bluuebunny/crossref_metadata_2025 huggingface dataset:
P4688Additional role of unmodifiable risk factors in pulmonary arterial hypertension risk stratification according to current ESC/ERS guidelines
Authors: Zuffa E , Dardi F , Palazzini M , Gotti E , Rinaldi A , De Lorenzis A , Guarino D , Pasca F , Magnani I , Rotunno M , Manes A , Galie' N
Published: October 2019

Background

Current pulmonary hypertension (PH) guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) using a multiparametric approach. Anyway, the role of unmodifiable risk factors is not taken into account.

Purpose

The aim of this study was to evaluate the role of unmodifiable risk factors (age, gender, PAH aetiology) in PAH risk stratification using the recently proposed simplified risk table and to test if these factors influence the response to PAH-specific treatment.

Methods

All patients with PAH referred to a single centre were included from 2003 to 2017. We applied a simplified risk assessment strategy using the following criteria: WHO functional class, 6-min walking distance, right atrial pressure or brain natriuretic peptide plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). The last 2 criteria were based on which parameter was available; if both were available the worst was chosen. Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. Then we performed multivariate Cox analysis to evaluate what are the independent predictors of survival (age, gender, PAH aetiology together with the recently proposed simplified PAH risk table) and we tested if these factors influence the response to PAH specific therapy comparing the % improvement of hemodynamic parameters from baseline to 3–4 months after starting treatment. Wilcoxon-Mann-Whitney test was used for comparisons.

Results

Six hundreds and twenty-one treatment-naïve patients were enrolled. Age [HR (95% CI) = 1.022 (1.014–1.030); p-value <0.001], male gender [HR (95% CI) = 1.881 (1.479–2.392); p-value <0.001] and connective tissue disease (CTD)-PAH aetiology [HR (95% CI)= 2.278 (1.733–2.995); p-value <0.001] were all independent predictors of prognosis in patients with PAH together with the recently validated simplified PAH risk table [HR (95% CI) = 2.161 (1.783–2.618); p-value <0.001] but they didn't significantly influence the response to PAH specific treatment as shown in the Figure.

Figure 1

Conclusions

Age, gender and CTD-PAH aetiology significantly influence prognosis together with the recently validated simplified PAH risk table but don't significantly influence the response to PAH-specific treatment.

Acknowledgement/Funding

None
P469440-year trends in incidence of simple congenital heart disease: a nationwide study
Authors: El-Chouli M , Mohr G H , Bang C N F , Ahlehoff O , Raunsoe J , Torp-Pedersen C , Gislason G H
Published: October 2019

Background

The methods for diagnosing congenital heart diseases (CHD) have changed radically over the last two decades. Since 2004, foetuses have been screened nationwide for congenital diseases in Denmark. In addition, the use of echocardiography has increased considerably during the last decades, facilitating the diagnosis of asymptomatic CHD. Despite the increased diagnostic possibilities, novel research regarding the incidence of simple CHD is lacking.

Purpose

To examine temporal trends in the incidence of simple CHD in the Danish population.

Methods

All Danish residents diagnosed with a ventricular septal defect (VSD), atrial septal defect (ASD) or patent ductus arteriosus (PDA) between 1 January 1977 and 31 December 2016 were identified by linking nationwide registers. Patients with simple CHD were defined as individuals diagnosed with an isolated VSD, ASD or PDA. Excluded was patients who had genetic disorders, other CHDs or developed a clinically significant morbidity such as myocardial infarction and chronic kidney disease before the age of 15 years.

Results

We included 10,464 patients diagnosed with simple CHD of whom 4,766 (45.5%) were men. During the study period, 4,317 (41.3%) were diagnosed with VSD, 4,148 (39.6%), with ASD and 1,999 (19.1%) with PDA.

Crude incidence rates (IR) of ASD (Figure 1, panel A) remained unchanged between 1977–2004, after which ASD rates increased markedly until reaching a plateau between 2013–2016. Between 1997–2016, the median age at diagnosis of ASD increased substantially (Figure 1, panel B) (median age in 1997 = 19 years (IQR 11–45); in 2016 = 40 years (IQR 1–56); in 1977–1996: 18 years (IQR 5–44); in 1997–2016: 31 years (IQR 1–52)). VSD rates did not change between 1977–1991, increased until 1994 (IR in 1991 = 14.46 per 1 mil person years (PY); in 1994 = 26.06 per 1 mil PY) and subsequently slowly decreased until 2016 (IR in 2016 = 13.99 per 1 mil PY). The median age at diagnosis of VSD was consistent throughout the study period and was overall 1 years (IQR 0–17). The rates of PDA were consistent during the study period, and the overall median age at diagnosis of PDA was 1 months (IQR 1–40).

Figure 1

Conclusion

In this nationwide study of simple CHD, the incidence rates and age at time of diagnosis of VSD and PDA remained stable during the 40-year period. Contrastingly, the incidence rates and age at time of diagnosis of ASD increased markedly from 2004 and onwards.

Acknowledgement/Funding

The Danish Heart Foundation
P4698Survival outcomes in patients with Eisenmenger syndrome after heart-lung or bilateral sequential lung transplantation
Authors: Kearney K , Bart N , Khush K , Hayes D , Keogh A
Published: October 2019

Background

Eisenmenger syndrome (ES) is defined as pulmonary hypertension secondary to a right to left intracardiac shunt, commonly an atrial septal defect (ASD) or ventricular septal defect (VSD). Heart-lung (HLTx) or bilateral sequential lung transplantation (BSLT) are both treatment options for some candidates. The choice between these two procedures has varied historically and according to transplant centre preference and donor availability. We completed a retrospective study to determine if BSLT with cardiac repair was associated with better outcomes compared to HLTx.

