke M
Published: October 2019

Background

Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone, which induces post-prandial glucose-dependent insulin secretion. GLP-1 receptor agonists improve cardiovascular outcomes in patients with diabetes at high cardiovascular risk. We recently found GLP-1 levels to be increased in patients with acute myocardial infarction.

Purpose

The aim of this study was to assess the predictive capacity of GLP-1 for cardiovascular outcome in patients with myocardial infarction.

Methods

Total GLP-1 levels, NT-proBNP concentrations and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of admission in 918 patients with myocardial infarction presenting with acute chest pain. Among these 597 patients presented with NSTEMI and 321 with STEMI. The primary composite outcome of the study was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with a median follow-up of 311 days.

Results

Kaplan-Meier survival plots (separated by tertiles with cut-off values 35.44 and 53.45) and univariate cox regression analyses found GLP-1 values to be associated with adverse outcome (combined endpoint and all-cause mortality) (logarithmized GLP-1 values HR: 5.459; p<0.0001). Further adjustment for age, sex, previous cardiovascular disease, diabetes, hypertension, hypercholesterinemia, kreatinin, CRP, troponin T and NT-proBNP levels did not affect the association of GLP-1 with adverse outcomes (p=0.0341). Receiver operating characteristic curve analyses illustrated that GLP-1 is a strong indicator for early events (area under the curve of the combined endpoint at 7 days: 0.79; 14 days: 0.81; 30 days: 0.80 and 183 days: 0.64), which proved to be superior to Troponin T, serum creatinin, NT-proBNP and CRP within the first 100 days. Adjustment of the GRACE risk estimate by GLP-1 increased the area under the receiver-operating characteristic curve (AUC) after 1 month from 0.86 to 0.89 in NSTEMI patients. Addition of GLP-1 to a model containing GRACE and NT-proBNP led to a further improvement in model performance (increase in AUC from 0.88 for GRACE + NT-proBNP to 0.90 for GRACE + NT-proBNP + GLP-1).

Conclusion

GLP-1 is a new biomarker of cardiovascular risk and adverse outcomes in patients with acute myocardial infarction and improves the predictive value of the GRACE score in patients with NSTEMI.
P1766Clinical impact of atrial fibrillation and heart failure in a cohort of patients with hypertrophic cardiomyopathy
Authors: Esteve Ruiz I , Llamas Gomez H , Esteve Ruiz I M , Romero Reyes M J , Pavon Jimenez R , Molano Casimiro F J
Published: October 2019

Background

Atrial fibrillation (AF) and heart failure (HF) are common complications in Hypertrophic Cardiomyopathy (HCM) patients, leading to a worsening of their quality of life, need of hospitalization and prognosis.

Purpose

To analyze clinical variables associated with the presence of AF and HF in HCM patients.

Methods

HCM patients followed-up in cardiological visits from 2005 to 2017 were included and a descriptive analysis of those with AF and HF was performed.

Results

Out of 168 patients, 28% had reported AF. They were older than those without arrhythmia (68±15 years (yrs) vs 56±20 yrs, p<0.001) and had more comorbidities such as diabetes (27.7% vs 12.4%, p=0.02) and chronic renal disease (21.3% vs 6.6%, p=0.006). Echocardiographic findings are summarized in Table 1.

In our cohort, 27.4% of the patients had HF with a functional class according to the New York Heart Association criteria ≥2. They were older than those without HF (69.3±11.6 yrs vs 55.9±20.6 yrs, p<0.001) and had higher rate of cardiovascular (CV) risk factors such as hypertension (65.2% vs 44.3%, p=0.015). The presence of HF was directly associated with the presence of AF: 52.2% of the patients with HF and 18.9% of the patients without HF developed this arrhythmia (p<0.001). HF patients associated larger left atrial diameter (48±8.1 vs 41.6±7.2mm, p<0.001), myocardial thickness (21.7±3.9 vs 19.2±5.8mm, p=0.002) and higher left ventricular outflow obstruction (LVOO) (55±32 vs 34.3±31.3mmHg, p=0.021), without any differences in the left ventricular ejection fraction. HF patients had a worse prognosis (Picture 1). Multivariate analysis showed that the presence of AF (OR 2.6, CI 95% 1.1–6.3) and LVOO (OR 4.8, CI 95% 1.5–14.8) were independent risk factors of developing HF.

Table 1. Echocardiographic findings AF (n=47) Non AF (n=121) p LVOO 27.7 19 0.22 Aortic regurgitation 12.8 3.3 0.02 Mitral regurgitation 27.7 12.4 0.02 Left atrial diameter (mm) 48.8±7.2 40.7±7 <0.001 Myocardial thickness (mm) 20±5.4 19±5.2 0.02 Qualitative variables are expressed as percentages (%) and quantitative variables as mean and standard deviation (M ± SD).

