bluuebunny/crossref_metadata_2025 huggingface dataset:
P6563Time trends in incidence rates of atrial fibrillation in Norway 2004–2014. A CVDNOR project
Authors: Kjerpeseth L J , Igland J , Selmer R , Ellekjaer H , Berge T , Kalsto S M , Christophersen I E , Myrstad M , Skovlund E , Egeland G M , Thell G S , Ariansen I
Published: October 2019

Background

The reported incidence and prevalence of atrial fibrillation (AF) has been inconsistent among studies.

Purpose

We aimed to study time trends in incidence (first time) of AF hospitalizations or AF deaths in Norway in the period 2004–2014 by age and sex.

Methods

Nationwide hospital discharge diagnoses in the Cardiovascular Disease in Norway (CVDNOR) database and in the National Patient Registry were linked to the National Cause of Death Registry. All hospitalizations with AF as primary or secondary diagnosis and out-of-hospital deaths with AF as underlying cause (ICD-9: 427.3 or ICD 10: I48; AF or atrial flutter) in individuals ≥18 years were obtained during 1994–2014. Incident AF was defined as first hospitalization or out-of-hospital death due to AF with no previous hospitalization for AF the past 10 years. Age-standardized incidence rates with 95% confidence intervals (CIs) were calculated using direct standardization to the age-distribution in the Norwegian population per Jan 1st 2004. Age-adjusted average yearly incidence rate ratios (IRR) with 95% CIs were estimated by Poisson regression analyses. Accumulated prevalence during 1994–2014 was assessed in Norwegian residents 18 years and older per Dec 31st 2014.

Results

During 39,865,498 person years of follow up from 2004 to 2014 we identified 175,979 incident AF cases of which 30% were registered with AF as primary diagnosis, 69% as secondary diagnosis and 1% as out-of-hospital cause of death. The age-standardized incidence rate of AF hospitalization or out-of-hospital death per 100,000 person years was stable at 433 (426–440) in 2004 and 440 (433–447) in 2014. IRR were stable or declining across age groups of both sexes, except for the youngest age group 18–44 years, where incidence rates of AF hospitalization or out-of-hospital death increased by 2% per year, IRR 1.02 (1.01, 1.03). By 2014, the prevalence of AF assessed from hospital or death records was 2.9% in the adult population 18 years and older.

Conclusion

We found overall stable incidence rates of AF from 2004 to 2014 in the adult Norwegian population. Increased incidence rates of AF in the population 18–44 years are worrying and need further investigation.

Acknowledgement/Funding

The Norwegian Atrial Fibrillation Reseach Network
P6569Additive value of evaluating patients with syncope by an implantable loop recorder: diagnosis of subclinical atrial fibrillation
Authors: Olivella San Emeterio A , Francisco Pascual J , Rivas Gandara N , Perez Rodon J , Santos Ortega A , Benito Villabriga B , Llerena Butron S I , Rodriguez Garcia J , Garcia-Dorado D , Ferreira Gonzalez I
Published: October 2019

Background

Few information exists about the additive value of implantable loop recorders (ILR) for the diagnosis of subclinical atrial fibrillation or flutter (AF) in patients (p) studied for syncope and its therapeutic and prognostic implications.

Purpose

To evaluate the burden of new onset AF diagnosed by ILR in patients studied for syncope and its therapeutic and prognostic implications.

Methods

We conducted an observational cohort study in a tertiary center. From April 2014 to January 2019, 355 ILR were implanted in patients with syncope according the ESC syncope guidelines. We excluded the ones with previous known AF and younger than 18 years old (yo), with a final cohort of 197 patients. All of them were therefore followed in outpatient clinic and treated according to current clinical guidelines. New AF diagnosis and consequent therapeutic changes and related clinical events were recorded.

Results

Of 197p, 38 had a first episode of AF (19.29%), with a mean AF burden of 4.19%, and a median of 0.15%. The incidence rate of AF detection was 10.67patients/year (p-y), with higher incidence among patients older than 65 yo (14.17p-y vs 5.27p-y, p<0.05). Only 1 patient out of 38 had a symptomatic episode that triggered consultation to the emergency room (2.63%). Oral anticoagulants (OAC) were started in 30 of 38 patients with new onset AF (78.94%). Only one stroke was reported secondary to new onset AF before OAC were started. 2 mayor bleedings were reported (1.01%), both of them related to OAC start for new AF diagnosis. 4 patients died (2.03%), all of them from non-cardiovascular causes.

Kaplan Meier survival from AF

Conclusions

New onset AF is frequent in patients with ILR implanted for syncope, especially among those older of 65 yo, with the vast majority consisting in short paroxysms. Following AF detection, generally OAC are initiated.
P6574Symptomatic palpitations causing anxiety in women, what are the underlying arrhythmias
Authors: Insulander P , Carnlof C , Jensen-Urstad M , Schenck-Gustafsson K
Published: October 2019

Background

Highly symptomatic palpitations are common, particularly in women, and may cause disturbing symptoms including anxiety, depression, and decreased health related quality of life. Palpitation in this context has been considered generally benign and caused by premature atrial or ventricular beats or stress-induced sinus tachycardia. However, how often arrhythmias of clinical importance such as atrial fibrillation and supraventricular or ventricular tachycardia is the cause is unknown.

Purpose

To evaluate to what extent symptomatic palpitation in women is caused by clinically important arrhythmias.

Methods

A new Swedish digital technique was used. The system uses a well-validated algorithm to analyze heart rhythm (both thumbs and chest recordings), is connected to the user's smartphone and provides immediate response to the user. The result is simultaneously available for the supervising physician. In cases of non-benign arrhythmias, the result was also analyzed manually. In all, 909 women (age 56±11 years) with palpitations causing anxiety were included. ECG was recorded twice a day and at symptoms for 60 days. Participants with known atrial fibrillation were excluded.

