bluuebunny/crossref_metadata_2025 huggingface dataset:
P6568Forecasting atrial fibrillation using machine learning techniques
Authors: Gregoire J.-M , Subramanian N , Papazian D , Bersini H
Published: October 2019

Background

Forecasting atrial fibrillation (AF) a few minutes before its onset has been studied, mainly based on heart rate variability parameters, derived from 24-hour ECG Holter monitorings. However, these studies have shown conflicting, non-clinically applicable results. Nowadays, machine learning algorithms have proven their ability to anticipate events. Therefore, forecasting AF before its onset should be (re)assessed using machine learning techniques. A reliable forecasting could improve results of preventive pacing in patients with cardiac electronic implanted devices (CEID).

Purpose

To forecast an oncoming AF episode in individual patients using machine learning techniques.

To evaluate the effect if the onset of an AF episode can be forecasted on longer time frames.

Methods

The totality of the raw data of a data set of 10484 ECG Holter monitorings was retrospectively analyzed and all AF episodes were annotated. Onset of each AF episode was determined with a precision of 5 msec. We only took AF events into consideration if they lasted longer than 30 seconds. Of all patients in the dataset, 140 presented paroxysmal AF (286 recorded AF episodes). We only used RR intervals to predict the presence of AF. We developed two different types of machine learning algorithms with different computational power requirements: a “dynamic” deep and recurrent neural net (RNN) and a “static” decision-tree with adaboost (boosting trees) more suitable for embedded devices. These algorithms were trained on one set of patients (around 90%) and tested on the remaining set of patients (around 10%).

Results

The performance figures are summarized in the table. Both algorithms can be tuned to increase their specificity (at a loss of sensitivity) or vice versa, depending on the objective.

Performance of forecasting algorithms RR-distance Boosting trees AUC RNN AUC 30–1 RR-Interval(s) before an AF event 97.1% 98.77% 60–31 RR-Intervals before an AF event 97.5% 99.1% 90–61 RR-Intervals before an AF event 96.9% 99.1% 120–91 RR-Inervals before an AF event 98.2% 98.9% AUC for Area Under ROC Curves.

Conclusion

Based upon this retrospective study, we show that AF can be forecasted on an individual level with high predictive power using machine learning algorithm, with little drop-off of predictive value within the studied distances (1–120 RR intervals before a potential AF episode). We believe that the embedding of our new algorithm(s) in CEID's could open the way to innovative therapies that significantly decrease AF burden in selected implanted patients.
P6573Adenosine plasma levels may determine tilt table test outcome in syncopal patients with prodromal symptoms
Authors: Sotiriadou M , Antoniadis A , Vergopoulos S , Lazaridis C , Konstantinidis P , Bakogiannis C , Virgiliou C , Gkika E , Theodoridis G , Mpalaouri I , Mpougiouklis D , Gerou S , Papadopoulos C , Fragakis N , Vassilikos V
Published: October 2019

Background/Introduction

Head-up tilt table test (HUTT) and Adenosine test (ADT) are tools frequently used in the diagnostic workup of syncope. It has been suggested that patient responses to HUTT and ADT can be related to the plasma levels of Adenosine (ADPL) and Adenosine receptors (ADR). However, the exact type of association and the role of (ADPL) and ADR levels in the risk stratification and management of patients with syncope has not yet been clarified.

Purpose

We sought to assess the ADPL and ADR levels in patients without structural heart disease who underwent HUTT and ADT tests as part of the diagnostic workup of syncope. We specifically investigated differences with regards to the presence of a history of prodromal symptoms.

Methods

HUTT and ADT were performed as per the standard protocols. ADT was considered positive in the event of asystole >6 seconds or heart block for >10 seconds after intravenous Adenosine administration in a supine position at a dose of 0.15 mg/kg. ADPL were assessed at three timepoints during the HUTT: in the supine position, immediately after bed tilt and, in cases of a positive test, at the time of syncope. Furthermore, we assessed the A2A ADR of monocytes in the study patients.

Results

We prospectively analyzed 77 patients (48 women, age 47.05±21.10 years). ADT was positive in 16.7% of patients and HUTT in 49.4% of patients. ADPL in the supine position did not differ between patients with negative vs. positive ADT but showed a significant correlation with the body mass index (p=0.002). There was a trend for reduced ADPL at the tilt phase in patients with positive HUTT (0.32±0.89 vs. 0.42±0.77 ppm/Um/L, p=0.09). Of all patients, 60 (77.9%, 41 women, age 46.80±21.83 years) had reported a history of prodromal symptoms at syncope. In the subset of patients with prodromal symptoms, the ADL at the tilt phase were lower in patients with positive vs. negative HUTT (0.15±0.23 vs. 0.51±0.89, p<0.05). ADR did not differ among groups but showed a significant correlation with the ADL during syncope in patients with prodromal symptoms (p<0.05).

Conclusion(s)

Patients with prodromal symptoms and a positive HUTT demonstrate reduced ADPL at the tilt phase of HUTT preceding syncope. In these patients, ADPL in syncope correlate with the ADR. Adenosine plasma levels and receptors warrant further investigation and may predict the response to HUTT thereby contributing to the diagnostic evaluation and risk stratification of patients with syncope.
P6576Use of atrioventricular nodal ablation after atrial fibrillation ablation failure: a nationwide cohort study
Authors: Bisson A , Mondout F , Bodin A , Clementy N , Pierre B , Babuty D , Brignole M , Deharo J C , Fauchier L
Published: October 2019

Atrial fibrillation (AF) catheter ablation is a validated therapy for patients with symptomatic AF after failure or intolerance to antiarrhythmic drug therapy. Despite improvements in ablation technique, 30 to 50% of the patients may have AF recurrences. The APAF-CRT trial recently demonstrated that atrio-ventricular node ablation (AVNA) and cardiac resynchronization pacing was superior to pharmacological therapy in reducing HF and hospitalization in patients with permanent AF. The purpose of the study was to quantify the use of AVNA after AF catheter ablation and to find independent predictors factors associated with AVNA in this setting.

