bluuebunny/crossref_metadata_2025 huggingface dataset:
P6421Can cardiologists rely on artificial intelligence to identify the culprit vessel in STEMI?
Authors: Mehta S , Fernandez F , Villagran C , Frauenfelder A , Matheus C , Ceschim M , Vieira D , Torres M A , Mazzini J , Quintero S , Safie R , Aboushi H , Munguia A , Cecilio E , Lopez C
Published: October 2019

Background

The importance of culprit lesion identification is critical for risk stratification of a patient with an ST-Elevation Myocardial Infarction (STEMI). The aforementioned provide patients with a more elaborated strategy of management and treatment either they are treated with PCI or less invasive techniques such as thrombolysis. We report a novel approach that employs AI-guided electrocardiogram (EKG) algorithms for rapid and accurate identification of the culprit STEMI vessel.

Purpose

To create an innovative, machine learning tool for a more effective risk stratification of STEMI patients.

Methods

An observational, retrospective, case-control study. Sample: 2,542 exclusively STEMI diagnosis EKG records that included post discharge feedback from healthcare centers, confirming diagnosis and culprit vessel (Left Main Coronary Artery [LMCA]; Left Anterior Descending [LAD]; Right Coronary Artery [RCA]; Left Circumflex Artery [LCX]; Saphenous Vein Graft [SVG]). Records excluded other patient and medical information. The sample was derived from the private International Telemedical Systems (ITMS) database. LUMENGT-AI Algorithm was employed. Preprocessing: detection of QRS complexes using a wavelet system, segmentation of each EKG into individual heartbeats (27,125 total beats) with fixed window of 0.4s to the left and 0.9s to the right of main QRS; Classification: A 1-D convolutional neural network was implemented; “LCMA”, “LAD”, “LCX”, “RCA”, “SVG”, and “No Information” classes were considered for each heartbeat; individual probabilities were aggregated to generate the final label for each record. Training & Testing: 90% and 10% of the sample was used, respectively. Experiments: Intel PC i7 8750H processor at 2.21GHz, 16GB RAM, Windows 10 OS with NVidia GTX 1070 GPU, 8GB RAM.

Results

Global Accuracy: 79.4%; LAD: Sensitivity 86.2%; Specificity 84.8%. RCA: Sensitivity 85.7%; Specificity 83.7%. LCX: Sensitivity 43.5%; Specificity 96.9%.

Conclusions

Coupling an AI-augmented algorithm and 12-lead EKG provides encouraging results for STEMI culprit vessel localization. Overall, risk stratification is possible for individual lesions located in the LAD and RCA. However, our approach yielded uncertain results in the LCX territory. We plan to continue to exploring variables for improvement of our results.
P6425Comparative effectiveness and costs of enoxaparin versus unfractionated heparin in treating acute coronary syndrome
Authors: Xiao Z M , Rosenthal N , Kartashov A , Levorsen A , Shah B
Published: October 2019

Background/Introduction

Enoxaparin and unfractionated heparin (UFH) are guideline-recommended anticoagulants for patients with acute coronary syndrome (ACS) including unstable angina (UA) and myocardial infarction with (STEMI) or without ST-elevation (NSTEMI). Prior efficacy and safety evidence are mainly from clinical trials. Economic data is lacking.

Purpose

To examine differences in utilization, effectiveness, safety, and costs in treating ACS between enoxaparin and UFH using real-world data.

Methods

Using Premier Healthcare Database from 859 U.S. hospitals, inpatients 18 years or older with a diagnosis of initial episode of ACS between 2010–2016 were analyzed. Outcomes included 30-day risk of non-fatal myocardial infarction (MI), recurrent angina, in-hospital mortality, composite ischemic complication (having MI/recurrent angina/death), major bleeding, and costs. Multivariable regression was used to compare outcomes between enoxaparin and UFH monotherapy.