Results

In all, 6 861 ECG recordings were done due to symptomatic palpitation. Underlying heart rhythms were as follows: normal sinus rhythm (73%), sinus tachycardia (12%), premature atrial beats or ventricular beats (7%), atrial fibrillation (4%), benign sinus bradycardia and second-degree AV block type 1 (4%), and supraventricular tachycardia (1%). In 1% of recordings, quality was too poor for analysis. No ventricular tachycardia was recorded. In all, 19 women with previously undiagnosed atrial fibrillation and 12 women with undiagnosed supraventricular tachycardia were found.

Conclusions

In the great majority of episodes causing symptomatic palpitation in women, the underlying arrhythmia is benign. However, in 5% previously undiagnosed atrial fibrillation or supraventricular tachycardia were found.
P6581Association of neuro-psycho-behavioral troubles to catecholaminergic polymorphic ventricular tachycardia: a more severe arrhythmic phenotype?
Authors: Placide L , Sacher F , Maury P , Probst V , Pasquie J L
Published: October 2019

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is defined by bidirectional or polymorphic ventricular tachycardia during adrenergic situations and is associated to a poor long-term prognosis. Clinical cases suggest an association between epilepsy and/or neuro-psycho-behavioral troubles (NPBT) to cardiac channelopathies.

Methods

This is a retrospective observational study based on case analysis from the INTEGRALIS database of the referral center for inherited cardiac arrythmias in Nantes. Epidemiological and clinical-biological features of the population have been studied. Patients with Presence or Absence of NPBT were compared. Results:From 8306 pts in the whole database, 533 presented with VT and 71 pts were diagnosed with CPVT and genotyped. Symptom onset occurred at a medium age of 17.1±13.5 years. Median LVEF was 65% (IQR 9,8%) and median corrected QT interval (QTc) was 399 ms (IQR 27 ms). 77.5% of pts had fainting and/or syncopes, and there were 28.2% patients with a history of cardiac arrest. Time to diagnosis was below1 year for 44.2% of symptomatic pts. Symptoms occurred during exertion for 42.3% of pts including swimming. The prevalence of NPBT was 23,9%. 74% of NPBT were convulsive seizures, 21% psycho-behavioral troubles and 5% epilepsy proved by EEG. Median age of symptom onset was younger in the group “NPBT” (12.2±4 yo vs 19.2±15.5 yo). The rate of patients with symptoms during exertion was higher in the group “NPBT” (29.4 vs 7.4% P=0.031). A mutation in the gene of Ryanodine receptor-2 was found in 64.8% of pts.

Comparisons patients w/wo NPBT NPBT (N=17) Without NPBT (N=54) Familial history of Sudden death 7/17 (41.2%) 24/54 (44.4%) NS Familial history of CPVT 5/17 (29.4%) 29/54 (53.7%) NS Medium age of symptom onset (yo) 12.1±4 19.2±15.5 P=0.021 Time to diagnosis <1 year 4/17 (23.5%) 16/54 (27.8%) NS Malaises and/or syncopes 17/17 (100%) 38/54 (70.4%) P=0.035 Cardiac arrest 9/17 (52.9%) 11/54 (20.4%) P=0.025 ICD Implantation 6/17 (35.3%) 12/54 (22.2%) NS Supraventricular arrhythmias 3/17 (17.7%) 6/54 (11.1%) NS Antiepileptic treatment 5/17 (29.4%) 2/54 (3.7%) P=0.009

Conclusion

NPBT appears to be associated to a younger age of symptom onset and a higher rate of serious cardiac events particularly during swimming. This study will serve as preliminary data for further clinical and experimental protocols.
P6582Control and stability theory, modelling ventricular dynamics in superficial 12-lead ECG as a novel contribution to non-invasive risk stratification of Brugada ECG patterns(?)
Authors: Sabatini A
Published: October 2019

Background

Brugada syndrome (BrS) risk stratification in asymptomatic subjects is still currently the most important yet unresolved clinical problem to determine the subset of patients with BrS requiring ICD implantation. The underlying pathophysiological mechanisms responsible for BrS ECG patterns remain unknown, as well as the mechanisms of the sudden onset of polymorphic ventricular tachycardia which leads to ventricular fibrillation and sudden cardiac death (SCD).

Purpose

This study aims to analyze from a totally alternative perspective, superficial 12-lead ECG signals. It departs from the numerous and various attempts to characterize and measure single morphology of specific and individual ECG segments, intervals and waves, rather focusing on and studying the dynamics and stability of the superficial 12-lead ECG signal as a whole to determine stability parameters able to contribute to BrS ECG pattern risk stratification and differential diagnosis of BrS.

Methods

A quantitative stability control closed loop system has been designed to model the electrophysiology dynamics of the cardiac conduction system with a 12-lead superficial ECG signal being the input and output of the system (Fig. 1). A normal ECG signal and a type-1 coved Brugada pattern ECG-V2 portion have been scanned, digitized and quantitatively processed to obtain stability parameters (poles and zeros in the S-plane). Scanning was performed by Digitizeit – Digital River GmbH. Processing in the S-plane was performed by ©2019 Wolfram Demonstrations Project & Contributors, http://demonstrations.wolfram.com/, poles and zeros and Microsoft Excel software was also used.

Results

Poles and zeros of the system for type-1 coved Brugada pattern ECG-V2 and for the normal ECG-V2 are shown in Fig. 2, together with stability.

Conclusions

Based on our data,

1. It appears that portions of the ECG patterns, approximated by mathematical continuous time models representing, at the infinitesimal limit, every possible pattern and behaviors of an ECG signal, such as repolarization patterns, may exhibit interesting dynamics characteristics of stability and can be stratified as stable, marginally stable or unstable.

2. Such a classification may then be implemented to risk stratify repolarization patterns. When tending to instability, such patterns seem to be associated to high risk repolarization patterns such as BrS coved type-1 pattern, hence indicating higher risk of developing polymorphic VT or SCD.

