bluuebunny/crossref_metadata_2025_split huggingface dataset:
2285Increased risk of out-of-hospital cardiac arrest associated with psychiatric disorders
Authors: Barcella C A , Mohr G H , Kragholm K , Christensen D M , Polcwiartek C , Wissenberg M , Lippert F K , Torp-Pedersen C , Kessing L V , Gislason G H , Soendergaard K B 
Published: October 2019

Abstract

Introduction
Patients with psychiatric disorders are at high risk of cardiovascular morbidity and mortality; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared to the general population remains unknown.

Purpose
We investigated whether the presence and severity of different psychiatric disorders were associated with a higher risk of OHCA.

Methods
We conducted a case-control study matching all adult patients with OHCA of presumed cardiac cause between 2001 and 2014 with up to nine controls from the entire Danish population on age, sex and ischemic heart disease (IHD). Patients with psychiatric disorders were identified using in- and out-patient hospital diagnoses – both primary and secondary - before index date. We identified six mutually exclusive psychiatric disorders that were separately examined: personality disorders, anxiety, substance-related mental disorders, depression, bipolar disorder and schizophrenia. The risk of OHCA associated with the six psychiatric disorders was evaluated by conditional logistic regression adjusting for comorbidities, concomitant pharmacotherapy, socioeconomic status and marital status.

Results
We included 32,447 OHCA cases matched with 291,999 controls from the general population. Overall, the median age was 72 years, 67% were male and 29% had IHD prior to index date. All the six psychiatric disorders examined were more common among cases than controls; depression was the most common psychiatric disorders in both groups: 5.0% among cases and 2.8% among controls. Concurrently, all six psychiatric disorders were associated with significantly higher odds of OHCA: personality disorders (odds ratio (OR) 1.30 [95% confidence interval (CI) 1.06–1.60], anxiety OR 1.26 [95% CI 1.15–1.39], substance induced-mental disorders OR 2.36 [95% CI 2.17–2.57], depression OR 1.27 [95% CI 1.19–1.35], bipolar disorder OR 1.32 [95% CI 1.16–1.50] and schizophrenia OR 1.80 [95% CI 1.58–2.05] (Figure). The association persisted unaffected when we studied psychiatric patients neither exposed to antipsychotics nor to antidepressants. We observed a trend towards a stronger association when we stratified according to the severity of the psychiatric disorder (Figure). Severe disorders where classified as at least one hospitalization for the specific psychiatric illness as primary diagnosis during the five years prior to index date.

Conclusions
Common psychiatric disorders including personality disorders, anxiety, substance-related mental disorders, depression, bipolar disorder and schizophrenia are significantly associated with higher odds of OHCA. These findings provide a rationale for early cardiovascular risk factor screening and, potentially, management among psychiatric patients to identify patients at high risk of OHCA.

Acknowledgement/Funding
ESCAPE-NET project
2396Long-term follow-up of patients with tetralogy of Fallot and implantable cardioverter defibrillator
Authors: Waldmann V , Bouzeman A , Marquie C , Labombarda F , Koutbi R , Sellal J M , Fauchier L , Mondoly P , Pasquie J L , Anselme F , Eschalier R , Iserin L , Thambo J B , Combes N , Marijon E 
Published: October 2019

Abstract

Background
Ventricular arrhythmias and sudden death are potential late complications in patients with tetralogy of Fallot. Data regarding the value of implantable cardioverter defibrillators (ICD) are scarce in this population.

Purpose
To assess long-term rates of appropriate ICD therapies and ICD-related complications in a large registry of ICD recipients with tetralogy of Fallot.

Methods
The DAI-T4F study is an ongoing national French registry including all patients with tetralogy of Fallot and ICD (NCT03837574). Information have been collected prospectively since 2010 with annual update. Baseline patient characteristics and clinical events during follow-up were analyzed with central adjudication. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies and complications.

