bluuebunny/crossref_metadata_2025 huggingface dataset:
P1806Diagnosis of isolated cardiac sarcoidosis using FDG-PET/CT on the basis of new guidelines
Authors: Kawai H , Sarai M , Kato Y , Naruse H , Ishii J , Morimoto S , Izawa H , Toyama H , Ozaki Y
Published: October 2019

Introduction

Sarcoidosis is a systemic inflammatory disease which can involve any organs. The reported prevalence of isolated cardiac sarcoidosis (CS) varies widely because of the lack of an agreed definition of isolated CS (iCS). ICS was newly defined in the new guidelines for CS by Japanese Circulation Society.

Purpose

We aimed to examine the diagnostic accuracy of 18F-FDG PET/CT and the ratio of iCS in the whole CS by reviewing the patients with suspected CS undergoing the whole-body and cardiac FDG PET/CT scans.

Methods

We retrospectively reviewed 74 consecutive patients undergoing 18F-FDG PET/CT from 2013 to 2018 (mean age 60±14 years, 37 male) without the initiation of corticosteroid. Myocardial FDG uptake in CS was defined as a “focal” or “focal on diffuse” pattern. Systemic sarcoidosis (sCS) and iCS were diagnosed according to guidelines for the diagnosis and treatment of CS by Japanese Circulation Society. In short, iCS was diagnosed clinically when no clinical findings of sarcoidosis in any other organs and FDG uptake in heart were shown in addition to the following three of four criteria: high-grade atrioventricular block or fatal ventricular arrhythmia, structural abnormality, left ventricular contractile dysfunction, and delayed Gadolinium enhancement of myocardium on MRI.

Results

Of 31 patients with extra-cardiac sarcoidosis, 10 already met the diagnostic criteria of sCS before undergoing 18F-FDG PET/CT and 11 was newly diagnosed as sCS after FDG PET/CT. Of the remaining 43 without extra-cardiac sarcoidosis, 18 had FDG uptake in heart. Of 18 with FDG uptake in heart, iCS was diagnosed in 7, and sCS in 3 with extra-cardiac uptake of FDG as well as myocardium. Finally, 24 and 7 patients met the criteria of sCS and iCS based on the guideline, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG PET/CT for CS including sCS and iCS were 90, 87, 88, 85, and 92%, respectively.

Conclusion

The ratio of iCS on the basis of new guidelines for diagnosis and treatment of CS was 22% of the whole CS.
P1809Impact of mitral regurgitation on clinical outcome in patients with cardiac sarcoidosis
Authors: Yoshikazu Y , Kimura H , Noumi H , Tsuchiya H , Hasegawa T , Yamamoto Y , Yanagisawa T , Ogiwara M , Tachibana T , Horigome M , Nouno Y , Koshikawa M , Kuwahara K
Published: October 2019

Background

Mitral regurgitation (MR) is sometimes observed in cardiac sarcoidosis (CS), and might be related to worsening heart failure. However, mechanism and clinical significance of MR associated with CS remains undetermined.

Methods

We retrospectively analyzed consecutive 51 CS patients, and identified 16 patients with moderate to severe MR evaluated by quantitative echocardiography. According to the assessment of coaptation point and tenting height, main mechanisms of the 16 patients with MR were classified into prolapse (P) in 5, and tethering in 11 (T). Prednisolone was started from 30 mg/day, gradually tapered over a period of 6 months to a maintenance dose of 5 to 10 mg/day and continued a lifetime.

Results

At the first visit, patients with MR showed higher incidence of NYHA class IV heart failure as compared to those without MR (56 vs. 9%, p<0.001). Abnormal uptake of fluorine-18 fluorodeoxyglucose in the papillary muscle was more frequent in patients with MR than those without MR (63% vs. 23%, p<0.05). Patients with tethering MR showed higher incidence of complete atrioventricular block (T: 74% vs. P: 40% vs. without MR: 31%, p<0.05), significantly reduced left ventricular (LV) ejection fraction (T: 33±7% vs. P: 52±9% vs. without MR: 52±16%, p<0.001) and increased LV end-diastolic volume index (T: 100±52ml/m2 vs. P: 66±23ml vs. without MR: 62±21ml, p<0.001). During the mean follow-up of 108 months, cardiac-event free survival was significantly worse in patients with tethering MR as compared to the other patients (log-rank; 11.7, p<0.001). Six of the 11 patients with tethering MR received cardiac resynchronization therapy, and then did not experience further hospitalization due to decompensated heart failure for at least 2 years. Multivariate analysis identified tethering MR as an independent predictor of cardiac event (HR: 6.7, p<0.05).

Conclusions

MR associated with CS has variety of mechanisms including prolapse, tethering and inflammation of the LV papillary muscle, and may be related to ventricular remodeling and poor clinical outcome.
P1811Association between the autonomic dysfunction and biomarker levels in patients with chagas disease without evidence of structural heart disease
Authors: Chirino D A , Guthmann M G , Iglesias D , Volverg V , Dizeo C , Calderon G
Published: October 2019

Background

Several studies have shown autonomic dysfunction in early stages of Chagas disease (ChD). These alterations may be involved in the progression of the disease. The Valsalva Ratio (VR) is one of the most used tests to evaluate parasympathetic function, because it is easy and reproducible. On the other hand, the Higth Sensitive T troponin (HS-TnT) and the N-terminal pro B-type natriuretic peptide (NT-proBNP) are specific markers of myocardial damage and elevation of filling pressures, respectively. Both elevations are asociated with higher risk.

The association between autonomic dysfunction and biomarker levels in ChD without evidence of structural heart affection, has been poorly studied.

Purpose

The aim of this study is to evaluate the presence of abnormal VR as an expression of disanutonomy in patients with Chagas without evidence of structural heart disease and its association with HS-TnT and NT-proBNP levels.