In conclusion, more work will be needed to further this methodology to improve the understanding of the effects of the various physiological and pathological substrates involved with malignant arrhythmias and to improve risk stratification strategies to determine the subset of patients with Brugada syndrome requiring ICD insertion. Control systems and stability theory may indeed indicate an interesting and effective procedure for future work.
P6590Androgenic effects on ventricular repolarization: a translational study from pharmacovigilance databases to iPSC-cardiomyocytes
Authors: Salem J E , Yang T , Moslehi J J , Waintraub X , Gandjbakhch E , Bachelot A , Hidden-Lucet F , Hulot J S , Knollmann B C , Lebrun-Vignes B , Funck-Brentano C , Glazer A M , Roden D M
Published: October 2019

Aim

Male hypogonadism, arising from various etiologies including androgen-deprivation therapies (ADT), has been reported as a risk-factor for acquired long-QT (aLQT) and Torsades de pointe (TdP). A full description of clinical features of aLQTS associated with ADT and of underlying mechanisms are lacking.

Method and results

We searched the WHO pharmacovigilance database for men (n=6,560,565) presenting with aLQT, TdP or sudden death (SD) associated with ADT. We identified 184 cases of aLQTS and/or TdP (11% fatal), and 99 with SD. Of the 10 ADT examined, 7 had a disproportional association (reporting-OR=1.4–4.7, p<0.05) with aLQT, TdP or SD. The minimum time to SD was 0.25 days. Enzalutamide (Enza, androgen antagonist) was associated with more deaths (17%, p<0.001) than other ADT used for prostate cancer (8.1%,Table). In cardiomyocytes derived from induced pluripotent stem cells (IPS-CMs) from men, we studied electrophysiological effects of enza and dihydrotestosterone (DHT). Acute and chronic enza (25μM) prolonged action potential durations (APD90-paced0.5Hz; 414±63 (control) vs. 951±67 (acute, p<0.01) and 1028±63msec (chronic, p<0.01), and generated early/delayed afterdepolarizations and/or triggered activity in drug treated cells (4/7 acute and 3/5 chronic). Enza acutely and chronically inhibited IKr, and chronically enhanced INa-L. DHT (30nM) reversed enza effects on IPS-CMs. In 7 men with aLQT and hypogonadism, ECGs showed low amplitude, bifid T-waves typical of IKr block which resolved with testosterone.

Table 1 ndeath/ntotal (%) aLQT TdP SD n/naLQTS±TdP±SD (%) with ADT considered suspect by reporter Leuprorelin 1,871/22,113 (8.5%) 33 16 18 28/55 (50.9%) Goserelin 471/5,821 (8.1%) 8 2 15 17/22 (77.3%) Triptorelin 52/1,517 (3.4%) 6 3 2 5/8 (62.5%) Degarelix 82/2,787 (2.9%) 7 4 3 10/11 (90.9%) Bicalutamide 724/10,144 (7.1%) 23 16 11 28/41 (68.3%) Flutamide 163/4075 (4%) 4 2 3 3/7 (42.9%) Enzalutamide 5,430/31,896 (17%) 19 4 13 30/32 (93.8%) Abiraterone 1,240/14,261 (8.7%) 19 7 10 29/31 (92.5%) Finasteride 1,062/33,877 (3.1%) 52 20 32 20/87 (23%) Dutasteride 248/15,177 (1.6%) 26 7 11 5/38 (13.2%) Total ADT* 10,540/127,385 (8.3%) 168 68 99 137/283 (48.4%) Number (n) of case reports in men in the WHO international pharmacovigilance database (VigiBase) by ADT through 08/09/2018. *Some patients were on combination ADT.

Enzalutamide electrophysiology IPS-CMs

Conclusion

ADT is a risk factor for aLQT and TdP. Androgens may be useful in TdP treatment of hypogonadic men.

Acknowledgement/Funding

INSERM
P6592Novel heart-specific LncRNAs identified by deep sequencing contribute to pathogenesis in arrhythmogenic cardiomyopathy
Authors: Chen L , Song J , Hu S
Published: October 2019

Background

Arrhythmogenic Cardiomyopathy (AC) is one of main causes of sudden cardiac death in young people with limited understanding of molecular mechanism. LncRNAs are emerging as important regulators of cardiovascular diseases, but their roles in AC remain elusive.

Purpose

This study is to identify novel lncRNAs in AC genome wide and investigate their functions.

Methods and results

Extremely deep RNA-seq was performed for AC right ventricles (RVs, n=9) and left ventricles (LVs, n=6), normal RVs (n=5) and LVs (n=6), and dilated cardiomyopathy (DCM) RVs (n=4). Novel lncRNAs were accurately identified with epigenetic annotations. In comparison with normal and DCM, 1,925 novel lncRNAs transcripts specifically upregulated in AC RVs were identified. Most of AC-specific lncRNAs were highly expressed in heart, located in distal regions (>3 kb) from coding gene and marked by H3K4me1 or H3K27ac, indicating that these lncRNAs might act as cis-elements to regulate gene expression. Enrichment analysis revealed that AC-specific lncRNAs were associated with AC phenotypes like RV enlargement and dysfunction. Interestingly, their potential target genes were significantly enriched in lipid metabolism and calcium signaling pathways. In-vitro experiments demonstrated that LncRNA AC1, a novel AC-specific lncRNA, was significantly positively correlated with adipogenic genes expression. And overexpression of LncRNA AC1 promoted adipogenic genes expression and droplet deposition in human derived iPSC-CM and cardiac fibroblast.

ESC-AC lncRNA study abstract

Conclusion

We identified novel AC-specific lncRNAs related to adipogenesis and validated them in-vitro. Our findings also provide fundamental resource for the potential development of basic translation study for AC.

