bluuebunny/crossref_metadata_2025 huggingface dataset:
2177Cardiac resynchronization therapy in patients greater than 75 years of age - results from the European Society of Cardiology Survey II with 11 088 patients
Authors: Normand C , Dickstein K , Linde C
Published: October 2019

Background

Cardiac Resynchronization Therapy (CRT) reduces morbidity and mortality in selected patients with heart failure (HF) and electrical dyssynchrony. The median age for patients included in the CRT landmark trials ranged from 62–68 years, therefore limited trial evidence exists on CRT in patients ≥75 years of age.

Purpose

To assess similarities and differences in patient demographics and implantation practice in different age groups implanted with a CRT device.

Methods

Between 2015 and 2017, two European Society of Cardiology (ESC) associations, European Heath Rhythm Society and the Heart Failure Association, conducted the CRT Survey II, a survey of CRT implantations in 11,088 patients in 42 ESC member states.

Results

In our survey 32% of patients included were ≥75 years of age. These patients were more frequently in NYHA Class III or IV, had more comorbidity (including hypertension, atrial fibrillation, anaemia and renal dysfunction) and had significantly higher NT-pro BNP levels than younger patients. Slightly fewer patients ≥75 years of age had LBBB but all groups had the same median QRS duration. Despite substantially more patients ≥75 years of age having HF of ischaemic aetiology compared with those <65 year of age, far fewer patients in oldest age group category were implanted with a CRT-defibrillator (CRT-D) compared with those in the youngest group.

CRT Survey II Patients by Age Categories Demographics Age <65 years Age 65–74 years Age ≥75 years N 3478 (32%) 4025 (36%) 3536 (32%) NYHA class III & IV 52% 59% 66%* Ischaemic HF aetiology 33% 49% 50%* Atrial fibrillation 17% 27% 33* NT proBNP (pg/ml, median, IQR) 1651 (670, 3811) 2319 (1070, 5169) 3510 (1647, 7631)* CRT-D 81% 76% 52%* Peri-procedural complications 5% 6% 6% Adverse Events during hospitalization 4% 5% 5% CRT-D, Cardiac resynchronization therapy – defibrillator; HF, heart failure; IQR, interquartile range. *Differences between groups is significant with p<0.001.

Conclusions

Patients ≥75 years of age had greater comorbidity and experienced more symptoms from their heart failure. However, they did not suffer more complications or adverse events during the index hospitalization, suggesting that CRT may safely be offered to elderly patients.

Acknowledgement/Funding

The work was supported by EHRA, the HFA, Biotronik, Boston Scientific, Medtronic, Sorin, St. Jude, Abbott, Bayer, Bristol-Myers Squibb and Servier
2181The prothrombotic transcriptome of reticulated platelets
Authors: Bongiovanni D , Santamaria G , Klug M , Santovito D , Felicetta A , Hristov M , Aslani M , Weber C , Peano C , Condorelli G , Laugwitz K L , Bernlochner I
Published: October 2019

Introduction

Reticulated platelets (RPs) are young, hyper-reactive platelets that are larger and contain significantly more RNA compared to older mature platelets. High levels of RPs in peripheral blood are predictors of an insufficient response to dual antiplatelet therapy in cardiovascular patients and of adverse cardiovascular events also in non-cardiac patients. However, the mechanisms underlying these correlations remains widely unknown and the biology of RPs has not been investigated yet.

Purpose

We aimed to compare for the first time the transcriptomic profiles of RPs and mature platelets (MPs).

Methods

RPs and MPs from peripheral blood of healthy donors were identified and isolated using FACS/Sorting based on their RNA-content. Immediately after sorting, RNA was extracted and quality, concentration and integrity was assessed with the Tapestation 4200 platform (Agilent). Total- and small-RNA libraries were prepared, multiplexed and sequenced on a NextSeq 500 Illumina platform

Results

Total-RNA-sequencing revealed 1744 differentially expressed genes (670 downregulated 1074 upregulated) in RPs compared to MPs (Figure 1A, B). In particular, transcripts for the collagen receptor GP6, thromboxane receptor A2 (TBXA2R), thrombin receptor PAR4 (F2RL3) and ATP receptor P2RX1 were significantly enriched in RPs, whereas several RNA regulators as the ribonuclease PARN, the RISC-component TNRC6A and the splicing factor LUC7L3 were downregulated in RPs. Gene ontology analysis revealed an enrichment of relevant biological categories in RPs including platelet activation and blood coagulation (Figure 1C). Gene Set Enrichment Analysis showed an enrichment of several activation pathways like thrombin, thromboxane and GPIIb/IIIa signaling in RPs. Small-RNA-sequencing reported 9 miRNAs significantly downregulated in RPs with targets involved in platelet reactivity.

Figure 1

Conclusions

This study represents the first comparative transcriptome analysis of RPs and MPs and reports for the first time a differential enrichment of transcripts involved in platelet activation. The clear upregulation of prothrombotic signaling in RPs could explain, at least in part, their hyper-activity and their correlation with cardiovascular events in different pathological settings (trancripts enriched in RPs: Figure 1D).

Acknowledgement/Funding

German Society of Cardiology (DGK Nr.102018) ESC First conctact initiative grant 2018
2200Predictors of patient decision time in ST elevation myocardial infarction data from an observational cross sectional survey study
Authors: Ericsson M , Thylen I , Hellstrom Angerud K , Swahn E , Stromberg A , Sederholm Lawesson S
Published: October 2019

Background

Short time from symptom onset until reperfusion is imperative in ST-elevation myocardial infarction (STEMI). System delay has been successfully shortened but patients delay has had less favorable development. The aim of this study was to find out clinical, contextual, behavioral and cognitive factors associated with decision time in STEMI.

Method

SymTime was a multicenter observational cross-sectional self-reported survey study performed at five Swedish hospitals representing geographic diversity. Early and late action was defined as decision to seek care <20 min and >90 min, respectively.

