bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1036Acute and long-term ablation results of extra pulmonary vein drivers detected by ultra high density mapping on top of PVI in persistent AF
Authors: Enache B , Latcu D G , Hasni K , Bun S S , Saoudi N 
Published: October 2019

Abstract

Background
Whether ultra-high density (UHD) contact mapping is useful in radiofrequency ablation of persistent atrial fibrillation (AF) is unknown.

Purpose
To sequentially map the left atrial (LA) activation during AF ablation (circumferential PVI and ablation of extra pulmonary vein drivers).

Methods
Time reference was an LA appendage (LAA) electrogram (EGM). Points were acquired with respiratory gating if reference, cycle length (10 ms tolerance) and electrode location were stable. For fragmented EGM the timing of the surrounding area was used. In case of extremely low voltage (<0.01 mV) or lack of local statistical coherence no colour-code was displayed (grey area). Circular propagation around single points was defined as organized rotating drivers (see figure). All pts had PVI followed by remapping and ablation of the centre of rotational regions and at sites with focal type propagation. DC or chemical cardioversion were not performed in the first 48 h.

Results
Out of 41 patients (pts) undergoing first time ablation with the above described protocol, 30 (66±8 y, mean current episode duration 8 months) were followed for a mean time of 14,7 months. At 48 hours post-procedure, 70% of pts were no longer in AF: 6 (20%) in sinus rhythm and 15 (50%) in atrial tachycardias. At 1 year after a single procedure, freedom from AF was 87% and freedom from AF and AT was 60%.

Conclusion
In persistent AF, sequential UHD activation mapping is useful in guiding and potentially improving long term results of ablation of extra pulmonary vein drivers after PVI.
1096Diastolic myocardial dysfunction by tissue doppler imaging predicts outcome following isolated coronary artery bypass grafting
Authors: Olsen F J , Lindberg S , Fritz-Hansen T , Pedersen S , Galatius S , Gislason G , Mogelvang R , Biering-Sorensen T 
Published: October 2019

Abstract

Background
Myocardial tissue velocities by tissue Doppler imaging (TDI) have proven superior predictors of outcome to left ventricular ejection fraction (LVEF) in ischemic heart disease, with early diastolic myocardial relaxation velocity (e') being an early sign of LV dysfunction in the ischemic cascade.

Purpose
We hypothesized that e' predicts outcome after coronary artery bypass grafting (CABG).

Methods
We included patients treated with isolated CABG (n=679). Before surgery, all patients had an echocardiogram performed with TDI to measure tissue velocities: systolic (s'), e' and late diastolic (a'). Endpoint was all-cause mortality retrieved from national registries. We performed Cox regressions and C-statistics. Net reclassification index was used to test improvement of EuroSCOREII.

Results
Of 679 patients, 79 (n=12%) died during follow-up (median: 3.8 years (IQR: 2.8; 5.0y). Follow-up was 100%. Mean age was 68 years, LVEF 50%, and 86% were male. All tissue velocities were univariable predictors of outcome (s': HR=1.46 [1.21; 1.78], p<0.001; e': HR=1.55 [1.33; 1.81], p<0.001; a': HR=1.19 [1.06; 1.33], p=0.004, per 1cm/s decrease for all). Overall, e' provided the highest C-statistics of all the tissue velocities (c-stat=0.69). In multivariable adjustments, e' remained an independent predictor after adjusting for clinical, biochemical and echocardiographic confounders (HR=1.24 [1.03; 1.49], p=0.022, per 1cm/s decrease). LVEF <40% modified the relationship between e' and outcome, so e' did not predict outcome in these patients (p for interaction = 0.013). However, e' was an independent predictor after multivariable adjustments in patients with LVEF >40% (HR=1.39 [1.11; 1.74], p=0.005, per 1cm/s decrease). When split by the median (−4.95cm/s), patients in the lowest group had a 3-fold increased risk of death (HR=3.31 [1.98; 5.56], p<0.001) compared to patients in the highest group (figure).
The e' improved the net reclassification improvement index when added to EuroSCOREII, with a net reclassification of 39%.