Acknowledgement/Funding

This study was supported by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-015)
P6596S100A8/A9 and sRAGE peripheral blood levels in patients with heart failure and an implanted cardioverter/defibrillator: relation with sustained, fast ventricular arrhythmias
Authors: Flevari P , Leftheriotis D , Kroupis C , Kitsinelis V , Stasinos V , Varlamos C , Dima K , Deftereos S , Iliodromitis E
Published: October 2019

Background

Prediction of sudden cardiac death in heart failure (HF) remains suboptimal. Blood levels of the S100A8/A9 heterodimer protein complex and the soluble receptor of advanced glucation end product (sRAGE) are promising biomarkers in HF, reflecting inflammatory/fibrotic and apoptotic pathways, possibly involved in ventricular arrhythmogenesis. The relation of S100A8/A9 and sRAGE with ventricular arrhythmias and sudden cardiac death risk has not been previously assessed.

Purpose

Purpose of the study was to investigate whether S100A8/A9 and sRAGE serum blood levels of patients (pts) with systolic heart failure are related to the occurrence of life-threatening ventricular tachyarrhythmias.

Patients and methods

We studied 60 pts with clinically stable heart failure due to coronary artery disease (n=37) and dilated cardiomyopathy (n=23), all with a chronically implanted ICD for primary (n=43) or secondary (n=16) sudden death prevention, all in sinus rhythm. Their mean age (±1 SE) was 62±2 years, NYHA class I-II, mean LVEF 28±1%, Nt-pro-BNP 893±85 pg/dl. Blood was drawn at study initiation for S100A8/A9 and sRAGE assessment (ELISA, R&D Systems). They all were systematically followed-up for 4 years regarding the occurrence of fast ventricular tachyarrhythmias (>180 bpm) necessitating antiarrhythmic intervention through the ICD.

Results

S100A8/A9 and sRAGE levels were 16±1.6 ng/ml and 1076±99 pg/ml respectively. S100A8/A9 levels were lower than in normal controls, while sRAGE levels were within normal limits. During the 4-year follow-up period, 39 pts had an uneventful course (Group I), while 16 pts exhibited fast ventricular tachyarrhythmic episodes necessitating ICD activation (anti-tachycardia pacing or shock, Group II). Three pts died of pump failure and 2 pts of non-cardiac causes. No differences were observed between Group I and Group II pts regarding mean NYHA class, Nt-pro-BNP levels. Group II patients had significantly lower LVEF as well as S100A8/A9 serum levels relative to pts without ventricular arrhythmias (LVEF: 30±1.2 vs, 25±1.3%, p<0.05, S1OOA8/A9: 18.9±2.2 vs 11.8±1.5 ng/ml, p<0.05), while no difference was observed between Groups regarding sRAGE levels 1097±101 1105±239 pg/ml, p:NS). S100A8/A9 levels were not related significantly to LVEF (r:-21, p=0.13).

Conclusion

S100A8/A9 protein levels are reduced in pts with stable HF and an implanted ICD. They are even lower among pts with rapid ventricular tachyarrhythmias occurring during follow-up. This finding implies that S100A8/A9 may constitute a biomarker of increased sudden cardiac death risk in HF, in addition to reduced LVEF.
29Prognostic safety of automatic cancellation of rest myocardial perfusion scan by machine learning: a report from multicenter REFINE SPECT registry of new generation SPECT
Authors: Hu L , Sharir T , Fish M B , Ruddy T D , Di Carli M , Dorbala S , Einstein A J , Betancur J , Eisenberg E , Commandeur F , Germano G , Damini D , Berman D , Slomka P J
Published: October 2019

Background

We aimed to develop a machine learning (ML) computer score derived from stress imaging and clinical data, which indicates if the rest scan could be automatically and safely canceled in the routine stress/rest myocardial perfusion SPECT (MPS).

Methods

A total of 20414 stress/rest cases from the REFINE SPECT registry collected from 5 sites in 3 countries with Tc-99m-based MPS images, clinical data, and clinical follow-up were included in the study. All images were automatically processed at our Medical Center. The automatically generated myocardial contours were checked by experienced technologists. In total, 93 variables (26 clinical, 17 stress-test, and 50 stress-imaging variables) were used to build a LogitBoost model for prediction of adverse events (AE), including coronary revascularization, death, myocardial infarction, and unstable angina. 10-fold cross-validation was performed to separate test from validation data for the assessment of ML. The overall ML predictive performance was compared to quantitative (stress total perfusion deficit [TPD]) by the area under the receiver operating characteristic curves (AUC). ML cut-off (ML1) to simulate the decision of cancellation of the rest scan was set to result in the same % of normal scans as these determined by the normal clinical reader diagnosis on a 4-point scale in the whole population, or the same % of scans with visual summed stress scores (SSS) = 0 in the subpopulation with available SSS. A second ML cutoff (ML2) was established to achieve a 1% annual risk of AE. The annual risk of AE of the normal ML score was compared with normal clinical diagnosis and with the finding of SSS = 0.

Results

The mean follow-up interval was 4.7±1.5 years. Overall, 3542 AE were observed (3.7% annual risk). The AUC for AE was higher for ML (0.780±0.005) than for stress TPD (0.698±0.006) (p<0.001). Normal clinical diagnosis was reported in 60% cases. In 70% (14242 scans) with available segmental scores, 53% had SSS=0. ML1 and ML2 thresholds were compared with normal visual diagnosis and with SSS = 0 for AE (Figure). ML1 achieved a lower annual risk (1.5%) than normal clinical diagnosis (2.1%) or SSS = 0 (1.6% versus 2.3%) (p<0.001). The more conservative ML2 threshold with a 1% annual risk of AE resulted in a 40% canceling rate.

Figure 1

Conclusion

ML could be used to automatically cancel the rest MPS scan with the same proportion as using normal visual MPS reading, but with significantly lower AE rate in stress-only scans.

