bluuebunny/crossref_metadata_2025_split huggingface dataset:
5205Electrocardiographic predictors of appropriate implantable cardioverter defibrillator therapies in patients with tetralogy of Fallot
Authors: Waldmann V , Bouzeman A , Koutbi R , Bessiere F , Hermida A , Duthoit G , Elbaz N , Messali A , De Guillebon M , Mansourati J , Da Costa A , Martins R , Gourraud J B , Combes N , Marijon E 
Published: October 2019

Abstract

Background
The electrocardiogram (ECG) is widely available and may contribute to a better risk stratification for sudden cardiac death in patients with tetralogy of Fallot. QRS duration has been consistently associated with outcomes, with a lack of specificity for sudden mortality and a relatively low predictive value. New markers such as QRS fragmentation and vectocardiographic parameters have been recently suggested.

Purpose
To identify ECG predictors of appropriate therapies in patients with tetralogy of Fallot and implantable cardioverter defibrillator (ICD).

Methods
The DAI-T4F study is a large 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 the follow-up were analyzed with central adjudication. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies.

Results
A total of 134 patients (median age 41.7 years, 70.7% males) were enrolled. During a median (IQR) follow-up of 6.1 (2.7–10.2) years, 59 (44.0%) patients received at least one appropriate ICD therapy, giving annual incidence of 5.5% and 7.1% in primary and secondary prevention, respectively (p=0.058). Overall, QRSd ≥180ms (p=0.073), QRS fragmentation (p=0.052), and QRS vector magnitude (vm, p=0.327) were not significantly associated with appropriate ICD therapies, whereas QRS fragmentation in right leads (HR=1.7, 95% CI: 1.1–2.9, p=0.039) and the association of QRSd ≥180ms and overall QRS fragmentation (HR=1.9, 95% CI: 1.1–3.4, p=0.036) were associated with an increased risk of appropriates ICD therapies. In patients with ICD for primary prevention (47 patients, 35.1%), 53.8% had QRS fragmentation, 48.6% had decreased QRS vm, and 41.0% had QRSd ≥180ms. In this group, while non-sustained ventricular tachycardia (NSVT) considered isolated was not associated with ventricular events during follow-up (p=0.069), respective combinations with QRSd ≥180 ms (HR=7.2, 95% CI: 1.6–32.7, p=0.011), QRS fragmentation (HR=3.8, 95% CI: 1.2–12.4, p=0.025), or decreased QRS vm (HR=3.6, 95% CI: 1.1–12.1, p=0.042) were all associated with a higher incidence of appropriate ICD therapies. Positive predictive value and negative predictive value were 0.33 and 0.85, 0.58 and 0.74, and 0.36 and 0.84 in patients with NSVT and QRS ≥180ms, NSVT and QRS fragmentation, and NSVT and decreased QRS vm, respectively.

Conclusions
Our findings highlight that cumulative risk score derived from ECG may contribute to improve risk stratification in patients with tetralogy of Fallot, in particular QRS fragmentation and QRS vm in association with QRS duration and other traditional risk factors.
5219A novel senolytic drug, seno-7284 ameliorates age-related cardiometabolic diseases
Authors: Katsuumi G , Katsuumi I , Suda M , Yoshida Y , Hayashi Y , Ikegami R , Wakasugi T , Nakao M , Nagasawa A , Sugimoto M , Mikawa R , Minamino T 
Published: October 2019

Abstract

Background
Senescence at cellular level develops with various genotoxic stresses and it plays a pivotal role in aging and age-related disorders. Recently, it was shown that elimination of senescent cells, so called “senolysis” has potential to become a next generation therapy for age-related disorders including cardiovascular diseases, pulmonary emphysema, Alzheimer's diseases, etc. However, currently there is no senolytic agent available in clinical settings.

Purpose
Present study was aimed to identify a novel senolytic agent effective for cardiometabolic diseases in compounds already available in clinical settings. Here we demonstrate a compound called “seno-7284” exhibits senolytic effect in murine models of type 2 diabetes, atherosclerosis and progeroid.