Methods

A prospective study was performed, which included outpatients with positive serology for Chagas, with electrocardiogram, ergometry, holter and Doppler echocardiogram within normal parameters. The exclusion criteria were the following: history of ischemic heart disease, neurological diseases, chronic renal failure (clearence <30 ml/min), arterial hypertension and diabetes mellitus. All patients underwent a valsalva maneuver (VM), with continuous recording of the R-R interval by electrocardiogram. The VR was calculated dividing the longest RR interval after VM over the shortest RR interval during VM. Abnormal VR was considerated as a value <1.1. In addition, HS-TnT and NT-proBNP were measured in all patients.

Results

One hundred and forty four patients were included, with 45±8 years old, 44% fameles. The VR was 1.22±0.12, HS-TnT 6.44±3.8 ng/L and the NT-proBNP was 55±44 pg/ml. Abnormal VR was found in 29.1% of patients (n=42).

The abnormal VR group showed a higher level of HS-TnT (8.11±3.8 versus 5.7±3.5 ng/L, p=0.0006) and higher level of NT-proBNP (78±54 versus 45±36 pg/ml, p<0.0001). In addition, the abnormal VR group presented a greater E/e'ratio (9.48±2.5 versus 7.1±1.8, p<0.0001) and greater s wave (0.08±0.02 versus 0.10±0.02 cm/sec, p=0.02).

In the multivariate análisis, abnormal VR was asociated with higher HS-TnT (OR 1.22 (CI 95% 1.04–1.43), p=0.01) and higher E/e'ratio (OR 1.54 (CI95% 1.17–2.02), p=0.001), but not with NT-proBNP (p=0,09).

Conclusions

About one third of patients with ChD without evidence of cardiopaty had autonomic dysfunction. The patients with abnormal VR had higher leves of HS-TnT and NT-proBNP, but in the multivariate analisys only the HS-TnT had associated with abnormal VR.
P1817Assessment of carotid stiffness indices in patients with ischemic stroke
Authors: Youssef G , Mekkawy D , El-Fayoumy N , Abbas A , Allam M
Published: October 2019

Background

Arterial stiffness is considered as an emerging new important risk factor for stoke development. Measuring carotid stiffness is easy and non-invasive and thus can be widely applicable.

Purpose

To evaluate the carotid stiffness indices in patients with ischemic stroke compared to normal healthy subjects.

Methods

Included in this study are 60 patients (group 1) with ischemic stroke and 60 healthy control subjects (group 2). Participants were exposed to routine clinical examination and Duplex assessment of both carotid arteries. A specific wall tracking system was used for the semiautomatic calculation of the carotid stiffness indices, which included; compliance coefficient (CC), distensibility coefficient (DC), carotid pulse wave velocity (PWV) and carotid intima media thickness (IMT). Results from both carotid arteries were averaged and data from group 1 patients were compared to group 2 subjects.

Results

The mean age was (60.1±6.9 years) in group 1 compared to (60.1±6.6 years) in group 2 (p=0.9). A significant difference was found between both groups in all carotid stiffness indices; including average CC (0.64±0.29 vs 0.82±0.36 m2/kpa, p=0.004); average DC (11.69±5.42 vs 18.61±11.87 1/kpa, p<0.001); average PWV (16.5±0.6 vs 12.5±3.7 m/s, p<0.001) and average IMT (0.78±0.13 vs 0.68±0.18 mm, p=0.001). Only the carotid PWV was found to be a predictor of vascular stroke (p=0.001)

Conclusion

Patients with vascular stroke have higher carotid stiffness indices than age matched control subjects. Measuring carotid stiffness indices in patients who have atherosclerotic risk factors may help predict those at risk of vascular stroke and thus guide a tighter and a more efficient risk factors control.
P1847Comparing outcomes and complications between transfemoral TAVI performed with or without echoguided puncture
Authors: Bouteau J , Bourguignon T , Caze C , Quilliet L , Ivanes F , Desveaux B , Clerc J M , Saint Etienne C
Published: October 2019

Objective

Transcatheter Aortic Valve Replacement (TAVI) has become the reference procedure in intermediate or high surgical risk patients with degenerative aortic stenosis. Vascular complications are associated with poorer outcomes in patients after TAVI. Transfemoral (TF) echoguided puncture (EGP) became a routine procedure in our center in May 2017. We conducted a retrospective analysis to compare outcomes between patients whose TAVI was performed with or without routine EGP in our population.

Methods

We included all patients with TF TAVI performed in our center between January 2016 and December 2018. Since May 2017, all TF TAVI were performed using TF EGP for the main access and transradial puncture for the secondary access. Patient population was divided into two historical groups: fluoroscopic guided puncture (FGP) and EGP. Patients whose TAVI were performed in May 2017 were excluded due to operators learning curve. Post procedure mortality and vascular complications were retrospectively extracted from our institution data system.

Results

Among the 611 TAVI performed between January 2016 and December 2018, 28 did not have TF access. Twelve patients with procedure in May 2017 (learning curve) were excluded. Thus, 573 patients were analyzed. Age was not significantly different between FGP and EGP groups (84.9±5,7 vs. 83.8±6.6 years, p=0.051). No significant differences in in-hospital and 1 month mortality were observed between FGP and EGP groups (1.9 vs. 1.5%, p=0.74 and 3.2 vs. 1.8%, p=0.26). Minor vascular complications were not significantly different between groups (12.5 vs. 12.3%, p=1) but major vascular complications were significantly less frequent in EGP (5.6 vs. 10.2%, p=0.046). After introducing EGP, surgical TF access were also less frequently needed (2.8 vs. 0.3%, p=0.02).

Conclusion

Our single center retrospective study suggests that using TF EGP to perform TAVI is safe and may reduce both the rate of major vascular complication and the need for surgical TF access.