Results

532 patients were included. Among those 19.5% called Emergency Medical Services (EMS) as first medical contact (FMC) within 20 min, whereas 10.7% acted within 20 min, but did not call EMS as FMC. Twenty-eight % called EMS as FMC, but delayed >20 min and 41.7% neither acted promptly, nor called EMS as FMC.

Predictors associated with decision time OR 95% CI Factors associated with decision time <20 min   Previous AF 0.43 0.19–0.94   Believing the symptoms originated from the heart 3.10 1.93–4.96   Symptoms waxing and waning 0.58 0.36–0.94   Getting STEMI off hours 0.66 0.45–0.97   Bystanders calling or recommending EMS (Emergency Medical Services) contact 1.67 1.07–2.59   Bystanders calling or recommending SHD (Swedish healthcare Direct) contact 0.56 0.37–0.85 Factors associated with decision time >90 min   Female gender 1.67 1.06–2.62   Diaphoresis 0.67 0.46–0.998   Nausea 0.60 0.36–0.998   Stomach pain 0.46 0.23–0.91   Believing the symptoms originated from the heart 0.46 0.32–0.68   Getting STEMI off hours 1.68 1.16–2.14   Low educational level 0.58 0.40–0.86   Bystanders calling or recommending EMS contact 0.45 0.30–0.67 Variable significant at the p 0.05 presented.

Conclusion

Surprisingly, no specific symptom or severity of symptom were associated with early action, neither age, nor gender. Instead correct interpretation of symptoms and bystanders assisting were factors associated with early action. Frightening symptoms such as diaphoresis was negatively associated, whereas female gender and getting MI off hours were positively associated with late action.
2229Apoptotic and non-apoptotic circulating microparticles in patients with acute coronary syndromes
Authors: Zacharia E , Papageorgiou N , Antonopoulos A S , Pallantza Z , Oikonomou E , Miliou A , Mistakidi C V , Kriebardis A , Orologas N , Valasiadi E , Papaioannou S , Tousoulis D
Published: October 2019

Background

Circulating microparticles (MP) are surrogate biomarkers of atherosclerosis but their role in patients with acute coronary syndromes (ACS) remain unknown.

Purpose

To explore the levels of apoptotic and non-apoptotic MP in patients with ACS.

Methods

We enrolled a total of 153 patients as follows: 49 patients with STEMI, 35 NSTEMI, 38 with unstable angina (UA), 15 with stable CAD (SCAD) and 16 non-CAD (controls). Flow cytometry analysis was used to quantify circulating apoptotic (annexin+) and non-apoptotic endothelial cell (EMP), red blood cell (RMP) and platelet (PMP) derived microparticles. Circulating C-reactive protein (hsCRP) levels and cardiac troponin I (cTnI) were also assessed. Brachial FMD was also determined as a marker of endothelial function.

Results

There was a stepwise increase in the total number of EMP, RMP and PMP in patients with ACS (STEMI/NSTEMI) compared to UA, SCAD and non-CAD patients. This was mainly explained by the increase in the number of apoptotic EMP, RMP and PMP (a-c), while there were no significant differences in the level of apoptotic EMP, RMP or PMP between patient subgroups (not shown). There was no association between circulating levels of apoptotic or non-apoptotic EMP, RBP or PMP with hsCRP (p=NS for all). Apoptotic EMP only were negatively associated with brachial FMD (rho=−0.185, p=0.04) and positively with cTnI levels (rho= 0.307, p<0.0001).

Conclusions

Circulating apoptotic (but not non-apoptotic) MP are increased in patients with ACS. A negative association is observed between the numbers of circulating apoptotic EMP only and systemic endothelial function. The biological role of circulating apoptotic microparticles' in the pathogenesis of ACS merits further investigation.
2232Circulating levels of ST2 are associated with myocardial injury, left ventricular function and future adverse clinical events in patients with ST-elevation myocardial infarction
Authors: Shetelig C , Ueland T , Limalanathan S , Hoffmann P , Aukrust P , Yndestad A , Seljeflot I , Eritsland J , Andersen G.Ø
Published: October 2019

Background

Soluble ST2, a member of the IL-1 receptor family, seems to be associated with adverse outcome in acute myocardial infarction and heart failure (HF), and is suggested to be involved in left ventricular (LV) remodelling.

Purpose

To elucidate a possible role of ST2 in LV injury, remodelling and prognosis in ST-elevation myocardial infarction (STEMI) patients. The main objectives of the study were to investigate whether circulating ST2 levels were associated with infarct size, LV function, adverse remodeling and clinical outcome in a cohort of patients with STEMI.

Methods

270 patients with clinically stable first-time STEMI treated with primary percutaneous coronary intervention (PCI) were included. Blood samples were drawn before and immediately after the PCI procedure, at day 1 (median 18.3 hours after PCI) and after 4 months. Cardiac magnetic resonance (CMR) was performed in the acute phase and after 4 months. Clinical events and all-cause mortality were registered during 12 months' and 70 months' follow-up, respectively. A composite endpoint was defined as death, MI, unscheduled revascularisation >3 months after the index infarction, rehospitalisation for HF or stroke. Associations between ST2 and CMR parameters and clinical events were evaluated with linear regression and logistic regression, respectively.

Results

There was a significant increase in ST2 levels from the PCI procedure to day 1 with a subsequent decline from day 1 to 4 months in the POSTEMI cohort. Patients with high ST2 levels (>median) at all sampling points during hospitalisation had significantly larger infarct size, lower myocardial salvage, lower LVEF, larger increase in EDV and higher frequency of MVO. After adjustment for relevant clinical variables, peak CRP and peak troponin T, ST2 measured at day 1 remained associated with infarct size (β 2.0 per SD of ST2, p<0.001) and LVEF (β −1.8 per SD of ST2, p=0.02) at 4 months. High levels of ST2 measured at day 1 (>75th percentile) were associated with increased risk of having an adverse clinical event during the first year and with long-term all-cause mortality (Figure). High levels of ST2 measured in a stable phase 4 months after STEMI were also associated with an increased risk of all-cause mortality (Figure).