Methods
We generated 1) diet-induced obase and diabetic model by imposing a high fat diet for two months, 2) atherosclerosis mice model by imposing western diet to ApoE homozygous knockout mice (ApoE-KO mice) for three months, and 3) Zmpste24 homozygous knockout mice (Zmpste24-KO mice) as a progeroid mice model. We administrated seno-7284 by mixing it into the diet (0.03% w/w). In one, two or four weeks after the administration of seno-7284 to each mice model, we collected tissue samples for further analyses.

Results
Seno-7284 reduced the accumulation of senescent cells in visceral adipose tissue of dietary obese mice as senescence-associated beta-galactosidase (SA-beta-gal) staining exhibits (Figure a). This effect was associated with the suppression in systemic glucose intolerance (Figure b), and adipose tissue inflammation in four weeks after the administration of seno-7284. Administrating seno-7284 for two weeks also reduced accumulation of senescent cells in atherosclerotic lesion in aorta of ApoE-KO mice (Figure c), and inhibited the progression of atherosclerosis (Figure d). Surprisingly, this drug significantly improved the lifespan of Zmpste24-KO mice by administering it from 12 weeks old. Further analysis including RNA-seq or metabolomic analysis suggested that seno-7284 stimulates endogenous senolytic function of NK cells and CD8+ T cells.

Conclusion
Our results indicate that seno-7284 mediates its biological effects by inducing senolysis in some murine aging models. Seno-7284 would become a promising therapeutic agent for age-related cardiometabolic diseases.
5948Circulating biomarkers of cell adhesion in relation to clinical outcomes in patients with chronic heart failure: the Bio-SHiFT study
Authors: Bouwens E , Van Den Berg V J , Akkerhuis K M , Baart S , Caliskan K , Brugts J J , Mouthaan H , Van Ramshorst J , Germans T , Umans V A , Boersma H , Kardys I 
Published: October 2019

Abstract

Background
Cardiovascular inflammation and vascular endothelial dysfunction are present in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. The temporal patterns of the blood biomarkers involved could provide further insights into these processes.

Purpose
We aimed to evaluate the prognostic value of the temporal patterns of blood biomarkers of cell adhesion in stable patients with CHF.

Methods
In 263 patients, a median of 9 (IQR: 5–10) serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The composite primary endpoint (PE) of cardiovascular mortality, HF-hospitalization, heart transplantation and LVAD was reached in 70 patients. For efficiency, we selected all baseline samples, the two samples closest to a PE, and the last sample available for event-free patients. Thus, in 567 samples we measured twelve biomarkers of cell adhesion using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and first PE were investigated by combining linear mixed effect models and Cox regression (so-called joint model).

Results
Median age was 68 (IQR: 59–76) years, with 72% men and 74% NYHA class I-II. Levels of CD93 (Complement component C1q receptor), CDH5 (VE cadherin), CHI3L1 (Chitinase-3-like protein 1), EPHB4 (Ephrin type-B receptor 4) and JAM-A (Junctional adhesion molecule A) differed at baseline already. The average biomarker evolutions of these markers, and additionally of ICAM-2 (Intercellular adhesion molecule-2), showed different patterns in patients approaching the PE versus those who remained event-free (Figure 1). Repeatedly measured levels of these biomarkers were independently associated with the PE. Corresponding HRs [95% CI] per 1SD increase in log2 level (arbitrary unit) were: CD93: 1.85 [1.29–2.70], CDH5: 1.72 [1.23–2.44], CHI3L1: 2.45 [1.73–3.56], EPHB4: 1.83 [1.33–2.55], ICAM2: 1.74 [1.24–2.46] and JAM-A: 2.07 [1.39–3.18], adjusted for clinical characteristics (age, sex, diabetes, atrial fibrillation, baseline NYHA class, diuretics, systolic blood pressure and eGFR).
Figure 1. Average temporal patterns of cell adhesion biomarkers during follow-up.

Conclusion
CD93, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A show different patterns as adverse events approach in CHF patients, and their temporal patterns strongly predict clinical outcome. These findings demonstrate the incremental value of repeated measurements of biomarkers of cell adhesion in stable patients with CHF.