Methods

This French longitudinal cohort study was based on the national hospitalization database covering hospital care from the entire population. The data for all patients admitted in France from January 2010 to December 2015 were collected from the national administrative database, the PMSI (Programme de Médicalisation des Systèmes d'Information). We included all patients, over 18 years old, with AF and at least one AF catheter ablation. Routinely collected medical information includes the principal or secondary diagnoses and procedures performed. Items from the baselines characteristics were pooled into a multivariate Cox model to identify predictors of AV node ablation.

Results

Of 1,663,284 patients identified with AF, 28,018 patients were treated with AF ablation (28% female, mean age 60±10 yo, 22,837 with 1 procedure, 4,576 with 2 procedures and 605 with 3 procedures). Of those 28,018 patients, there were only 369 patients (1.3%) treated with AVNA after a mean follow-up of 374±488 days (median 210, interquartile 15–798). AVNA was less commonly performed than redo AF ablation with 3 procedures, and among these latter patients, only 3.8% were treated with AVNA during follow-up. Most powerful independent predictors of AV node ablation (HR >1.7) were age≥75 yo, heart failure at baseline, abnormal renal function and valve disease. Other independent predictors for AV node ablation (HR 1.2–1.7) were age 65–74 yo, female gender, obesity, coronary artery disease, thyroid disorders, lung disease and hypertension.

Conclusion

Our findings indicate that AVNA is rarely used after AF ablation failure and is probably an underrated strategy in these patients for now. Considering evidence from the APAF-CRT trial indicating a beneficial effect on mortality of this treatment in symptomatic AF patients, a wider use of AVNA should be more widely proposed in these patients. Its optimal timing during rate and rhythm control management still remains to be established.
P6583Prevalence of long QT interval in thailand and its association with all cause and cardiovascular mortality from a long-term cohort study
Authors: Trithiphen S , Vatesatogkit P , Vatesatogkit P , Ngarmukos T , Ngarmukos T , Chandanamattha P , Chandanamattha P , Apiyasawat S , Apiyasawat S
Published: October 2019

Background

Long QT interval elevates risks of life-threatening arrhythmias, cardiovascular mortality and all-cause mortality. The prevalence of prolonged QTc among Caucasians is approximately 8.7%. In Thai population, the prevalence and prognosis of prolonged QTc remain unexplored.

Objectives

1. To identify the prevalence of long QT interval in the Thai population without prior cardiovascular disease. 2. To evaluate the association between long QT interval and long-term cardiovascular (CV) event and all-cause mortality.

Materials and methods

A total of 2756 participants from the Electricity Generating Authority of Thailand (EGAT) study from 1997 to 2015 were studied. Among those, 2456 participants had completed EKGs and were included into the final analysis. The long QT interval was defined as QTc longer than 450 milliseconds (ms) in male and 460 ms in female respectively. Mortality endpoints included CV event and all-cause mortality were collected. Multivariable cox-proportional hazard model adjusted for all major CV risk factors was used to determine the association between prolonged QTc and outcomes.

Results

The majority of the population are male (N=1941, 79%). The mean QT interval calculated by Bazett's formula is 424±28.27 ms. Prolonged QTc was observed 12.5% in male and 17.7% in female. There were 509 (20.7%) deaths during the follow-up period. After 18 years of follow up, 10.5% of the prolonged QTc group had cardiovascular events, compared with 6.8% in the normal QTc group (P=0.09). All-cause mortality occurred in 30% of the prolonged QTc group and 19.3% in the normal QTc group (adjusted HR 1.33, 95% CI 1.05–1.68, P=0.018). After dividing QTc into deciles, the lowest mortality was observed in the 3rd to 7th deciles (17.6%, 19.7%, 16.3%, 23.2% and 18.9% respectively) and the highest mortality was observed in the 2nd deciles (22.09%) and the 8th to 10th deciles (22%, 27.15% and 28.38% respectively).

Hazard function of prolonged QTc

Conclusion(s)

1. In this worker cohort from Thailand, prolonged QTc was observed in 14% of the population.

2. During 18 years follow up, prolongation of QT interval is an independent risk factor for all-cause mortalities but not cardiovascular mortality.

3. There was a J-curve effect in association between the duration of QT interval and all-cause mortality.
P6584Prevalence of early repolarization in Thailand and long term risk of cardiac mortality
Authors: Yodteerug S , Vathesatogkit P , Ngamukos T , Apiyasawat S , Chandanamattha P
Published: October 2019

Introduction

Early repolarization syndrome is associated with long-term cardiac mortality in Western countries. However, there is no study of this association in Southeast Asian population.

Purpose

To determine the prevalence of early repolarization and long term risk of cardiac mortality in general Thai population.

Methods

A total of 2,756 consecutive individuals participating in from the electricity generating authority of Thailand (EGAT) study between 1997 and 2015 were included in this study. Early repolarization pattern (ERP) was defined either as “notching” or “slurring” and was localized into inferior leads, lateral leads, or both. Mortality endpoints included cardiovascular (CV) events and all-cause mortalities. Multivariable Cox-proportional hazard model, adjusted for all major CV risk factors, was used to determine the association between ERP and outcomes.