Figure 1

Conclusions

High levels of ST2 in STEMI patients were associated with large infarct size, impaired recovery of LV function, and adverse clinical outcome in patients with STEMI. ST2 measured 4 months after STEMI remained associated with all-cause mortality.
2284Sex and age differences in short-term exposure to ambient fine particulate matter and out-of-hospital cardiac arrest: a nationwide case-crossover study in Japan
Authors: Zhao B , Johnston F H , Salimi F , Negishi K
Published: October 2019

Introduction

Accumulating evidence has shown the elevated risk for cardiovascular diseases (CVD) with exposure to air pollution, such as fine particles <2.5μm in aerodynamic diameter (PM2.5). A bi-directional relationship exists between air pollution and traditional CV risk factors like obesity, diabetes, and hypertension. However, little is known about the effect of age and sex on association between ambient air pollution and out-of-hospital cardiac arrest (OHCA).

Purpose

This study aimed to identify sex and age differences in the associations between exposure to PM2.5 and OHCA in Japan.

Methods

A case-crossover design was used to determine the odds ratio (OR) of OHCA across Japan with daily PM2.5 exposure on the day of the arrest or 1–3 days before it (lag 0–3). OHCA cases were identified through the All-Japan Utstein registry of the Fire and Disaster Management Agency from January 1, 2014 to December 31, 2015. OHCAs were investigated by conditional logistic regression adjusted for daily temperature and relative humidity with stratification by sex and age.

Results

A total of 249,372 OHCAs were included during study period. Their mean age was 75 years and 57% were male. Each 10 μg/m3 increase in daily PM2.5 exposure over 4 days was associated with all cause OHCA risk for male (lag 0: OR 1.022, 95% confidence interval (CI) 1.013, 1.031; lag 1: OR 1.016, 95% CI 1.007, 1.025; lag 2: OR 1.016, 95% CI 1.007, 1.026; lag 3: OR 1.017, 95% CI 1.008, 1.027; lag 0–1: OR 1.025, 95% CI 1.015, 1.036). Increased risk in OHCA was also found with lag 1 to lag 3 PM2.5 exposure among women. Lag 0 to lag 3 PM2.5 exposures were significantly associated with OHCA among patients older than 65 years. Among 35 to 64 years, only lag 3 PM2.5 exposure was associated with an increased risk in OHCA. No significant association was observed between PM2.5 exposure and OHCA among patients less than 35 years.

Conclusions

Short-term exposure to PM2.5 is associated with an increased risk of OHCA in both sexes. Patients older than 65 years were more susceptible to PM2.5 exposure than younger age group.
2289Extracellular Vesicle-incorporated Long Noncoding RNA PUNISHER as a novel biomarker and effector of vascular function
Authors: Li Q , Liu Y Y , Hosen M R , Levermann P , Flender A , Latz E , Nickenig G , Werner N , Jansen F
Published: October 2019

Background

Circulating long noncoding RNAs (lncRNAs) have emerged as biomarkers and regulators in cardiovascular diseases. Whether small extracellular vesicles (sEV)-incorporated lncRNAs expression is regulated in coronary artery disease (CAD) is largely unknown. We aimed to explore the expression of plasma sEV-lncRNAs in patients with and without CAD as well as elucidate specific cellular function of sEV-incorporated lncRNA PUNISHER (also known as AGAP2-AS1) in vascular endothelial cells.

Methods and results

We quantified the expression level of 13 cardiac- or atherosclerosis-related lncRNAs by quantitative real-time PCR (qRT-PCR) in plasma sEV from 6 stable CAD, 6 ACS and 6 non-CAD (NCAD) patients. 4 lncRNAs showing stable expression (PUNISHER, GAS5, MALAT1, and H19) were further evaluated in the validation study including 65 stable CAD, 43 ACS and 42 NCAD patients. Among those, PUNISHER was significantly increased in patients with stable CAD and ACS compared to NCAD. Area under the curve (AUC) value was 0.7 for stable CAD and 0.8 for ACS respectively, suggesting plasma sEV-PUNISHER as a potential diagnostic biomarker for CAD. In vitro, atherosclerotic stimuli consisting of oxLDL or TNF-a treatment upregulated PUNISHER level in human coronary artery endothelial cell (HCAEC) and in corresponding sEV in a dose-dependent way. Mechanistically, RNA immunoprecipitation (RIP) assay identified hnRNPK as an interaction partner of PUNISHER regulating its packaging into sEV. In vitro, endothelial-derived sEV were internalized into recipient ECs and transported incorporated PUNISHER into recipient cells promoting an angiogenic response. Mechanical downstream analysis using PCR array showed that sEV-mediated PUNISHER transfer altered expression of vascular endothelial growth factor A (VEGFA) in recipient ECs.

Conclusion

This translational study highlights sEV-incorporated lncRNA PUNISHER as biomarker and effector in vascular disease.
2387Recurrent cardiovascular events and mortality in relation to antiplatelet therapy in patients with myocardial infarction without obstructive coronary artery disease (MINOCA)
Authors: Bossard M , Yusuf S , Tanguay J F , Faxon D P , Boden W E , Steg P G , Granger C , Kastrati A , Budaj A , Di Pasquale G , Valentin V , Diaz R , Joyner C , Gao P , Mehta S
Published: October 2019

Background

Approximately 10% of patients presenting with myocardial infarction (MI) do not have obstructive coronary artery disease (MINOCA). The role of antiplatelet therapy and outcomes in this group remain unclear. We assessed prognosis and the effect of an intensified clopidogrel regimen in MINOCA patients.

Methods

We analyzed data from the CURRENT-OASIS 7 trial, which randomized 25,086 patients with acute coronary syndromes (ACS) referred for early intervention to receive either double-dose (600mg day 1; 150mg days 2–7; then 75mg daily) or standard-dose (300mg day 1; then 75mg daily) clopidogrel. We evaluated clinical outcomes at 30-days in patients with versus without obstructive CAD and in relation to standard versus double-dose clopidogrel.