Acknowledgement/Funding

None
P1853Comparative evaluation of risk model performance for prediction of 30-day mortality in transcatheter aortic valve replacement
Authors: Wolff G , Klein K , Parco C , Lin Y , Maier O , Karathanos A , Brockmeyer M , Zeus T , Polzin A , Westenfeld R , Jung C , Blehm A , Lichtenberg A , Kelm M , Veulemans V
Published: October 2019

Background and purpose

EuroSCORE (ES) and Society of Thoracic Surgeons (STS) risk prediction models are routinely used to guide decision-making for transcatheter aortic valve replacement (TAVR), however their accuracy remains limited, especially in very old and high-risk patients. New and updated scoring models have thus been developed to improve risk stratification. We performed a comparative evaluation of classical and new risk scoring models for prediction of 30d mortality in transcatheter aortic valve interventions.

Methods and results

A total of 1,569 patients undergoing transfemoral (TF, n=1.235) or transapical (TA, n=334) TAVR from 2009 to 2018 were included in a single-center all-comer analysis. Six risk scoring models (logES_I, ES_II, STS-PROM, FRANCE-2, OBSERVANT, GAV-2) were calculated for all patients and evaluated for prediction of 30d mortality in their model discrimination (c-indices with 95% confidence intervals (CI)) and calibration (graphical evaluation). Mean classical risk scores confirmed an intermediate-to-high-risk patient collective (logES_I 27.0±16.9%; STS-PROM 7.0±6.4%), mean 30-day mortality was 3.4% (TF 2.3%; TA 7.8%). Overall discrimination performance was best in FRANCE-2 (c-index 0.73, 95% CI 0.67–0.80), followed by STS-PROM (c-index 0.68, 95% CI 0.62–0.75), OBSERVANT (c-index 0.68, 95% CI 0.61–0.76), ES_II (c-index 0.64) and logES_I and GAV-2 (both c-indices 0.63). FRANCE-2 discriminated best in TF TAVR (c-index 0.72; range of c-indices 0.63 to 0.72), while OBSERVANT performed best in TA TAVR (c-index 0.70; range of c-indices 0.61 to 0.70). All risk scoring models – with the exception of lowest-risk deciles of STS-PROM and ES_II – showed an overestimation of mortality probability in all risk strata.

Conclusion

FRANCE-2 and OBSERVANT risk models showed superior discrimination performance to classical risk scoring models in TF and TA TAVR, however all models tended to overestimate mortality probability.
P1857Risk calculator for prediction of iatrogenic atrial septal defect persistence following percutaneous mitral valve repair
Authors: Maier O , Hellhammer K , Boenner F , Afzal S , Spieker M , Zeus T , Horn P , Westenfeld R , Kelm M , Veulemans V
Published: October 2019

Background

The rising number of new percutaneous interventions for left-sided heart disease leads to increased occurrence of iatrogenic atrial septal defect (iASD). The percutaneous mitral valve repair (PMVR) for severe, symptomatic mitral regurgitation (MR) also requires intraprocedural puncture of the interatrial septum. In some cases iASD is persisting and becomes haemodynamically relevant with enhanced right heart overload due to significant left-to-right-shunting.

Purpose

This study aimed to evaluate pre- and periprocedural factors that may favour persistence and haemodynamic relevance of iASD in patients after PMVR.

Methods

In 2015, 75 consecutive patients with severe MR (age 74.8±10.5y) and following PMVR were enrolled. After 12 months, 57 patients completed their follow up (FU) including clinical conditions, transthoracic echocardiography (TTE), and cardiovascular magnetic resonance (CMR) whenever feasible. We evaluated the impact of comorbidities as well as intraprocedural, haemodynamic and functional characteristics that may favour persistence of iASD by multivariate analysis. Haemodynamic relevance of iASD was defined as right heart overload with predominantly significant enlargement of the right atrium (RA), impairment of right heart function as defined by fractional area shortening (FAC), and ratio of pulmonary to systemic blood flow (Qp/Qs>1) when available.

Results

18 out of 57 patients (32%) showed a persistent iASD (+iASD), being associated with a specific combination of comorbidities as well as pre-procedural and periprocedural factors that can be summarised by a multifactorial iASD risk calculator (+iASD vs. -iASD: 6.3±2.9 vs. 3.9±2.7; p=0.0058). 11 iASD (61%) became haemodynamically relevant (+hd iASD) with a significant right heart overload (RA area +hd iASD vs. -hd iASD: baseline 23.1±4.1 vs. 23.2±4.3; FU 30.7±6.3 vs. 20.1±4.6; p<0.0001), reduced RV function (FAC +hd iASD vs. -hd iASD: baseline 41.0±10.3 vs. 29.9±7.2; FU 25.3±7.2 vs. 29.1±13.2; p<0.0156) and left-to-right shunting (Qp/Qs -iASD vs. +hd iASD vs. -hd iASD: 1.0±0.3 vs. 1.7±0.4 vs. 0.8±0.1 L/min; p=0.0011).

Conclusion

This study shows for the first time, that persistence of iASD can be predicted by pre- and periprocedural factors using a risk calculator that may additionally guide careful follow up imaging and therapeutic action after PMVR to avoid development of progressive heart failure.
P1868Risk of arrhythmias after myocardial infarction in patients with left ventricular systolic dysfunction according to mode of revascularization: a CARISMA substudy
Authors: Thomsen A , Pedersen S , Jacobsen P K , Huikuri H V , Bloch Thomsen P E , Jons C
Published: October 2019

Introduction

The CARISMA trial was the first study to use continuous monitoring for documentation of long-term arrhythmias in post-infarction patients with left ventricular dysfunction. During the study duration (2000–2005), primary PCI (pPCI) as treatment of acute myocardial infarction was introduced approximately midway (2002) on the enrolling centres.