Acknowledgement/Funding

R01HL089765 from the National Heart, Lung, and Blood Institute/National Institutes of Health (NHLBI/NIH)
56The SGLT2 inhibitor empagliflozin reduces mortality in experimental pulmonary hypertension
Authors: Chowdhury B , Luu V Z , Luu A Z , Kabir M G , Pan Y , Teoh H , Quan A , Mazer C D , Verma S
Published: October 2019

Introduction

Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion and profoundly reduces hospitalisation for heart failure and cardiovascular mortality in individuals with type 2 diabetes. While empagliflozin has been reported to reduce blood pressure, its effect on pulmonary arterial hypertension (PAH) is unknown. PAH is a serious and progressive disease that is characterised by pulmonary artery vasoconstriction, vascular remodelling, right ventricular hypertrophy, and ultimately heart failure.

Purpose

To investigate the impact of empagliflozin on PAH-associated mortality and the progression as well as reversal of PAH in monocrotaline (MCT)-treated Sprague-Dawley rats.

Methods

A total of 66 male rats (220–250 g) were randomly assigned to one of three studies. PAH was induced with a single intraperitoneal injection of MCT on day 0 and empagliflozin (10 mg/kg) was administered daily by oral gavage. Survival study: PAH was induced with 60 mg/kg MCT. Starting on day 1, rats were treated with empagliflozin (n=8) or vehicle (n=8) for 28 days and monitored for up to 45 days post-MCT injection. Prevention study: Rats were administered 60 mg/kg MCT and treated with empagliflozin (n=12) or vehicle (n=12) for 20 days from day 1 onwards. Reversal study: 21 days after being injected with 40 mg/kg MCT, rats were given empagliflozin (n=8) or vehicle (n=8) for 14 days. At the end of the treatment window, rats in the latter two studies underwent haemodynamic assessments before their tissues were harvested for histological review.

Results

Mortality rates between the two groups were significantly different (median survival 24 vs 33 days for vehicle vs empagliflozin; p<0.05). Compared to the MCT-vehicle-treated rats, the MCT-empagliflozin group had significantly lower mean pulmonary artery pressure (77.4±8.6 vs 51.0±4.9 mmHg [Prevention study]; 56.0±4.3 vs 43.0±3.4 mmHg [Reversal study]); higher pulmonary acceleration time (21.0±0.8 vs 27.4±1.4 ms [Prevention study] and 27.1±1.0 vs 33.4±1.3 ms [Reversal study]); and less right ventricular hypertrophy (0.52±0.01 vs 0.41±0.04 [Prevention study]). Histological assessments revealed significantly less medial wall thickening (50.8±2.2 vs 44.7±1.1 mm) and muscularisation (53.2±1.3 vs 43.6±2.1 mm) in pulmonary arterioles from the empagliflozin- vs vehicle-treated rats (p<0.001 for both).

Conclusion

This is the first study demonstrating that SGLT2 inhibition with empagliflozin lowers mortality in experimental pulmonary hypertension in part via reduced pulmonary vascular remodelling.

Acknowledgement/Funding

This study was supported by grants from the Canadian Institutes of Health Research.
66Clinical outcomes after catheter ablation for atrial fibrillation in elderly patients: a French nationwide cohort study
Authors: Bisson A , Mondout F , Bodin A , Clementy N , Pierre B , Gaborit C , Herbert J , Guillon Grammatico L , Babuty D , Fauchier L
Published: October 2019

Catheter ablation for atrial fibrillation (AF) is a validated therapy for patients with symptomatic AF to prevent recurrences. The CASTLE AF trial indicated that ablation for AF in patients with heart failure was associated with a lower rate of death from any cause or hospitalization for worsening heart failure than was medical therapy. However, the benefit of AF ablation was not significant in older patients (>65 yo). The purpose of our study was to compare the incidence of these events in patients after AF catheter ablation versus patients not treated with AF ablation at a nationwide level and to analyse whether the possible benefit with AF ablation may differ among patients younger or older than 75 yo.

Methods

This French longitudinal cohort study was based on the national hospitalization PMSI (Programme de Médicalisation des Systèmes d'Information) database covering hospital care from the entire population. We included all patients, over 18 years old, with AF from January 2010 to December 2015.

Results

Among the 1,663,284 patients identified with AF, 28,018 patients were treated with AF ablation (28% female, mean age 60±10 yo) and 1,635,266 did not have AF ablation (48% female, mean age 78±11 yo). Among those treated with AF ablation, 1,605/28,018 patients (5.7%) were aged >75 yo.

During follow-up (456±546 days), hospitalization with a primary diagnosis of HF and death were recorded. Incidences of hospitalization for HF and death were significantly lower in AF ablation group (respectively 6.09% vs 13.29% person per year, p<0.0001, and 1.49% vs 17.11% person per year, p<0.0001). These associations were confirmed in a multivariable analysis after adjustment on age and other comorbidities (HR 0.66, 95% CI 0.63–0.69, p<0.0001 for HF and HR 0.21, 95% CI 0.19–0.23, p<0.0001 for all-cause death). Results were significant and relatively similar whether patients were aged below or above 75 yo: HR 0.63, 95% CI 0.60–0.66, p<0.0001 when age <75 yo and HR 0.60, 95% CI 0.51–0.70, p<0.0001 when age >75 yo for hospitalization for HF; HR 0.21, 95% CI 0.19–0.24, p<0.0001 when age <75 yo and HR 0.36, 95% CI 0.29–0.45, p<0.0001 when age >75 yo for all-cause death.

Conclusion

In the nationwide analysis of unselected AF patients seen in hospitals, AF ablation was independently associated with a lower risk of hospitalization for HF and death whether patients were aged below or above 75 yo.
101Characterization of the calcium component of vulnerable coronary plaque in patients with NSTEMI: prospective comparison between coronary CT and optical coherence tomography
Authors: Pezel T , Sideris G , Dillinger J G , Logeart D , Manzo-Silberman S , Cohen-Solal A , Beauvais F , Laissy J P , Henry P
Published: October 2019

Background

Acute Coronary Syndrome (ACS) remains a leading cause of mortality worldwide with a high risk of recurrence. Apart culprit plaques, the presence of vulnerable plaques could be associated with the occurrence of future cardiac events and need to adapt treatments. Several studies have demonstrated a role for Coronary Computed Tomographic Angiography (CCTA) to predict the vulnerability of the plaque but with limited analysis of its calcium component. Recent works suggest a role for calcification in this vulnerability.