Results
A total of 134 patients (median age 41.7 years, 70.7% males) were enrolled. The median (IQR) follow-up duration was 6.1 (2.7–10.2) years. ICDs were implanted for primary prevention in 47 (35.1%) patients and for secondary prevention in 87 (64.9%) patients. Overall, 14 (29.8%) and 45 (51.7%) patients received at least one appropriate ICD therapy in primary and secondary prevention, respectively, giving annual incidences of 5.5% and 7.1% (p=0.06). Patients with altered left ventricle ejection fraction (LVEF) at inclusion ≤35% experienced less appropriate ICD therapies (HR=0.31, 95% CI: 0.11–0.86, p=0.02), whereas a history of sustained or non-sustained ventricular arrhythmia (HR=2.7, 95% CI: 1.2–3.9, p=0.03) was positively associated with appropriate therapies. Fifty-seven (42.5%) patients had ICD-related complications, including 32 (24.2%) inappropriate ICD shocks, 22 (16.4%) significant lead dysfunction, 14 (10.4%) device infection, and 5 (3.7%) generator dysfunction/recall. History of supraventricular arrhythmias (HR=2.2, 95% CI: 1.2–3.7, p=0.01) and congestive heart failure (HR=2.0, 95% CI: 1.2–3.6, p=0.01) were both associated with a higher risk of complications. During follow-up, 7 (5.2%) patients underwent cardiac transplantation and 12 (9.0%) patients died, mainly from progressive heart failure (n=5). Only one sudden death due to electrical storm was recorded.
Figure 1

Conclusions
Appropriate therapies are frequent in patients with tetralogy of Fallot and ICDs, including in primary prevention. The relatively important proportion of ICD-related complication highlights the need for improving risk stratification in this population, considering associated conditions in the individual benefit-risk equation.
2397Lesion-specific risk for sudden cardiac death or life-threatening ventricular arrhythmias in adult congenital heart disease
Authors: Gallego Garcia De Vinuesa P , Gonzalez Garcia A E , Avila P , Alonso A , Garcia Hamilton D , Peinado R , Dos Subira L , Pijuan-Domenech A , Rueda Soriano J , Rodriguez-Puras M J , Garcia-Orta R , Martinez-Quintana E , Bermejo J , Fernandez-Aviles F , Oliver J M 
Published: October 2019

Abstract

Background
Risk models for primary prevention strategies in adult congenital heart disease (ACHD) must incorporate the heterogeneous risk for sudden cardiac death (SCD) and life-threatening ventricular arrhythmias (LTVA) as stratified by underlying lesion.

Objectives
To determine lesion-specific risk for SCD and LTVA in ACHD.

Methods
We analyzed 3311 ACHD patients (50% males) prospectively followed-up for 37510 person/years. SCD cases were confirmed by means of the Spanish National Death Registry. In addition, we identified all cases of resuscitated cardiac arrest or ventricular tachycardia requiring cardioversion. According to the incidence rate of the composite end-point of SCD and LTVA, lesions were stratified into four groups of risk. Cumulative freedom from SCD or LTVA in patients at high, moderate, low and very low risk were compared by using Cox regression model with left truncation. The c-index of this lesion-specific risk stratification was calculated by using the β-coefficients. The discriminative ability of this lesion-specific risk stratification was also tested in an external cohort of 203 SCD-LTVA cases and 2287 controls from 20 different centers.

Results
71 patients experienced an event (53 SCD, 18 LTVA). Patients at highest risk (incidence rate >1%) were those with Rastelli procedure, severe coronary abnormalities, complex Fallot and cyanotic patients, either Eisenmenger or non-Eisenmenger; at moderate risk (incidence rate 0.25–1.0%) non-complex Fallot, Mustard/Senning repair, Fontan procedures and congenitally corrected transposition; at low risk (incidence rate 0.1–0.25%) Ebstein anomaly and left heart lesions; and at very low risk (incidence rate <0.1%) left-to-right shunts and right ventricular outflow lesions. The discriminative ability in a multicenter external cohort was excellent (c-index ranged from 0.748 to 0.819 by center).
Lesion-specific risk and C-index

Conclusions
A lesion-specific risk stratification based on the incidence rate of SCD and LTVA was performed and validated. This approach could result in a more individualized risk assessment.