Results

Out of 2756 individuals,2,689 had complete data (80% male, mean age 55). ECGs and risk factor profiles were included for analysis. Mean follow up duration was 11.2±6.7 years. There were 444 (16.5%) cases with early repolarization pattern (slurr 54.3%, notching 38.3% and both 7.4%). Inferior leads were the most common localization at 49.8%, followed by lateral leads (35.6%) and both (14.6%). Five-hundred and sixty-six participants were dead during the follow-ups. Of these, 21 were sudden death. ERP was not associated with a greater likelihood of all causes of deaths, 20.5% in ERP and 21.2% in non-ERP (hazard ratio,1.04; 95% confidence interval (CI), 0.81 to 1.34; p=0.75). The death rates from coronary heart disease were 7.2% in ERP and 7.6% in non-ERP (HR,1.06; 95% CI, 0.71 to 1.56; p=0.79). The death rates from cardiovascular disease were 11.7% in ERP and 12.0% respectively (HR,1.03; 95% CI, 0.75 to 1.41; p=0.872) and sudden cardiac death was not difference between both groups 1.2 and 1.4% respectively.

Conclusion

The prevalence of early repolarization in Thai middle-aged population is relatively high. Over a long-term follow-up of 18 years, we did not find any differences in sudden cardiac death or death from any causes between an early repolarizationgroup and non-early repolarization group.
P6589Genetic risks for arrhythmia phenotypes in dilated cardiomyopathy
Authors: Gigli M , Merlo M , Graw S , Barbati G , Rowland T , Stolfo D , Slavov D , Dal Ferro M , Sweet M , Altinier A , Brun F , Mc Kenna W , Taylor M , Sinagra G , Mestroni L
Published: October 2019

Background

Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and in particular the effects of gene variants on clinical outcomes remain poorly understood.

Purpose

To investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients.

Methods

We analyzed 487 DCM patients by next-generation sequencing and categorized the disease genes into functional gene groups. The following composite outcome measures were assessed: 1) all-cause mortality, heart transplantation or left ventricular assist device (D/HTx/VAD); 2) sudden cardiac death or malignant ventricular arrhythmias (SCD/MVAs); 3) heart failure related death, heart transplantation or left ventricular assist device implantation (DHF/HTx/VAD).

Results

A total of 187 pathogenic/likely pathogenic variants were found in 180 patients (37%): 55 (11%) TTN; 19 (4%) LMNA; 24 (5%) structural cytoskeleton-Z disk genes; 16 (3%) desmosomal genes; 47 (10%) sarcomeric genes; 8 (2%) ion channels genes; 11 (2%) other genes. The occurrence of D/HTx/VAD was no different between variant carriers and non-carriers (p=0.17). However, carriers of desmosomal and LMNA variants experienced the highest rate of SCD/MVA, which was independent of the left ventricular ejection fraction.

Conclusions

Desmosomal and LMNA gene variants identify the subset of DCM patients at greatest risk for SCD and life-threatening ventricular arrhythmias, regardless the left ventricular ejection fraction.

Acknowledgement/Funding

National Institutes of Health grants R01 HL69071, HL116906, and AHA17GRNT33670495
P6603The predictive role of T786C single nucleotide polymorphism in endothelial no-synthase gene in late left ventricular remodeling after ST-segment elevation myocardial infarction
Authors: Petyunina O , Kopytsya M P , Berezin A E , Berezin A A
Published: October 2019

Introduction

Endothelial NO-synthase (eNOS) is constitutive enzyme, which is expressed in mature endothelial cells and promotes direct vascular dilatation. Single nucleotide polymorphism (SNP) of T786C in eNOS gene may influence on adverse cardiac remodeling after ST-elevation myocardial infarction (STEMI).

Purpose

To investigate possible associations between SNP T786C in eNOS gene and adverse cardiac remodeling after STEMI

Methods

177 acute STEMI patients treated with primary and facilitate percutaneous coronary intervention that were admitted to intensive care unit of a Therapy National Institute were enrolled in the study. Anthropometry, cardiovascular risk assay, coronary angiography, echocardiography and biomarkers' measure were performed at baseline. The DNA extraction was performed with a commercial kit using real-time polymerase chain reaction PCR. All procedures performed in the study involving human participants were in accordance with the ethical standards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and approved by the local ethics committee (Protocol No. 8, 29.08.2016). Written informed consent was obtained from each patient.

Results

There were correlations between 786CC polymorphism in eNOs gene and adverse cardiac remodeling (r=0.48; p=0.001), LDL cholesterol (r=0.32; p=0.012), type 2 diabetes mellitus (r=0.30; p=0.042), diastolic BP (r=−0.26; p=0.048), unstable angina prior to STEMI (r=0.25; p=0.047) and total quantity of complicated STEMI (r=0.23; p=0.042). Additionally, there were not significant relations between 786CC polymorphism in eNOs gene and multiple coronary vessel injury, STEMI localization, levels of circulating biomarkers of myocardial injury, and amount of damaged coronary arteries. Using univariate and multivariate regressive logistic analysis we found that 786CC genotype of eNOS was independent predictor for late adverse LV remodeling (β-coefficient = 1.57342; odds ratio = 4.8231; 95% confidence interval = 1.5349–15.1552; p=0.0071).

Conclusions

The polymorphism 786CC in eNOs gene was found as an independent predictor for late adverse cardiac remodeling after STEMI.

Acknowledgement/Funding

None
90Risk-adjusted comparison of in-hospital outcomes of transcatheter and surgical aortic valve replacement
Authors: Stachon P , Kaier K K , Heidt T H , Zehender M Z , Bode C B , Von Zur Muehlen C M
Published: October 2019

Background

Transcatheter aortic valve replacement (TAVR) is recommended for patients suffering from aortic valve stenosis at increased operative risk or age over 75 years. Beyond that patients with different co-morbidities could profit from TAVR.

Purpose

The present study analyzes in-hospital outcomes of aortic valve replacement procedures in order to identify subgroups of patients in which TAVR might be preferable.

