bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5683Incremental hazard associated with the degree of advanced intaratrial block in cardiac resynchronization therapy treated heart failure patients
Authors: Jacobsson J K D , Reitan C , Borgquist R , Carlson J , Platonov P P 
Published: October 2019

Abstract

Background
Advanced Inter Atrial Block (aIAB) reflects a disruption of the electrical signal between the atria and develops gradually. It has been predictive of atrial fibrillation and death in patients with Cardiac Resynchronization Therapy (CRT). A higher number of inferior ECG leads demonstrating biphasic P waves was proposed as a measure of aIAB severity, however its prognostic importance has not been proven.

Purpose
To assess if aIAB is associated with poor prognosis in CRT recipients and to see if there is a dose-response relationship between the aIAB severity and the outcome.

Methods
CRT recipients with sinus rhythm on digitally stored preoperative ECG were included (n=565, median age 70 years, 82% male, 55% ischemic heart failure [HF] etiology, 54% CRT-P, 70% left bundle branch block [LBBB]). Automated analysis of P-wave duration [PWD] and morphology in leads II, aVF and III assessed as positive, negative or biphasic +/− was performed and patients classified as having either No IAB (PWD <120ms), Partial IAB (pIAB, PWD ≥120 ms, positive P-waves in inferior leads), aIAB (PWD ≥120 ms and biphasic p-waves in one of the inferior leads). aIAB patients were further stratified by the presence of biphasic P waves in only one (aIAB-1) or more (aIAB-2) inferior leads. Extreme aIAB was defined as biphasic P waves in lead II and negative in leads III and aVF. Cox regression analyses adjusted for age, gender, NYHA class, ischemic HF etiology, left ventricular ejection fraction, LBBB, CRT-P versus CRT-D and PWD were performed to assess the impact of aIAB and its types on the endpoint hospitalization for HF or death at 5 years of follow up.

Results
Advanced IAB was observed in 65 patients (10 with aIAB-1, 53 with aIAB-2 and 2 with extreme aIAB) and pIAB in 151. No clinically relevant significant differences in baseline characteristics were observed between groups. Compared to the NoIAB group, aIAB-2 and extreme aIAB independently predicted the combined endpoint with adjusted HR=1.82 (95% CI 1.14–2.90, p-value 0.012) and HR=4.70 (95% CI 1.10–20.16, p-value 0.037), respectively.

Conclusion
Advanced IAB is associated with HF admissions or death from any cause in HF patients treated with CRT. Our findings indicate dose-response relationship between the severity of aIAB and the outcome.
P5687CRT-D device replacement strategy according to previous ventricular tachycardia events: Preliminary Results of the BioCONTINUE Study
Authors: Gras D , Ploux M D , Babuty M D , Guyomar M D , Bongiorni M D , Blangy M D 
Published: October 2019

Abstract

Background
The need for ICD back-up may be questionable in candidates for CRT-D device replacement, who no longer meet ICD criteria due to an improved left ventricular ejection fraction (LVEF) and/or an event-free CRT-D service life.

Purpose
To evaluate the clinical relevance of ICD back-up after CRT-D device replacement in patients with primary prevention ICD indication and to investigate factors predictive of ventricular arrhythmic events (VAE).

Methods
BioCONTINUE is an observational, multicentre, prospective and international trial. Patients were enrolled after CRT-D replacement and are currently followed up to a minimum of 2 years. We investigated the rate of patients with at least 1 sustained VAE, as defined by ventricular tachycardia >30s and/or ventricular arrhythmic event treated either by ATP or shock. Predictive factors of VAE were evaluated using univariate analyses based on demographics and clinical variables observed at enrolment, followed by a multivariate analysis. These multivariate analyses were adjusted confusion demographic or clinical covariates emerging at a p<0.2 level of significance by single variable analysis.

Results
A total of 276 patients are enrolled (70±10 years, 77% men, mean LVEF 40.6±12.6%, 23.6% secondary ICD indication). The mean FU duration at the interim analysis is 19.8±8.7 months, including 98 patients (35.5%) with a 2-year FU. The rate of patients free of VAE, is 91.2%, 88.4% and 85.1% respectively at 1, 2 and 3 years of FU. In patients with persistent ICD indication at enrolment (defined by LVEF <40% and/or previous VAE), the risk of VAE after device replacement is 3.3 times higher (95% CI: 1.4–8.2; p=0.007) than patients with no persistent ICD indication. The risk of VAE remains in patients with no persistent ICD indication, with a rate of 4.9% (95% CI 1.8%-10.4%). On multivariate analysis, age, ICD indication and ischemic heart disease, predicted VAE after the device replacement, with HR 0.96 (95% CI: 0.92–0.99; p=0.02), HR 3.01 (95% CI: 1.21–7.46; p=0.02) and HR 3.60 (95% CI: 1.54–8.42; p=0.003) respectively.