Conclusion
After CABG, e' is a strong predictor of all-cause mortality and improves the predictive value of the established prediction model, the EuroSCOREII. We identified a possible effect modifier in LVEF, such that e' was a strong predictor in patients with LVEF >40% and not when LVEF is below 40%.
1170Tafamidis versus liver transplantation as first-line therapy for hereditary transthyretin amyloidosis
Authors: Socie P , Benmalek A B , Lallemand A L , Cauquil C C , Rouzet F R , Le Guludec G L , Samuel D S , Adams D A , Slama M S , Algalarrondo V A 
Published: October 2019

Abstract

Introduction
By stabilizing transthyretin tetramer, tafamidis delays neurological progression in mutated Transthyretin amyloidosis (mATTR) and has replaced liver transplantation (LT) as the first-line therapy in European patients with stage I mATTR. To date, no study compared these two therapeutic strategies.

Material and methods
Stage I mATTR patients treated either with tafamidis or with LT were compared using a propensity score. The primary endpoint was the all-cause mortality. Secondary endpoints were the neurological progression (assessed by a worsening in the PND score) and the cardiac progression of mATTR (defined by a cardiovascular death or the onset or the worsening of symptomatic heart failure).

Results
The files of 345 patients with proven mATTR were analyzed and 144 patients entered the final analysis (72 patients in each group, median age 54 years, 60% carrying the V30M mutation). Patients treated by tafamidis had a better survival than patients with LT (HR: 0.93; 95% CI: 0.17–0.91; P=0.029). Conversely, the worsening-free survival of the neurological status was significantly shorter for patients that received tafamidis than for LT patients (HR: 6.08; 95% CI: 2.97–12.45; P<0.0001). A similar non-significant trend was documented regarding the progression of the cardiac status (HR: 1.99; 95CI: 0.91–4.34; P=0.084).

Conclusions
In mATTR, first-line therapy with tafamidis was associated with a better survival than LT. Conversely, LT provided better neurological stabilization than tafamidis. These results confirm that LT remains a major treatment in mATTR. In patients treated with tafamidis, close follow up of the treatment efficacy is mandatory.
1178Unsuspected role of the cardiac PKA type I in excitation-contraction coupling and in heart failure development
Authors: Gandon-Renard M , Bedioune I , Karam S , Varin A , Lechene P , Bichali S , Leroy J , Algalarrondo V , Stratakis C , Mercadier J J , Benitah J P , Gomez A M , Fischmeister R , Vandecasteele G 
Published: October 2019

Abstract
The cAMP-dependent protein kinase (PKA) consists of two regulatory (R) and two catalytic (C) subunits and comprises two subtypes, PKAI and PKAII, defined by the nature of their regulatory subunits, RIα and RIIα respectively. Whereas PKAII is thought to play a key role in β-adrenergic (β-AR) regulation of cardiac contractility, the function of PKAI is unclear. To address this question, we generated mice with cardiomyocyte-specific and conditional invalidation of the RIα subunit of PKA. Tamoxifen injection in 8 weeks-old mice resulted in a >70% decrease in RIα protein without modification of other PKA subunits, which was associated with ∼2-fold increased basal PKA activity in RIα-KO mice (p<0.05, N=6/group). This translated into enhanced cardiac contraction and relaxation, as observed in vivo by increased fractional shortening and E-wave velocity (p<0.05, N=10/group) and ex vivo by increased LV pressure and maximal rate of contraction and relaxation (p<0.05, N=9/group). L-type Ca2+ current density was increased in ventricular myocytes from RIα-KO, and β-AR stimulation was decreased by ∼50% (p<0.05, n=38 cells for WT, and, n=40 for RIα-KO). Consistently, Ca2+ transients amplitude and relaxation kinetics were increased, along with increased occurrence of Ca2+ sparks and waves (p<0.05, n=44 cells for WT, and, n=50 for RIα KO). Phosphorylation of Ca2+ channels (CaV1.2), PLB, RyR2 and cMyBP-C at PKA sites was increased >2-fold (p<0.05, N=6/group) in RIα KO without modification of total protein expression. With age, these mice developed a congestive heart failure (HF) phenotype with massive hypertrophy and fibrosis which eventually led to death in 50% of RIα-KO mice at 50 weeks (versus 0% in WT, p<0.01). These results reveal a previously unsuspected role of PKA type I in cardiac excitation-contraction coupling and HF.
1206Doxapram is a promising new antiarrhythmic drug for an atrial-specific therapy of atrial fibrillation
Authors: Schmidt C , Wiedmann F , Beyersdorf C , Zhao Z , El-Battrawy I , Kraft M , Lang S , Szabo G , Karck M , Zhou X , Borggrefe M , Thomas D , Haefeli W E , Decher N , Katus H 
Published: October 2019