Methods

For all 33,789 isolated transfemoral TAVR and SAVR procedures performed in Germany in 2014 and 2015, co-morbidities and in-hospital outcomes were identified by ICD- and OPS-codes.

Results

Patients undergoing TAVR were older with more co-morbidities and at increased estimated risk (logistic EuroSCORE TAVR: 13.9±10.3%; SAVR: 5.3±4.7%; p<0.001). In order to allow comparison of outcomes after TAVR and SAVR, a covariate and propensity-adjusted analysis was performed in different subgroups. The risk of mortality is significantly lower in patients undergoing TAVR with an age over 80 years (TAVR vs. SAVR 80–84: OR 0.55; p=0.002; ≥85 OR 0.42, p=0.006) and at high operative risk (patients with EuroSCORE >9: OR 0.62, p=0.001). No significant difference in in-hospital mortality occurs between TAVR and SAVR in patients under 80 and intermediate or low risk (<75: OR 0.85; p=0.404; 75–79 OR 0.82, p=0.219; EuroSCORE <4: OR 1.44, p=0.308; EuroSCORE 4–9: OR 0.81, p=0.156). In contrast, patients with advanced renal failure and patients in NYHA-class III/IV had better outcomes after TAVR (GFR<30: OR 0.45, p=0.005; NYHA III/IV: OR 0.72, p=0.015). Female sex, previous CABG, peripheral arterial disease, COPD, pulmonary hypertension, and diabetes were not found to be factors which favor a treatment strategy. Patients undergoing TAVR suffered more often from strokes and acute kidney failure. After risk-adjustment TAVR was associated with a lower risk for acute kidney injuries (OR 0.62, p<0.001). Risk for stroke was similar (OR 1.07, p=0.558). Risk of bleeding (OR 0.17, p<0.001) and requiring prolonged mechanical ventilation (>48h, OR 0.21, p<0.001) was decreased in patients undergoing TAVR. As expected, the TAVR procedure is associated with an increased risk for pacemaker implantations (OR 4.61, p<0.001).

Conclusions

The present study analyzing over 33.000 real-world procedures confirms that TAVR is the safer procedure in clinical practice for patients with severe aortic valve stenosis at increased operative risk, over 80 years, in NYHA-class III/IV, and with renal failure.
98Mitral annular calcification, mitral valve diseases and clinical outcomes in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis
Authors: Okuno T , Asami M , Praz F , Heg D , Lanz J , Kassar M , Hoeller R , Khan F , Raeber L , Stortecky S , Windecker S , Pilgrim T
Published: October 2019

Background

Mitral annular calcification (MAC) and mitral valve diseases (MVD) have been identified as strong predictors of mortality in patients undergoing transcatheter aortic valve replacement (TAVR). However, the association between MAC and MVD, and the prognostic implications in these patients remain unclear.

Purpose

This study sought to investigate the association between severity of MAC and the prevalence of MVD as well as to assess the prognostic impact of MAC depending on the presence or absence of MVD in patients undergoing TAVR.

Methods

We identified 967 patients who have comprehensive echocardiographic and computed tomographic assessment of MVD and MAC from our institutional registry that is a part of the Swiss TAVI registry (NCT01368250) between August 2007 and June 2017.

Results

Among these patients, mild or moderate MAC was present in 45.2% and severe MAC was present in 17.8%. The prevalence of MVD was significantly higher in severe MAC patients, while the prevalence in patients with mild and moderate MAC was similar to patients without MAC. Compared to patients without severe MAC and MVD, an increased risk of all-cause death at 1 year was observed in patients with severe MAC and MVD (hazard ratio [HR]: 2.81, 95% confidence interval [CI]: 1.72–4.59, p<0.001) as well as in patients with non-severe MAC and MVD (HR: 2.80, 95% CI: 1.87–4.20, p<0.001) but not in patients with severe MAC and non-MVD (HR: 0.68, 95% CI: 0.27–1.70, p=0.409). In a multivariable analysis, severe MAC concomitant with MVD was found to be an independent predictor of new permanent pacemaker implantation after TAVR (Odds ratio: 2.08, 95% CI: 1.27–3.41, p=0.004).

Conclusions

Severe MAC was associated with higher prevalence of MVD. Severe MAC concomitant with MVD was associated with increased risks of mortality at 1 year and conduction abnormalities after TAVR, whereas severe MAC without MVD was not.
100Culprit plaque morphology in patients with and without preinfarction angina: an optical coherence tomography imaging study
Authors: Vergallo R , Porto I , Ricchiuto A , Buonpane A , Coletti F , Di Muro F , La Porta Y , D'Amario D , Montone R A , Niccoli G , Leone A M , Aurigemma C , Burzotta F , Trani C , Crea F
Published: October 2019

Background

The relation between culprit plaque morphology and the clinical presentation of an acute myocardial infarction (AMI) has not been examined in detail.

Purpose

To study the culprit plaque morphology in patients with AMI with or without preinfarction angina using optical coherence tomography (OCT) imaging.

Methods

A total of 102 patients with AMI (32 STEMI, 70 NSTEMI) who underwent OCT imaging before percutaneous coronary intervention were enrolled. Patients were classified as: i) having either intermittent chest pain in the six hours preceding the final episode of pain, or unstable angina (or both) in the week preceding AMI (preinfarction angina group); or ii) having a single episode of chest pain without unstable symptoms in the preceding week (no preinfarction angina group). Culprit plaque was classified as plaque rupture (PR) or intact fibrous cap (IFC), as previously described. Prati thrombus score was calculated, and the prevalence of calcification, neovascularization, and OCT-defined macrophage accumulation was assessed.