Results

Overall, 23,783 MI patients were included, of which 1,599 (6.7%) had MINOCA. MINOCA patients were younger, more frequently presented with non-ST-segment elevation MI and had fewer comorbidities. Rates of all-cause mortality (0.7% versus 2.4%, p=0.0046), cardiovascular mortality (0.6 versus 2.2%, p=0.0056), repeat MI (0.5% versus 2.3%, p=0.0009) and major bleedings (0.7% versus 2.5%, p=0.0001) were significantly lower among patients with MINOCA versus those with obstructive CAD. Compared with the standard-dose clopidogrel regimen, the double-dose regimen appeared to increase the risk of cardiovascular death, MI or stroke in MINOCA patients (0.8% versus 2.1%, hazard ratio (HR) 2.74, P=0.033). There was no difference in those with obstructive CAD (4.7% versus 4.4%, HR 0.93, P=0.226; P-for-interaction=0.023) (see Figure 1A). Major bleeding did not occur more frequently in MINOCA patients with double- versus standard-dose clopidogrel regimen (0.7% versus 0.6%, (HR 1.16 (95% CI 0.35–3.80), p=0.805), but their rate was higher In MI patients with obstructive CAD (2.7% versus 2.2% (HR 1.26 (95% CI 1.06–1.49), p=0.008) (Figure 1B).

Figure 1A & B

Conclusions

Compared to MI patients with obstructive CAD, patients presenting with MINOCA represent a distinct cohort, which is generally younger, has a higher NSTEMI prevalence and fewer comorbidities. Their risk for adverse events, especially repeat MI, stroke, death, and bleeding, is low (<1%) at 30 days. Applying an intensified clopidogrel regimen in MINOCA patients appears to be related to a higher risk for CV death, MI and stroke. Accordingly, more potent antiplatelet regimens might be harmful among MINOCA patients and should not be administered routinely. Nevertheless, there is a need for more prospective studies evaluating the role of dual antiplatelet therapies in MINOCA patients.

Acknowledgement/Funding

The CURRENT-OASIS 7 trial was sponsored by Sanofi-Aventis and Bristol-Myers Squibb.
2398Efficacy of remote controlled catheter ablation for atrial arrhythmias in patients with atrial switch
Authors: Guarguagli S , Cazzoli I , Dimopoulos K , Kempny A , Ernst S
Published: October 2019

Introduction

Since arterial switch procedure replaced the Mustard and Senning (M/S) operations for D-transposition of great arteries (TGA) in 1980s, there are many M/S survivors who are now over 30 yrs old. Atrial arrhythmias are common in these patients and catheter ablation is a valid alternative to medical treatment.

Purpose

Assess the efficacy of atrial arrhythmia ablation using remote magnetic navigation (RMN) in M/S patients.

Methods

All ablations performed on patients with M/S by a single operator in a tertiary center over a 10 year period (2008–2019) were reviewed and analyzed. All documented sustained recurrences were recorded.

Results

Twenty-eight patients (57% M, age 41 [33–44] yrs, 2 Senning), underwent 41 procedures, 40 of which consisted of ablation for atrial tachycardia (AT, 36, 91%: 81% in PVA, 8% SVA, 11% in PVA+SVA), atrio-ventricular nodal re-entry tachycardia (1, 1%) or atrial fibrillation (AF 3, 8%). All procedures were carried out using remote navigation, electroanatomical mapping and 3D image integration. Pre-procedure echo showed at least moderately impaired systemic ventricle in 68% and moderate or severe tricuspid regurgitation in 58% of patients. Access to pulmonary venous atrium (PVA) was gained retrogradely in all cases while to access systemic venous atrium (SVA) either via femoral, subclavian or jugular veins.

All except one procedure (98%) were acutely successful. At 1 and 3 years, 82% and 74% of patients were free from recurrent arrhythmia. Multiple procedures were required to control arrhythmias in 10 (36%) patients ablated for AT (60% in PVA, 30% in PVA+SVA). After the 2nd ablation 60% of these patients were in sinus rhythm at 3 years. On multivariate Cox analysis, Senning repair was associated with a higher recurrence risk after ablation compared to patients undergone a Mustard procedure (HR 1.47, p=0.01). Overall median procedural duration was 210 [155–265] min with a median fluoroscopy time of 0.9 [0.4–1.5] min and fluoroscopy exposure of 60 [43–120] μGy·m2.

Conclusions

Remote magnetic navigation represents a valid treatment for atrial arrhythmias in patients post M/S operation, with good short and longer-term results. Moreover, it allows the retrograde approach sparing the transbaffle puncture and enables a low fluoroscopy exposure.
2399Contemporary outcomes of catheter ablation for adult Fontan patients using advanced technologies
Authors: Cazzoli I , Larsen S H , Guarguagli S , Dimopoulos K , Kempny A , Kongstad O , Gatzoulis M A , Ernst S
Published: October 2019

Background

The Fontan operation, followed by the total cavo-pulmonary connection (TCPC), has been the primary technique for surgical treatment of patients with functionally univentricular heart. Post-surgical arrhythmias contribute considerably to the morbidity and mortality within this cohort

Purpose

To demonstrate feasibility and outcome of catheter ablation procedures aided by three-dimensional (3D) image integration combined with advanced technologies in adult Fontan patients, as well as correlation of arrhythmia type.

Methods

We included adult pts who underwent catheter ablation between 2008 and 2018. Procedures were carried out with electro-anatomical mapping and 3D image integration. Mapping and ablation were performed manually or with remote magnetic navigation (RMN). A retrograde access via the aortic valve was used to reach the atria in TCPC pts.