Conclusions
The interim results of the BioCONTINUE trial show a persistent risk of VAE after CRT-D device replacement, both in patients with and without persistent ICD indication. The risk of VAE is dependent on age, ICD indication and ischemic heart disease.

Acknowledgement/Funding
Supported by Biotronik
P5693Critical sites for scar-related ventricular tachycardias treatment: an approach based on sinus rhythm late activation zones
Authors: Xavier Fontes A , Oliveira A F , Matos D , Rodrigues G , Carmo J , Carvalho M S , Santos I , Carmo P , Cavaco D , Morgado F , Adragao P 
Published: October 2019

Abstract

Introduction
Despite advances in antiarrhythmic and device therapy, ventricular tachycardia (VT) is a major cause of increased morbidity and mortality. During scar-mediated monomorphic VT ablation, the search for critical isthmus sites continues to be the primary goal during successful ablative procedures. However, catheter ablation based on conventional mapping techniques is associated with low success rates and is limited to patients with stable VT.

Objective
The aim of the study was to evaluate, in patients with history of VT, the success of a strategy based on substrate mapping and ablation during sinus rhythm.

Methods
Retrospective single center analysis of patients undergoing VT ablation from November 2015 to November 2017. Clinical profiles and procedural details were determined. We used high-density structural map to identify voltage abnormalities as well a functional map of sinus rhythm activation to identify the regions of late potentials. Radiofrequency applications were performed in the areas with the latest activation. Recurrence of VT was considered the end-points of the follow-up.

Results
A total of 22 patients were included in the analysis, 95% male, with an median age of 65,5 (57–71) years old. The majority of the patients (18) with ischemic cardiomyopathy, 3 with nonischemic cardiomyopathy, and 1 with arrhythmogenic right ventricular cardiomyopathy were included. Epicardial mapping was performed in 27% of the cases. CARTO mapping system was used in 10 patients and Rhythmia in the remaining cases. Areas with the latest activation corresponded to regions of abnormal voltage in 21 patients. During a 26,5 (21,5–29,3) months of follow-up, the observed VT recurrence rate was 35%. 25% of the patients needed hospital admission due to arrhythmias and one patient died due to an arrhythmic cause. Treatment success was higher in epicardial approach (100% VS 50%, p=0,03). The location of the scar in the left ventricle was not a determinant of success (anterior-66,7% VS lateral/inferior-61,5%, p=0,806).

Conclusion
A substrate-based approach that targets regions of late activation within the scar seems attractive and may be a simple way to perform VT ablation with success. In our population, this strategy seams successful, especially in epicardial approach. Substrate modification strategies aiming to eradicate all potential reentrant circuits may be the most successful way to treat VT and avoid recurrences.
P5699Endocardial vs. epicardial ventricular tachycardia ablation: a propensity score matched analysis
Authors: Nascimento Matos D J , Cavaco D , Freitas P , Ferreira A M , Rodrigues G , Carmo J , Carvalho M S , Costa F , Carmo P , Morgado F , Mendes M , Adragao P 
Published: October 2019

Abstract

Introduction
Direct comparisons of long-term clinical outcomes of endocardial vs. epicardial catheter ablation techniques for drug-resistant ventricular tachycardia (VT) have been scarcely reported.
We aim to compare the long-term efficacy and safety of endocardial vs. epicardial catheter ablation (END-ABL and EPI-ABL, respectively) in a propensity score (PS) matched population.

Methods
Single-center observational registry including 215 consecutive patients who underwent END-ABL (181) or EPI-ABL (n=34) for drug-resistant VT between January 2007 and June 2018. Efficacy endpoint was defined as VT-free survival after catheter ablation, while safety outcomes were defined by 30-days mortality and procedure-related complications. A propensity score was used to match patients in a 1:1 fashion according to the following variables: VT storm at presentation, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class III/IV at presentation, ischemic ethology, presence of implantable cardioverter-defibrillator (ICD), and previous endocardial catheter ablation. Independent predictors of VT recurrence were assessed by Cox regression.