Results

Patients with preinfarction angina showed a significantly higher prevalence of IFC than PR, while those without preinfarction angina showed a significantly higher prevalence of PR than IFC (Figure). PR in patients with preinfarction angina were more frequently associated with macrophage accumulation, while those in patients without preinfarction angina were not (Figure). White thrombus tended to be more frequent in patients with preinfarction angina than in those without (85.7% vs. 63.6%, p=0.097), and Prati thrombus score tended to be lower [22.0 (15.8–30.3) vs. 38.5 (12.8–67.5), p=0.145]. Calcifications were significantly less frequent in patients with preinfarction angina than in those without (22.0% vs. 40.4%, p=0.045), while neovascularization tended to be more frequent (58.0% vs. 42.3%, p=0.113).

Conclusions

Patients with preinfarction angina have a distinct culprit plaque phenotype, frequently characterized by IFC and a relatively lower thrombotic burden, probably reflecting a prevalence of reparative mechanisms and spontaneous thrombolytic activity in these patients.
129Elevated plasma xanthine oxidoreductase activity predicts cardiovascular events in patients with heart failure with preserved ejection fraction
Authors: Watanabe K , Watanabe T , Otaki Y , Shishido T , Kato S , Tamura H , Nishiyama S , Takahashi H , Arimoto T , Watanabe M
Published: October 2019

Background

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains poorly understood, although reactive oxygen species (ROS) is reportedly involved in underlying mechanisms. Xanthine oxidoreductase (XOR) is the rate-limiting enzyme of purine metabolism that plays an important role in producing uric acid, and also generates the ROS. However, the impact of plasma XOR activity on the clinical outcomes in patients with HFpEF remains unclear.

Purpose

The aim of this study was to assess whether plasma XOR activity predicts cardiovascular events in patients with HFpEF.

Methods and results

We measured plasma XOR activity in 257 patients with HFpEF. The patients were divided into 3 groups based on XOR activity: low XOR group (<33 pmol/h/mL, n=45), normal XOR group (33 - 120 pmol/h/mL, n=160), and high XOR group (≥120 pmol/h/mL, n=52). During a median follow-up period of 809 days, there were 74 major adverse cardiovascular events (MACEs). Kaplan-Meier analysis demonstrated that the patients with high XOR activity were at greatest risk for MACEs. A multivariate Cox proportional hazard regression analysis showed that high XOR activity was significantly associated with MACEs after adjustment for confounding factors. Furthermore, we divided the patients into 4 groups according to the presence of high XOR activity and/or hyperuricemia. Cox multivariate hazard regression analysis revealed that the patients with high XOR activity were associated with cardiovascular events in patients with HFpEF, regardless of whether hyperuricemia was present or not.

Conclusions

Elevated plasma XOR activity is significantly associated with adverse clinical outcomes in patients with HFpEF. Inhibition of XOR could be a potential therapy for HFpEF.
194SGLT-2 inhibitors versus GLP-1 receptor agonists and risk of mortality, chronic kidney disease and hospitalisation for heart failure in patients with type 2 diabetes
Authors: Noergaard C , Torp-Pedersen C , Vestergaard P , Wong N , Gerds T , Starkopf L , Bonde A , Fosbol E , Kober L , Lee C
Published: October 2019

Background

Two promising classes of second-line glucose-lowering drugs, the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have both been shown to lower the risk of cardiovascular (CV) outcomes in patients with type 2 diabetes, however no head-to-head comparisons exist.

Purpose

The aim of this study was to examine the risk of CV and all-cause mortality, incident chronic kidney disease (CKD) and hospitalisation for heart failure (HF) in association with SGLT-2i versus GLP-1RA use.

Methods

New users of SGLT-2i and GLP-1RA, with no prior use of drugs from the comparison class, were identified between 2012–2016, using individual-level linkage of Danish nationwide registries. The absolute risk of CV was calculated using the Aalen-Johansen Estimator with non-CV mortality as competing risk. The hazard ratios (HR) of CV and all-cause mortality, incident CKD and hospitalisation for HF were estimated using Cox regression and adjusted for age, sex, diabetes duration and other outcome specific risk factors.

Results

The study included a total of 8,304 SGLT-2i users (median age: 63 years [interquartile range (IQR): 54–70], males: 63%, dapagliflozin: 60.5%, empagliflozin: 36.5%) and 13,318 GLP-1RA users (median age: 60 years [IQR: 50–68], males: 54%, liraglutide: 97.4%) with a median follow-up time of 2.0 [(IQR): 1.5–2.9] years and 3.6 [IQR: 2.1–5.0] years, respectively. At baseline 29% of SGLT-2i and 30% of GLP-1RA users had CV disease. The absolute risks are shown in Figure 1. Compared with GLP-1RA, initiation of SGLT-2i was in adjusted analyses associated with a lower risk of CV mortality (HR: 0.49 [confidence interval (CI): 0.37–0.65]), all-cause mortality [HR: 0.79 [CI: 0.68–0.93], incident CKD (HR: 0.42 [CI: 0.34–0.53] and hospitalisation for HF (HR: 0.68 [CI: 0.59–0.78]).

Figure 1

Conclusion

SGLT-2i use was associated with a significantly lower risk of CV and all-cause mortality, incident CKD and hospitalisation for HF in comparison with GLP-1RA use.

Acknowledgement/Funding

The Danish Heart Foundation (18-R125-A8381-22082)
219Serum Trimethylamine N-Oxide levels and 16S rRNA gut microbiota profiling in patients with heart failure and preserved ejection fraction and healthy individuals
Authors: Kaburova A N , Poyarkov S V , Makarov V V , Drapkina O M , Uydin S M , Pokrovskaya M S , Koretsky S N , Efimova I A , Matskevich L A , Gomiranova N V
Published: October 2019

Introduction

Recent evidence suggests the role of gut microbiota dysregulation in the pathophysiology of chronic heart failure (HF). Elevated levels of Trimethylamine N-Oxide (TMAO) have shown to increase the risk of cardiovascular events and HF. Among patients with HF and preserved ejection fraction (HF-pEF) the link between TMAO levels and ventricular fibrosis was observed in studies, however, the data regarding 16S rRNA microbiome profiling in this particular group of HF are lacking.

