bluuebunny/crossref_metadata_2025 huggingface dataset:
P5628Resolution of incomplete stent apposition in the early phase after stent implantation: serial optical coherence tomography analyses at 2-week and 4-month
Authors: Shimoda M , Ando H , Takashima H , Waseda K , Sakurai S , Suzuki A , Sawada H , Fujimoto M , Ohashi H , Amano T
Published: October 2019

Background

Previous optical coherence tomography (OCT) study demonstrated that the incomplete stent apposition (ISA) distance <355 μm immediately after an index procedure was the corresponding cut-off point for predicting the resolution of ISA at 8–12 months follow-up in the second-generation DES. However, the natural course of acute ISA in the earlier phase remains unknown. The aim of the present study is to evaluate the natural course of acute ISA in the early phase after second-generation everolimus-eluting stent (EES) using serial OCT analyses at 2-week and 4-month.

Methods

From the population of the ACS-OCT trial, we identified a total of 45 patients who successfully underwent serial OCT examinations at post-stenting, 2-week follow-up, and 4-month follow-up. The presence of ISA was assessed in the OCT images, and ISA distance was measured within the stented segment. The target site for OCT analysis was the cross-section at the proximal edge of implanted stent. Serial OCT images at post-stenting, 2-week follow-up and 4-month follow-up were reviewed side by side on the screen, and maximum ISA distance and cross-sectional ISA area were measured.

Results

Incomplete stent apposition was observed in all EES at post-stenting, and it was persistent in 37.8% at 2-week follow-up and 11.1% at 4-month follow-up. Maximum ISA distance was significantly decreased over time (post-stenting, 144±150mm; 2-week follow-up, 88±146mm; 4-month follow-up, 34±111mm). Receiver-operating curve analysis identified that the best cut-off value of OCT-estimated ISA distance at post-stenting for predicting persistent ISA at 2-week follow-up and 4-month follow-up was >140μm and >215μm, respectively.

ROC curve analysis

Conclusion

ISA distance at post-stenting is an useful predictor for the resolution of ISA in the early phase after EES implantation.
P5641Impact of lethal arrhythmias on medical castration in patients with prostate cancer
Authors: Hasegawa K , Miyazaki S , Kaseno K , Hisazaki K , Ito H , Uzui H , Tada H
Published: October 2019

Background

Prostate cancer is the most common non-cutaneous malignancy in men and has been steadily rising in an aging society. Medical castration had been widely applied as a treatment for prostate cancer. Sex steroid hormones regulate cardiac ion channels. However, the proarrhythmic properties of medical castration have not been reported.

Methods

This prospective observational study consisted of 149 patients (75±6 years) who underwent hormonal therapy using gonadotropin-releasing hormone with or without anti-androgen for prostate cancer. The changes of electrocardiogram (ECG) findings during the therapy and the associations of ECG findings with lethal arrhythmias were studied.

Results

QT (394±32 to 406±39 ms, p<0.001) and QTc intervals (416±27 to 439±31 ms, p<0.001) significantly prolonged during the therapy as compared to baseline. Heart rate significantly increased during the therapy as compared to baseline (68±11 to 71±14 / min, p=0.006). PQ interval and QRS duration were similar before and during the therapy. During the hormonal therapy, 2 patients (1.3%) presented with torsades de pointes and ventricular fibrillation. The first patient was 71 year-old and the second patient was 70 year-old. The period of the therapy was 6 and 45 months, respectively. Both patients had no structural heart disease. The magnitude of QTc interval change during the therapy as compared to baseline (Δ QTc interval) was significantly greater in patients with VF than those without (p<0.001), however the magnitude of Δ heart rate, Δ PQ interval, and Δ QRS duration were similar between the 2 groups.

Conclusions

Medical castration significantly prolonged QT/QTc interval and could be a trigger of lethal arrhythmias in patients with prostate cancer.
P5642A clinical risk score for estimating sudden cardiac death risk in the general population
Authors: Aro A , Holkeri A , Eranti A , Kerola T , Junttila M J , Rissanen H , Heliovaara M , Knekt P , Huikuri H V
Published: October 2019

Background

Sudden cardiac death (SCD) remains a major cause of premature mortality worldwide, so there has been an ongoing pursuit for tools for SCD risk stratification. Coronary artery disease is the major cause for SCD in adults, but the level of risk associated with multiple cardiovascular risk factors is not well established.

Purpose

To create a clinical risk score for estimating SCD risk in the general population.