Results
The PS yielded two groups of 31 patients each well matched for baseline characteristics (Table 1). Over a median follow-up of 2 years (IQR 1–3), 58% (n=18) ENDO-ABL patients had VT recurrence vs. 26% (n=8) in the EPI-ABL group (P=0.020). The yearly rates of VT recurrence were 28%/year for END-ABL vs. 11%/year for EPI-ABL (P=0.021). Multivariate survival analysis identified previous endocardial ablation (HR= 3.52; 95% CI 1.17–10.54, p=0.026) and VT storm at presentation (HR=3.57; 95% CI 1.50–8.50, p=0.004) as independent predictors of VT recurrence. EPI-ABL was independently associated with fewer VT recurrences (HR=0.28; 95 CI 0.12–0.69, p=0.005), but only in patients with a previous endocardial ablation (p for interaction = 0.004) – Figure A.
No patients died at 30-days post-procedure. Hospital length of stay was similar between END-ABL and EPI-ABL (5 vs. 4 days respectively, p=0.139), as was the complication rate (6.5% vs. 12.9% respectively, p=0.390), although driven by different causes (Table 1).

Conclusion
VT storm at presentation and previous catheter ablation were independent predictors of VT recurrence. In patients with a previous failed endocardial catheter ablation, epicardial ablation seems to provide greater VT-free survival than repeat endocardial ablation. Both strategies seem equally safe.
P5701Impact of VT pleomorphism on the prognostic value of non-inducibility after catheter ablation in patients with non-ischemic cardiomyopathy
Authors: Kimura Y , Ebert M , Wijnmaalen A P , Trines S , De Riva Silva M , Zeppenfeld K 
Published: October 2019

Abstract

Background
In patients with non-ischemic cardiomyopathy (NICM), non-inducibility after catheter ablation has been associated with lower VT recurrence rates. We hypothesized that induced VT pleomorphism (PL-VT) may be indicative for a complex VT substrate that might be associated with poor ablation outcome independently of non-inducibility at the end of the procedure.

Methods
Consecutive patients with left-dominant NICM undergoing VT ablation (2008–2018) were included. All patients underwent genetic screening. PL-VT was defined as occurrence of ≥1 morphologically distinct QRS lasting for ≥6 consecutive beats during the same induced VT episode. Complete acute success was defined as non-inducibility of any VT at the end of procedure.

Results
Eighty-five patients (56±15 yrs, LVEF 38±12%), inducible for 365 VTs (median 3/patient, IQR 1–6) were included. PL-VT was observed in 29 patients (34%). Patients with PL-VT had more often anteroseptal substrates, a higher number of induced VTs, and larger endocardial bipolar (<1.5 mV) and unipolar low voltage (<8.01 mV) areas. Pathogenic genetic mutations were more frequently recognized in patients with PL-VT than in those without (59 vs. 34%, P=0.03), but there was no significant correlation in each representative mutation (Lamin A/C, Phospholamban, or Titin). Complete acute success was achieved in 34 patients (40%) and comparable between patients with PL-VT and those without (41 vs. 39%, P=0.85). After a median of 24 months, 53 patients (62%) had VT recurrence and 23 (27%) died. In multivariate Cox regression analysis, PL-VT and inducibility of any VT were significantly associated with VT recurrence (HR 4.07, CI 1.82–8.92; P=0.001, HR 2.22, CI 1.10–4.78; P=0.026, respectively) independent of NYHA, LVEF, electrical storm, genetic mutations, low voltage area, substrate location, and number of induced VTs. Of importance, the co-existence of PL-VT and persistent VT inducibility identified those at highest risk for VT recurrence after 2-years. (PL-VT (−)/complete success, 27%, PL-VT (−)/non-complete success, 50%, PL-VT (+)/complete success, 58%, PL-VT (+)/non-complete success 94%, Log-rank P<0.001, see figure).
Figure 1

Conclusions
Induced PL-VT was not associated with acute outcome but higher VT recurrence rate after catheter ablation in patients with NICM. Moreover, co-existence of PL-VT and persistent VT inducibility identifies patients at highest risk for VT recurrence whereas non-inducible patients without PL-VT have a favorable prognosis.
P5708Balancing risk and benefit in patients with atrial fibrillation: the GARFIELD-AF risk score
Authors: Fox K , Virdone S , Pieper K 
Published: October 2019

Abstract

Background
The GARFIELD-AF risk tool was originally developed to predict future risk of adverse events in patients with atrial fibrillation (AF) using a range of baseline clinical variables. In the present work a new, improved risk tool was developed using data from all five GARFIELD cohorts gathered over 2 years' follow-up.

Purpose
To derive a new integrated risk tool for predicting mortality, stroke/systemic embolism (SE), and major bleeding in AF patients up to 2 years after enrolment and compare the risk tool versus CHA2DS2-VASc and HAS-BLED.