Purpose

The research was aimed at investigating the gut microbiome diversity and composition as well as the serum TMAO levels among two groups of patients: healthy controls (HC) and HF-pEF.

Methods

44 patients with HF-pEF and 45 HC with body mass index <35 kg/m2, no history of acute coronary syndrome, myocardial infarction or diabetes were enrolled in the study. All patients underwent transthoracic echocardiography with Doppler study to exclude diastolic dysfunction (E/e' <8 cm/s) or to prove HF-pEF (according to the recent ESC guidelines based on E/e' ratio, N-terminal pro-B type natriuretic peptide >125 pg/ml and symptoms of HF). The intestinal microbiome was investigated using high-throughput sequencing of bacterial 16S rRNA gene. TMAO levels were determined by liquid chromatography tandem mass spectrometry.

Results

The age in HC was 57,5 [48; 63] (28% men), age in HF-pEF group was 67 [64; 74] years (52% men). The serum concentration of TMAO in HC was 3.72 uM, in HF-pEF was 5.24 uM. The group of HF-pEF had significantly higher levels of the marker, p=0,003. Bacterial communities of both groups were dominated by the Firmicutes and Bacteroidetes phyla. The most abundant genus in both groups were Bacteroides. The Shannon index, the Chao 1 estimator, and the Simpson index assessing α diversity were not significantly different between groups. However, Bacteroides, Alistipes, Pseudomonas, and Fusobacterium were enriched in the common core microbiota of HF-pEF patients, while Lachnospira, Roseburia, Eubacterium, Methanobrevibacter and Faecalibacterium were depleted. To note, Lactobacillus and Bifidobacterium were depleted in HF-pEF patients too.

TMAO levels in HC and HF-pEF groups

Conclusions

We have shown significant structural alterations of the intestinal microbiome and increased TMAO levels in HF-pEF patients' serum compared to HC. These findings may enable deeper understanding of the complex multifactorial pathogenesis of HF-pEF for the future development of personalized microbiome-based diagnostics and therapies for individuals at risk.
278Clinical outcomes of state-of-the-art percutaneous coronary revascularization in patients with three-vessel disease: 3-year follow-up of the SYNTAX II study
Authors: Serruys P W J C , Walsh S , Sabate M , Davies J , Lesiak M , Moreno R , Cruz-Gonzalez I , West N , Piek J , Stables R , Van Mieghem N M , Farooq V , Escaned J , Banning A , Onuma Y
Published: October 2019

Background

The clinical implication of state-of-art PCI at long term follow-up in patients with three vessel disease is undetermined.

Purpose

The purpose of the study was to investigate whether the favourable outcomes of state-of-the-art PCI in the SYNTAX-II trial, demonstrated up to 2 years, are maintained at 3-year follow-up.

Methods

The SYNTAX-II study was a multicentre, single arm study that investigated the impact of a state-of-art PCI strategy on clinical outcomes in patients with de novo three vessel coronary artery disease, without left main disease. State-of-art PCI includes: heart team decision-making utilizing the SYNTAX score II, hybrid iFR-FFR decision-making strategy, intravascular ultrasound guided stent implantation, contemporary chronic total occlusion revascularization techniques and guideline-directed medical therapy. The primary endpoint is major adverse cardiac and cerebrovascular events (MACCE – a composite of all-cause death, any stroke, myocardial infarction, or revascularization) at 3 years. Clinical outcomes in SYNTAX-II were compared to the predefined PCI (SYNTAX-I PCI) and coronary artery bypass graft (SYNTAX-I CABG) cohorts from the landmark SYNTAX Trial (SYNTAX-I), selected on the basis of equipoise for long-term (4-year) mortality utilising the SYNTAX Score II.

Results

Between February 2014 and November 2015, 454 patients out of 708 screened patients were enrolled in SYNTAX-II. In SYNTAX-I, 643 (58.8%) patients with 3VD without left main disease had an equipoise recommendation for CABG or PCI based on the SYNTAX Score II and were used as the comparator. At 2 years, MACCE rate in SYNTAX-II was significantly lower compared to SYNTAX-I PCI (13.2% vs. 21.9%, p=0.001). Furthermore, similar two-year outcomes for MACCE were evident between SYNTAX II-PCI and SYNTAX-I CABG (13.2 vs. 15.1%, p=0.42). Three-year results will be presented at ESC2019.

Conclusions

Three-year results of his study may offer an attractive option of revascularization strategy in predefined patients with de novo 3VD (SYNTAX Score II inclusion) even if the patients have moderate to severe anatomical complexity (anatomic SYNTAX score >22).

Acknowledgement/Funding

European Cardiovascular Research Institute (ECRI) with unrestricted research grants from Volcano and Boston Scientific
279Clinical outcome after coronary bifurcation stenting: a systematic review and network meta-Analysis of PCI bifurcation techniques comprising 5572 patients
Authors: Di Gioia G , Sonck J , Colaiori I , Mizukami T , Kodeboina M , Barbato E , De Bruyne B , Collet C
Published: October 2019

Background

The optimal PCI technique for bifurcation lesions remains a matter of debate. Several RCT have compared different bifurcation PCI techniques. Provisional stenting has been recommended as the default technique for most bifurcation lesions. However, emerging data suggests that double-kissing crush technique can be considered in true left main bifurcation lesions and has been endorsed by the European Society of Cardiology Guidelines.