Purpose

The aim of this study was to describe the influence of mode of revascularization after myocardial infarction (AMI) on long-term risk of risk of new onset atrial fibrillation, ventricular tachyarrhythmias and brady arrhythmias.

Methods

The study is a sub-study on the CARISMA study population that consisted of patients with AMI and left ventricular ejection fraction ≤40%, which received an implantable loop recorder and was followed for 2 years. After exclusion of 15 patients who refused device implantation and 26 with pre-existing arrhythmias, 268 of the 312 patients were included. Choice of revascularization was made by the treating team independently of the trial and was retrospectively divided into primary percutaneous intervention (pPCI), subacute PCI (24 hours to 2 weeks after AMI), primary thrombolysis or no revascularization.

Endpoints were new-onset of arrhythmias and major cardiovascular events (MACE). The Kaplan-Meier (figure 1) and Mantel-Byar methods were used for time to first event risk analysis.

Results

A total of 77 patients received no revascularization, whereas 49 received thrombolysis only and 142 received PCI. At two-years follow up patients treated with any PCI had a significant lower risk (0.40, n=63) of any arrhythmia compared to patients treated with trombolysis (0.60, n=30) or no revascularization (0.68, n=16) (p<0.001, unadjusted) (figure 1). Risk of MACE was significant higher in patients with any arrhythmia (0.25, n=76) compared to no arrhythmia (0.11, n=93) at two years follow-up (p=0.004, unadjusted).

Figure 1

Conclusion(s)

The long-term risk of new onset arrhythmias after AMI was significantly lower in patients treated with any PCI compared to patients not revascularized or treated with thrombolysis. Risk of MACE was significantly higher in patients with new onset arrhythmias compared to patients with no arrhythmias.
P1875Nonspecific intraventricular conduction delay is associated with future occurrence of atrial fibrillation in patients with structurally normal heart and sinus rhythm
Authors: Uhm J S , Jin M N , Kim I S , Bae H J , Yu H T , Kim T H , Kim J Y , Joung B , Pak H N , Lee M H
Published: October 2019

Background

This study aimed to elucidate long-term prognosis of nonspecific intraventricular conduction delay (NIVCD) in patients with structurally normal heart.

Methods

We included 107,838 patients (age, 52.1±15.5 years; men, 46.8%) who underwent electrocardiography in outpatient clinics or medical checkup (model 1). NIVCD was defined as QRS duration ≥110 ms and incompatibility with bundle branch block. The patients with structurally normal heart and sinus rhythm were assigned to the NIVCD group and normal QRS group according to propensity score with matching variables of age, sex, hypertension, and diabetes (model 2), and additional PR interval (model 3). Baseline characteristics, electrocardiographic parameters, and clinical outcomes were compared in model 1, 2, and 3, respectively.

Results

In model 1, the frequencies of male and preexisting atrial fibrillation (AF) were significantly higher in the NIVCD group than in the normal QRS group. In model 2, sinus rate and PR interval were significantly slower and longer in the NIVCD group than in the normal QRS group. In model 3, cumulative incidence of AF was significantly higher in the NIVCD group than in the normal QRS group during follow-up of 8.8±2.9 years (Figure). NIVCD significantly increased risk of AF (hazard ratio, 2.571; 95% confidence interval, 1.074–6.156; p=0.034). NIVCD did not significantly increase risk of sick sinus syndrome, complete atrioventricular block, and heart failure.

Atrial fibrillation-free survival

Conclusions

NIVCD is associated with slow sinus rate and prolonged PR interval. NIVCD is an independent risk factor of AF in patients with structurally normal heart.
P1880Entropy-based algorithm for atrial fibrillation detection using photoplethysomgraphic signal recorded by a smart watch
Authors: Chiang J Y , Fu C M , Lin Y C , Ku B W , Hsu S U , Wu C K , Lin L Y , Lin J L , Chiang F T , Juang J M
Published: October 2019

Background

Atrial fibrillation (AF) is the most common arrhythmia, and its paroxysmal and short duration nature makes its detection challenging. The most important limitation of current smartwatches is that patients need to touch to the sensor of the watch to record signals when patients feel discomfort. We developed a wearable smart watch and evaluated its accuracy to differentiate AF from sinus rhythm, which can continuously detecting heart rhythm without hand touching the device.

Methods and results

A wearable smart watch with PPG sensor and electrocardiogram (ECG) recording function was used for signal acquisition. A total 399 patients with a mean age of 67 years old were enrolled in the study, of whom 237 (81.5%) were male, and 101 have been diagnosed with AF. Pulse wave extracted from the green light spectrum of the signal and ECG were recorded for about 10 minutes for each patient. Pulse-to-pulse intervals (PPI) were automatically identified. All ECG signals were verified by two cardiologists. The correlation between R-to-R interval on ECG and PPI were excellent, with a correlation coefficient R >0.99 (p<0.05). An entropy-based algorithm which combined Shannon entropy of successive difference of PPI and sample entropy of PPI was used to discriminate between AF and sinus rhythm. This method had high sensitivity and specificity (96% and 98%, respectively), the area under receiver operating characteristic curve reached 0.98.

Conclusions

We developed an entropy-based algorithm for AF detection with PPG signal recorded by a wearable smart watch. This algorithm discriminates AF from sinus rhythm accurately. This advance in technology overcomes an important clinical obstacle and can increase the AF detection rate tremendously.
P1883Arrhythmias in transplanted hearts: Lessons from Europes largest cohort of patients who underwent orthotopic heart transplantation
Authors: Bergau L , El-Hamriti M , Molatta S , Alzain K , Rubesch-Kuetemeyer V , Fox H , Sommer P , Sohns C
Published: October 2019

Introduction

Cardiac arrhythmias are regulary seen in patients following orthotopic heart transplantation (OHT). So far, there is no data available about the prevalence in a large cohort.