Methods

Using data from a Finnish general population cohort of 7200 adults (mean age 51y, 46% male) with a mean follow-up of 24±11 years, we assessed the incremental SCD risk associated with the presence of several cardiovascular risk factors. SCD events were adjudicated based on death certificates according to the established criteria (autopsy was performed on 48% of SCD cases). Hazard ratios (HR) for SCD and all-cause mortality were calculated using the Cox proportional hazards model. Of the multiple parameters analysed, male sex, increasing age, diabetes, hypertension, smoking and previously diagnosed cardiac disease were independently associated with SCD in a multivariable model. Based on the magnitude of risk, a SCD risk score was created (2 points: age >70y; 1 point: male sex, age 60–70y, diabetes, hypertension, smoking, cardiac disease).

Results

75.2% of the study subjects had 0–2 risk points, 12.8% 3 risk points, and 12.0% >3 risk points. During the follow-up, 400 SCDs occurred. Increasing risk score was associated with a progressively greater risk for SCD (Figure). Compared with subjects without risk factors, those with a risk score of 3 had a HR of 21.2 (95% CI 12.7–35.4, p<0.001) and those with a risk score of >3 had a HR of 52.6 (95% CI 31.3–88.3, p<0.001) for SCD. Clinical risk score predicted significantly also all-cause mortality (HR 31.5 with risk score >3 [95% CI 27.6–35.9, p<0.001]).

Risk of SCD according to the risk score

Conclusions

Accumulation of multiple cardiovascular risk factors is associated with a markedly elevated risk for SCD in the general population. This highlights the need for SCD prevention efforts with lifestyle interventions and medical therapy in the high-risk subjects. Studies on focused SCD risk stratification may be warranted in the subjects at highest risk.
P5652Catheter ablation outcome and heart failure hospitalization in atrial fibrillation patients with preserved left ventricular ejection fraction: insights from the Kansai plus atrial fibrillation (KPAF)
Authors: Tanaka N , Inoue K , Kobori A , Kaitani K , Morimoto T , Morishima I , Yamaji H , Nakazawa Y , Kusano K , Tanaka K , Hirao Y , Iwakura K , Fujii K , Kimura T , Shizuta S
Published: October 2019

Background

Heart failure (HF) is the leading cause of death in patients with atrial fibrillation (AF), and AF is an independent prognostic factor in HF patients with preserved left ventricular ejection fraction (LVEF). Radiofrequency catheter ablation (RFCA) for AF is effective to maintain sinus rhythm.

Purpose

We sought to clarify incidence of HF hospitalization and whether AF ablation outcome influenced incidence of HF hospitalization after the procedures in patients with preserved LVEF.

Methods

We conducted a large-scale, prospective, multicenter, observational study. A total of 4522 consecutive patients with normal LVEF (>/- 50%) who underwent an initial RFCA for AF in 26 centers were enrolled (average age, 64±10 years; non-paroxysmal AF, 33.7%). The median follow-up duration was 2.9 years.

Results

The 3-year cumulative incidence of AF recurrence after a single procedure was 40.3%. Hospitalization for HF was observed in 60 patients (1.3%) and was significantly higher in patients with AF recurrence than those without it (2.63% vs 0.44%, log-rank p<0.001). After adjustment by age ≥65 years, estimated glomerular filtration rate ≤60ml/min, history of HF, and female, all of which were statistically associated with a risk of HF hospitalization, AF recurrence after the index RFCA was an independent predictor of HF hospitalization (hazard ratio; 4.75, 95% confidence interval; 2.59–9.42, p<0.001).

Conclusions

Recurrence after RFCA for AF was a significant risk of HF hospitalization among AF patients with preserved LVEF.

Acknowledgement/Funding

This study was supported by the Research Institute for Production Development in Kyoto, Japan.
P5654Brain natriuretic peptide and left atrial volume predict the reduced flow velocity of left atrial appendage during sinus rhythm in patients with atrial fibrillation
Authors: Fukuhara E , Mine T , Kishima H , Ashida K , Ishihara M
Published: October 2019

Background

It remains controversial whether or not to discontinue anticoagulation therapy after catheter ablation (CA) for atrial fibrillation (AF). The reduced flow velocity of the left atrial appendage (FV-LAA) during AF causes left atrial appendage thrombus and increases the risk of stroke. However, some AF patients show reduced FV-LAA even during sinus rhythm (SR).