Results

Among 1,048,053 eligible patients (UA: 219,259; NSTEMI: 582,134; STEMI: 246,660), prevalence of enoxaparin monotherapy was 12.0%, 13.9%, and 5.1% and of UFH monotherapy was 45.1%, 43.1% and 59.8% for UA, NSTEMI, and STEMI patients, respectively. Compared to UFH, enoxaparin was associated with lower odds of MI (Adjusted Odds Ratio [OR]=0.95; 95% Confidence Interval (CI): 0.92, 0.99), recurrent angina (OR=0.88; 95% CI: 0.78, 0.98), in-hospital mortality (OR=0.88; 95% CI: 0.81, 0.95) and composite ischemic complications (OR=0.95; 95% CI: 0.92, 0.98) among NSTEMI patients but not in UA or STEMI patients. Enoxaparin was associated with lower odds of major bleeding in all three patients cohorts (UA: OR=0.77, 95% CI: 0.66, 0.91; NSTEMI: OR=0.68; 95% CI: 0.64, 0.72; STEMI: OR=0.72, 95% CI: 0.63, 0.83). Cost savings per patient during index admission and 30-day follow-up for enoxaparin over UFH was $2,813 for UA, $2,332 for NSTEMI and $2,928 for STEMI patients.

Conclusions

Enoxaparin was associated with lower odds of ischemic complications including death, lower costs and better safety than UFH among NSTEMI patients. Its relative effectiveness varied between patients with different ACS presentations. Improving upstream selection of appropriate anticoagulants in different type of ACS patients has the potential to optimize clinical outcomes and costs.

Acknowledgement/Funding

This study was funded by Sanofi Inc
P6431Association of circulating miR-765, miR-93-5p and miR-433-3p with obstructive coronary heart disease evaluated by cardiac computed tomography
Authors: Infante T , Forte E , Punzo B , Cademartiri F , Cavaliere C , Soricelli A , Salvatore M , Napoli C
Published: October 2019

Background

Although advances in diagnosis, treatment and prognosis, coronary heart disease (CHD) is still the most prevalent cause of mortality and morbidity worldwide. Thus, there is still the need to identify both novel diagnostic and prognostic biomarkers to improve the clinical decision-making and help to stratify patients for early preventive treatment. Epigenetic-sensitive mechanisms may be related both to pathogenesis and prognosis of CHD. Among the epigenetic hallmarks, microRNAs (miRNAs), acting as flexible modulators of gene expression, could represent attractive candidate biomarkers useful in clinical practice.

Purpose

We prospectively investigated the expression pattern of circulating miRNAs in patients undergoing Cardiac Computed Tomography (CCT) for suspected CHD (n=95) with the aim to integrate molecular findings with morphological and clinical parameters derived by CCT.

Methods

CCT was performed with a third-generation dual source multidetector computed tomography scanner. Peripheral venous blood samples were collected into EDTA after a 12 h fasting in the same day of CCT, before imaging execution and the levels of 42 selected plasmatic miRNAs were analyzed by qRT-PCR.

Results

Let-7c-5p, miR-765, miR-483-5p, miR-31-5p and miR-206 were upregulated in CHD patients (n=66) vs healthy subjects HS (n=29) as well as let-7c-5p, miR-765, miR- 483-5p showed higher expression in obstructive CHD (n=36) compared to no obstructive CHD patients (n=66). In addition, miR-93-5p and miR-433-3p showed an upregulation in patients with critical coronary stenosis. Multivariate regression analysis demonstrated that miR-765, miR-31-5p and miR-206 were independently associated with CHD also in combination with Framingham risk score. Relevantly, miR-765, miR-93-5p and miR-433-3p were obstructive CHD predictors. ROC curve analysis also revealed a good performance for miR-765, miR-93-5p and miR-433-3p on predicting CHD severity.

Circulating microRNA expression

Conclusions

Our study represents a combined epigenetic/imaging approach useful to support the diagnosis and prediction of CHD.

Acknowledgement/Funding

Italian Ministry of Health grants: “Giovani Ricercatori 2011-12” (project code GR-2011-02349436) and “Ricerca Corrente 2018”
P6436Soluble urokinase plasminogen activator receptor and functionally relevant coronary artery disease: a prospective cohort study
Authors: Walter J E , Amrein M , Koechlin L , Du Fay De Lavallaz J , Zimmermann T , Twerenbold R , Mueller C
Published: October 2019

Background

The urokinase system is pivotal in the pathogenesis of atherosclerosis. Therefore, soluble urokinase plasminogen activator receptor (suPAR) concentrations may help in the detection of functionally relevant coronary artery disease (fCAD).