Abstract

Background
TASK-1 (K2P3.1) is an atrial-specific two-pore domain potassium channel that is significantly upregulated in atrial fibrillation (AF) patients resulting in shortened atrial action potential duration (APD). Inhibition of TASK-1 in human atrial cardiomyocytes reverses AF-related APD shortening to values observed in patients with sinus rhythm (SR). By in silico-modelling and experimental characterization of drug binding sites, doxapram was identified as specific inhibitor of TASK-1.

Purpose
In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF to convert and suppress AF.

Methods
We established a new porcine model of persistent AF without induced tachymyopathy. AF was induced in domestic pigs by intermittent atrial burst stimulation using implanted pacemakers. During AF episodes, burst stimulation was inhibited by an integrated pacemaker biofeedback algorithm. AV-node ablation was performed to prevent AF-associated heart failure. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days doxapram treatment. Pigs in the treatment group received intravenous applications of doxapram twice per day. Rhythm status was continuously recorded by intracardiac long-term ECG monitors. The application of doxapram for cardioversion and long term suppression of AF in pigs with persistent AF was evaluated. Subsequent to the doxapram treatment, porcine cardiomyocytes were isolated from right and left atria and electrophysiologically investigated by patch-clamp and multi-electrode experiments. Atrial electrical remodeling was characterized by analyses of ion channel expression at mRNA and protein levels.

Results
TASK-1 mRNA, protein and transmembrane current were significantly increased in AF pigs compared to SR controls, resulting in shortened atrial APDs. In doxapram-treated AF pigs the AF burden was significantly reduced. After 14 days treatment with doxapram, TASK-1 currents and atrial APDs recorded in porcine cardiomyocytes were reduced and similar to values of SR animals. Doxapram could be successfully applied for cardioversion in pigs with persistent AF. On average, cardioversion was observed 3 minutes after doxapram application.

Conclusion
Doxapram significantly suppressed AF episodes and normalized cellular electrophysiological characteristics in a porcine model of AF through inhibition of the TASK-1 ion channel. Furthermore, doxapram rapidly converted AF into SR in pigs. Therefore, doxapram might serve as a new antiarrhythmic drug to treat AF in patients.
1268A comparison between the diagnostic performance of quantitative flow ratio and non-invasive imaging modalities for diagnosing myocardial ischemia defined by FFR, a PACIFIC-trial interim analysis
Authors: Van Diemen P A A , Driessen R S , Kooistra R A , Stuijfzand W J , Raijmakers P G , Schumacher S P , Bom M J , Everaars H , Min J K , Leipsic J A , Knuuti J , Underwood S R , Van Rossum A C , Danad I , Knaapen P 
Published: October 2019

Abstract

Background
Quantitative flow ratio (QFR) uses fast computational algorithms based on 3-dimensional quantitative coronary angiography and estimation of contrast flow velocity during invasive coronary angiography (ICA) to obtain QFR values equivalent to fractional flow reserve (FFR).

Objective
To compare the diagnostic performance of QFR with coronary computed tomography angiography (CCTA), single-photon emission tomography (SPECT), and positron emission tomography (PET) for diagnosing myocardial ischemia defined by FFR.

Method
QFR computation was attempted in 109 patients (286 vessels without a subtotal/total lesion) of the 208 patients included in the PACIFIC-trial. Patients underwent 256-slice CCTA, Tetrofosmin SPECT, and [15O]H2O PET prior to ICA in conjunction with 3 vessel FFR measurements. ICA images were obtained without the use of a dedicated QFR acquistion protocol. QFR was calculated using a fixed empiric hyperemic flow velocity (fQFR) as well as using a patient specific flow velocity based on contrast passage through the coronary (cQFR). All analysis were performed on a per vessel level.