Aim

This study compared post-transplant survival in patients with ES undergoing HLTx or BSLT.

Method

Using the International Society Heart and Lung Transplantation Registry data, we identified all patients with ES between October 1, 1987 and March 31, 2018.

Results

A total of 177 patients underwent HLTx for ES ASD and 101 who underwent BSLT with cardiac repair. Median follow up was 890 days (range 0–9888 days) for the entire post-transplant cohort. 126 HLTx and 66 BSLT patients died in the follow up period.

A total of 173 ES VSD patients underwent HLTx in the database, and 52 underwent BSLT with cardiac repair. Median follow up was 460 days (range 0–8406 days) for the entire post-transplant cohort. 116 HLTx and 36 BSLT patients died during the follow up period.

Figure 1 demonstratres the comparative Kaplan-Meier survival curves following BSLT or HLTx for Eisenmenger's ASD and VSD patients. No statistically significant difference in Eisenmenger survival between combined heart-lung transplantation or bilateral sequential lung transplantation group (ASD log rank test p value = 0.99, VSD log rank test p value = 0.1 performed for the first 6 year).

Figure 1

Conclusions

Our analysis determined that patients with ES and either VSD or ASD had similar long-term survival comparing HLTx with BSLT and cardiac repair.
P4700Work during treadmill rehabilitation predicts clinical benefit and muscle mitochondrial improvements in intermittent claudication
Authors: Murrow J , Brizendine J , Djire B , Young H , Rathbun S , Nilsson K , McCully K
Published: October 2019

Background

Supervised exercise training is recommended for intermittent claudication in peripheral artery disease (PAD), but the relationship between work achieved during exercise and clinical outcomes is not well described. As in other training modalities, increased effort measured by cumulative work production is expected to be translate into to positive performance adaptations. In settings of constrained limb blood flow, this relationship is unknown. In addition, the impact of exercise on skeletal muscle oxygen use capacity changes is unknown. Near infrared spectroscopy (NIRS) offers a method of characterizing skeletal muscle mitochondrial adaptations before and after training programs.

Methods

We enrolled subjects (n=17, age 71±8.8 years, 20% female) with PAD and intermittent claudication (ankle brachial index [ABI]=0.76±0.21) in a 12-week supervised training program, randomized to traditional pain-based training strategy versus hypoxia-based training (using NIRS to direct training). Muscle work was calculated based on training performance. NIRS-based determination of mitochondrial capacity and microvascular flow were measured at baseline and after 12 weeks.

Results

Subjects trained for an average of 32.9±5.9 sessions walking at 54.4±13.4 m/min per session. Subjects achieved a mean of average workload of 4767±5112 kilogram force meter (kpm) per session and an aggregate of 148536±148020 kpm for the training program. Baseline pain-free walking time of 2.95±2.10 minutes increased by a mean of 3.74±2.47 minutes. Increase in walking time was proportional to the average work level achieved per session, with a correlating trend to the overall work level performed over 12 weeks (r=0.543, p=0.024). There was no increase in blood flow measured by ABI or limb microcirculation perfusion index over the training period. Skeletal muscle mitochondrial capacity increased over the training period and correlated with the overall work performed (r=0.573, p=0.016).

Figure 1

Conclusions

Treadmill exercise rehabilitation for intermittent claudication may be guided by total dose of exercise and NIRS-based indices of mitochondrial capacity rather than pain-levels achieved or changes in perfusion measures.

Acknowledgement/Funding

American Heart Association
P4705Transpedal access for below-the-knee lesions in critical limb ischemia
Authors: Ruzsa Z , Csavajda A , Deak M , Vegh E , Orias V , Nemes B , Merkely B , Kwan T W
Published: October 2019

Background

Traditional access for the treatment of below-the-knee (BTK) lesions is the femoral approach, but in failed anterograde cases transpedal access can be utilized. The aim of the study was to evaluate the safety and technical and clinical success of endovascular BTK artery revascularization by a primarly retrograde transpedal access.

Methods

The clinical and angiographic data of 115 consecutive patients treated via transpedal access with symptomatic BTK stenosis were evaluated two cardiovascular centers (Europe and USA). We have selected patients with good distal run-off and non-infected distal puncture zone. The distal pedal artery was punctured by ultrasound guidance, and the procedural guidance was done by transpedal (TPA) or transradial angiography (TRA). Distal pressure at the end of the pedal sheath was also measured before and after the intervention. The primary endpoint was a composite of procedural success, major adverse events, and rate of access site complications. Secondary endpoints were: angiographic result of BTK intervention, fluoroscopy time, X-ray dose, procedure length, cross over rate to another puncture site and duration of hospitalization.