Acknowledgement/Funding
This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.
5969The experiences of women with a subcutaneous implantable cardioverter defibrillator
Authors: Van Der Stuijt W , Quast A B E , Baalman S W E , Wilde A A M , Knops R E 
Published: October 2019

Abstract

Introduction
The subcutaneous implantable cardioverter defibrillator (S-ICD) is positioned in close proximity of the left mamma. In female patients, this may result in issues, such as limitations in clothing, breastfeeding or self-perception. Moreover, female patients are underrepresented in most large S-ICD studies, thus underexposing these gender-specific issues which may impact their daily life substantially.

Objective
To assess the issues female S-ICD patients are experiencing and provide practical “tips and tricks” for cardiologists and implanters to minimalize gender-specific issues.

Methods
All female patients implanted with an S-ICD in a large tertiary center between February 2009 and November 2018 received a single questionnaire with questions on physical, esthetical and situational issues.

Results
Patients were categorized in three age groups, 18–39 years (n=32), 40–55 years (n=35) and >55 years (n=19). Eighty-four percent of the patients experienced pain after S-ICD implant, almost half (42.9%) of those patients reported extreme pain. After S-ICD implant, self-perception was altered in a small group (20%) and a third of the patients does not wear the same clothing as before. During sexual activity, many female patients actively avoid the touch of their partner on the lead and generator due to discomfort. While no-one reported problems with childbirth or breastfeeding, two patients did experience irritation from the lead during their pregnancies, possibly due to growth of the mammae. The majority of patients (64%) experiences daily discomfort while wearing a bra, specifically with the linings and the sideband (figure A and B). Women prefer a more cranial position of the S-ICD generator with the lower sideband supporting the device (figure C). A position of the S-ICD generator posterior from the lining of the left cup also reduces discomfort.

Conclusion
Female S-ICD patients experience a variety of gender-specific issues with a substantial impact on their daily life. Implanters should provide adequate counseling and use bra position during pre-implant marking to minimize daily discomfort of female patients.
6072Risk of stroke in hypertensive patients with atrial fibrillation treated with oral anticoagulants
Authors: Harskamp R E , Lucassen W A M , Lopes R D , Van Weert H C 
Published: October 2019

Abstract

Background
Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes.

Purpose
To gain insights into the risks of hypertension in the setting of AF and explore possible interactions with the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs).

Methods
We performed a systematic review and meta-analysis of studies that randomised patients to NOACs or VKAs and reported outcomes stratified by presence of hypertension. Collected outcomes included: ischaemic stroke or systemic embolism (SE), death from any cause, hemorrhagic stroke, major bleeding, and intracranial hemorrhage. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool.

Results
Five high-quality studies were eligible, including 71,602 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. 89.2% of participants had a history of hypertension. Compared with patients without hypertension, those with controlled and uncontrolled hypertension had higher risk for stroke/SE (HR: 1.21 [1.04–1.41] and HR: 1.50 [1.12–2.01], respectively) and haemorrhagic stroke (HR: 1.78 [1.06, 3.00] and HR: 1.66 [0.99–4.01], respectively). On a continuous scale, the risk of stroke increased 7% per 10mmHg increase in systolic blood pressure. As shown in the Table, no interactions were found between hypertension status and the efficacy or safety of NOACs versus VKAs.
Table 1. Interaction of presence of hypertension on the comparative efficacy and safety of NOAC versus VKA Hypertension (n=63,869) No hypertension (n=7,733) P-value (int) Adjusted HR, 95% CI Adjusted HR, 95% CI Stroke or systemic embolism 080, 0.72–0.89 0.79, 0.53–1.19 0.98 Haemorrhagic stroke 0.55, 0.41–0.74 0.24, 0.04–1.37 0.36 Death from any cause 0.91, 0.84–0.98 0.89, 0.76–1.04 0.82 Major bleeding 0.90, 0.76–1.07 0.84, 0.69–1.01 0.57 Intracranial haemorrhage 0.41, 0.24-.068 0.48, 0.14–1.69 0.81 Major or clinically relevant non-major bleed 0.90, 0.68–1.18 0.91, 0.55–1.53 0.96

Conclusions
Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.
6076Improvement of exercise capacity over the course of outpatient cardiac rehabilitation is an independent predictor of prognosis after a myocardial infarction
Authors: Novakovic M , Novak T , Vizintin Cuderman T , Krevel B , Tasic J , Rajkovic U , Fras Z , Jug B 
Published: October 2019

Abstract

Background
Cardiac rehabilitation after myocardial infarction improves cardiovascular health and quality of life. However, data on long-term prognostic impact of surrogate rehabilitation parameters–such as exercise capacity improvements–remain scarce.