To our knowledge, no studies have been performed to assess if the study of the calcium component of plaques with CCTA can help to predict vulnerability in non-ST elevation myocardial infarction (NSTEMI).

Purpose

To assess if the CCTA study of the calcium component of plaques can help to predict plaque vulnerability defined by intracoronary OCT analysis in patients with non-ST elevation myocardial infarction (NSTEMI).

Methods

Monocentric prospective study of consecutive patients referred for NSTEMI with elevated high-sensitivity cardiac troponin I level (hs-TnI>50 ng/ml) from January to October 2018. CCTA was systematically performed before coronary angiography to assess the presence of CAD. When CCTA demonstrated significant lesions, coronary angiography was performed within 24 hours associated with systematic OCT study of three coronary arteries. Apart culprit plaques, vulnerable plaques were defined in OCT by a fibrous screed thickness <65 microns. Calcified plaques were analysed with CT and then classified into 3 groups: vulnerable culprit plaque (VCP), vulnerable non-culprit plaque (VNCP) and stable plaque (SP).

Results

Of 1478 patients with chest pain, 257 (17%) had NSTEMI with high level of hs-TnI. From this 257 NSTEMI patients, 44 (17%) were without known CAD and among these, 33 (75%) had received coronary angiography with 29 (66% - mean age 59±13 years, 73% men) having coronary anatomy compatible with OCT assessment. A total of 123 calcified plaques were identified. Among them, OCT allowed to identify 77 (63%) SP and 47 calcified vulnerable plaques; 28 (23%) VNCP and 19 (15%) VCP. After CCTA analysis of the calcium component, predictive factors of plaque vulnerability were identified: longer calcification length (p<0.001), larger calcification volume (p<0.001), lower calcium mass (p=0.003), higher single plaque Agatston score (p<0.001), lower sphericity index (p=0.001), more spotty calcifications (p=0.001), as well as more intimal position in the wall (p<0.001). No significant differences were observed comparing VNCP and VCP (Figure).

OCT and “Virtual Histology” CT

Conclusion

CCTA study of the calcium component of plaque allows to identify predictors of plaque vulnerability defined by OCT in patients with NSTEMI.
105Calcified nodule in coronary artery: clinical features and prognosis with optical coherence tomography-guided percutaneous coronary intervention
Authors: Shibata H , Kijima Y , Nagoshi R , Kozuki A , Fujiwara R , Suzuki A , Kakizaki S , Fujimoto D , Kyo S , Masuko E , Miyata T , Shite J
Published: October 2019

Background

Calcified nodule (CN) in coronary artery is known to be a significant factor for stent underexpansion, however, its baseline characteristics and long-term prognosis is unclear.

Method

421 consecutive severe calcified lesions (Defined as maximum calcium arc >180 degrees) which underwent optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) were analyzed between January 2013 and December 2017. We investigated baseline characteristics and OCT parameter (maximum arc of calcium, maximum thickness of calcium, and length of calcium) and long-term clinical outcome (Major adverse cardiac event (MACE), any cause of death, acute myocardial infarction (AMI) and target vessel failure (TVF)). Median follow up period was 33.7 months.

Result

CN was seen in 22.3% (94 lesions) of all severe calcified lesions. Baseline characteristics and OCT parameters were significantly different in CN and non-CN groups (Hemodialysis; 23.6% vs. 14.1%, p=0.03, Multivessel Disease; 57.4% vs. 44.6, p=0.03, maximum arc of calcium; 305.4 vs. 286.1, p=0.02, maximum thickness of calcium (μm); 1206.2 vs 1123.8, p=0.01, length of calcium (mm); 24.6 vs. 19.0, p=0.01). CN lesions was strongly associated poor long-term clinical outcome (MACE; 50.5% vs. 25.7%, p<0.01), any cause of death; 18.1% vs. 9.5%, p=0.02, AMI; 7.4% vs. 2.4%, p=0.02, TVF; 38.3% vs. 19.2%, p<0.01).

Conclusion

Hemodialysis, multivessel disease and abundant calcium component may have accompanied with CN which may result in poor long-term prognosis.
108Biologic significance of healed culprit plaques in stable angina versus acute coronary syndromes
Authors: Fracassi F , Sugiyama T , Yamamoto E , Kurihara O , Kim H O , Thondapu V , Lee H , Fujimoto J G , Fuster V , Jang I K
Published: October 2019

Background

Healed plaques, the signature of prior subclinical plaque destabilization, are frequently found in autopsy studies and have recently been described in patients with acute coronary syndromes (ACS).

Objectives

To compare the prevalence and features of plaque vulnerability of healed culprit lesions in stable angina pectoris (SAP) versus ACS patients by using Optical Coherence Tomography (OCT).

Methods

A total of 752 patients were included: 376 patients with SAP were selected using propensity score matching, comparable to 376 patients with ACS. Healed plaques were identified using established criteria, defined as layers of different optical density on OCT. Healed plaque prevalence along with angiographic and OCT findings were compared between the two groups.

Results

Healed plaques were more frequent in SAP than in ACS patients (42.0% vs 28.7%, p<0.001). LDL-cholesterol and high sensitive C-reactive protein (hs-CRP) levels were significantly lower in SAP patients with layered plaque as compared to ACS patients with layered plaque [97.9±36.9 mg/dL vs 116.7±39.2 mg/dL, p<0.001; 0.20 (0.10–0.83) mg/L vs 4.98 (1.00–11.32) mg/L, p<0.001, respectively]. Thin-cap fibroatheroma, macrophage accumulation and microvessels were significantly less frequent in layered plaques in SAP patients as compared to those in ACS patients (12.7% vs 56.5%, p<0.001, 7.0% vs 79.6%, p<0.001, and 20.3% vs 43.5%, p<0.001, respectively). Calcifications were found more frequently among layered plaques in SAP patients than in ACS patients (51.3% vs 33.6%, p=0.006).