Acknowledgement/Funding
Instituto de Salud Carlos III, Ministerio de Economía y Competividad, Spain (Exp PI14/02099 and PI17/01327) and co-financed by FEDER
2402Reduced heart rate variability is linked to clinical status in patients with a systemic right ventricle
Authors: Zandstra T E , Kies P , Man S , Maan A C , Bootsma M , Vliegen H W , Schalij M J , Jongbloed M R M 
Published: October 2019

Abstract

Background
Adult patients with congenital heart disease and a systemic right ventricle (sRV) are prone to develop heart failure. Decreased heart rate variability (HRV), a measure of autonomic dysfunction, is associated with morbidity and mortality in patients with congestive heart failure. The standard deviation of all intervals between normal sinus beats (SDNN) is a HRV parameter commonly reported as an indicator of autonomic function in these patients. Data about HRV and its clinical implications in patients with a sRV are scarce.

Purpose
To compare HRV parameters between patients with a sRV and healthy controls, and to assess their association with clinical status.

Methods
All available 24-hour Holter monitoring records of sRV patients under follow-up in our center and one record per healthy control subject were analysed. Holters with non-sinus rhythm were excluded. Time and frequency domain parameters were calculated and compared between both groups. Clinical landmarks such as arrhythmias or an episode of congestive heart failure, which occurred up until the time of the ambulatory ECG, were combined in a clinical event score. Determinants of SDNN were investigated with mixed model linear regression in the patients and with multivariate linear regression in the controls. Baseline characteristics, medication use, global longitudinal strain, validity as measured with bicycle exercise testing, and the clinical event score were taken into account.

Results
113 Holters of 43 patients and 39 Holters of healthy controls were analysed. The patient group included 30 patients (70%) late after Mustard or Senning correction for transposition of the great arteries, and 13 patients with congenitally corrected transposition of the great arteries (30%). Age and gender were comparable in patients and controls. Several HRV parameters were significantly worse in patients compared with controls, including SDNN (138 in patients vs. 161 in controls, p=0.021). In the patients, clinical event score was the only significant determinant of a lower SDNN (p<0.001). In the controls, age was the only significant determinant of a lower SDNN (p=0.039).

Conclusion
Contrary to the healthy population, in patients with a sRV, HRV is associated with clinical status rather than age. This indicates that disease progression affects autonomic function more than ageing in this group. Further research is needed to clarify the relation between clinical outcome and autonomic function in sRV patients.

Acknowledgement/Funding
The Department of Cardiology of the LUMC received research grants from Medtronic, Biotronik, Boston Scientific and Edwards Lifesciences
2403Experience with the wearable cardioverter-defibrillator by disease etiology: results from the wearit-II registry
Authors: Kutyifa V , Vermilye K , Zareba W , McNitt S , Goldenberg I 
Published: October 2019

Abstract

Background
The use of the wearable cardioverter-defibrillator (WCD) in patients with non-ischemic cardiomyopathy has been less characterized.

Objective
We aimed to characterize WCD use and outcomes for patients with ischemic or non-ischemic cardiomyopathy, enrolled in the WEARIT-II Registry.

Methods
In WEARIT-II, we stratified 1,732 patients into ischemic (n=805) and non-ischemic etiology (n=927). WCD wear time, arrhythmia events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates, or ejection fraction (EF) improvement at the end of WCD were evaluated for etiology subgroups.

Results
The WCD median wear time was higher in patients with non-ischemic cardiomyopathy (93 vs. 87 days, p=0.003), however daily use was similar (22.4 vs. 22.6 hours, p=0.07). There were 24 ischemic patients (3%) with sustained VT/VF events compared to 10 patients (1%) with non-ischemic cardiomyopathy (p=0.013). About 2/3 of these events were treated with WCD shock in ischemic patients, half of them in the non-ischemic group (1.9% vs. 0.4%). Atrial arrhythmias were frequent in both groups (3.1% vs. 3.1%, p=0.06). At the end of WCD use, 36% of the non-ischemic patients were implanted with an ICD compared to 42% in ischemic (p=0.01), likely due to the lower rate of sustained ventricular arrhythmias (Figure).
Figure 1

Conclusions
In WEARIT-II, patients with non-ischemic cardiomyopathy had longer WCD use than ischemic patients with good compliance. The rate of sustained ventricular arrhythmia events was lower in non-ischemic patients avoiding the need for an ICD implantation in more patients compared to ischemic, following a time period of risk stratification.