Results

A total of 63 pts were reviewed with either TCPC or Fontan operation (see figure). A total of 215 arrhythmias were inducible (117 in Fontan, 2/procedure, range 1–5; 98 in TCPC, 1/procedure, range 1–5), in 2 pts (3%) no ablation was performed, whereas 8 (3.7%) arrhythmias were not sustained. In TCPC pts 36 (36.7%) were macro-reentrant atrial tachycardia (MRAT) mostly from the right atrium (RA), 31 focal AT (FAT, 31.6%) almost equally from either the RA or the TCPC; 10 (10.2%) were atrio-ventricular nodal re-entrant tachycardia (AVNRT), 7 from twin AV node, and 3 concealed accessory pathways (AP) with AVRT (3%). Nine AT originated from several sites within the left atrium (9.1%). For the MRAT, most of the ablation lines were performed between the TCPC and the tricuspid annulus. In Fontans, all ATs originated from the RA, either MRAT (54, 46.1%) mostly around surgical scars, or FAT (58, 49.6%). Three pts (2.5%) presented in AF, while 1 (0.8%) had a left AP. Irrigated tip ablation resulted in acute success of 78.3% in the TCPC cohort and 76.7% in the Fontan cohort. The mean procedure time was 254±99 min and 255±106 min with a mean fluoroscopy time 2.3±1.9 min and 5.5±4.8 min for each TCPC and Fontan, respectively. During a mean follow-up of 4.2±3.0 years (maximum of 10.8 years), 58% (41–72) of TCPC pts and 22% (10–38) of Fontan pts remained free of symptoms/significant arrhythmia [at 2 years: 69% (55–79) and 31% (18–46), respectively]. Eleven TCPC (26%, 4 new arrhythmias) and 14 Fontan patients (70%, 3 new arrhythmias) needed repeat procedures. In multivariate Cox regression analysis, Fontan operation and female gender were associated with worse outcome, independently of the type of arrhythmia.

Conclusions

Advances in 3D mapping, image integration and the introduction of RMN has facilitated a dramatic improvement of ablation outcomes for adult patients after single ventricle repair. Patients with TCPC have fewer arrhythmias than Fontans and are more likely to benefit longterm, whilst transbaffle puncture can be avoided using RMN.
2400Early and late effects of cardiac resynchronization therapy in adult congenital heart disease
Authors: Yin Y , Dimopoulos K , Shimada E , Lascelles K , Griffiths S , Wong T , Gatzoulis M A , Babu-Narayan S V , Li W
Published: October 2019

Background

There are limited data regarding cardiac resynchronization therapy (CRT) in adult congenital heart disease (ACHD).

Purpose

We aimed to assess early and late outcomes of CRT amongst patients with ACHD.

Methods

We retrospectively studied ACHD patients receiving CRT (2004–2017). Clinical and echocardiographic data were analyzed at baseline, early (1.8±0.8 years) and late (4.7±0.8 years) follow-up after CRT.

Results

Fifty-four ACHD patients (median age 46 years, range 18–73 years, 74% male) had CRT (biventricular paced >90%) and were followed for 5.7±3.0 years. Thirty-nine (72%) patients had a systemic left ventricle (LV). Underlying cardiac anatomy included left ventricular outflow tract lesions (n=17; 32%), tetralogy of Fallot (n=11; 20%), right ventricular outflow tract lesions (n=5; 9%), atrioventricular septal defects (n=5; 9%) and atrial septal defect with right aortic arch (n=1; 2%). Fifteen (28%) patients had a systemic right ventricle (RV): 13 (24%) with congenitally corrected transposition of great arteries, and 2 (4%) with transposition of the great arteries after Mustard repair.

Compared to baseline, CRT was associated with significant improvement at early follow-up in NYHA functional class, QRS duration, cardiothoracic ratio, left and right atrial volume index (P<0.05 for all) in the overall population; improvement in NYHA class was sustained at late follow-up. Amongst patients with a systemic LV, there was significant increase in LV ejection fraction and reduction in LV end-systolic volume at early and late follow up (P<0.05 for both). There is trend in improvement of RV fractional area change in the patients with a systemic RV but not met statistical significance (P=0.070). Findings were summarized in Figure 1.

Eleven patients died and 2 had heart transplantation unrelated to systemic ventricular morphology. Thirty-five (65%) patients responded positively to CRT but only baseline QRS duration was a predictor of the positive response.

Conclusion

CRT results in sustained improvement in functional class, systemic LV size and function. QRS duration but not QRS morphology was a predictor of the positive response seen at early follow-up in 2/3 of ACHD patients.
2406Role of implantation access on complication rates in pacemaker implantation
Authors: Droth K , El-Armouche A , Andresen D , Bestehorn K P
Published: October 2019

Introduction

The implantation access (IA) either via vena cephalica (VC) or vena subclavia (VS) is the usual procedure in pacemaker implantation (PI). Valid data on head-to head comparisons between access via CV and VS regarding serious complications are missing.

Purpose

We analyzed potential associations between the type of implantation access and complication rates in a real world data set with 69.957 cases.

Methods

The 2013 dataset of the German Federal Council, containing information about all 1st pacemaker implantations for Germanywas analyzed. First two cohorts of patients treated via CV or CS access were compared for all relevant variables through descriptive statistics. Secondly all patient-clusters with exactly the same risk-/condition-vector were identified based on the following variables: age, sex, ASA classification (ASA 1–ASA 5), leading symptom, indication for implantation, etiology, ejection fraction (EF), estimated need of stimulation, and all possible 1:1 exact matchings were compared.

Results

Out of the total cohort of 69,957 patients (mean age 76.2 years, 43.3% females, VC access 36%, VS access 64%) 19,643 pairs with identical profile of all factors contained in the database could be identified. These pairs of all 1:1 matchings had following profile: age 77.07 years, ASA 1 to 4 6.3%, 2 45.0%, 46.9%, 4 1.7%, leading symptoms (dizziness 51.9%, singular cardiac syncope 10.3%, recurring syncope 28,7%), pacemaker indication (AV-Block II/III 11.6%/26.3%, sick sinus syndrome 39,8%, bradycardia in atrial fibrillation 20.0%), unknown etiology 90.3%, estimated need of stimulation (permanent (>90%) 20.9%, frequent (5–90%) 70.2%, rare (<5%) 8.9%), EF (≤35%: 0.4%: 35, 50%: 9.1%, >50%: 79.9%, unknown: 10.5%).