Results

The indication of the intervention was critical limb ischemia in all patients. Overall technical success was achieved in 99.1% of the patients at least in one BTK artery. The distal puncture was successful in 114/115 patients 99.1% of the patients and the access site was anterior tibial artery in 96 patients (83.55), posterior tibial artery in 15 patients (13%) and peroneal artery in 4 patients (3.5%). Pedal to femoral access site cross over was 0.5%. Control angiography was done in 73 patients (63.5%) from radial and in 42 patients (36.5%) from transpedal access. The average contrast, procedure and fluoroscopy time was 109.9 [97–123]vs 31.4 [27–35]ml (p<0.001), 43.2±22.3 vs 47.8±25.5 min and 581±448.7 vs 788±605 sec in the TR and TP group.The average systolic transpedal pressure has been increased from 100.1 mmHg ±44 to 131±36.4 mmHg after the procedure. Major adverse event at one month was detected in six patients (5.2%).Radial and pedal artery access site complications were encountered by ultrasound in 3/73 (4.1%) and 3/115 patients (2.6%) during follow up.

Conclusion

Below-the-knee artery angioplasty can be safely and effectively performed using radial and transpedal access in selective patient population.
P4715Association of heart failure duration with clinical prognosis after transcatheter mitral valve repair
Authors: Sugiura A , Tabata N , Weber M , Oezturk C , Zimmer S , Sinning J M , Nickenig G , Werner N
Published: October 2019

Background/Introduction

Transcatheter mitral valve repair (TMVR) in patients with heart failure (HF) and severe mitral regurgitation (MR) entails better clinical and symptomatic status. While emerging evidence indicate that HF duration is linked to adverse outcomes in patients with HF, it is not known whether the HF duration before TMVR has an effect on adverse outcomes.

Purpose

We aimed to assess the association between duration of HF before TMVR and clinical prognosis after the procedure.

Methods

We retrospectively enrolled a total of 345 patients who underwent TMVR procedure with MitraClip or Cardioband system for the treatment of symptomatic MR after guideline recommended therapy. The patients were divided into 2 groups according to the duration of HF (>18 months:, n=161, ≤18 months: shorter HF group, n=184). Cox proportional hazards analysis was performed to assess the association between duration and two-year composite endpoint (all-cause mortality, unexpected hospitalization due to HF, and repeat mitral valve therapy).

Results

Patients with longer duration of HF were more likely to be male, had greater incidence of coronary artery disease (77.0% vs. 51.6%, p<0.001), had received more frequently implantable cardioverter defibrillator or cardiac resynchronization therapy (41.0% vs. 10.3%, p<0.001), and had more decreased left ventricular ejection fraction (41.1±14.5% vs. 49.3±16.0%, p<0.001) compared to patients with shorter duration of HF. Two-year event-free survival rate was significantly lower in patients with longer duration of HF (66.3% vs. 83.8%, Log-rank p=0.01) compared to whose with shorter duration of HF. Similar trends were observed for all-cause mortality (84.8% vs. 95.9%, p=0.06) and repeat mitral valve therapy (93.4% vs. 100%, p=0.02). In the Cox proportional hazard analysis, longer duration of HF was independently associated with increased risk of adverse outcomes (Hazard ratio, 2.26; 95% confidence interval, 1.11–4.62; p=0.02) compared with shorter duration of HF.

Conclusion

Patients with the longer duration of HF before TMVR is independently associated with increased risk of adverse outcomes after the procedure. It is, however, accompanied by higher prevalence of cardiac co-morbidities in these patients. Our findings suggest that a longer duration of HF is a risk indicator and should be considered into in future clinical trials of TMVR.
P4716One-year outcomes of the tri-repair study assessing cardioband tricuspid valve reconstruction system for patients with severe tricuspid regurgitation
Authors: Nickenig G , Von Bardeleben R S , Schaefer U , Kuck K H , Vahanian A , Juliard J M , Latib A , Baldus S , Maisano F , Hausleiter J
Published: October 2019

Background

Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options.

Objectives

We report the one-year outcomes of the Cardioband™ Tricuspid Valve Reconstruction System in the treatment of severe functional TR in 30 patients enrolled in the TRI-REPAIR study.

Methods

Between October 2016 and July 2017, 30 patients were enrolled in this single-arm, multicenter, prospective study. Patients were diagnosed with severe, symptomatic TR in the absence of untreated left-heart disease and deemed inoperable because of unacceptable risk for open-heart surgery by the local heart team. Clinical, functional, and echocardiographic data were prospectively collected before and up to one year post-procedure. An independent core lab assessed all echocardiographic data and an independent clinical event committee adjudicated the safety events.

Results

Mean patient age was 75 years, 73% were females, 23% had ischemic heart disease, and 93% had atrial fibrillation. At baseline, 83% were in NYHA Class III-IV, 63% had edema, and LVEF was 58%. Technical success was 100%. Through one year, one patient had a reintervention and exited the study. Five patients died of which one was device-related. Between baseline and one year (paired analyses), echocardiography showed average reductions of annular septolateral diameter of 16% (44mm vs. 37mm; p<0.0001), PISA EROA of 49% (0.73cm2 vs. 0.37cm2, p=0.0037), and mean vena contracta of 30% (1.2cm vs. 0.9cm, p=0.0046). Clinical assessment showed that at one year 78% of patients were in NYHA Class I-II (p=0.0003). Six minute walk distance improved by 42m (p=0.0525). Kansas City Cardiomyopathy Questionnaire score improved by 19 points (p=0.0009). Edema was absent in 70% of the patients.

Conclusions

These results show that the Cardioband tricuspid system performs as intended and appears to be safe in patients with symptomatic and severe functional TR. At one year significant reduction of TR through a sustained decrease of annular dimensions, improvements in heart failure symptoms, quality of life, and exercise capacity were observed. Further studies are warranted to validate these initial promising results.