Methods

398 patients who showed SR during transesophageal echocardiography (TEE) before CA for AF were studied (259 males, 68±10 years, 77 with non-paroxysmal AF). Clinical factors, transthoracic echocardiography and blood samples were obtained before TEE. Reduced FV-LAA was defined as <35 cm/sec of FV-LAA.

Results

Reduced FV-LAA was observed 70/398 patients (18%). Reduced FV-LAA was significantly associated with elevated brain natriuretic peptide (BNP) (p<0.0001), increased LA volume index (p<0.0001), reduced left ventricular ejection fraction (p=0.0017), high prevalence of non-paroxysmal AF (p=0.0048), prior history of heart failure (p=0.0172), and no administration of angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) (p=0.0403), while CHADS2 factors were not significantly associated.

On multivariate analysis, LA volume index (p<0.0001, OR 1.049 for each 1 increase in LA volume index, 95% CI 1.025–1.073) and no administration of ACEI/ARB (p=0.0015, OR 0.339 for administration, 95% CI 0.173–0.662) and BNP (p=0.0048, OR 1.035 for each 10 pg/ml increase in BNP, 95% CI 1.011–1.061) and were associated with reduced FV-LAA.

Rate of reduced flow velocity

Conclusion

The elevated BNP level and large LA volume index predict reduced FV-LAA during SR. AF patients with increased BNP and larger LA volume index might require long-term anticoagulation taking after CA procedure.
P5657Fibrosis detected by late-gadolinium enhancement cardiac MRI is associated with atrial fibrillation and poorer ablation outcome: A meta-analysis
Authors: Agbaedeng T A , Emami M , Munawar D A , Rattanakosit T , Khadim K I , Elliott A , Linz D , Mahajan R , Lau D H , Sanders P
Published: October 2019

Background

Fibrosis is a hallmark of atrial fibrillation (AF) substrate. Recent data suggests that fibrosis detected by late-gadolinium enhancement (LGE) cardiac MRI (CMR) can predict AF. However, this relationship is not well described.

Objective

To delineate the association of cardiac fibrosis detected by LGE CMR with AF prevalence, AF recurrence after catheter ablation.

Methods

PubMed, Embase, Web of Science and Ovid MEDLINE were searched through November 2018, using the keywords: LGE AND Fibrosis AND CMR AND AF. Inclusion criteria: 1. LGE CMR of left atrial (LA LGE), ventricular wall (LV LGE) or right ventricular wall (RV LGE); 2. Studies reporting AF or recurrent arrhythmia after ablation; 3. Patient ≥18 years; and 4. ≥50 participants. Included studies were pooled in a random effects meta-analysis and reported as: mean difference (MD); unadjusted risk ratios (RR); adjusted hazard ratios (HR); and 95% confidence intervals (95% CI).

Results

After exclusions, we identified 9 studies (2,307 patients [65.9% males, 34.1% females]) conducted between 2003 and 2015 for LGE and AF. Fibrosis was present in 666 (35.1%) and detected by LV LGE in 7 (78%) and RV LGE in 2 (22%). The presence of AF was higher in patients positive for ventricular LGE than those negative, trending towards significance (RR: 1.51, 95% CI: 0.94–2.45, p=0.09). Pooled LV fibrosis associated with AF progression (RR [NPAF vs. PAF]: 2.2, 95% CI: 1.22–3.94, p=0.009). We identified 8 studies (2,041 patients [65.8% males, 34.2% females]) conducted between 2006 and 2016 reporting LGE and AF recurrence after catheter ablation, with fibrosis detected in 644 (31.6%) by LA LGE in 8 (88.9%, biased towards one centre). After 17.8±14.2 follow-up years, atrial fibrosis was significantly greater in recurrent AF than controls (MD: 4.97%, 95% CI: 1.23–8.7, p<0.01), and predicted 16% increased risk of AF recurrence (RR: 1.16, 95% CI: 1.07–1.26, p<0.05).

Conclusion

Myocardial fibrosis detected by LGE associates with prevalence and progress of AF and is predictive of AF recurrence post ablation. This further supports the proarrhythmic role of fibrosis and selection of patients for ablation therapy based on LGE.
P5662Development of a prognostic model for prevalent atrial fibrillation using individual patient data: Results of CATCH ME
Authors: Chua W , Easter C L , Guasch E , Sitch A , Casadei B , Haase D , Hatem S , Kaab S , Mont L , Schotten U , Sinner M , Hemming K , Deeks J J , Kirchhof P , Fabritz L
Published: October 2019

Background/Introduction

Atrial fibrillation (AF) can be challenging to diagnose due to asymptomatic and paroxysmal presentation. Identifying prognostic factors of AF would elucidate potential mechanisms causing AF and refine screening for at risk patients.