Methods

We retrospectively screened our database for subjects with OHT who received inpatient or outpatient treatment in our center between January 2000 and December 2018. All these patients were carefully reviewed with special attention to rhythm disturbances after successful transplantation.

Results

We identified a total number of 1890 subjects with history of OHT being treated in our center during the pre-defined time-period. The prevalence of supraventricular tachycardias was as follows: atrial fibrillation/atypical flutter and atrial ectopy 10%, AV-node-re-entry tachycardia 3%, typical atrial flutter 2% and higher degree AV-Block or Sick-Sinus-Syndrom (SSS) was 6%. Sustained ventricular tachycardia or ventricular premature contractions were present in 2%. Regarding the patients with arrhythmias, 13% received catheter ablation for arrhythmias, thereof 53% an atrial ablation (24% left atrial ablation), the remainder received a ventricular ablation.

Conclusion

In this very large cohort and following a long observational time, there was a higher incidence of atrial arrhythmias in patients following OHT as reported in healthy subjects with an emphasis on atrial fibrillation and flutter. This data gives a valuable background information on morbidity following OHT.
P1898Prevalence and risk of DOACs inappropriate dosing in atrial fibrillation. An analysis of the Swiss-AF and BEAT-AF registries
Authors: Montrasio G , Coslovsky M , Wiencierz A , Baumgartner C , Rodondi N , Kuehne M S , Moschovitis G , Preiss H , Reiner M F , De Perna M L , Conen D , Osswald S , Beer J H , Koepfli P
Published: October 2019

Background

Direct oral anticoagulants (DOACs) have a similar efficacy in terms of stroke and mortality reduction as compared to Vitamin K-Antagonists (VKAs) and improved safety with regards to intracranial haemorrhage in patients with non-valvular atrial fibrillation (AF). Dose of DOACs needs to be adjusted according to age, weight, renal function and concomitant medication. Yet, off-label dosages have been reported in 11 - 45% of patients (on average 20%).

Purpose

To assess the prevalence of inappropriate DOAC-dosing according to the official prescribing information in two large prospective Swiss AF cohorts (Swiss-AF and BEAT-AF) and to evaluate its correlation with adverse clinical outcomes.

Methods

All 3267 patients taking oral anticoagulants were stratified at baseline as receiving DOACs (adequately dosed, under- or overdosed) or VKAs. Appropriateness of DOAC dosing was assessed based on age (≥80 years), weight (≤60kg) and renal function (serum creatinine ≥133μmol/l [apixaban]; creatinine clearence ≤50ml/min [all other DOACs]). Clinical outcomes were collected during a median follow-up of 2.96 years. Major adverse clinical events (MACE) consisted of a combination of myocardial infarction, cardiac death, ischemic stroke and systemic embolism. Safety was assessed by occurrence of any bleeding event.

Results

1902 patients (58%) were on VKAs and 1365 on DOACs (42%). In the DOAC group, 1149 patients received a dose consistent with drug labelling (84%), 133 (10%) received an inappropriately high and 83 (6%) an inappropriately low dose. Overdosed patients were older than those adequately treated and more likely female, had a lower BMI and a higher CHA2DS2-VASc score (4 vs. 3 points) (p<0.001 for all). Underdosed patients were more likely to have concomitant antiplatelet therapy (p<0.001). Both off-label groups were more likely to have a history of coronary artery disease, heart failure and chronic kidney disease (p<0.001). Kaplan-Meier cumulative incidence rates for the first occurrence of MACE or bleedings are provided in Figure 1. Overdosed patients had an almost two-fold higher risk of bleeding (9.0 vs. 5.0 events per 100 patient-years compared to correctly dosed DOACs and to VKAs) and a higher rate of MACE (5.1 vs. 2.3 events per 100 patient years compared to correctly dosed DOACs and 5.1 vs. 3.4 compared to VKAs). Underdosing did not seem to be associated with a relevant increase in ischemic or bleeding events as compared to correctly dosed DOACs and VKAs (see Figure 1).

Figure 1. Kaplan-Meier incidence curves

Conclusion

Inadequate DOACs dosing was found in 1 in 6 patients and correlated with a higher burden of comorbidities at baseline. Underdosing correlated with concomitant antiplatelet therapy. Overdosing was associated with adverse clinical outcome for ischemic and bleeding events.
P1899Heparin and low-molecular-weight heparin switch associated with an increase in bleeding complications in patients on apixaban undergoing catheter ablation: The AMPER ABLATION study
Authors: Amara W , Garcia R , Mansourati J , Taieb J , Gandjbackh E , Dompnier A , Gorka H , Zannad N , Da Costa A , Sacher F , Jourda F , Fromentin S , Cheggour S , Mlayeh D , Milhem A
Published: October 2019

Background

The aim of this study was to identify the factors associated with bleeding complications in patients taking apixaban and undergoing a catheter ablation in everyday clinical practice.

Methods

AMPER ABLATION is a multicenter, observational, prospective study of patients with non valvular atrial fibrillation (AF) undergoing a catheter ablation. Eligible patients had been taking apixaban (2.5 or 5 mg twice daily) for ≥3 weeks before the procedure, and were followed for 30 days afterwards.