Picture 1. Main outcomes of HF patients

Conclusions

AF and HF were directly associated in our cohort, especially in elderly patients with higher comorbidities, leading to a worse prognosis with a higher hospitalization rate and CV death. This emphasizes the importance of a thorough search of both complications in order to initiate early treatment and improve the prognosis of HCM patients.
P1776Identifying the ideal MitraClip candidate - a COAPT-derived, retrospective subgroup stratification of a large real-life cohort
Authors: Tigges E , Kalbacher D K , Gossling A G , Ludwig S L , Schofer N S , Conradi L C , Schirmer J S , Girdauskas E G , Reichenspurner H R , Blankenberg S B , Lubos E L
Published: October 2019

Background/Introduction

Recently published, diverging data of the COAPT and Mitra.fr trials yielded discussion on the impact of the magnitude of mitral valve insufficiency and of left ventricular end-diastolic volume index (LVEDVI) in patients with functional mitral regurgitation (FMR) prior to MitraClip intervention on outcome measures.

Purpose

We sought to evaluate the leverage of the effective orifice area (EROA) and LVEDVI on long-term outcome in a real-life cohort.

Methods

We stratified 394 patients (74.4±8.6 years, 60.9% male) that had been treated by MitraClip from 09/2008 to 01/2018 into four subgroups: I (FMR, EROA ≤30mm2 [n=76]), II (FMR, EROA 30–40mm2 [n=87]), III (FMR, EROA >40mm2 [n=105]) and IV (degenerative MR [DMR], n=126). Follow-up was conducted at on-site visits 6 months and annually after MC procedure up to 60 months.

Results

At baseline, patients of subgroup IV were oldest (p=0.0011), while subgroups I to III demonstrated significantly higher rates of any cardiomyopathy (I: 78.4%, II: 93.1%, III: 86.7%, IV: 47.6%, p<0.001). The left ventricular ejection fraction (LVEF) differed significantly (I: 38±13%, II: 35±14%, III: 34±14%, IV: 54±12%, p<0.001), as did EuroSCORE values (median, I: 20.4%, II: 24%, III: 23%, IV: 18.4%, p<0.001). Procedural success (placement of ≥1 Clip, residual MR ≤2+) differed significantly (I: 96.1%, II: 96.6%, III: 89.5%, IV: 87.3%, p=0.039).

Up to 60 month follow-up lasting success was noted in 87.5% (I), 81.8% (II), 87.5% (III) and 77.8% (IV) and all subgroups demonstrated a significant improvement in New York Heart Failure Association classification.

In further stratification according to LVEDVI (A: ≤96ml/m2 and B: >96ml/m2), no differences were noted in Kaplan-Meier estimates for death (A: p=0.36 and B: p=53) or in post-hoc comparison of each group (I-IV). Likewise, the combined endpoint of death and cardiac rehospitalization (A: p=0.18, B: p=0.94), MACE (A: p=0.37, B: p=0.54) and MACCE (A: p=0.16, B: p=0.49) and post-hoc comparisons of each group (I-IV) yielded no significant differences in outcome measures.

Conclusions

Despite distinct differences in baseline characteristics of each subgroup, we observed high procedural success rates, long-lasting reductions of MR and beneficial clinical outcome in all patients. In this retrospective analysis of a real-life cohort, EROA and LVEDVI did not influence long-term outcome measures. These results indicate no limitation for MitraClip treatment based on advanced stages of FMR and its underlying pathology, yet mark the necessity for further pre-procedural stratification.
P1779Quantitation of severe degenerative mitral regurgitation by echocardiography and CMR with acetate PET for external reference for left ventricular volumes
Authors: Baron T , Holm Orndahl L , Kero T , Sorensen J , Bjerner T , Hedin E.-M , Harms H J , Stahle E , Astudillo R , Flachskampf F A
Published: October 2019

Background

Quantitative echocardiographic assessment of severity of primary mitral regurgitation (MR) is challenging. CMR is recommended if MR severity cannot be clearly determined, since quantitation of regurgitation as well as of left ventricular (LV) volumes and function is crucial for the indication for surgery especially in asymptomatic patients.

Purpose

We aimed to compare volumetric measurements obtained from transthoracic echo (TTE) and cardiovascular magnetic resonance (CMR) using ECG-gated [(11)C]acetate PET as reference for assessment of LV volumes.

Methods

A total of 51 asymptomatic patients with severe primary mitral regurgitation underwent TTE, CMR and PET on the same day. Mitral regurgitant volumes (RVol) were measured by TTE using proximal convergence (PISA) method and by CMR, subtracting aortic forward flow volume from LV stroke volume. LV volumes were measured by TTE, CMR and PET.