Purpose

To compare the clinical outcome between different bifurcation PCI techniques.

Methods

We searched MEDLINE for randomized clinical trials (RCT) comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE) defined as the composite of cardiac death, myocardial infarction (MI) and target vessel or lesion revascularization (TVR/TLR), and the individual components of MACE. Stent thrombosis was assessed as defined by the ARC. Stratification based on left-main or distal bifurcations was performed. We evaluated the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We estimated summary odds ratios (ORs) using pairwise and Bayesian network meta-analysis.

Results

We identified 263 studies and of these included 19 RCT including 5572 patients treated with 5 bifurcation PCI techniques namely provisional stenting, systematic T-stenting, crush, culotte and double-kissing crush. Median follow-up was 12 months (IQR 8 to 36). When all bifurcation lesions were combined, double-kissing crush technique reduced the occurrence of MACE (OR 0.42; CrI 0.28 to 0.61) compared to provisional stenting. This difference was driven by a reduction in TVR/TLR (OR 0.39; CrI 0.25 to 0.65). No differences were found in cardiac death, MI or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed between provisional stenting, systematic T-stenting, crush. In distal bifurcations (n=17 studies, 4634 patients), double-kissing crush also showed to reduce MACE (OR 0.48; CrI 0.29 to 0.67 vs. Provisional). In left-main bifurcations (n=3 studies, 938 patients) no differences in MACE were found between PCI techniques.

Conclusions

In this network meta-analysis, PCI bifurcation techniques were similar with respect to the occurrence of cardiac death, myocardial infarction and stent thrombosis. When all coronary bifurcations were combined, an advantage of double-kissing crush was observed in terms of MACE driven by lower rate of repeated revascularization. Further studies are required to define the best PCI bifurcation technique for left main coronary artery disease.
391Gadobutrol enhanced CMR to detect significant coronary artery disease defined by quantitative coronary angiography. Results from two blinded phase III clinical trials
Authors: Arai A
Published: October 2019

Background

The FDA regulated GadaCAD1 trial and the nearly identical GadaCAD2 clinical trial aimed to determine whether gadobutrol-enhanced CMR can detect significant CAD.

Methods

Two multicenter, international trials enrolled patients with known or suspected CAD and used cine MRI, gadobutrol enhanced stress/rest perfusion, and late gadolinium enhancement. Endpoints, primary, and secondary minimum performance thresholds versus QCA and stress cine MRI are summarized in the table. There were 3 blinded, core-lab CMR readers per trial (6 readers overall) and 2 core-lab QCA readers. A meta-analysis combined results from all 6 CMR readers.

Results

765 patients were analyzed (GadaCAD1: n=376, GadaCAD2: n=389). The meta-analysis of 6 readers had 79% sensitivity, 87% specificity, and AUC of 0.82 to detect a 70% QCA stenosis and met all study endpoints (figure & table). Versus a 50% QCA stenosis, the meta-analysis also met all study endpoints. At an individual reader level, all 6 readers met all study endpoints versus a 70% QCA stenosis. Versus a 50% QCA stenosis, only 1 of 6 readers exceeded the minimum performance threshold for sensitivity but all 6 readers met all other endpoints. For all readers, stress perfusion was more sensitive than stress wall motion (p<0.05).

Diagnostic Accuracy Results

Conclusions

CMR stress perfusion has high diagnostic accuracy for significant CAD. The ROC analysis and overall results support prior literature that a 70% QCA threshold is a more appropriate threshold for physiologically significant CAD.

Acknowledgement/Funding

Bayer
445Effects of losartan and beta-blockers on aortic root dilatation in patients with Marfan Syndrome - results of the extended COMPARE trial
Authors: Van Andel M M , Jalalzadeh J , Indrakusuma R , Balm R , Timmermans J , Van Den Berg M P , Scholte A J H A , De Waard V , Zwinderman A H , Mulder B J M , Groenink M
Published: October 2019

Introduction

Despite several randomized trials, beneficial effects of Losartan and β-blockers in adults with Marfan syndrome (MFS) are not entirely clear. The COMPARE trial previously showed a small but significant beneficial effect of Losartan on top of β-blocker use on aortic root dilatation rate. Yet, this effect was not reproduced by other trials, although in general a favourable effect of Losartan could be demonstrated. All trials in adults with MFS showed lower than expected aortic root dilatation rates, suggesting mildly affected study populations. Therefore we extended the follow-up period of the COMPARE trial up to 10 years and aimed to assess the clinical outcomes of the study cohort, as well as the effect of medication regimes on aortic root dilatation rates in the subgroup of patients with a native aortic root at initial randomization.

Methods

Patients previously enrolled in the COMPARE trial were retrospectively analyzed. Cardiovascular events (aortic dissections, ruptures and operations) and all-cause mortality were assessed. Individual aortic root dilatation rates were estimated in patients with a native aortic root at time of randomization on the basis of linear regression analysis of multiple transthoracic echocardiogram (TTE) results. Correlations between aortic root dilatation rates and cumulative Losartan or β-blocker treatment days were assessed with Spearman's rho (ρ).

Results

During a median follow-up of 8.0 years, two dissections and three deaths occurred in the 151 patients with a native aortic root at time of randomization. The 122 patients that were eligible for aortic root dilatation analysis, underwent a median of 6 TTEs. The median aortic root dilatation rate in these patients was 0.28 (interquartile range 0.09 - 0.59) mm/y. These patients were further classified as either patients with a stable aortic root (n=102) or with aortic root growth (n=20), based on the threshold of 0.9 mm per year. Patients with aortic root growth had significantly more aortic root replacements during follow-up (17/20 vs 18/102, P=0.001).