Acknowledgement/Funding

Edwards Lifescieinces
P4726Functional mitral regurgitation treated with percutaneous repair: a relative survival analysis of a national Swiss cohort
Authors: Biasco L , Klersy C , Corti R , Moccetti T , Pedrazzini G
Published: October 2019

Introduction

Percutaneous treatment of functional mitral regurgitation (FMR) with MitraClip (MC) has led to discordant results in recent randomized clinical trials. We aimed at estimating excess mortality (EM) and to evaluate its predictors in a large Swiss FMR population treated with MC.

Methods

FMR patients enrolled in the MitraSwiss Registry (479 pts) with a mean age of 74.7±9.42 years were evaluated. We computed and plotted EM up to 5 years after implant using the Swiss 2008–20013 mortality tables, stratified by age and sex. A Poisson regression was used to model EM as a function of age, sex, pre-implant RV/RA gradient, calendar period (2011–2013; 2014–2015,2016–2017), ischemic vs non ischemic aetiology, acute procedural success and residual MR.

Results

Patient's survival at 1,2,3,4 and 5 years were respectively 0.84, 0.72, 0.59, 0.53 and 0.48. FMR patients treated with MC showed excess mortality of +13% (95% CI,10%-18%), +22% (95% CI,17%-28%), +34% (95% CI,27%-41%), +37% (95% CI,28%-46%) and +39% (95% CI,28%-50%) at each time point as compared to the Swiss population, with not differences over the entire follow up (p=0.481). Age group, sex, RV/RA gradient calendar period, ischemic vs non ischemic and residual MR were not associated with excess mortality while a clear association was recognized with acute procedural success (p=0.011).

Conclusions

In FMR patients treated with MC a persistent EM was observed at a 5 years follow up. Acute procedural success is the only determinant of EM with a 65% lower EM as compared to procedural failures.
P4751Underdosing fragile patients - Are we helping or harming?
Authors: De Almeida J P L , Martinho S , Girao A , Barreiro I , Baptista R , Ferreira J , Goncalves V , Milner J , Ferreira C , Alves P , Azul A , Goncalves L
Published: October 2019

Background

An individualized approach should be taken regarding the utilization of direct oral anticoagulants (DOAC) in frail and elderly populations with atrial fibrillation (AF). We hypothesized that among an elderly and frail population, where the risk of bleeding, both real and perceived, is very high, the proportion of patients with a dose regimen different from the formal indication would be particularly high due to potential underdosing.

Methods

We conducted a retrospective, observational study enrolling 327 patients with AF admitted to an Internal Medicine ward during a 1-year period and discharged with a DOAC prescription. We divided the population in 2 groups: patients prescribed a reduced dose without formal dose reduction criteria (underdosed, n=170) and the rest of the population (n=157), which included adequately dosed patients, both with normal dose (n=99) and correctly reduced dose (n=43) and overdosed patients (n=15). A 1-year follow-up was completed for all patients, assessing the following outcomes: all-cause mortality, stroke, systemic embolism and major bleeding.

Results

Patients were elderly (81.9±7.68) and frail (Katz index 3.35±2.36). Apixaban was the most commonly prescribed NOAC (38.8%), followed by rivaroxaban (36.4%) and dabigatran (24.8%). Among underdosed patients, apixaban was prescribed in 45.3% of patients, dabigatran in 29.4% and rivaroxaban 25.3%. Although only 18.3% of patients had clinical criteria for dose reduction, 65.4% were discharged with reduced dose and thus 52% were underdosed.

Regarding 1-year outcomes, mortality (40.8% vs 25.5%, RR=1.6, p=0.003) and the combined stroke, systemic embolism and major bleeding event rate (10.1% vs 3.2%, RR=3.16, p=0.015) were higher for underdosed patients.

Among underdosed patients, comparing with the rest of the population, the increased ischemic events rate (ischemic stroke and systemic embolism) did not reached statistical significance (3.7% vs. 1.9%, p=0.5), but it did for hemorrhagic events (major bleeding and hemorrhagic stroke) (6.1% vs 0.6%, p=0.01)

On multivariate analysis, even after considering adjustment for age, Katz and CHAD2VAS2C scores, renal function and DOAC prescribed, DOAC underdosing was associated with a higher risk of both ischemic and hemorrhagic events (HR = 3.51, 95% CI 1.08–11.38). However, it lost its independent negative effect regarding mortality (HR 1.32, 95% CI 0.87–1.99).

Survival and event rate in underdosed

Conclusions

There is a significant proportion of frail and elderly patients with AF that are underdosed. This subset has a significant survival disadvantage, eventually reflecting prescription bias. However, underdosed patients have also a higher event rate of both ischemic and hemorrhagic events, suggesting that underdosing fragile patients is not an effective strategy and that instead it may be hazardous.
P4763High power radiofrequency ablation with fixed short duration is rapid, efficient and safe for circumferential pulmonary vein isolation
Authors: Schreieck J , Duckheim M , Yurtbil U , Flassak J , Scheckenbach C , Stimpfle F , Heinzmann D , Gawaz M , Seizer P
Published: October 2019

Background

Short duration 50 Watt radiofrequency (RF) ablation has been shown to be feasible for atrial fibrillation (AF) ablation with short procedure times.

Purpose

We evaluated 50 Watt RF power with a different fixed short application duration at the anterior and posterior left atrial wall using contact force (CF) sensing catheters for circumferential pulmonary vein isolation (PVI).