Purpose
To assess the independent prognostic impact of exercise capacity improvement over the course of outpatient cardiac rehabilitation after myocardial infarction.

Methods
Consecutive patients undergoing outpatient cardiac rehabilitation (3-times weekly for 12 weeks) after a myocardial infarction at a university centre were included. Exercise testing was performed at inclusion and after completion of the rehabilitation programme, with exercise capacity improvement defined as ≥2 MET increase over the course of the programme. Clinical data and risk factors were systematically collected, and patients were followed up for a minimum of 2 years. Kaplan-Meier curves and a multivariate Cox proportional hazard model were constructed for prediction of events (defined as a composite of incident cardiovascular death, re-infarction and coronary revascularsiation), with age, sex, LDL-cholesterol levels and body mass index as co-variates.

Results
A total of 409 patients were included (20% women). Exercise capacity and expected exercise performance were significantly improved after cardiac rehabilitation programme (6.6 to 9.5 METs, p<0.001, and 82 to 117%, p<0.001, respectively). After a median follow-up of 6.5 years, 93 patients experienced an event. Exercise capacity improvement of ≥2 METs was associated with reduced event rates (Figure 1), retaining statistical significance even after adjusting for age, sex, LDL-cholesterol and body mass index (HR 0.485, 95% CI 0.285–0.824).
Kaplan-Meier curve

Conclusion
Improvement of exercise performance over the course of outpatient cardiac rehabilitation is an independent predictor of prognosis after a myocardial infarction, with improvements of ≥2 METs associated with a 50% reduction in events.
6081Efficacy and limitations of quinidine therapy in patients with Brugada Syndrome
Authors: Mazzanti A , Tenuta E , Marino M , Pagan E , Morini M , Memmi M , Curcio A , Monteforte N , Bloise R , Napolitano C , Bagnardi V , Priori S G 
Published: October 2019

Abstract

Background
Quinidine at high-dose is used in patients with Brugada Syndrome (BrS), but its efficacy to prevent life-threatening arrhythmic events (LAE) in BrS is unproven and its use is limited by side effects.

Objective
We assessed whether low-dose quinidine in BrS patients reduces: 1) the occurrence of a first LAE; 2) the arrhythmic burden in the high-risk group of cardiac arrest survivors.

Methods
We first compared the clinical course of 53 BrS patients treated with quinidine to that of 441 untreated controls, matched by sex, age, and symptoms. Furthermore, we calculated the annual incidence of LAEs off- and on-quinidine in 123 BrS patients who had survived a cardiac arrest.

Results
First, we compared the clinical course of 53 BrS patients treated with quinidine (i.e. “cases”: 89% males, median age 40 years) to that of 441 untreated, clinically-matched BrS patients (i.e. “controls”: 91% males, median age 41 years) present in our database of patients with inherited arrhythmias. Cases received quinidine (median dose of 450 mg per day) for 5.0±3.7 years. Quinidine was interrupted in only 3/53 cases (6%) for side effects and it conferred a nonsignificant reduction of the risk of a first LAE in cases versus controls (HR 0.74, 95% CI 0.22–2.48, P=0.62).
Secondly, we calculated the annual recurrence of LAE off- and on-quinidine in 123 BrS cardiac arrest survivors, 27 of whom were treated with quinidine for 7.0±3.5 years. The annual rate of recurrent LAEs decreased significantly from 14.7% while off-quinidine to 3.9% while on-quinidine (P=0.03). Notably, recurrent life-threatening arrhythmic events were recorded in 4/27 (15%) symptomatic patients while on-quinidine.

Conclusion
We demonstrated for the first time in the long-term that low-dose quinidine reduces the recurrence of life-threatening arrhythmias in symptomatic BrS patients, with few side effects. Remarkably, about one-fifth of symptomatic patients experience life-threatening arrhythmias while on-treatment, suggesting that quinidine cannot replace implantable defibrillators in high-risk subjects.
6109A novel parameter for stent expansion is superior to conventional parameters for predicting adverse events after drug-eluting stent implantation
Authors: Katsura A , Minami Y , Kato A , Sato T , Muramatsu Y , Kakizaki R , Nemoto T , Hashimoto T , Fujiyoshi K , Meguro K , Shimohama T , Tojo T , Ako J 
Published: October 2019

Abstract

Background
Among several parameters for stent expansion, which is better for predicting adverse events remains to be elucidated.