Methods
GARFIELD-AF is an international prospective registry of nonvalvular AF patients diagnosed within 6 weeks prior to enrolment and having at least one risk factor for stroke. In this study only the first occurrence of events was considered. Event rates were estimated using a Poisson model. Potential predictors of events including a large set of demographics, clinical characteristics, choice of treatment, and lifestyle factors were identified, and a Cox proportional hazards model chosen for each outcome by least absolute shrinkage and selection operator (LASSO). Indices were compared versus models of CHA2DS2-VASc and HAS-BLED.

Results
Among a total 52,080 patients enrolled 52,032 (male, 55.8%; median age, 71 years) had available follow-up data. At 2 years, 3702 patients had died (event rate, 3.82 [95% CI, 3.70–3.95] per 100 patient-years) whereas non-haemorrhagic stroke/SE was noted in 957 patients (rate, 1.00 [95% CI, 0.94–1.06] per 100 patient-years) and major bleed/haemorrhagic stroke in 673 patients (rate, 0.70 [95% CI, 0.65–0.75] per 100 patient-years). The GARFIELD risk tool outperformed CHA2DS2-VASc and HAS-BLED at predicting all adverse events in the overall population and pre-selected subpopulations over 2 years. Notably, the new model identified use of OAC therapy, which is not included in CHA2DS2-VASc, as one of the strongest predictors of risk of mortality and stroke, and unlike HAS-BLED, could discriminate a lower risk of bleeding in patients treated with NOACs versus VKAs.
Population All-cause mortality Stroke/SE Major bleeding* GARFIELD CHA2DS2-VASc GARFIELD CHA2DS2-VASc GARFIELD CHA2DS2-VASc Overall 0.76 (0.75–0.76) 0.66 (0.65–0.67) 0.68 (0.67–0.70) 0.64 (0.62–0.66) – – AC treated 0.74 (0.73–0.75) 0.65 (0.64–0.66) 0.68 (0.66–0.70) 0.65 (0.62–0.67) 0.67 (0.64–0.69) 0.63 (0.61–0.65) *Model only considers AC-treated patients.

Conclusions
The GARFIELD-AF risk tool demonstrated good calibration and discrimination, outperforming CHA2DS2-VASc at predicting risk of death and non-haemorrhagic stroke and HAS-BLED for major bleed in AF patients over 2 years.

Acknowledgement/Funding
The GARFIELD-AF registry is funded by an unrestricted research grant from Bayer AG.
P5710Clinical applications of machine learning for prediction of incident atrial fibrillation from the general population: a nationwide cohort study
Authors: Kim I.-S , Yang P S , Yu H T , Kim T H , Uhm J S , Pak H N , Lee M H , Kim J Y , Joung B 
Published: October 2019

Abstract

Background
To evaluate the ability of machine learning algorithms to predict incident atrial fibrillation (AF) from the general population using health examination items.

Methods
We included 483,343 subjects who received national health examinations from the Korean National Health Insurance Service-based National Sample Cohort (NHIS-NSC). We trained deep neural network model (DNN) of a deep learning system and decision tree model (DT) of a machine learning system using clinical variables and health examination items (including age, sex, body mass index, history of heart failure, hypertension or diabetes, baseline creatinine, and smoking and alcohol intake habits) to predict incident AF using a training dataset of 341,771 subjects constructed from the NHIS-NSC database. The DNN and DT were validated using an independent test dataset of 141,572 remaining subjects. C-indices of DNN and DT for prediction of incident AF were compared with that of conventional logistic regression model.

Results
During 1,874,789 person·years (mean±standard-deviation age 47.7±14.4 years, 49.6% male), 3,282 subjects with incident AF were observed. In the validation dataset, 1,139 subjects with incident AF were observed. The c-indices of the DNN and DT for incident AF prediction were 0.828 [0.819–0.836] and 0.835 [0.825–0.844], and were significantly higher (p<0.01) than conventional logistic regression model (c-index=0.789 [0.784–0.794]).

Conclusions
Application of machine learning using simple clinical variables and health examination items was helpful to predict incident AF in the general population. Prospective study is warranted to construct an individualized precision medicine.
P5717Risk of QTC interval prolongation among cancer patients treated with tyrosine kinase inhibitors
Authors: Abu Rmilah A , Lin G , Hermann J 
Published: October 2019

Abstract

Objective
QTc interval prolongation can lead to life-threatening complications such as torsade de pointes (TdP), ventricular tachycardia (VT), and sudden cardiac death (SCD). It can occur with various tyrosine kinase inhibitors (TKIs) but comparative analyses on the incidence and complication rates are scarce. We thus conducted a comprehensive analysis of TKI use and QTc prolongation in clinical practice.