Methods

Consecutive patients (pts) with indication for de novo AF ablation (n=40, age 64±12 years) with paroxysmal (n=23) or persistent (n=17) AF underwent high density 3D mapping of the left atrium. Low voltage areas of more than 5% of the left atrium were only found in 20% of pts. Thereafter, circumferential PVI using CF sensing catheters was performed. For each RF application (50 Watt, RF duration 11–13s at the anterior wall, 9–11s at the posterior wall) a stable catheter tip position with minimal mean CF of 3g was required and application was stopped in case of CF more than 30g. Esophageal temperature measurement was performed with temperature cut off 39.0°C. In case of temperature rise, ablation protocol was switched to conventional 20 Watt RF applications for ablation adjacent to the esophagus.

Results

Complete PVI was achieved in all pts with 81±29 short RF applications resulting in cumulative RF applications duration of 13.1±4.2min and an ablation duration of 59±17min for complete PVI. Even RF application with low CF (3–5g) were effective. Due to esophageal temperature rise, switch to conventional RF application with 20 Watt was performed in 43% of pts at least at one posterior PV entrance. After a waiting period of 20 min only in 33% of pts any PV conduction recurs, in 28% of pts only at a single spot and reconnected fibers were not associated with low CF application at that spot, but clearly associated with low energy application at the posterior wall. All PV were successfully re-isolated in most of pts with a single spot high energy RF application. No serious complications occurred in association with PVI. Follow up will be available at presentation time.

Conclusion

RF ablation with 50 Watt fixed short duration is efficient and safe for circumferential PVI. Ablation procedure durations are shorter and early recurrence rates are lower compared to reported conventional ablation procedures. The importance of CF titration seems to be diminished by 50 Watt RF applications in the left atrium. Further follow up have to be waited.
P4782Direct comparison of dabigatran, apixaban, rivaroxaban and edoxaban for effectiveness and safety among patients with non-valvular atrial fibrillation
Authors: Choi E.-K , Lee S R , Lee S R , Kwon S , Kwon S , Han K D , Han K D , Jung J H , Jung J H , Oh S , Oh S , Lip G Y H , Lip G Y H
Published: October 2019

Background

Although the prescription of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been rapidly increasing in Asian countries since their introduction, limited evidence exists on the effectiveness and safety of warfarin and all 4 available NOACs from current clinical practice in the Asian population. We aimed to evaluate comparative effectiveness and safety of warfarin and all 4 available NOACs

Methods

We studied a retrospective observational cohort of oral anticoagulant (OAC) naïve non-valvular AF patients treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using inverse probability of treatment weighting (IPTW). Ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), major bleeding (MB) and a composite clinical outcome were evaluated.

Results

A total of 116,804 patients were included (25,420 with warfarin, 35,965 with rivaroxaban, 17,745 with dabigatran, 22,177 with apixaban, and 15,496 with edoxaban). Patients treated with warfarin were younger (mean age 67 years) compared to NOAC users (71 to 73 years) and had lower mean CHA2DS2-VASc score (3.18) than the NOAC groups (3.58 to 3.76). Among the NOAC users, patients prescribed apixaban were older (mean age 73 years) than other NOAC groups (71 to 72 years), had higher mean CHA2DS2-VASc score (3.76) than others (3.55 to 3.63) and higher burden of comorbidities. More than half of patients were prescribed reduced dose regimes. After IPTW, all baseline covariates were well balanced across 5 treatment groups. Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, ICH, GIB, MB and composite outcome (Figure A). Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran (Figure B). Apixaban, dabigatran and edoxaban had a lower rate of GIB and MB compared with rivaroxaban. The composite clinical outcome was non-significantly different for apixaban vs edoxaban.

Conclusions

In this large contemporary observational Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared to warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.
P4787Use of direct oral anticoagulants in patients with atrial fibrillation having a history of intracranial hemorrhage
Authors: Chao T F , Chen S A
Published: October 2019

Background

Patients with atrial fibrillation (AF) having a history of intracranial hemorrhage (ICH) were excluded from the pivotal randomized trials comparing direct oral anticoagulants (DOACs) and warfarin. We aimed to compare the effectiveness and safety of DOACs and warfarin among AF patients having a history of ICH.

Method

A total of 4,540 AF patients having a CHA2DS2-VASc score ≥1 for males and ≥2 for females who had a history of ICH and received oral anticoagulants (DOACs in 3,493 and warfarin in 1,047) were identified from the Taiwan National Health Insurance Research Database. A propensity matching analysis was performed to balance the baseline differences, and 973 patients were finally identified in each groups.

Results

The risk of ischemic stroke did not differ significantly between warfarin and DOACs (4.41%/yr vs 4.87%/yr; HR 0.985, p=0.927). The risks of bleeding events were lower with DOACs compared to warfarin with a HR (95% CI) of 0.752 (0.573–0.986, p=0.040) for major bleeding and 0.614 (0.379–0.995, p 0.048) for ICH. The risk of mortality was also lower in patients treated with DOACs (HR = 0.539; 95% CI = 0.453–0.642, p<0.001). The cumulative incidence curves of each events for 2 groups are shown in Figure.

Conclusion

Compared to warfarin, DOACs were associated with a similar risk of ischemic stroke and better safety profiles among AF patient with a history of ICH.
P4789Comparisons of direct oral anticoagulants and warfarin in patients with atrial fibrillation and liver cirrhosis
Authors: Chao T F , Lip G Y H , Chen S A
Published: October 2019

Background

Patients with atrial fibrillation (AF) and severe liver cirrhosis were excluded from the pivotal randomized trials comparing direct oral anticoagulants (DOACs) and warfarin. In the present study, we compared the effectiveness and safety of DOACs and warfarin among AF patients with liver cirrhosis.