Intra- and post-procedural complication [C] rates different between VC and VS are: at least one C: 2.6% (VC), 3.0% (VS) p=0.018; surgical C with need for intervention (haematothorax, pericardial effusion, pouch hematoma): 0.5% (VC), 1.0% (VS) p=0.005; asystole: 0.1% (VC), 0.2% (VS) p=0.047; pneumothorax: 0.1% (VC), 0.7% (VC) p<0.001; dislocated atrial lead: 0.8% (VC), 0.6% (VS) p=0.027. Intra-hospital mortality was 1.0% (VC), 1.1% (VS) p=0.521.

Conclusion

Our analysis of a large-scale database shows that in patients with first pacemaker implantation the overall rate of complications is relatively low. But even after adjustment for available risk factors there are differences between the access routes: whereas VS access route is associated with statistically significant higher risk of overall complications, i.e. surgical complications, asystole, pneumothorax the VC access has a greater risk of dislocated atrial lead. In view of the two times higher rate of implantations via VS (64 vs. 36%) the clinical implications should be considered when choosing the access route and the VC access should be preferred.

Acknowledgement/Funding

None
2421Immunosuppressive therapy and prognosis in biopsy-proven fulminant lymphocytic myocarditis requiring veno-arterial extracorporeal membranous oxygenation support
Authors: Okumura T , Sawamura A , Kondo T , Ito M , Ozaki Y , Ohte N , Amano T , Murohara T
Published: October 2019

Background

Fulminant myocarditis is one of the fatal diseases for which effective management has not yet been established. Immunosuppressive therapy (IST) using corticosteroid has been actively applied to giant cell or eosinophilic myocarditis, there is no consensus on the efficacy of lymphocytic myocarditis, which is suspected of involving viral infection. Actually, IST for lymphocytic myocarditis is not recommended in the European Society of Cardiology guidelines, but in the Japanese Circulation Society guidelines, it is approved for use in refractory cases in the absence of curative therapy for myocarditis established.

Purpose

The purpose of this study was to explore the potential efficacy of immunosuppressive therapy on acute phase in fulminant lymphocytic myocarditis (FLM) requiring veno-arterial extracorporeal membranous oxygenation (VA-ECMO) support.

Method

We conducted CHANGE-PUMP study that was retrospectively enrolled 99 patients with fulminant myocarditis required VA-ECMO support in the Tokai area (central part of Japan) for the past 20 years. Lymphocytic myocarditis was defined by pathological category. Patients were divided into two groups depending on whether IST using corticosteroid was performed in the clinical course. Results: Sixty-six patients were pathologically diagnosed as fulminant myocarditis by endomyocardial biopsy, of which only 49 patients were FLM. IST were indicated in 8 (16%) out of 49 patients of FLM (IST group; n=8, non-IST group; n=41). Kaplan-Meier survival analysis showed a lower survival rate in the IST group than in the non-IST group (p=0.073). However, in all cases, based on our guidelines, IST was initiated after becoming refractory to MCS treatment.

Immunosupressive therapy and prognosis

Conclusion

In the retrospective analysis, biopsy-proven FLM patients with IST required VA-ECMO support had low survival rates. However, the timing of IST introduction was late and concerned. In the present era when advanced mechanical support appears and the survival rate of fulminant myocarditis is expected to improve, a multicenter prospective study is needed to establish an indication of IST in the acute phase of fulminant myocarditis.
2423Familial cardiomyopathy in patients affected by acute myocarditis is strongly associated to DSP gene mutations
Authors: Marteau L , Kyndt F , Toquet C , Serfaty J M , Guijarro D , Le Gloan L , Lande G , Gourraud J B , Warin Fresse K , Conan E , Thollet A , Le Tourneau T , Trochu J N , Probst V , Piriou N
Published: October 2019

Background

The link between acute myocarditis (AM) and familial cardiomyopathy remains unclear.

Purpose

To assess the clinical significance of AM in families with cardiomyopathy.

Methods and results

We describe the pedigree of 6 families with at least one familial case of AM and a familial history of cardiomyopathy or sudden death (SD). AM was defined as an infarct-like clinical presentation with normal coronary arteries and myocardial inflammation (MI) documented by cardiac magnetic resonance (CMR), or as an autopsy proven AM. Detailed familial pedigrees are shown in the picture. In family 1 to 5, genetic testing was triggered by the association of a documented case of AM with an index case of cardiomyopathy or early SD. In this setting, all genetic testing revealed a mutation in the desmoplakin (DSP) gene. In family 1, patient II.1 (15 y.o) was diagnosed with AM, 6 months after his sister died suddenly at the age of 12. In family 2, patient II.4 (17 y.o) was diagnosed with AM. His mother had a DCM, with a CMR revealing the presence of MI. In family 3, patient IV.3 (22 y.o) died suddenly from an AM, attested by post-mortem autopsy. Her aunt had a DCM. In family 4, patient II.4 (41 y.o) had an AM, progressing toward a DCM. Her mother had died suddenly at the age of 39, and her niece had a DCM. In family 5, patient V.16 (9 y.o) presented 4 recurrent episodes of AM. Her cousin's mother had a DCM. In family 6, patient IV.3 had 3 episodes of AM, his father had previously been diagnosed with an arrythmogenic right ventricular cardiomyopathy (ARVC) with a desmoglein 2 (DSG2) mutation. Table shows detailed genotype-phenotype relationship in all mutation carriers screened in the 6 families.