Methods
We retrospectively reviewed the electronic medical records of all cancer patients who were treated with TKI between 01/2005 and 12/2018 at our institution. QTc prolongation was defined as a QTc ≥450 ms or 460 ms among male or female patients, respectively. For each type of TKIs, we determined the administration rate and incidence of QTc interval prolongation. We also studied the frequency of QTc prolongation ≥500 ms, the rate of increase of the QTc interval by ≥60 ms, and the development of complications (VT, TdP, and SCD).

Results
In the present study, we analyzed the data of 685 cancer patients (431 male and 254 female), including 299 patients with RCC, 188 with chronic leukemia, 55 with acute leukemia, 65 with thyroid cancer, 48 with lung cancer and 39 with GIST. These patients received 902 TKI administrations and QTc prolongation was reported in 1/3 of these (289 administrations). The highest frequency was seen with imatinib, nilotinib, and dasatinib (30, 40 and 50%). Among cases of QTc prolongation, a QTc interval ≥500 ms was documented in 53 (18.3%) and QTc progression ≥60 ms in 72 (25%). Complications were found in 14 cases (5%) including VT in 9, TdP in 2 and SCD in 3 administrations. Table 1 demonstrates the findings for each TKI.
Findings for TKIs in all patients Total Prolonged QTc QTc ≥500 QTc progression ≥60 VT SCD TdP Imatinib 165 54 13 10 2 Nilotinib 75 33 8 19 Dasatinib 115 58 10 16 2 1 Sunitinib 134 31 1 2 1 1 Pazopanib 165 36 5 6 2 1 Others 248 77 16 18 2 1 1

Conclusion
The current findings suggest that TKI therapy leads to QTc prolongation in 1/3 of patients on average and most commonly with the Bcr-Abl TKIs, imatinib, nilotinib, and dasatinib. While SCD is rare (1%) it can still evolve and in 5% of all QTc prolongations with TKIs are potentially life-threatening. These data support recommendations for serial ECGs in cancer patients undergoing TKI therapy.

Acknowledgement/Funding
None
P5722Thermodynamic phenotypes guide the pathogenicity assessment of a variant of uncertain significance in cardiac myosin binding protein C
Authors: Pricolo M R , Herrero-Galan E , Mazzaccara C , Losi M A , Alegre-Cebollada J , Frisso G 
Published: October 2019

Abstract

In the era of Next Generation Sequencing (NGS), genetic testing for inherited disorders identifies an ever-increasing number of variants, whose pathogenicity remains unclear. These variants of uncertain significant (VUS) limit the reach of genetic testing in clinical practice. The VUS for Hypertrophic Cardiomyopathy (HCM), the most common familial heart disease, constitute over 60% of entries for missense variants shown in ClinVar database.
We have proposed a workflow to determine pathogenicity of VUS, which integrates bioinformatics evaluation and functional studies of RNA splicing and protein thermodynamic stability. This workflow was applied on a novel VUS in MYBPC3 gene, coding for cardiac myosin-binding protein C (cMyBP-C), which is the most mutated gene in HCM. The c.1809T>G-p.I603M variant was identified during genetic screening of patient clinically affected by HCM and it was classified as VUS applying ACMG criteria.
In silico prediction and mRNA analysis of c.1809T>G-p.I603M variant indicated no alteration of RNA splicing (Figure 1). At protein level, the p.I603M mutation maps to the C4 domain of cMyBP-C. The homology modelling of domain C4 shows I603 to be buried in the protein structure, suggesting a potential destabilising role of this mutant. The Circular Dichroism (CD) confirms that the I603M variant does not perturb much the structure of domain, according to the far-UV and near-UV CD spectra. However, the thermodynamic stability of domain C4 is severely compromised, as shown by lower Tm and van't Hoff enthalpy (ΔHv) in thermal denaturation experiments by CD and Differential Scanning Calorimetry (DSC) (Figure 1). Furthermore, the Gibbs free energy change (ΔG) at 25°C of the unfolding process was also calculated from the DSC thermograms. The resulting ΔΔG of C4 I603M (4.5 kcal/mol) is comparable to other pathogenetic variants in other MYBPC3 domains. Taking into account our results, we propose reclassification of variant p.I603M as likely pathogenic.
Figure 1. Workflow
In conclusion, our strategy is useful to refine the assignment of pathogenicity in the absence of enough genetic support, improving the clinical management of HCM patients and their families.

Acknowledgement/Funding
MCNU: BIO2014-54768-P, BIO2017-83640-P (AEI/FEDER, UE), RYC-2014-16604, SEV-2015-0505- ISCIII: CB16/11/00425. Comunidad de Madrid: PEJ16/MED/TL-1593.