Results

A total of 595 patients (65 [interquartile range 59, 72] years, 67% male, mean CHA2DS2-VASc score 1.85±1.37) were enrolled at 25 academic/nonacademic centers in France; 524 patients (88%) were receiving apixaban 10 mg/day and 71 (12%) 5 mg/day. 323 patients (54%) underwent an AF ablation, and 272 (46%) an atrial flutter (AFL) ablation. The most prevalent concomitant disorders were hypertension (51% of patients), diabetes (15%) and vascular disease (10%). Mean creatinine concentration was 1.06±0.28 mg/dL, median weight was 83±18 kg and mean creatinine clearance (Cockcroft-Gault) was 82±34 mL/min. The management of apixaban in the periprocedural period was left to the investigator's preference. Overall, 264 patients were switched to unfractionated heparin or enoxaparin (238 for AF ablations and 26 for AFL ablations). The median duration of switch was 29 hours. Complications were reported at 30 days, and included 12 bleeding events (1 tamponade needing drainage, 1 pericardial effusion without drainage, 7 International Society on Thrombosis and Haemostasis [ISTH] non major bleedings for AF ablations and 1 pericardial effusion without drainage, and 2 ISTH non major bleedings for AFL ablations) and 1 embolic event (non disabling stroke for an AF ablation). Comparing patients with and without a bleeding event revealed a higher rate of heparin or low-molecular-weight heparin (LMWH) switching in patients with a bleeding event (60% vs 35%; p=0.02). A switch to heparin or LMWH was the only factor associated with an increase rate of bleeding (odds ratio 2.5; [CI 95%; 1.1, 7.1]; p=0.01).

Conclusion

Heparin or LMWH switch in the periprocedural AF and AFL-ablation period is associated with an increased rate of bleeding complications at 30 days.

Acknowledgement/Funding

Financial support from BMS
P1900Amiodarone treatment duration and reasons for permanent drug discontinuation in patients with atrial fibrillation
Authors: Mihajlovic M , Mihajlovic A , Marinkovic M , Kovacevic V , Vajagic L , Kocijancic A , Mujovic N , Potpara T
Published: October 2019

Background and purpose

Amiodarone is commonly use in patients with atrial fibrillation (AF), but the organ toxicity side effects limit its long-term use. We investigated the rates of and reasons for permanent amiodarone discontinuation among patients with AF in contemporary clinical practice.

Methods

A single-centre, ongoing, registry-based observational longitudinal study included consecutive AF patients prescribed with amiodarone in our hospital from January 2015 to December 2017. All patients underwent a loading protocol of 400–600 mg of amiodarone daily for 1–2 weeks, followed by 200–400mg daily for 4–8 weeks and 200mg daily or 1000mg weekly thereafter.

Results

Of 657 AF patients taking amiodarone (Mean age 62.2±11.0, female n=215 (32.6%), hypertension n=504 (76.7%), diabetes mellitus n=107 (16.3%), coronary arterial disease n=139 (19.8%), History of Myocardial infarction 86 (13.1%), Stroke/TIA 60 (9.1%), chronic kidney disease 157 (23.9%)), the drug was permanently discontinued in total of 248 patients (37.7%). The reasons for amiodarone discontinuation are shown in Figure. On multivariable Cox-regression analysis, physician's decision (HR 5.6; 95% CI 3.9–7.9, p<0.001) and amiodarone side effects (HR 3.9; 95% CI 2.9–5.1, p<0.001) were significantly associated with permanent amiodarone discontinuation.

The overall time to discontinuation was 23.2±24.1 months. Compared with others, time to discontinuation was shorter in patients post AF ablation (17.3±21.3 vs 24.5±24.5, p=0.05), longer in those with AF progression (29.2±31.0 vs 20.9±20.3, p=0.014) and similar in patients with amiodarone side effects (23.7±17.7 vs 23.0±26.8, p=0.813). Pulmonary toxicity and proarrhythmia were not observed among study patients (Figure).

Chart 1

Conclusion

Our study showed that permanent discontinuation of amiodarone in contemporary clinical practice was due to the drug side effects in 12% of amiodarone-treated AF patients, occurring after a mean 2-year treatment course. The most prevalent side effect was thyroid dysfunction, whereas the prevalence of proarrhythmic effect was low. Notably, physician's fear of complications (which may not always be justified), also was an independent driver of permanent amiodarone discontinuation. More data are needed to inform optimal amiodarone use in AF patients in daily practice.
P1903Efficacy and safety of dronedarone after recent cardioversion in patients with atrial fibrillation/flutter: a post-hoc analysis of the EURIDIS/ADONIS trials
Authors: Thind M , Crijns H J , Naccarelli G V , Reiffel J A , Corp Dit Genti V , Wieloch M , Koren A , Kowey P R
Published: October 2019

Background

Cardioversion is commonly performed prior to antiarrhythmic drug initiation for atrial fibrillation/flutter (AF). There are limited data describing baseline differences in patients requiring cardioversion to maintain sinus rhythm compared to those who do not. Likewise, response to antiarrhythmic drugs, including dronedarone, specifically in patients requiring cardioversion has not been well defined.

Purpose

To evaluate efficacy and safety of dronedarone versus placebo in patients with non-permanent AF who had cardioversion within 5 days prior to randomization in EURIDIS/ADONIS.

Methods

To qualify for enrolment in EURIDIS/ADONIS patients were required to be in sinus rhythm for at least 1 hour preceding randomization. Of 1237 patients randomized (2:1 dronedarone to placebo), 364 needed cardioversion for study entry (dronedarone 243, placebo 121). AF recurrence was evaluated by ECG obtained during study visits, scheduled transtelephonic monitoring, or at symptom recurrence.

Results

Cardioversion patients were more likely to have rheumatic heart disease, valvular heart disease, any structural heart disease, and heart failure. Nonetheless, the median time to 1st AF recurrence was longer for dronedarone versus placebo both in cardioversion patients (50 versus 15 days, hazard ratio 0.76, 95% CI 0.59, 0.97) and no cardioversion patients (150 versus 77 days, hazard ratio 0.76, 95% CI 0.64, 0.90), as was time to 1st symptomatic recurrence (cardioversion: 347 versus 87 days, hazard ratio 0.65, 95% CI 0.49, 0.87; no cardioversion: 288 versus 120 days, hazard ratio 0.74, 95% CI 0.62, 0.90) (Figure 1). There was a trend towards fewer 1st AF hospitalizations within 12 months for dronedarone versus placebo (7.8 versus 12.4%, hazard ratio 0.60, 95% CI 0.31, 1.18 in cardioversion patients; 8.4 versus 10.4%, hazard ratio 0.74, 95% CI 0.47, 1.17 in no cardioversion patients). In cardioversion patients, rates of treatment-emergent adverse events with dronedarone versus placebo were 64 versus 66%, serious treatment-emergent adverse events were 19 versus 26%, permanent discontinuations were 9 versus 6%, and deaths were 0 versus 1%.