Method

A total of 3,691 AF patients with liver cirrhosis having a CHA2DS2-VASc score ≥1 for males and ≥2 for females and received oral anticoagulants (DOACs in 2,548 and warfarin in 1,143) were identified from the Taiwan National Health Insurance Research Database. The effectiveness and safety were compared between DOACs and warfarin groups.

Results

There was a trend suggesting a lower risk of ischemic stroke with DOACs compared to warfarin (2.91%/yr vs 3.41%/yr; HR 0.743, p=0.060). The risks of bleeding events were lower with DOACs compared to warfarin with a HR (95% CI) of 0.718 (0.573–0.899, p=0.004) for major bleeding and 0.509 (0.292–0.889, p=0.018) for ICH. The risk of mortality was also lower in patients treated with DOACs (HR=0.483; 95% CI: 0.424–0.551, p<0.001). The cumulative incidence curves of each events for 2 groups are shown in Figure. The results were essentially similar after the propensity matching analysis of 2 groups.

Conclusion

Compared to warfarin, DOACs were associated with a lower risk of ICH, major bleeding and mortality among AF patient with liver cirrhosis.
4935Prognostic influence of MDCT-derived global left ventricular longitudinal strain in patients with aortic stenosis treated with transcatheter aortic valve implantation
Authors: Gegenava T , Bijl P , Vollema M , Kley F , Weger A , Hautemann D , Reiber J , Ajmone-Marsan N , Bax J , Delgado V
Published: October 2019

Introduction

Transcatheter aortic valve implantation (TAVI) is an effective treatment for patients with severe aortic stenosis (AS), It can lead to an improvement in symptoms and quality of life but there is also an increasing recognition that some patients simply fail to derive a functional, morbidity, or mortality benefit post-TAVI. Left ventricular (LV) ejection fraction is the LV systolic function parameter to risk stratify patients with severe AS. However, LV global longitudinal strain (GLS) provides incremental prognostic value to LVEF. Computed tomography plays an essential role in the evaluation of TAVI candidates. Novel software permits analysis of LV GLS from dynamic Multi-detector row computed tomography (MDCT) data.

Purpose

The present study aimed at investigating the prognostic value of MDCT-derived LV GLS in patients undergoing TAVI.

Methods

LV GLS was measured on dynamic MDCT using novel CT-software (Figure, panel A) at baseline. Patients were followed up for all-cause mortality and cumulative event rates were analyzed with Kaplan-Meier method.

Results

A total 214 patients (51% male, 80±7 years) were analysed retrospectively. Mean value of MDCT-derived LV GLS was −12.5±4%. During a median follow-up of 1378 days (interquartile range: 881–1895 days), 67 (31%) patients died. The Kaplan-Meier curve shows, that TAVI recipients with MDCT-derived LV GL S>−14% experienced higher cumulative rates of all-cause mortality, compared to patients with MDCT-derived LV GLS ≤−14% (Chi-square 10.549; Log rank p=0.001) (Figure, panel B). On uni- and multivariate Cox-regression models, MDCT-derived LV GLS demonstrated significant association with all-cause mortality (hazard ratio [HR]: 0.851; 95% confidence interval [CI]: 0.772–0.937; p=0.001).

MDCT LV GLS and survival

Conclusions

MDCT-derived LV GLS is independently associated with all-cause mortality in patients treated with TAVI.
4964Loss-of-spen disturbs cardiac conduction in zebrafish mediated by impaired connexin43 function
Authors: Rattka M , Westphal S , Pott A , Kessler M , Weinmann K , Just S , Rottbauer W
Published: October 2019

Introduction

Genome-wide association studies identified SPLIT ENDS (SPEN) gene as an interesting candidate in the pathogenesis of heart failure. SPEN is known to be of importance in transcriptional regulation in several pathways and knockout in mice results in severe cardiac structural abnormalities and premature intrauterine lethality. Moreover, SPEN was associated with human 1.36 syndrome and is located in the critical region for congenital heart defects. Hence, spen seems to be of importance in cardiac physiology, but not much is known about its biologic function in the heart.

Purpose

The aim of our study was to further deepen the insights on spen's role in cardiac pathology.

Methods

Morpholino-mediated gene knockdown is an excellent method to approach in vivo function of cardiac candidate genes in zebrafish. We conducted spen-specific knockdown experiments and first analyzed the emerging heart failure and arrhythmia phenotype. Next, we assessed possible target genes of the transcriptional regulator spen by gene expression profiling and verified our results by quantitative real-time PCR (qPCR), Western Blot, in situ hybridization and further knockdown- and rescue-experiments.