Phenotypes observed in mutation carriers Mutation DCM ARVC AM Isolated LGE (no cardiomyopathy, no AM) Family 1 (n=3) DSP 0 0 1 1 Family 2 (n=3) DSP 1 0 1 0 Family 3 (n=11) DSP 5 0 1 0 Family 4 (n=3) DSP 2 0 1 0 Family 5 (n=7) DSP 2 0 1 3 Family 6 (n=5) DSG2 0 1 1 1

Family Pedigrees

Conclusion

AM is strongly associated to desmosomal mutations when a familial history of cardiomyopathy is present, particularly in DSP gene. In these families, DCM phenotype and SD are frequent, and a notable proportion of isolated LGE suggestive of myocardial fibrosis is present in asymptomatic relatives. These results highlight the need for a comprehensive familial screening in case of AM.
P1223Attributable risk proportion of uncontrolled low-density lipoprotein cholesterol in recurrent acute coronary syndromes
Authors: Cordero A , Rodriguez Manero M , Bertomeu Gonzalez V , Agra Bermejo R , Garcia Acuna J M , Moreno Arribas J , Moreno M J , Alvarez B , Martinez Rey-Ranal E , Bertomeu Martinez V , Gonzalez-Juanatey J R
Published: October 2019

Background

Coronary heart disease is chronic condition that usually has recurrent events. Risk factors for incident coronary heart disease are well known conditions related to recurrences have not been clearly outlined. Attributable risk proportion (ARP) refers to the proportion of incident cases in subjects exposed to risk factors that are attributable to that risk factor so we analysed ARP in wide cohort of patients admitted for an acute coronary syndrome (ACS).

Methods

Cross-sectional analysis of all patients admitted in two hospitals between January 2006 and December 2016. ARP was calculated by the equation: prevalence in exposed – (prevalence in exposed/odds ratio). LDL uncontrolled was codified as >70 mg/dl in patients with previous cardiovascular disease; >100 mg/dl in patients with diabetes without previous cardiovascular disease or; >155 mg/dl in patients without cardiovascular disease.

Results

We included 7,518 patients, mean age 66.9 (12.9) years, 72.5% males, median GRACE score 143.2 (40.3) and 35.3% STEMI. Previous coronary heart disease total was present in 2,032 (23.2%) patients and they had statistically higher mean age (70.6±11.11 vs. 65.8±13.3), prevalence of diabetes (37.9% vs. 25.3%) and hypertension (72.9% vs. 53.3%) and lower smoking habit (15.5% vs. 30.9%). LDLc was lower in patients with previous coronary heart disease (90.3±33.8 vs. 111.7±38.1; p<0.01), as well as HDLc (33.5±14.29 vs. 35.9±35.5; p<0.01) and haemoglobin (13.5±3.7 vs. 14.0±2.4; p<0.01). Uncontrolled LDLc was present in 83.4% of the patients with previous coronary heart disease, in contrast to the 28.7% of patients without previous coronary heart disease; this resulted in an ARP of 13.8%. The ARP for diabetes and hypertension were 1.6% and 1.4%, respectively.

Conclusions

The proportion of attributable risk of uncontrolled LDL on recurrent ACS is 13.8% and, therefore, 1 out of every 7 recurrent ACS could be prevented by an accurate LDLc control.
P1227Remnant lipoprotein is a residual risk of future cardiovascular events in patients with stable coronary artery disease and on statin LDL-cholesterol levels less than 70 mg/dl
Authors: Fujihara Y , Nakamura T , Horikoshi T , Obata J E , Fujioka D , Watanabe Y , Watanabe K , Kugiyama K
Published: October 2019

Background

Recent guidelines recommend a target of low density lipoprotein cholesterol (LDL-C) <70 mg/dL in patients at very high risk of cardiovascular disease (CVD). However, a considerable residual risk of CVD persists despite achievement of the LDL-C goal on statin treatment.

Purpose

This study examined the predictive value of remnant lipoprotein levels for cardiovascular events (CVE) in patients with stable coronary artery disease (CAD) and LDL-C levels <70 mg/dL on statin treatment.

Methods

Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method in 247 consecutive patients with CAD who had on-statin LDL-C levels <70 mg/dL. All the patients were followed prospectively for a period of ≤60 months or until the occurrence of the primary composite endpoint of cardiac death, nonfatal myocardial infarction, unstable angina requiring coronary revascularization, worsening heart failure, peripheral artery diseases requiring endovascular or surgical intervention, aortic events, and ischemic stroke.

Results

During a mean follow-up period of 38 months, 33 CVEs occurred. Kaplan-Meier estimates in time-to-first-event analysis demonstrated that higher RLP-C levels (>3.9 mg/dL, determined by ROC-curve) resulted in a significantly higher probability for the primary endpoint than did lower RLP-C levels (<3.9 mg/dL) (p<0.01 by log-rank test). Stepwise multivariate Cox proportional hazard analysis showed that RLP-C was a significant predictor of the primary endpoint after adjustment for known risk factors and lipid variables including triglycerides (TG), and total apolipoprotein B (ApoB) (HR 1.62, 95% CI 1.26–2.07, p<0.01). The c-statistics showed that addition of RLP-C had a significant incremental effect on the predictive value of traditional risk factors (area under curve; traditional risk factors: 0.68 vs. traditional risk factors + RLP-C: 0.77, p=0.02). Category-free NRI and IDI demonstrated the additive value of RLP-C to the traditional risk factors plus non-high-density lipoprotein (HDL)-C and ApoB levels (NRI 0.52, p<0.01; IDI 0.06, p<0.01).

Conclusions

RLP-C levels are a residual risk factor for future CVEs in patients with CAD and on-statin LDL-C <70 mg/dL.
P1250Validation of quantitative flow reserve and residual quantitative flow reserve to predict fractional flow reserve post stenting from the DOCTORS study population
Authors: Guillon B G , Rubimbura V R , Fournier S F , Amabile N A , Chi Pan C C P , Combaret N C , Eeckhout E E , Silvain J S , Wijns W , Schiele F , Muller O , Meneveau N , Adjedj J
Published: October 2019

Background

Quantitative flow reserve (QFR) is a computation of fractional flow reserve (FFR) based on angiography without use of a pressure wire. The ability to predict post-PCI FFR using residual QFR after virtual stenting (pre-PCI), and using QFR (post-PCI) remains unknown. We sought to evaluate the correlation and diagnosis accuracy of residual QFR and post-PCI QFR to predict post-PCI FFR.

Methods

From the DOCTORS (Does Optical Coherence Tomography Optimize Results of Stenting) study population, we blindly analyzed the following from angiography, and compared them to post-PCI FFR: pre-PCI residual contrast QFR (cQFR) and fixed QFR (fQFR), and post-PCI cQFR and fQFR.