Conclusions

1) Cardioversion-requiring patients have more baseline structural heart disease and overall shorter time to AF recurrence. 2) Dronedarone effectively delayed 1st AF recurrence versus placebo in patients with or without recent cardioversion. 3) Safety of dronedarone in cardioversion patients was similar to placebo and overall observations from EURIDIS/ADONIS despite baseline differences in comorbidities.

Acknowledgement/Funding

Sanofi, New York, New York, United States of America
P1921Impact of cryoballoon freeze duration on long-term durability of pulmonary vein isolation in atrial fibrillation: insights from Re-mapping procedures (the ICE Re-map study)
Authors: Chen S , Schmidt B , Bordignon S , Perrotta L , Bologna F , Chun K R J
Published: October 2019

Background

Second-generation cryoballoon (CB2) represents a powerful pulmonary vein isolation (PVI) tool. Recently, the randomized time-to-effect guided (ICE-T) CB2 strategy targeting a 240s single freeze demonstrated fast and efficient PVI. To further optimize safety and efficacy, a shortened 3min freeze duration has been suggested but PVI durability remains unclear.

Methods

Between May 2013 and December 2017 all CB2 ablations followed the ICE-T concept (target-freeze: 240s or 180s). Patients undergoing a second procedure for arrhythmia recurrence were analyzed. Two groups were defined based on the index freeze duration (group 240s vs. group 180s). In all repeat procedures a 3D left-atrial map was obtained. Durability of PVI and localization of conduction gaps were compared.

Results

A total of 106/788 (13%) patients underwent a second procedure (group 240s: 80/604 vs. group 180s: 26/184) after a mean of 377 days. There was no difference regarding PV occlusion and time-to-isolation in the index procedure between two groups. No major complications occurred. During the second procedure significantly more patients demonstrated durable isolation of all PVs in group 240 (61% vs 35%, p=0.02) along with a significantly increased rate of PVI durability (88% vs. 69%, per vein, p<0.001). Left sided PVs did significantly benefit from 240s freezes (reconnection LSPV: 6% vs 27%, p=0.004, LIPV: 14 vs. 39%, p=0.006).

Conclusions

The ICE-T strategy is associated with a high rate of durable PVI in patients with arrhythmia recurrence. Target freeze duration of 240s vs. 180s is associated with significantly increased lesion durability, particularly at left sided PVs, without increasing complications.
P1938In vitro characterization of a novel PI 3-kinase inhibitor for growth factor-induced effects in pulmonary artery smooth muscle cells
Authors: Berghausen E M , Moeller F , Vantler M , Hirsch E , Baldus S , Rosenkranz R
Published: October 2019

Rationale

Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling in pulmonary arterioles. Increased activation of receptor tyrosine kinase (RTK)-mediated signaling pathways lead to increased proliferation and chemotaxis of pulmonary arterial smooth muscle cells (PASMCs). In previous studies, we identified phosphatidylinositol-3-kinase (PI3K) as a key enzyme for these processes. Since systemic PI3K inhibition is potentially associated with undesired side effects, we here for the first time tested the efficacy of the novel PI3K inhibitor CL27c to impede growth factor-mediated cellular effects in human PASMCs. CL27c is topically applicable and as a prodrug it is intracellularly activated and thus offers optimal efficacy in target cells while at the same time minimizing undesired effects in non-target cells.

Methods

Using Western blotting and immunohistochemistry, activation of the central PI3K effector AKT in human and murine lung tissue was investigated. Quantification of cell proliferation was performed by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. PASMCs were incubated with CL27c [0.1; 0.3; 1; 3; 10μM] and stimulated either with PDGF-BB [30ng/ml] or with a growth factor combination (GFC) [PDGF-BB 30ng/ml, FGF 2ng/ml, EGF 0.5ng/ml, insulin 0.5μg/ml, FCS 5%]. Chemotaxis was quantified using modified Boyden chambers. The signal transduction cascade was investigated by Western blotting.

Results

Analysis of AKT activation revealed hyperphosphorylation in both the vascular wall and complete lung homogenates from PAH patients and hypoxia-treated mice. Examination of the mitogenic signal transduction revealed a markedly reduced phosphorylation of AKT and GSK3β in CL27c pretreated PASMCs. In addition, central cell cycle events, such as expression of cyclin D1, were reduced. This was in line with a CL27c concentration-dependent significant reduction of PDGF- and GFC-induced proliferation (control: 2.53±0.26 vs. CL27c: 0.73±0.14 and control: 5.27±0.61 vs. CL27c: 2.80±0.71 both at 10μM, p<0.001). Furthermore, PDGF- and GFC-induced chemotaxis were as well significantly reduced (100% ± 19 vs. CL27c: 24.43% ± 8.58 and 100% ± 5.76 vs CL27c: 25.23% ± 10.57 at 10μM p<0.001).