Conclusions

Healed plaques, detected more frequently in SAP than in ACS patients, portend different atherosclerotic backgrounds. In SAP patients, plaque destabilization frequently does not lead to occlusive thrombosis, possibly due to low level of local vulnerability and systemic inflammation. In ACS patients, the presence of high level of local vulnerability and systemic inflammation may play an important role in occlusive thrombus formation, resulting in terminating the cycles of subclinical thrombosis and healing.
130The effect of parity on exercise physiology in women with heart failure with preserved ejection fraction
Authors: Beale A L , Cosentino C , Segan L , Mariani J , Vizi D , Evans S , Nanayakkara S , Kaye D M
Published: October 2019

Introduction

Women are overrepresented amongst patients with HFpEF, however the underpinning mechanism for this asymmetric distribution is unclear. Pregnancy has been demonstrated to contribute to cardiovascular risk, and represents a potential gender specific risk factor for HFpEF.

Purpose

To investigate the relationship between parity and severity of HFpEF on invasive haemodynamic and echocardiographic studies.

Methods

Patients referred for investigation of dyspnoea with exercise right heart catheterisation from 2008–19 were included and classified as HFpEF with an ejection fraction (EF) ≥50% and a resting PCWP ≥15mmHg or exercise PCWP ≥25mmHg. All patients underwent detailed haemodynamic and echocardiographic assessment, and an obstetric history including socioeconomic data were obtained using a questionnaire.

Results

58 women were included, and categorised as having either 0–2 births, or ≥3 births, dividing the cohort equally. Women with ≥3 births achieved a lower peak exercise workload than those with 0–2 births (46 [31–68] vs. 38 [24–51] W, p=0.04). Women with ≥3 births had a greater rise in pulmonary capillary wedge pressure indexed to workload with exercise (0.5 [0.3–0.8] vs. 0.3 [0.2–0.5] mmHg/W, p=0.03), paralleled by a greater rise in right atrial pressure (10 [8–12] vs. 7 [3–11] mmHg, p=0.01), pictured. Pulmonary vascular resistance was also higher in women with ≥3 births (1.9 [1.6–2.4] vs. 1.6 [1.4–1.9] mmHg/L/min rest, p=0.046, and 1.9 [2.4–2.4] vs. 1.4 [1–1.8] mmHg/L/min exercise, p=0.024). Left ventricular ejection fraction was lower at rest (60 [57–61] vs. 63 [60–66] %, p=0.008) and during exercise (65 [62–67] vs. 68 [66–70] %, p=0.038) in women with higher parity. Otherwise, echocardiographic parameters did not differ according to parity. There were no significant differences between parity groups in baseline characteristics, including age, body mass index, systemic blood pressure, natriuretic peptides or dyspnea class. Similarly, comorbidities and socioeconomic status did not differ.

Conclusion(s)

Higher parity is associated with impairments in multiple physiologic parameters of HFpEF severity in women, including diastolic reserve, pulmonary vascular resistance, and systolic function. This may indicate a role for pregnancy in the development of HFpEF, and suggests that multiparous women should be targeted for intensification of preventative measures for HFpEF.
171Intravascular polarimetry in patients with coronary artery disease: a first-in-human pilot study
Authors: Otsuka K , Villiger M , Karanasos A , Van Zandvoort L J C , Doradla P , Daemen J , Diletti R , Van Geuns R J , Zijlstra F , Van Soest G , Dijkstra J , Nadkarni S K , Regar E , Bouma B E
Published: October 2019

Background

Polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties of tissue together with conventional cross-sectional OFDI images of subsurface microstructure. PS-OFDI offers refined insight into plaque morphology and composition, which are implicated in the pathogenesis of acute coronary syndromes (ACS).

Purpose

This first-in-human pilot study of intravascular polarimetry aimed to investigate birefringence and depolarization features of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional OFDI and with clinical presentation.

Methods

30 patients undergoing PS-OFDI (acute coronary syndrome; ACS, n=12 and stable angina pectoris; SAP, n=18) participated in this study. 342 cross-sectional images evenly distributed along all imaged coronary arteries were classified into one of seven plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross-section were compared between plaque types and with structural parameters. Further, we assessed the polarization properties in the fibrous caps of ACS and SAP culprit lesions and compared them with structural features using a generalized linear model.

Results

The median birefringence and depolarization showed statistically significant differences among plaque types (both p<0.001, one-way ANOVA). Depolarization significantly differed between individual plaque types (p<0.05), except between fibro-fatty and fibro-calcified plaques. Caps of ACS lesions and ruptured caps exhibited lower birefringence than caps of SAP lesions (p<0.01). In addition to clinical presentation, cap birefringence also associated with macrophage accumulation as assessed by normalized standard deviation.

Intravascular polarimetry

Conclusions

Intravascular polarimetry provides quantitative metrics that help to characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients (Figure). Quantitative assessment of plaque polarization properties by intravascular polarimetry may open new avenues for studying plaque progression and detecting high-risk patients.

Acknowledgement/Funding

The JSPS Overseas Research Fellowship, the Uehara Memorial Foundation, and the Japan Heart Foundation and Bayer Yakuhin
172Coronary 18F-sodium fluoride uptake predicts progression of coronary arterial calcification
Authors: Doris M , Moss A J , Andrews J P M , Williams M , Van Beek E J R , Forsyth L , Dweck M R , Newby D E , Adamson P D
Published: October 2019

Background

Combined positron emission tomography and computed tomography (PET-CT) using 18F-sodium fluoride (18F-NaF) to detect microcalcification provides the opportunity to gain important insights into disease activity in coronary atherosclerosis. However, the relationship between 18F-NaF uptake and progression of coronary calcification has not been determined.