Acknowledgement/Funding
WEARIT-II was funded by an unrestricted research grant from ZOLL Inc.
P1233Differential effects of five risk variants for atrial fibrillation at the 4q25 region on L-type calcium current and transient inward currents in human atrial myocytes
Authors: Tarifa C , Herraiz-Martinez A , Llach A , Jimenez-Sabado V , Colino H , Lozano-Velazquez E , Franco D , Rosello E , Rodriguez-Font E , Cinca J , Hove-Madsen L 
Published: October 2019

Abstract

Background
An increasing number of single nucleotide polymorphisms (SNPs) at the chromosomal region 4q25 have been associated with risk of atrial fibrillation (AF) and we have recently reported that carriers of the rs13143308 risk variant have an increased incidence of spontaneous calcium release-induce transient inward currents (ITI). However, it is not known if different 4q25 variants have similar effects.

Purpose
This study aimed to compare the effects of five SNPs at 4q25 on L-type calcium current (ICa) and ITI frequency, features that are altered in patients with AF.

Methods
To avoid confounding effects of AF on calcium homeostasis, atrial samples from 63 patients without AF were genotyped and divided into groups according to the genotype of the SNPs rs1448818, rs6817105, rs13143308, rs6843082, rs3853443 ordered according to their location and identified by the three last digits + an R for risk or N for normal variants. ICa density and ITI frequency were measured with perforated patch clamp technique in atrial myocytes from these patients.

Results
Three SNPs 818, 308 and 443 segregated independently of the genotype at the other loci. The 105 and 082 loci always co-segregated with 308 but never together. The ICa density was smaller in carriers of 818R and 443N variants (−1.6±0.3pA/pF, p=0.01) or 818N and 443R variants (−1.6±0.4pA/pF, p=0.02) than in patients with 818N and 443N variants (−3.2±0.4pA/pF), independently of the genotype at 105, 308 and 082 (these loci did not affect ICa). In contrast, to this, the ITI frequency was increased only in myocytes from patients carrying 105R, 308R and 082N (1.4±0.2events/min, p<0.001) or 105N, 308R and 082R (1.6±0.5events/min, p=0.002) when compared to patients with 105N, 308N and 082N (0.36±0.09events/min) independently of the genotypes at 818 and 443, or when compared to patients without risk at any of the five loci (0.55±0.30events/min). The table shows schematically the qualitative effects of the different risk variants.
Risk variant rs1448818C rs6817105C rs13143308T rs6843082T rs3853445C ICa Decreased Unchanged Unchanged Unchanged Decreased ITI Unchanged Increased Increased Increased Unchanged

Conclusion
Different SNPs at the chromosomal region 4q25 are associated with differential pathological changes in intracellular calcium homeostasis. Risk variants at rs1448818 or rs3853445 cause loss of ICa without affecting ITI frequency while a risk variant at rs13143308 elevates the ITI frequency without affecting ICa. These findings afford a framework for stratification of pharmacological therapy based on the functional effects of the 4q25 risk variants

Acknowledgement/Funding
SAF2017-88019; Marato2015-20-30; SGR2017-1769; CIBERCV
P1237Left ventricular myocardial work characteristics and CRT response in patients with LBBB according to Strauss criteria and ESC 2013 definition
Authors: Kostyukevich M V , Van Der Bijl P , Vo N M , Ajmone Marsan N , Delgado V , Bax J J 
Published: October 2019

Abstract

Background
The impact of left bundle branch block (LBBB) on left ventricular (LV) myocardial work may vary according to the specific definition of a LBBB. Quantification of the interplay between LV myocardial work and the underlying electrical dyssynchrony may improve our understanding of cardiac resynchronization therapy (CRT) response.