Conclusion

These results indicate that CL27c reduces both proliferation and chemotaxis of PASMCs. As these processes play a key role in the development and progression of PAH, this approach is currently being investigated in preclinical models for its therapeutic potential. This “prodrug” approach could avoid non-specific effects and systemic side effects of Pan-PI3K inhibition, especially since the substance is suitable for topical application (inhalation). Thus, CL27c represents a promising treatment option.
P1949Changes in prevalence patients with arterial hypertension in Russia
Authors: Badin Y , Fomin I V , Polyakov D S , Yakushin S S , Smirnova E A , Galyavich A S , Kamalov G M , Kechedzhieva S G , Koziolova N A , Malchikova S V , Ionova T S
Published: October 2019

Aim

The present study shows the dynamics of the prevalence different grades of AH and treatment coverage over15 years of observation.

Methods

8740 apartments were randomized in 2002 year in eight regions of Russia and 19449 individuals were included. Re-examination was carried out in 2017 year. The representative sample was separated in four groups: Grade 0 – individuals with systolic blood pressure (BP) <140 mm Hg and diastolic blood pressure <90 mm Hg; and three Grades of arterial hypertension (AH) in accordance with European guidelines. Also, we select patient with and without antihypertensive drug treatment (AHDT).

Results

The mean age individuals was 44.4±19.3 years in 2002 year. Grade 0 had 63.3% participants (mean age 36.5±17.1 y.), Grade 1 – 19.5% (mean age 55.2±15.4 y.), Grade 2 – 11.7% (mean age 60.6±13.5 y.) and Grade 3 – 5.6% (mean age 62.4±12.8 y.). 3.0% participants had AHDT and blood pressure meets Grade 0. Patients with AH Grade 1 used drugs in 25.5% cases, with Grade 2 – 49.4% and with Grade 3 – 60.8% patients respectively. The mean age of participants with AHTD was significantly higher than mean age group without AHTD in Grade 0, 1 and 2 (p<0.001). In group Grade 3 mean age was not difference (p=0.16). The mean age individuals (51.3±16.9 y.) in 2017 year was significantly higher on 6.9 years than mean age in 2002 year (p<0.001). The proportion of patients with AHDT in all grades groups in sample 2017 year were significantly higher than in sample 2002 year (Table). The prevalence of AH in 2002 y. amounted to 38.6%. In 2017 y. prevalence of AH was significantly higher – 41.4% (p<0.001).

Structure of samples Grade 2002 2017 AHDT Mean age AHDT P value Mean age 0 63,3% No 35,8±16,8 70,1% 42,6±13,9 Yes 3,0% 57,4±14,5 16,3% <0,001 63,6±12,0 1 19,5% No 53,3±15,7 23,6% 57,3±13,3 Yes 25,5% 60,9±13,0 68,4% <0,001 66,3±11,3 2 11,7% No 58,5±14,2 5,4% 58,0±14,9 Yes 49,4% 62,7±12,3 80,6% <0,001 66,5±11,5 3 5,6% No 61,7±13,9 1,0% 63,6±17,6 Yes 60,8% 62,8±12,0 71,1% 0,03 66,0±12,8 ALL 100% 44,4±19,3 100% 51,3±16,9 AHDT: antihypertensive drug treatment.

Conclusion

Over 15 years follow up period the prevalence of hypertension in Russia increased to 41.4%, but the effectiveness of therapy remains low.
P1953Risk of upper gastrointestinal bleeding following myocardial infarction: a novel prediction model for assessing appropriateness of proton pump inhibition therapy
Authors: Sehested T S G , Blanche P , Hansen P W , Charlot M G , Torp-Pedersen C , Fosboel E L , Gislason G H , Gerds T A , Carlson N
Published: October 2019

Background

Upper gastrointestinal bleeding following myocardial infarction continues to be a severe complication associated with increased mortality; however, bleeding events might be avoided by appropriate therapy with proton pump inhibitors.

Purpose

To develop and validate a prediction model aimed at identifying patients at increased risk of upper gastrointestinal bleeding following myocardial infarction.

Methods

Based on multiple nationwide Danish registers, all patients initiating dual antiplatelet or anticoagulant therapy in combination with antiplatelet following myocardial infarction between 2003 and 2016 were identified. Primary outcome of interest was one-year risk of upper gastrointestinal bleeding. A derivation cohort including all patients between 2003 and 2013 was selected, whereas patients identified between 2014 and 2016 was employed for internal validation. Multiple logistic regression was used to predict person specific risks based on age, history of gastrointestinal bleeding or peptic ulcer, anaemia or gastrointestinal cancer, use of nonsteroidal anti-inflammatory drugs, oral anticoagulants, selective serotonin reuptake inhibitors or loop diuretics. We compared our model with the European Society of Cardiology (ESC) guideline recommendation on gastrointestinal bleeding risk assessment.

Results

A total of 61 543 patients with myocardial infarction were identified for the study. In the total cohort, the median age was 68 years (IQR: 58–77), 85.0% (52 334) underwent coronary angiography, 2.6% (1 608) had a history of gastrointestinal bleeding and 7.1% (4 354) used oral anticoagulants. The average one-year risk of upper gastrointestinal bleeding was 1.04% (95% CI: 0.95–1.14%), and mean predicted risk of the model was 1.04% (IQR: 0.64–1.26%). The discriminative ability of the model evaluated by area under the curve was 74.2% (95% CI: 66.9–78.6%) in the validation cohort. The proposed risk model demonstrated improved sensitivity and specificity at the specific threshold of the ESC risk schemes (Figure 1). Results remain principally unchanged regardless of inclusion or exclusion of patients initiating proton pump inhibitors at baseline. Furthermore, using cross-validation for the model evaluation produced similar discrimination results.

Figure 1

Conclusion

Based on nationwide registers a novel prediction model aimed at identifying patients at increased risk of upper gastrointestinal bleeding was developed and validated; the model observed moderate discrimination in the validation cohort providing possible benefit for clinicians in terms of communicating absolute risk to the patients and determining the appropriateness of initiating preventive therapy.

Acknowledgement/Funding

The Danish Heart Foundation