Furthermore, aortic root dilatation rate was negatively correlated with the number of Losartan treatment days (ρ=−0.272, P=0.003), β-blocker treatment days (ρ=−0.217, P=0.017) and with the duration of follow-up (ρ=−0.437, P<0.001).

Conclusions

Our results support previous findings that Losartan and β-blockers appear to be equally effective on aortic root dilatation rate in Marfan Syndrome patients. The low event rate in the long term follow-up of this subgroup of the COMPARE trial represent a relatively mildly affected study population and an aggressive prophylactic surgical regime.
467FFR guided acute complete revascularization versus culprit lesion only treatment in patients presenting with STEMI; 3-year cost-analysis data from COMPARE-ACUTE trial
Authors: Smits P C , Abdel-Wahab M , Neumann F J , Boxma-De Klerk B M , Laforgia P L , Schotborgh C E , Wlodarczak A , Hambrecht R , Angeras O , Fischer H , Richardt G , Omerovic E
Published: October 2019

Background

Compare-Acute trial showed a 1-year superior outcome of FFR-guided acute complete revascularization (FFR-CR) compared to culprit-lesion-only revascularization (CLO) in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Long-term results and financial impact of this strategy are unknown.

Purpose

To evaluate if FFR-CR strategy is superior to CLO strategy in terms of health care costs at 3 year follow-up.

Methods

Compare-Acute is a multicenter, investigator-initiated prospective randomized controlled trial that involved 24 sites. Patients with STEMI and MVD were randomized 1:2 after successful primary PCI, towards FFR-CR or CLO treatment strategies (295 vs 590 pts). All stenosis ≥50% by angiography in the non-infarct artery were investigated by FFR in both arms. In the FFR-CR arm, all non-culprit (NC) lesions with a FFR ≤0.80 were treated by PCI. In the CLO arm pts underwent blinded FFR procedure of the NC lesions. Further treatment of these lesions was based on symptoms and/or ischemia testing during follow-up with an allowed treatment window of 45 days. The primary endpoint was defined as a composite of all-cause mortality, non-fatal myocardial infarction, any revascularization and cerebrovascular events (MACCE) at 12 months. The major secondary endpoints are MACCE and health care costs from both strategies up to 3-year follow-up. Cost-analysis is done from an insurance/governmental perspective in countries that use Diagnosis Related Group (DRG) costs: the Netherlands, Germany, Sweden and Poland.

Results

1-year results have already been published and showed superior outcome of patients in the FFR-CR arm. According to the Dutch system, at 1 year of follow-up the average cost per patient was 8.150€ in the FFR-CR arm, and 10.319€ in the CLO arm (−21%). The better cost-effectiveness of FFR-CR strategy remained at 3 years of follow-up: average cost per patient was 8.653€ in the FFR-CR arm and 11.100€ in the CLO arm (−22%). Same 3-year data was confirmed using DRG analysis according to the German system (FFR-CR 4.887€ vs CLO 5.200€; −6.0%) and the Swedish system (FFR-CR 6.205€ vs CLO 8.133€; −23.7%). FFR-CR strategy was not more costly according to the Polish system (FFR-CR 3.704€ vs CLO 3.685€; +0.5%). Moreover, the better outcome of the FFR-CR group was mantained at 3 year follow-up (data not shown).

Figure 1

Conclusion

Our cost-analysis of the Compare Acute Trial shows that the strategy of FFR-guided complete revascularization in patients with STEMI and MVD is not only superior in terms of outcome, but also in terms of health care costs at 1 year. This benefit is maintained at 3 years follow-up.
468Patients eligible for proprotein convertase subtilisin/kexin type9 inhibitors (pcsk9i) after acute myocardial infarction. The ESC position applied to patients included in the FAST-MI 2015 registry
Authors: Schiele F , Puymirat E , Ferrieres J , Onceanu S , Beard T , Marchand X , Landel J , Meneveau N , Simon T , Danchin N
Published: October 2019

Background

PCSK9i on top of high intensity statins have shown clinical benefit in patients after Acute Myocardial Infarction (AMI) who are not at LDL-c target. The ESC Task Force has defined guidance for the prescription of PCSK9i. Among patients discharged after AMI, the rate of those eligible for PCSCK9i is poorly documented.

Methods

We used data from the nationwide French FAST-MI 2015 registry. PSCK9-eligible patients were defined as those discharged with high intensity statins with expected-LDL>140 mg/dL, or >100mg/dL if they had additional high risk features such as diabetes with renal dysfunction or hypertension, multivessel coronary disease, associated peripheral artery disease or recurrent MI. The expected LDL-c was estimated from admission LDL-c and changes in lipid-lowering treatment. The rate of eligible patients was estimated from actual treatment and optimized treatment (i.e. addition of ezetimibe).

Results

Among 5291 pts included, 4715 (89%) were discharged with statins, at high intensity in 3655 (71%). Expected LDL was 71mg/dL (IQ 56, 95). Among patients discharged with high intensity statins, 3146 (59%) had an expected LDL-c<100/mg (figure, in green). PCSK9-eligible patients were those with LDL-c>140mg/dL (n=178, 3.3%, in red) and, among those with LDL-c 100–140mg/dL (n=331, 6.2%, in yellow), patients who had additional risk features (n=227 (4%)). As a result, the population eligible for PSCK9i according to the ESC guidance would represent 7.6% (405 pts) of the population admitted with AMI. Expanding the indication to patients with statins, but not at high intensity would add 159 (3%). Conversely, optimizing discharge treatment with ezetimibe would reduce the rate of eligible patients to 3% (181 pts, in brown).

Conclusions

In real life, according to the ESC Task Force, 7.6% of the whole population admitted for AMI would be eligible for PCK9i. This rate could be reduced to 3% with the addition of ezetimibe.