Results

Despite a fair correlation between regurgitant volumes measured by TTE and CMR (r=0.53, p<0.001), PISA method heavily overestimated regurgitant volumes on TTE as compared to CMR (103±60ml vs. 78±35ml, p<0.001). TTE systematically underestimated LV volumes as compared to CMR (see table) despite a good correlation (r=0.81, 0.67 and 0.76 respective for LV EDV, ESV and SV, p<0.001 for all). There was no difference in LV EF between the methods. LV volumes obtained by CMR and PET showed a strong correlation (r=0.92, 0.79 and 0.89 respective for LV EDV, ESV and SV, p<0.001 for all) and agreement (see table).

Comparison of TTE, CMR and PET TTE CMR PET PET TTEvs.CMR PET CMRvs.PET F-test LV EDV, ml 145±34 241±57 234±51 <0.001 0.004 <0.001 LV ESV, ml 47±11 76±22 81±23 <0.001 0.067 <0.001L LV SV, ml 99±26 164±38 152±34 <0.001 <0.001 <0.001 LV EF, % 68±5 69±5 65±6 0.236 <0.001 <0.001

Conclusions

As compared to CMR, PISA method used by TTE substantially overestimates regurgitant volumes in patients with asymptomatic primary mitral regurgitation. Conversely, LV volumes in spite of good correlation are heavily underestimated by TTE in comparison with CMR. A strong correlation and agreement between LV volumes measured by CMR and PET confirms the accuracy of the former method which is considered as a golden standard for assessment of ventricular function and volumes. Thus, even so-called quantitative echo measures should be understoas essentially semi-quantitative indicators of severity.
P1810May early myocardial involvement detection in chagas disease have a prognosis impact?
Authors: Fernandez Valledor A , Jorda P , Pajuelo C , Vinas D , Hernandez J , Culotta V , Pinazo M J , Posada E , Aldasoro E , Gascon J , Sitges M , Garcia Alvarez A N A
Published: October 2019

Background

Brain natriuretic peptide (BNP) and novel echocardiographic techniques such as speckle-tracking and a comprehensive evaluation of diastolic function can detect early myocardial involvement in patients with Chagas disease. However, there is lack of longitudinal studies that can confirm whether this early myocardial involvement translates into a worse prognosis.

Purpose

To assess if early myocardial involvement detected by BNP or a comprehensive echocardiographic evaluation was associated with future events in Chagas disease.

Methods

182 consecutive individuals from endemic areas who underwent T. cruzi screening where prospectively included from 2007 to 2014. ECG, BNP and a comprehensive echocardiography including diastolic function and longitudinal myocardial strain were performed. Four different groups were defined: healthy controls (N=77); Chagas indeterminate form (positive serology, normal ECG and left ventricle (LV) diameter (<55 mm), LV ejection fraction (>50%) and no segmental abnormalities, N=88); Chagas patients with abnormal ECG but normal LV dimensions and motility (N=7); and Chagas patients with LV diameter>55 mm or LV ejection fraction<50% or segmental abnormalities (N=13). The primary outcome included advanced atrioventricular block, sustained ventricular tachycardia, heart failure, heart transplant or death. Kaplan Meier with Long rank test and Cox regression analysis was used.

Results

Mean age was 37±9 and 34% were male. Median follow-up was 63 months (range 1 to 137). The primary endpoint occurred in a total of 11 (10%) individuals: 2 (2.4%) in the Indeterminate group; 3 (43%) in the abnormal ECG group; and 6 (46%) in the group with abnormal LV dimension or motility, with no events among controls (long-rank test<0.01, Figure). In the global population, age, BNP, diastolic dysfunction parameters and longitudinal strain at the inferior and lateral walls were significant predictors. In the cohort of Chagas patients with normal standard echocardiography (N=92), ECG abnormalities (HR=49, p=0.001), Em (HR=0.68, p=0.03), deceleration time (HR=0.01, p=0.01), left atrial diameter (HR=1.24, p<0.01) and longitudinal strain at the midventricular lateral wall (HR=0.75, p=0.028) remained significantly associated with outcome.

Cumulative survival without events

Conclusions

Outcome was significantly more frequent in Chagas patients with abnormalities in ECG or standard echocardiography. In early forms of the disease, myocardial involvement detected by BNP or a comprehensive echocardiography was associated with prognosis, and may help to individualize treatment and follow-up.
P1814A novel method of transradial approach for left ventricular endomyocardial biopsy
Authors: Lan M I N G , He Q I N G
Published: October 2019

Background

Left ventricular endomyocardial biopsy (LV-EMB) may offer a superior diagnostic yield compared with right ventricular endomyocardial biopsy (RV-EMB) in conditions predominantly affecting the LV. Recently, transradial way is used for LV-EMB, and it has lower complication rates and has an advantage of immediate post-procedural ambulation compared with transfemoral technique. Previous reports of transradial LV-EMB need relatively complicated sheathless guiding catheter exchanging.