Purpose

To identify the main predictors of AF and to develop a prognostic model for prevalent AF.

Methods

Data of 120 potential predictors were harmonised in individual patient data from 4 independent European studies. A three stage Delphi expert consensus process identified predictors based on clinical knowledge. The predictors were further reduced using statistical selection (backward elimination), and a logistic regression model was fitted. We calculated odds ratios (OR) for each of the selected predictors and evaluated model performance using the C-statistic.

Results

Overall, 2420 patients (mean [standard deviation] age = 62.7 [14.5] years, 35.6% female, 43.1% with AF) were included in the analysis. Thirty-one potential predictors identified from the Delphi process which had sufficient data across all datasets were modelled. Of these 14 were deemed prognostic in predicting AF (age, sex, BMI, height, hypertension, diabetes, history of coronary artery disease, left atrial volume, left ventricular end systolic diameter, abnormality on echo, tricuspid valve disease of at least moderate intensity, aldosterone-antagonists, beta-blockers and P2Y12 blockers; see Figure 1). There was a clear interaction between age and sex indicating that males are at higher risk than females early in life, while females are at increased risk of AF at older age (Figure 1). The risk prediction model combining these prognostic factors performed well (C-statistic 0.79; 95% CI 0.77–0.81).

Figure 1. (a) Forest plot; (b) Interaction

Conclusion(s)

Our preliminary analysis identified important prognostic factors and a complex relationship between age and sex, which predicts prevalent AF, highlighting the different potential causes of AF in different patients. There is a clear need to validate these factors in external datasets and for further investigation into the molecular mechanism underlying these factors.

Acknowledgement/Funding

European Commission H2020 framework
P5666Impact of metabolic syndrome on the incidence of atrial fibrillation; a nationwide longitudinal cohort study in South Korea
Authors: Kwon C H
Published: October 2019

Background/Introduction

There is a lack of studies for the association between the status of metabolic syndrome (MetS) and the risk of atrial fibrillation (AF)

Purpose

The present study aimed to evaluate the impact of MetS status for the incidence of AF in Korean population.

Methods

We used the data obtained from the Korean National Health Insurance Service from 2009 to 2016. This study enrolled a total of 7,830,602 men and women aged between 30 and 69 years without baseline AF who underwent national health examination between January 2009 and December 2009. They were evaluated to determine the risk of AF based on the status of MetS until December 2016. Based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III, the status of MetS was defined into three groups according to number of MetS components: the normal (0), Pre-MetS (1–2), and MetS (3–5).

Results

During follow-up, 20,708 subjects (0.26%) were diagnosed with AF. After multivariable adjustment, the risk of AF was significantly higher according to the status of MetS (hazard ratios [HR] 1.391, 95% confidence interval [CI] 1.322–1.464 in Pre-MetS and HR 1.722, 95% CI 1.621–1.829 in MetS). Among the components of MetS, central obesity (HR 1.316, P<0.001), elevated blood pressure (HR 1.451, P<0.001), and elevated fasting glucose (HR 1.163, P<0.001) were associated with an increased risk of AF.

Conclusion

MetS and pre-MetS are significantly associated with an increased risk of AF in Korean adults. Of the components of MetS, central obesity, elevated blood pressure, and elevated fasting glucose are potent risk factors for the risk of AF in this population.
P5672Diagnostic accuracy and clinical utility of point-of-care ultrasound among syncope patients in the emergency department
Authors: Pivetta E , Moretto F , Bianchi G , Masellis S , Bovaro F , Manasievska M , Maule M M , Lupia E
Published: October 2019

Background/Introduction

Syncope is still a challenge for risk stratification in the Emergency Department (ED), and the indication to discharge is not well established for all patients.

Purpose

To evaluate diagnostic accuracy and clinical utility of integration of clinical assessment and point-of-care ultrasound (POCUS) in evaluating non high-risk syncopes in the ED.

Methods

This observational prospective cohort study enrolled patients between February 2016 and January 2019.

All adult patients presenting in the ED for a non-high risk syncope were eligible (defined according to the 2015 ESC consensus on management of syncope in the ED). Subject for whom event etiology was identified right after the clinical assessment (i.e. history, physical exam, and EKG) or showing a clinical high risk for short term serious outcomes or refuse to participate in the study were excluded.