Results
Fixed QFR computation succeeded in 152 (53%) vessels while cQFR analysis was successful in 140 (49%) vessels. A good correlation between FFR and fQFR/cQFR was observed (R=0.774, p<0.001/R=0.790, p<0.001). The diagnostic performance in terms of sensitivity, specificity, negative predictive value, positive predictive value, and accuracy is presented in table 1. In total, 133 vessels with matched FFR, fQFR, cQFR, CCTA, SPECT, and PET results were available for the comparative C-statistic analysis, figure 1. The diagnostic performance of fQFR and cQFR was comparable (p=0.451) and superior to CCTA (p=0.004/p=0.003), SPECT (p<0.001/p<0.001), and PET (p=0.008/p=0.006), figure 1. CCTA, and PET performed alike (p=0.568) and outperformed SPECT (p=0.023, p=0.002).
Table 1 % (95% Confidence Interval) fQFR n=152 cQFR (n=140) CCTA (n=152) SPECT (n=150) PET (n=149) Sensitivity 76 (59–89) 71 (53–86) 70 (51–84) 30 (16–49) 76 (58–89) Specificity 94 (88–98) 93 (86–97) 73 (64–81) 96 (90–99) 80 (72–87) Negative Predictive Value 93 (88–96) 92 (86–95) 90 (84–94) 83 (79–86) 92 (86–96) Positive Predictive Value 79 (64–89) 74 (59–85) 42 (33–51) 67 (42–84) 52 (42–62) Accuracy 90 (84–94) 88 (81–93) 72 (65–79) 81 (74–87) 79 (72–85)
Figure 1.

Conclusion
Fixed QFR and cQFR correlate well with FFR with a high diagnostic accuracy as result. QFR outperformed CCTA, SPECT, and PET for the diagnosis of myocardial ischemia on a per vessel basis with the important footnote that fQFR and cQFR could only be computed in 53%, and 49% of the vessels.
1270Early systolic lengthening in patients with ST-segment elevation myocardial infarction: a novel predictor of cardiovascular events
Authors: Brainin P , Haahr-Pedersen S , Olsen F J , Fritz-Hansen T , Jespersen T , Gislason G H , Biering-Soerensen T 
Published: October 2019

Abstract

Background
Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force. We sought to evaluate the prognostic potential of ESL in patients with ST-segment elevated myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).

Methods
We prospectively enrolled 372 patients with STEMI who were treated with primary PCI. All patients underwent a speckle tracking echocardiographic examination with a median of 2 days (interquartile range 1, 3 days) after the PCI. We assessed a novel viability index, the ESL index, defined as: (100 x [peak positive systolic strain/peak negative global strain]), obtained as the average value from all 18 segments. We also calculated ESL duration from 18 segments, defined as time from onset of QRS complex on the electrocardiogram to time to peak of positive systolic strain.

Results
During a median follow-up time of 5.3 years (interquartile range 2.5, 6.0), 145 (39%) experienced major adverse cardiovascular events (MACEs), which was a composite of incident heart failure, new myocardial infarction and all-cause mortality. The ESL index and ESL duration were significantly increased in culprit lesion areas (6.7±6.2% vs. 5.0±4.1% and 43±33ms vs. 33±24ms, P<0.001 for both). In Cox proportional hazards models the ESL index (HR 1.27 per 1% increase, 95% CI 1.13–1.43, P<0.001, Fig A) and ESL duration (HR 1.49 per 1ms increase, 95% CI 1.15–1.92, P=0.002, Fig B) yielded prognostic information on MACE. Both associations remained significant after adjusting for clinical (age, sex, hypertension, heart rate), echocardiographic (LVMI, E/e', WMSI, LVEF, postsystolic index) and invasive (postprocedural TIMI flow, TnI) confounders. Additionally, tertiles of the ESL index and ESL duration yielded significant prognostic information on MACE (Fig C-D).
ESL index and ESL duration and MACE

Conclusions
Assessment of ESL following primary PCI in patients with STEMI yields independent and significant prognostic information on the future risk of cardiovascular events.
1271Short-term effects of exposure to ambient fine particulate matter on out-of-hospital cardiac arrest: a nationwide case-crossover study in Japan
Authors: Zhao B , Johnston F H , Salimi F , Negishi K 
Published: October 2019

Abstract

Introduction
The cardiovascular health consequences of ambient air pollution generally equal or exceed those due to pulmonary diseases and cancers. Particulate matter less than 2.5μm in aerodynamic diameter (PM2.5) has become a major focus of research on the short-term exposure to air pollution and cardiovascular disease. However, the evidence regarding the association between several air pollutants and out-of-hospital cardiac arrest (OHCA), has been inconsistent, which could be due to limited sample sizes (∼11,000). Thus, a larger study may assist in characterising possible associations.