Purpose
To assess the predictive significance of several parameters for stent expansion on the incidence of adverse cardiac events.

Methods
A total of 183 consecutive patients with de novo lesion treated with drug-eluting stent (DES) under optical coherence tomography (OCT) guidance were enrolled. The stent expansion was retrospectively assessed on the final OCT images after the stent implantation by both conventional and novel parameters. The conventional parameters included the minimum stent cross-sectional area (MSA) and %stent expansion defined as [MSA/mean reference lumen cross-sectional area × 100]. The novel parameter was the minimum expansion index (MEI) calculated by using a novel algorhythm which yields the ideal lumen area in each frame by taking into account vessel tapering. The expansion index was calculated by [actual lumen area/ideal lumen area × 100] in each frame through the stented segment. The MEI was the minimum value of expansion index through the stented segment. The both conventional and novel parameters were compared between cases with and without device-oriented cardiac events (DoCE). Receiver operating characteristics (ROC) curves were constructed to assess the ability of those parameters to predict DoCE.

Results
The MSA and MEI in the DoCE group (n=12) were significantly smaller than the no DoCE group (n=171) (3.29±0.72 vs. 4.45±1.97 mm2, p<0.001, 66.9±10.6 vs. 78.3±14.8%, p=0.01, respectively), although the %stent expansion was not significantly different between the two groups (62.7±11.9 vs. 70.7±16.3%, p=0.094). In ROC analyses, the area under curve of MEI to predict DoCE was the largest among the parameters (Figure).

Conclusion
Among several parameters for stent expansion, a novel MEI was better to predict device-oriented cardiac events after DES implantation.
6113Gender differences in long-term outcomes in patients with deferred revascularization following fractional flow reserve assessment: international collaboration registry of physiologic evaluation
Authors: Hoshino M , Yonetsu T , Kanaji Y , Sugiyama T , Yamaguchi M , Hada M , Ohya H , Sumino Y , Kanno Y , Hirano H , Horie T , Murai T , Koo B K , Escaned J , Kakuta T 
Published: October 2019

Abstract

Background
Studies of sex differences in fractional flow reserve (FFR) measurements have shown that in comparison with men, angiographic lesions of similar visual severity are less likely to be ischemia producing in women. Gender specific differences may influence revascularization decision making and prognosis after deferred revascularization following FFR measurement.

Purpose
This study sought to investigate the gender difference in long-term prognosis of patients of deferred revascularization following FFR assessment.

Methods
A total of 879 patients (879 vessels) with deferred revascularization with FFR >0.75 who underwent FFR and CFR measurements were enrolled from 3 countries (Korea, Japan, and Spain). Long-term outcomes were assessed in 649 men and 230 women by the patient-oriented composite outcome (POCO, a composite of any death, any myocardial infarction [MI], and any revascularization). We applied inverse-probability weighting (IPW) based on propensity scores to account for differences at baseline between women and men (age, hypertension, hyperlipidemia, diabetes mellitus, lesion location, clinical status, FFR, Reference diameter, Diameter stenosis, lesion length). The median follow-up duration was 1855 days (745–1855 days).

Results
Median FFR values were 0.88 (0.83–0.93) in men and 0.89 (0.85–0.94) in women, respectively. The occurrences of POCO were significantly high in men compared with that in women (10.5% vs 4.2%, P=0.007). Kaplan–Meier analysis revealed that women had a significantly lower risk of POCO (χ2=7.2, P=0.007). Multivariate COX regression analysis revealed that age, male, diabetes mellitus, diameter stenosis, lesion length, and coronary flow reserve were independent predictors of POCO. After applying IPW, the hazard ratio of male for POCO was 2.20 (95% confidence interval: 1.12 to 4.33, P=0.023).

Conclusion
This large multinational study reveals that long-term outcome differs between women and men in favour of women after FFR-guided revascularization deferral.

Acknowledgement/Funding
None