Results

93 post-PCI QFR measurements and 84 residual QFR measurements were compared to post-PCI FFR measurements in 93 patients. Compared to the post-PCI FFR mean value of 0.92±0.05, mean values of residual cQFR, residual fQFR, post-PCI cQFR and post-PCI fQFR were, respectively: 0.94±0.05, 0.93±0.05, 0.93±0.06 and 0.93±0.05 (p values >0.05 for all pairs except for residual cQFR versus FFR (p=0.01)). Pearson correlation coefficients of residual cQFR, residual fQFR, post-PCI cQFR and post-PCI fQFR compared with post-PCI FFR were, respectively: 0.62, (95% CI: 0.46–0.73); 0.61, (95% CI: 0.45–0.73); 0.75, (95% CI: 0.64–0.83) and 0.73, (95% CI: 0.62–0.81). Area under the curves for these indices with a post-PCI FFR cutoff value of 0.90 were, respectively: 0.79, 0.78, 0.85 and 0.84.

Conclusions

cQFR and fQFR correlated well and had similar diagnostic performance. Pre-PCI QFR analysis with virtual PCI, and post-PCI QFR analysis, correlated well with post-PCI FFR, and had similar diagnostic accuracy. Further studies are needed to prospectively validate a QFR-guided PCI strategy.
P1253Long-term risk stratification of patients undergoing coronary angiography according to the TIMI risk score for secondary prevention
Authors: Zafrir B , Adawi S , Khalaily M , Jaffe R , Eitan A , Saliba W
Published: October 2019

Background

A risk score for secondary prevention after myocardial infarction (TRS2P) was recently developed from the TRA2°P-TIMI50 trial based on 9 established clinical factors [age≥75, hypertension, diabetes, smoking, kidney dysfunction, peripheral artery disease, heart failure, prior stroke and prior coronary artery-bypass surgery (CABG)], classifying the risk for major adverse cardiovascular events (MACE). We aimed to evaluate the performance of TRS2P for predicting long-term outcomes in real-world patients presenting for coronary angiography.

Methods

Retrospective analysis of 13,593 patients that were referred to angiography for the assessment or treatment of coronary artery disease between 2000–2015 in a single center. Risk stratification for 10-year MACE (myocardial infarction, ischemic stroke or all-cause death) was performed using the TRS2P score, divided into 6 categories (0 to ≥5 points), and in relation to the presenting coronary syndrome.

Results

All clinical variables, except of prior CABG, were independent risk predictors. The annualized incidence rate of MACE increased in a graded manner with increasing TRS2P score, ranging from 1.65 to 16.6 per 100 person-years (ptrend<0.001). The pattern was similar for 10-year cumulative incidence of MACE. Compared to the lowest-risk group (risk indicators=0), the hazard-ratios (95% confidence interval) for MACE were 1.60 (1.36–1.89), 2.58 (2.21–3.02), 4.31 (3.69–5.05), 6.43 (5.47–7.56) and 10.03 (8.52–11.81), in those with 1,2,3,4 and ≥5 risk indicators, respectively. Risk gradation was consistent across the individual clinical endpoints. TRS2P score showed reasonable discrimination with c-statistics of 0.704 for MACE and 0.735 for mortality. The graded relationship between the risk score and event rates was observed in both patients presenting with acute and non-acute coronary syndromes.

Cumulative 10-year incidence of MACE

Conclusions

The use of TRS2P, a simple risk score based on routinely collected variables, enables risk stratification in patients undergoing coronary angiography. Its predictive value was demonstrated in real-world setting with long-term follow-up, and irrespective of the acuity of coronary presentation.

Acknowledgement/Funding

None
P1453Safe multidisciplinary management of new therapies: the ritmo project (real time continuous web monitoring)
Authors: Lupi L , Glisenti F , Castiello C , Bonelli A , Arabia G , Papa I , Piazzani M , Fioretti F , Gheza M , Guerini V , Nodari S
Published: October 2019

Background

Fingolimod is an immunosuppressive drug that prevents the typical autoimmune responses of multiple sclerosis (MS). This drug can cause, even after the first dose, bradycardia and atrioventricular conduction block (AVB). According to a decree of the Committee for Medicinal Products for Human Use (CHMP), the first administration of a dose of fingolimod must meet the following conditions: a) 12-lead electrocardiogram (ECG) and blood pressure (BP) evaluations before first dose administration; b) continuous ECG and BP monitoring every hour during the first 6 hours of treatment. The aim of the study was to evaluate the efficacy of our virtual Intensive Care Unit connected to selected Departments of Neurology for cardiology monitoring via web, during the first dose administration of fingolimod in patients with MS.

Methods

Health Telematic Network, in collaboration with our Cardiology Department, has installed in several Neurology Departments in the country intensive care equipment with real time monitoring via the web of ECG, BP and oximetry. The telemonitoring system is composed of an IntelliVue MP2 monitor, for 12-lead ECG recording, and by an IntelliVue Philips M3150 Central, for continuous remote monitoring of ECG and the detection and storage of arrhythmias. The HTN Cardiologist thus can evaluate in real time ECG monitored and each alarm detected.

Results

From Jan 2014 to Dec 2018, 172 sites participated and 6041 patients were enrolled. The telemonitoring system recognized 5116 episodes of bradycardia, 297 first degree AVB, 213 second degree AVB Mobitz I, 48 second degree AVB Mobitz II, 618 pathological lengthening of the QTc interval, single monomorphic ventricular ectopic beats in 266 patients, bigeminy ventricular extrasystoles in 15 patients and polymorphic ventricular extrasystoles in 3 cases. 6 cases of nonsustained ventricular tachycardia occurred and were recognized.

Conclusion

This web-based real time telemonitoring project was an optimal solution for the administration of the first dose of fingolimod, according to current indications of the CHMP. The RITMO project could lead the way for the use of a multidisciplinary approach for the management of new therapies.