Purpose

To determine the relationship between 18F-NaF uptake and progression of coronary calcification in patients with clinically stable coronary artery disease (CAD).

Methods

Patients with established, multivessel CAD underwent 18F-NaF PET-CT and CT coronary calcium scoring at baseline, with repeat CT calcium scoring at one year. Coronary arterial PET uptake was analysed qualitatively and semi-quantitatively in diseased vessels by measuring maximum tissue-to-background ratio (TBRmax) – defined as the maximum standardised uptake value in a plaque divided by mean blood pool activity measured in the right atrium. Coronary calcification was quantified by measuring calcium mass, volume, average calcium density and total Agatston score (AU).

Results

In total, 185 patients underwent baseline and repeat imaging (median age 66 years, 80% men), and 118 (64%) had increased 18F-NaF uptake in at least one vessel. Median total calcium score, volume, mass and average density were higher in patients with compared to those without increased 18F-NaF uptake (Table 1). At one year, patients with evidence of increased 18F-NaF uptake demonstrated more rapid progression of coronary calcification (97 [39–166] AU) versus those without uptake (35 [7–93] AU; p<0.0001). Amongst 18F-NaF-positive patients, the calcium score increased only in coronary segments with 18F-NaF uptake (baseline 90.5 [27.5–202] AU versus one year 135.5 [59.3–281.8] AU; p<0.0001) and not in 18F-NaF-negative segments (baseline 44.5 [16–110.5] AU versus one year 46.5 [18.25–114] AU; p=0.446). There was a moderate correlation between TBRmax and change in total calcium score, volume and mass at 1 year (Spearman's Rho = 0.37, 0.38, 0.46 respectively; p<0.0001 for all).

Coronary calcification at baseline in PET-negative and PET-positive patients All patients (n=185) 18F-NaF Positive (n=118) 18F-NaF Negative (n=67) P value Agatston Score (AU) 381 [107–892] 541 [245–1130] 136 [55–361] p<0.0001 Calcium Volume (mm3) 358 [131–787] 506 [251–1014] 131 [64–343] p<0.0001 Calcium Mass (mg) 71 [23–155] 100 [48–222] 24 [11–69] p<0.0001 Average Density (mg/mm3) 0.19 [0.17–0.22] 0.20 [0.18–0.23] 0.18 [0.16–0.20] p<0.0001

Conclusions

Coronary 18F-NaF uptake identifies both patients and individual coronary segments with greater disease and more rapid progression of coronary calcification over one year.

Acknowledgement/Funding

AstraZeneca (unrestricted educational grant). British Heart Foundation (CH/09/002, RE/13/3/30183, FS/17/79/33226) Wellcome Trust (WT103782AIA).
209Glucose is associated with future atrial fibrillation and heart failure already at prediabetes levels, a 19 year follow up of 243,665 subjects
Authors: Lind V , Hammar N , Lundman P , Friberg L , Tallback M , Walldius G , Norhammar A
Published: October 2019

Background

Dysglycaemia is associated with cardiovascular disease even below the diagnostic diabetes threshold. Atrial fibrillation (AF) has been found to be associated with the metabolic syndrome and life-style changes after AF have been found to reduce recurrence of AF.

Purpose

We explored the association glucose and risk of first event of AF, HF and combined event.

Methods

Subject with fasting glucose in the AMORIS cohort, obtained 1985–1996 at routine occupational health check-ups or primary care in the Stockholm area were included. Subjects with prevalent AF, HF, ischemic heart disease, revascularization and cerebrovascular disease were excluded. Glucose levels were categorised as low (<3.9 mmol/L), normal (3.9–6.0mmol/L), impaired (IFG; 6.1–6.9 mmol/L) and diabetes (≥7.0 mmol/L or a diabetes diagnosis) according to WHO definition in 2006. First events of AF, HF or a combined event was identified until December 2011 by linkage to national registries. Information on co-morbidities was obtained from the National Patient Register. Hazard ratios (HR and 95% CI) by glucose group for AF and heart failure were calculated using Cox proportional hazards with attained age as timescale and adjusting for gender, total cholesterol and triglycerides. The change in AF risk by increasing glucose level was described by using splines (Figure).

Results

243 665 subjects with mean age 48.3 at index date, 54% male were included. During a mean follow-up time of 19.1 years and 4,7 million person years, 23 522 events of AF, 21 411 events of HF and 35 131 combined events occurred. The proportion with IFG and diabetes were 3.2% and 3.3% respectively. In the diabetes group about half were diagnosed prevalent cases (1.5%). Glucose was continuously associated with developement of AF (Table and Figure) and even more of HF (Table).

Events (n) and HR by glucose category Atrial fibrillation Heart failure Combined event Event HR [95% CI] Event HR [95% CI] Event HR [95% CI] Low 405 0.97 [0.88–1.08] 326 0.97 [0.87–1.08] 598 1.00 [0.92–1.09] Normal 20 663 1.00 17 811 1.00 30 159 1.00 IFG 1185 1.20 [1.13–1.28] 1319 1.43 [1.35–1.51] 1901 1.30 [1.24–1.36] Diabetes 1269 1.28 [1.20–1.35] 1955 2.19 [2.08–2.29] 2473 1.73 [1.66–1.81] Events (n) of AF, HF and combined and HR (95% CI) by fasting glucose category.

HR for AF by glucose level spline graph

Conclusion

Dysglycaemia, including glucose levels below the diabetes threshold, is continuously associated with future risk of both AF and HF. These data are important considering the large population with undetected dysglycaemia at risk for AF and HF where preventive measures including life-style changes could be of importance even before the onset of overt diabetes.

Acknowledgement/Funding

Swedish Heart and Lung foundation