Purpose

We aimed at finding a novel and easier transradial method with a 6F sheath and a 6F guiding catheter.

Methods and results

In this manuscript, we described a method that allowed interventional cardiologists to obtain LV-EMB via transradial access with a 6F sheath and a 6F guiding catheter. This technique was successfully conducted in 25 consecutive patients at our institution. The transradial success rate was 100% (25 of 25). Mild or moderate radial artery spasm occurred in only 1 (4%) patient, but no severe radial spasm was observed. All the patients were performed coronary angiography and left ventricular angiogram according to the indication, and they were performed EMB through the same radial sheaths without sheathless guiding catheter exchanging. Heparin was administered to 100% of patients at a dose of 5000IU. Median fluoroscopy time was 13.45min. Median total skin dose was 1478mGy. Median area product was 15486 cGy·cm2. All biopsy samples were graded as excellent quality. Immediate patient mobilization could be achieved in all patients. Radial artery patency was confirmed by doppler ultrasonography 24 hours after the sheath removal. There were no major complications (pericardial tamponade, life-threatening arrhythmia, cerebrovascular accident or death).

Transradial LV-EMB with a 6F sheath

Conclusions

The present article demonstrates a result of feasibility, safety and efficacy of a novel transradial access for LV-EMB using a 6F sheath and a 6F guiding catheter. This is of clinical importance since this new technique may overcome the currently existing methods, and may be regarded as an interventional “one stop shop” technique.
P1815The impact of PVB19 presence in myocardium in recent onset dilated cardiomyopathy
Authors: Krejci J , Hude P , Poloczkova H , Ozabalova E , Mlejnek D , Godava J , Honek T , Freiberger T , Zampachova V , Svobodova I , Spinarova L
Published: October 2019

Introduction

The most common virus in myocardium of patients with recent onset dilated cardiomyopathy (RODCM) is PVB19. Opinions on its pathogenicity are different. According to some, viral load has to be evaluated and if it is low, the PVB19 has no potential to induce inflammation. Others recommend assessment of viral replication, while “innocent” are those cases where replication activity is low.

Purpose

To compare the development of echocardiographic parameters in patients with RODCM with isolated presence of PVB19 in low viral load (below 500 copies per μg nucleic acid) against a group in which no virus was detected in the myocardium.

Patient and methods

243 patients with RODCM, in 151 cases (62%), the virus was detected in the myocardium (PCR+ group), in 92 cases the finding was negative (PCR−; ie 38%). In the PCR+ group, PVB19 was captured in 135 cases (89% of all PCR+), in 121 cases of them was PVB19 the only one isolated virus (PCRPVB19+; 80% of all PCR+). The viral presence was assessed by real time PCR.

Results

In the PCR− group, the left ventricular ejection fraction (LVEF) was 23.5±7.2%, in the PCRPVB19+ group 24.6±7.1% (p=0.26). Left ventricle end-diastolic diameter (LVEDD) in PCR− was 66.4±8.9mm vs 65.5±7.9mm in PCRPVB19+ (p=0.42), right ventricle diameter (RV) 33.1±5.7mm vs. 33.4±5.2mm (p=0.69), TAPSE 19.5±4.1mm vs 18.9±4.0mm (p=0.28) and E/é 14.0±5.7 vs. 14.9±7.0 (p=0.32). In the 12-month control, LVEF in the PCR− was 35.5±12.3% (p<0.001 for comparison with baseline), in PCRPVB19+ 35.3±12.3% (p<0.001 for comparison with baseline; p=0.92 for difference between groups); LVEDD in PCR− was 62.0±9.3mm vs 62.1±9.3mm in PCRPVB19+ (both p<0.001 for comparison with baseline, p=0.91 for difference between groups), RV 31.6±5.5mm vs. 31.6±5.4mm (p=0.033, resp. p=0.003 for comparison with baseline; p=0.98 for difference between groups), TAPSE 20.7±4.3mm vs. 20.7±4.4mm (p=0.026, resp. p<0.001 for comparison with baseline; p=0.98 for difference between groups), and E/e' 10.3±4.1 vs. 10.4±4.1 (both p<0.001 for comparison with baseline; p=0.93 for difference between groups).

Conclusion

PVB19 presence in myocardium had no effect on the development of echocardiographic parameters in RODCM patients in one-year follow-up.

Acknowledgement/Funding

Supported by Ministry of Health of Czech Republic AZV Grant 16-30537A