Results

Spen-deficiency results in severe heart failure and arrhythmia in zebrafish. While in the first 24 hpf (hours post fertilization) spen-morphant embryos develop normally, they exhibit reduced contractility and bradycardia at 48 hpf. From 60 hpf onwards impaired spen function is associated with electrophysiological abnormalities, closely resembling human second grade av block as well as atrial and ventricular fibrillation. Transcriptional profiling of pooled spen-morphant hearts revealed connexin43 (cx43) to be severely downregulated. This finding was verified by qPCR, Western Blot analysis and in situ hybridization experiments. Consequently, we hypothesized cx43 to be transcriptionally controlled by spen and that inadequate function of spen lowers cx43 levels, thereby causing cardiac conduction abnormalities. Subsequently, we performed cx43-knockdown, which phenocopied the spen-morphants phenotype. Importantly, all loss-of function experiments could be rescued by overexpression of wild type cx43 mRNA. Moreover, sensitizing via double injection of sub-phenotypic concentrations of spen- and cx43-morpholinos resulted in a supra-additive effect, validating molecular crosstalk between spen and cx43 on the signaling level. Compared to unaffected controls, over 90% of sensitized embryos display the arrhythmia phenotype and show atrial- and ventricular fibrillation already at 48 hpf.

Conclusion

Our results demonstrate that the transcriptional regulator spen controls the transcription of connexin43 and that impairment of this mechanism leads to severe cardiac arrhythmia in zebrafish.
4972Upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous treprostinil in incident patients with severe pulmonary arterial hypertension
Authors: D'Alto M , Romeo E , Argiento P , Badagliacca R , Papa S , Farro A , Sarubbi B , Russo M G , Vizza C D , Golino P
Published: October 2019

Aim

Current treatments strategies for high-risk patients with pulmonary arterial hypertension (PAH) are based on the use of parenteral prostanoids. The evidence to support triple upfront combination therapy remains largely based on expert consensus or small studies. Aim of this study was to evaluate the efficacy and safety of an upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous (sc) treprostinil in patients with severe PAH.

Methods

This is a multi-center retrospective analysis of patients with newly diagnosed severe PAH treated with upfront triple combination therapy with ambrisentan, tadalafil and sc treprostinil between 2014 and 2018. Clinical evaluations, WHO functional class (FC), 6-min walk distance, biomarkers and right heart catheterization were collected from the patients' medical records at baseline and during the follow-up.

Results

Overall, 20 patients (mean age 44±15 years, 15 female) were included.

Over a median follow-up of 12 months, all patients were still alive on triple combination therapy. At baseline 11 patients were in WHO-FC 3 and 9 patients in WHO-FC 4. At follow-up, WHO-FC (2.0±0.5 vs 3.5±0.5, p<0.001, improved in all: 2, 16, and 2 patients in FC 1, 2 and 3, respectively), exercise capacity (431±67 vs 152±130 m, p<0.001), NT-proBNP (423±260 vs 3492±1864 pg/ml; p<0.001), and haemodynamics (right atrial pressure 5±2 vs 13±3 mmHg, p<0.001; mean pulmonary artery pressure 42±5 vs 60±9 mmHg, p<0.001; cardiac index 3.5±0.8 vs 1.8±0.3 l/min/m2, p<0.001; pulmonary vascular resistance 5.5±1.3 vs 16.4±4.4 Wood units, p<0.001; pulmonary arterial compliance 2.5±0.9 vs 0.8±0.3 ml/mmHg, p<0.001) significantly improved compared with baseline. No patient discontinued the therapy due to serious adverse events.

Conclusions

Triple upfront combination therapy with ambrisentan, tadalafil and sc treprostinil is safe and offers clinical and heamodynamics benefits in incident patients with severe PAH.
5035Comparative assessment of diagnostic algorithms of myocardial inflammation by endomyocardial biopsy and tissue mapping by CMR against high-sensitive troponin in viral myocarditis
Authors: Zainal Abidin H A , Klingel K , Rolf A , Keller T , Zhou H , Vasquez M , Escher F , Lassner D , Vasa-Nicotera M , Zeiher A , Schultheiss P , Nagel E , Puntmann V
Published: October 2019

Background

Myocarditis is defined by inflammatory involvement of the myocardium, either histologically by evidence of myocardial necrosis and cellular infiltration on endomyocardial biopsy (EMB), or non-invasively by presence of myocardial oedema using tissue mapping with cardiovascular magnetic resonance (CMR). Objective: to undertake intra-individual comparisons of EMB vs. CMR diagnostic algorithms of myocardial inflammation, as well as against an independent gold-standard of myocardial injury, high-sensitive troponin (hs-TropT).

Methods

Prospective multicentre study of consecutive patients (n=109) with clinical diagnosis of myocarditis. EMBs were analysed by 2 reference centres using the ESC diagnostic and their local algorithms. The CMR criteria used sequence-specific cut-offs for native T1 and T2 (standard deviation, SD); myocardial inflammation T1 ≥2SD, T2 ≥2SD and no inflammation: T1 and T2<2SD, with subcategories for acute/high-grade: T1 ≥5SD, T2 ≥2SD; chronic/low-grade: T1 ≥2SD, T2 ≥2SD; healed: T1 <2SD, T2 <2SD but myocardial impairment and non-inflammatory cardiomyopathy: T1 ≥2SD, T2 <2SD.

Results

The agreement between ESC criteria and CMR criteria (AUC: 0.56, p=0.381) was poor. There was a significant agreement between myocardial injury (hs-TropT ≥13.9 ng/L) and CMR criteria (AUC: 0.84, p<0.001), but not ESC algorithm. hs-TropT levels had significant associations with native T1 and T2 (r=0.37 and 0.35, p<0.001), but not with immunohistochemical inflammatory markers. Viral presence was similarly proportioned between inflammatory/non-inflammatory subjects, irrespective of the algorithm.