Purpose
This study aimed to identify the associations between exposure to ambient air pollution and the incidence of OHCA in Japan.

Methods
A case-crossover design was used to determine the odds ratio (OR) of OHCA across Japan with daily exposure of PM2.5, carbon monoxide (CO), photochemical oxidants (Ox), and sulfur dioxide (SO2) on the day of the arrest or 1–3 days before it (lag 0–3). OHCA cases were identified through the All-Japan Utstein registry of the Fire and Disaster Management Agency from January 1, 2014 to December 31, 2015. All cause OHCAs were investigated by conditional logistic regression adjusted for daily temperature and relative humidity.

Results
A total of 249,372 OHCAs were included during study period. Each 10 μg/m3 increase in daily PM2.5 exposure over 4 days was associated with all cause OHCA risk (lag 0: OR 1.017, 95% confidence interval (CI) 1.010, 1.024; lag 1: OR 1.015, 95% CI 1.008, 1.022; lag 2: OR 1.018, 95% CI 1.011, 1.025; lag 3: OR 1.021, 95% CI 1.014, 1.028; lag 0–1: OR 1.022, 95% CI 1.014, 1.030). CO, Ox and SO2 also showed significant associations with OHCAs. In the multi-pollutant model, the effects of PM2.5 remained independent of CO, Ox and SO2 (Table).

Conclusion
Short-term exposure to PM2.5 was independently associated with an increased risk of OHCA.
1385Combined tricuspid and mitral vs. isolated mitral valve repair for severe mitral and tricuspid regurgitation: An analysis from TriValve and TRAMI registries
Authors: Mehr M , Taramasso M , Ourrak T , Lurz P , Von Bardeleben R S , Fam N , Lubos E , Boekstegers P , Schillinger W , Plicht B , Eggebrecht H , Baldus S , Senges J , Maisano F , Hausleiter J 
Published: October 2019

Abstract

Background
Edge-to-edge repair has been shown to be a successful therapeutic option for patients with severe mitral regurgitation (MR). Lately, it has also been emerging as a treatment perspective for severe tricuspid regurgitation (TR) in patients at high-risk for cardiac surgery. In patients, with both severe MR and TR the best treatment strategy for patients at high risk for surgery is unknown.

Purpose and methods
We retrospectively analyzed data from the international multicentre TriValve (Transcatheter Tricuspid Valve Therapies) registry and from the German multicentre TRAMI (Transcatheter Mitral Valve Interventions) registry. All patients included into the analysis had both severe MR and TR. Patients from the TRAMI registry (n=106) were treated with edge-to-edge repair in mitral position only. In patients from the TriValve registry (n=122), both valves were treated concomitantly in compassionate and/or off-label use. We sought to compare baseline characteristics, procedural data and 1-year mortality in both treatment groups.

Results
228 patients (77±8 years; 44.3% female) were included into the analysis. All patients showed significant dyspnea on exposure (NYHA III or IV 93.9%). Kidney function (eGFR 42 ml/min/1,72m2) and the proportion of patients with significant pulmonary hypertension (59.0%) and COPD (23.7%) did not differ between the groups, but the proportion of patients with LV-EF <30% (34.9% vs. 18.0%, p<0.001) were higher in the TRAMI cohort.
At discharge, MR was comparably reduced in both groups (MR ≤ I° 75.9% vs. 77.3%, p=0.67). While all patients in both registries had significant TR at baseline, the percentage of patients with TR≥3+ at discharge was reduced to 18.6% in TriValve by the placement of 2±1 tricuspid clips/patient. The rate of in-hospital adverse events and the time of hospitalization did not differ in both cohorts. At 1-year, overall all-cause mortality was 34.0% in the TRAMI cohort and 16.4% in the TriValve cohort (p=0.0002, see figure; after adjustment for LVEF <30%: p=0.049). The rate of patients with NYHA ≤ II at 1 year did not differ between both cohorts (69.4% vs. 67.0%, p=0.54).
1-year mortality TriValve vs. TRAMI

Conclusion
Transcatheter mitral and tricuspid valve repair can result in a significant clinical improvement at 1 year. The concomitant treatment of both valve regurgitations may result in an improved survival, which needs to be confirmed in dedicated prospective trials.