After the initial clinical assessment, the physician responsible for patient care was asked to categorize the syncope as low or neither high nor low risk. Immediately after, the same physician performed POCUS, and a new risk assessment, based on the results of both clinical and sonographic findings, was recorded. Thirty days after the ED evaluation, all participants were telephonically followed up by the investigators in order to assess the risk of short-term outcomes as defined in the San Francisco Syncope Rule cohorts. Both diagnostic accuracy, defined as sensitivity (SE) and specificity (SPE), and clinical utility, evaluated as net reclassification index (NRI) and net benefit were evaluated for clinical and POCUS-integrated assessment.

Results

A total of 415 patients with a syncope were eligible. Of these, 194 were enrolled (107 women - 55.2%). Median age was 63 years (interquartile range, IQR, 30 years). During the follow up, 21 patients experienced 28 events.

SE and SPE of the clinical evaluation were 33.3% (95% confidence interval, CI, 14.6–57%) and 79.5% (95% CI 72.7–85.3%), and they were 42.9% (95% CI 21.8–66%), and 92.4% (95% CI 87.4–95.9) for the POCUS-integrated evaluation (p<0.01 for SE and 0.05 for SPE).

NRI for events and non-events during follow up was 9.5% and 12.7%, respectively.

Using the prevalence of events in our cohort (10.8%) as the threshold probability, the use of the POCUS-integrated approach would reduce the diagnostic error of the clinical evaluation by 4.6 cases/100 patients.

The median time between clinical and POCUS-integrated evaluation was 15 minutes (iqr 20 minutes).

Conclusion

The results of our study suggest that the integration of the clinical evaluation with POCUS for patients presenting to the ED for non high-risk syncope might be able to increase the diagnostic accuracy and the utility of the clinical assessment alone.
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

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

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

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

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

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

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

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

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

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.
P5747The effect of additional intracoronary papaverine administration during hyperemia with intravenous adenosine triphosphate infusion, on fractional flow reserve values
Authors: Podmetin P , Burak T Y , Kochanov I N , Kaledin A L
Published: October 2019

Introduction

Fractional flow reserve (FFR) measurement requires the achievement of steady-state maximum hyperemia. One of the main agents used for the induction of hyperemia is adenosine-triphosphate (ATP). But, in some cases, hyperemia may be insufficient, which leads to an underestimation of the true value of the FFR.

Purpose

To determine the effect of additional intracoronary papaverine administration during hyperemia with intravenous ATP infusion, on FFR values in a group of patients with borderline values.

Methods

A total of 165 measurements of FFR were performed in 119 patients. Intravenous infusion of ATP 140 μg/kg/min was used in all patients. In the group of patients with borderline FFR values (28 pts, 0.79–0.86), during achieved ongoing hyperemia, papaverine was additionally administered intracoronary (20 mg for LCA and 12 mg for RCA) with a reassessment of FFR values. The change in the FFR values and hemodynamic parameters were determined.

Results

The average values of FFR during hyperemia with ATP were 0.82±0,02. After additional administration of papaverine, a significant decrease in the mean values of FFR to 0.79±0,03 (p<0.001) occurred. Wherein a decrease in the FFR value by 0.03 or more was noted in 12 patients (43%), a decrease by 0.01–0.02 - in 12 patients (43%), unchanged in 4 patients (14%).

In 15 patients (53%), a change in FFR led to a crossing of the threshold value of 0.80 and a change in treatment strategy.

With intravenous infusion of ATP, was observed a decrease in systolic blood pressure (BP) by 10.6% (132 vs 118 mm Hg, p<0.001), a decrease in mean BP by 12% (101 vs 88 mm Hg, p<0.001) compared to the base pressure. With additional administration of papaverine, systolic BP decreased by more 12% (to 104 mm Hg, p<0.001), mean BP – by more 11% (to 78 mm Hg, p<0.001).

Changes in blood pressure Rest ATP Papaverine Systolic BP, mm Hg 132±22 118±23 104±19 Mean BP, mm Hg 100±13 88±14 79±11

Changes in the values of FFR

Conclusions

Additional intracoronary papaverine administration during hyperemia with intravenous adenosine triphosphate infusion led to a decrease in FFR values of 0.02 or more in 68% of cases. It may indicate a insufficiency of the initial hyperemia induced by only one vasodilator and require a combination of pharmacological agents to achieve lower and more accurate values.

At borderline values of FFR obtained by induction of hyperemia with a single hyperemic agent (ATP), the additional administration of a second hyperemic agent (papaverine) in 53% led to a crossing of the threshold value of 0.80 and a change in treatment strategy.