Objective
To evaluate the impact of LBBB, defined according to Strauss and ESC 2013 ECG criteria, as well as non-LBBB morphologies on different LV myocardial work indices and response to CRT.

Methods
LBBB was defined according to the Strauss criteria and ESC 2013 guidelines on heart failure. LV myocardial constructive and wasted work (CW and WW) were derived from pressure-strain loop analysis integrating valvular opening and closing times, speckle tracking strain echocardiography and noninvasive blood pressure measurement. LV myocardial work efficiency (WE) was calculated from the ratio of constructive work, divided by the sum of constructive and wasted work. CRT response was defined as a decrease in LV end-diastolic volume (EDV) ≥15% at 6 months' follow-up.

Results
Patients were divided into 3 groups: 1) LBBB according to Strauss criteria (group 1, n=109, age 64±10 years), 2) LBBB according to ESC 2013 criteria (group 2, n=22, age 64±10 years) and 3) non-LBBB (group 3, n=44, age 69±10 years). Patients from group 1 were 4.2 times more likely to respond to CRT than patients from group 3 (odds ratio [OR] 4.182; 95% confidence interval [CI], 1.999–8.750; p<0.001), whereas CRT response between groups 2 and 3 did not differ significantly (OR 1.100; 95% CI 0.387–3.124; p=0.859). Patients in group 1, were characterized by significantly lower WE, compared to groups 2 and 3 (67.6±9.9 mmHg% vs. 72.7±9.7 mmHg% and 75.4±9.6 mmHg%, respectively; p<0.001) as well as higher WW (313.2±144.9 mmHg% vs. 215.1±102.5 mmHg% and 229.0±113.5 mmHg%, respectively; p<0.001). There was no significant difference in CW between any of the groups (811.6±353.4 mmHg% vs. 798.6±440.6 mmHg% and 893.6±420.2 mmHg% respectively for groups 1, 2 and 3; p=0.447).

Conclusion
Patients with a LBBB according to Strauss criteria had a higher probability of response to CRT, compared to those with a LBBB defined by ESC 2013 guidelines criteria or with non-LBBB morphology. This is reflected in a greater amount of wasted work and more impaired LV myocardial work efficiency at baseline in patients with LBBB satisfying Strauss criteria, compared to the other two groups, representing the substrate for CRT.

Acknowledgement/Funding
Study was supported by ESC Research grant 2018
P1247FLNC pathogenic variants in patients with various cardiomyopathies:prevalence and genotype-phenotype correlations
Authors: Ader F , De Groote P , Reant P , Dupin-Deguine D , Rambaud C , Khraiche D , Pruny J F , Mathieu Dramard M , Troadec Y , Gouya L , Jeunemaitre X , Van Maldergem L , Villard E , Charron P , Richard P 
Published: October 2019

Abstract

Background/Introduction
Pathogenic variants FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes.However, few data on phenotype-genotype correlation are available.

Purpose
Our aim was to estimate the prevalence of FLNC pathogenic variants in cardiomyopathies and to study the relations between phenotype and genotype.

Methods
DNAs from a cohort of 1150 unrelated index-patients with an isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non-compactions) have been sequenced on a custom panel of 52 cardiomyopathy disease-causing genes.

Results
A FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1 to 8% depending on the cardiomyopathy subtypes. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in-frame variants were found in other phenotypes. This work reported for the first time a left ventricular non-compaction associated with FLNC pathogenic variant.
In the cohort, nine patients (32%) were implanted with an automatic defibrillator. In 7 families (25%), history of sudden cardiac death (SCD) before 50 years was reported. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (p=0.01). Four patients died of cardiac cause including 3 from SCD and 1 from heart failure.

Conclusion
This work highlights the role of FLNC in cardiomyopathies. A correlation between the type of the variant and the cardiomyopathy subtype was observed as well as with SCD risk. These new data should be taken into consideration for patient's management and primary prevention of sudden cardiac death.

Acknowledgement/Funding
La ligue contre la Cardiomyopathie