AUC of CMR and EMB versus hs-TroponinT

Conclusions

Poor agreement between CMR and EMB-based diagnostic algorithms suggests non-overlapping definitions of myocardial inflammatory involvement. Excellent agreement between CMR algorithm and hs-TropT reiterates its high sensitivity for inflammatory myocardial injury.

Acknowledgement/Funding

1. National Institute for Health Research (NIHR) Biomedical Research Centre 2. German Centre for Cardiovascular Research (DZHK)
5106A pattern-discovery-based outcome predictive tool integrated with clinical data repository: design and a case study on contrast related acute kidney injury
Authors: Li Y X , Jiang J , Zhang Y , Li J P , Huo Y
Published: October 2019

Introduction

Clinical data repositories (CDR) including electronic health record (EHR) data have great potential for outcome prediction and risk modeling. However, most CDRs were only used for data displaying, and using data from CDR for outcome prediction often requires careful study design and sophisticated modeling techniques before a hypothesis can be tested.

Purpose

We built a prediction tool integrated with CDR based on pattern discovery aiming to bridge the above gap and demonstrated a case study on contrast related acute kidney injury (AKI) with the system.

Methods

A cardiovascular CDR integrated with multiple hospital informatics systems was established. For the case study on AKI, we included patients undergoing cardiac catheterization from January 13, 2015 to April 27, 2017, excluding those with dialysis, end-stage renal disease, renal transplant, and missing pre- or post-procedural creatinine. To handle missing data, a prior-history-note composer was designed to fill in structured data of 14 diseases related to cardiovascular problem. Crucial data such as ejective fraction was extracted from the structured reports. AKI was defined according to Acute Kidney Injury Network by increase of serum creatinine from most recent baseline to the post-procedure 7-day peak. To build predictive modeling, we selected 17 variables covered in existing AKI models. Pattern discovery was recently developed as an interpretable predictive model which works on incomplete noisy data. In this study, we developed a pattern discovery based visual analytics tool, and trained it on 70% data up to August 2016 with three interactive knowledge incorporation modes to develop 3 models: 1) pure data-driven, 2) domain knowledge, and 3) clinician-interactive. In last two modes, a physician using the visual analytics could change the variables and further refine the model, respectively. We tested and compared it with other models on the 30% consecutive patients dated afterwards, which is shown in Figure 1.

Results

Among 2,560 patients in the final dataset with 17 pre-procedure variables derived from CDR data, 169 (7.3%) had AKI. We measured 4 existing models, whose areas under curves (AUCs) of receiver operating characteristics curve for the test set were 0.70 (Mehran's), 0.72 (Chen's), 0.67 (Gao's) and 0.62 (AGEF), respectively. A pure data-driven machine learning method achieves AUC of 0.72 (Easy Ensemble). The AUCs of our 3 models are 0.77, 0.80, 0.82, respectively, with the last being top where physician knowledge is incorporated.

Demo and demonstration

Conclusions

We developed a novel pattern-discovery-based outcome prediction tool integrated with CDR and purely using EHR data. On the case of predicting contrast related AKI, the tool showed user-friendliness by physicians, and demonstrated a competitive performance in comparison with the state-of-the-art models.
5192Management and outcomes of patients with unstable angina with undetectable, normal, or intermediate hsTnT levels - A RAPID CPU substudy
Authors: Biener M , Giannitsis E , Hund H , Mueller-Hennessen M , Vafaie M , Gandowitz J , Riedle C , Loehr J , Katus H A , Stoyanov K M
Published: October 2019

Background

Patients with unstable angina (UA) are regarded to be at low risk for future coronary events. Guidelines discourage routine coronary angiography and recommend early discharge after individualized risk stratification. The relative value of clinical risk indicators as compared to cardiac troponin (cTn) alone is unsettled in the era of high-sensitivity cardiac troponin (hsTn) assays.

Purpose

We aimed to investigate the clinical characteristics, therapies and outcomes of UA patients with different hsTnT concentrations.

Methods

During 12 months, 2,525 patients were enrolled. UA was defined as unstable symptoms and either undetectable (<5 ng/L), normal (5–14 ng/L) or stable elevated hsTnT (15–51 ng/L). Follow up for 1-year mortality was available in 98.7%.

Results

A total of 280 patients (11.1%) received a diagnosis of UA. Mortality rates at 12 months were 0%, 1.9% and 6.9% in presence of undetectable, normal and stable elevated hsTnT. Elevated hsTnT >99th percentile but not unstable symptoms carried an independent 3.25-fold (1.78–5.93) higher risk for all-cause death after adjustment for other clinical risk indicators or the GRACE score. Utilization of guideline recommended therapies was high albeit lower than for non-ST-elevation myocardial infarction (NSTEMI). Significantly fewer patients with UA received dual antiplatelet therapy (DAPT, odds ratio (OR): 0.51 [95% CI: 0.44–0.59], p<0.0001), coronary angiography (CA, OR 0.79, [95% CI: 0.74–0.87], p<0.0001), and percutaneous coronary intervention (PCI, OR 0.50, [95% CI: 0.40–0.61], p<0.0001), compared to NSTEMI. However, prevalence of significant obstructive coronary artery disease (CAD) requiring PCI was 31.8%, even in patients with undetectable hsTnT, indicating the need for stress testing.

Conclusions

The current dichotomization of patients into UA and NSTEMI is no longer appropriate. Additional risk stratification seems warranted including the presence and magnitude of hsTn concentration and additional risk indicators.

Acknowledgement/Funding

Research Grant by Roche Diagnostics