Purpose

To evaluate suPAR as diagnostic marker for fCAD.

Methods

Among consecutive patients with symptoms suggestive of fCAD, fCAD was adjudicated blinded to suPAR concentrations in two domains: first, diagnosis of fCAD according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, fCAD according to cardiovascular death, non-fatal acute myocardial infarction (AMI) and all-cause death during 2-year follow-up.

Results

Among 968 patients, symptoms were adjudicated to be causally related to fCAD in 26% (255/968). SuPAR concentrations were higher in patients with fCAD as compared to those without (3.45 ng/mL versus 3.20 ng/mL, p=0.007), but overall had only low diagnostic accuracy (area under the curve [AUC]: 0.56, 95% CI 0.52–0.60) and were not independent predictors of fCAD after multivariable adjustment. Circulating suPAR concentrations were modestly correlated with high-sensitivity cardiac troponin (hs-cTn) T (Spearman's rho 0.393, p<0.001), NT-proBNP (Spearman's rho 0.327, p<0.001) and age (Spearman's rho 0.364, p<0.001), but only weakly correlated with the extent of coronary atherosclerosis as quantified by perfusion defects (Spearman's rho 0.123, p<0.001). Prognostically, suPAR concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.72, 95% CI 0.62–0.81) and all-cause death (AUC 0.72, 95% CI 0.65–0.79) at 2-years, and remained a significant predictor for all-cause death after multivariable adjustment (p=0.001). SuPAR concentrations did not predict non-fatal AMI.

Conclusions

SuPAR is an independent predictor of death, but not helpful in the detection of fCAD.

Acknowledgement/Funding

European Union, Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel,
P6440The perils of polyvascular disease with concomitant type 2 diabetes in a real-world cohort of patients with acute coronary syndrome
Authors: Denegri A , Magnani G , Rossi V A , Raeber L , Windecker S , Gencer B , Mach F , Rodondi N , Heg D , Nanchen D , Matter C M , Luescher T F
Published: October 2019

Background

Despite substantial improvement in type 2 diabetes (DM2) care, the burden of recurrent cardiovascular (CV) events remains high. Polyvascular disease (PVD), has recently emerged as a potential marker of heightened residual ischemic risk in DM2 patients, that are likely to derive a greater absolute risk reduction from more intense, individualized therapy.

Purpose

We sought to assess the relationship between DM2, PVD and CV outcomes among 2,168 all-comers patients admitted to four Swiss University Hospital for acute coronary syndrome (ACS) and enrolled in the prospective multicenter SPUM registry (NCT 01000701).

Methods

PVD was defined as concomitant peripheral artery disease, stroke or transient ischemic attack, or both. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE: Stroke, myocardial infarction, CV death). Adjusted Cox proportional hazards regression models were implemented to determine the risk associated with PVD disease in DM2 and outcomes, and intention-to-treat analysis was performed.

Results

Out of 2,168 ACS patients, 396 patients (18.3%) had DM2; of these 62 (15%) had PVD. Despite compared with the general ACS population, those with PVD + DM2 were more likely to have a complex history of CV disease, such as previous MI (27.4% vs 14.7%, p=0.021), prior percutaneous (37.1% vs 17%, p<0.001) or surgical (24.2% vs 5.1%, p<0.001) coronary revascularization, one third was not on statin therapy. At 1 year, patients with PVD + DM2 had a higher rate of MACCE compared to those presenting with PVD or DM2 alone. Rates of the single components of the primary endpoint and all-cause of death were all significantly higher in patients with PVD + DM2 vs. PVD or DM2 alone (Fig. 1A, all p<0.001). This enhanced risk persisted after adjustment for significant baseline differences, with a 34% (Adj. HR 1.34, 95% CI 1.15–1.49, p=0.02) increase in MACCE and a 44% increment of all cause of death (Adj. HR 1.44, 95% CI 1.06–1.54, p=0.02, Fig. 1B).

Outcomes by PVD and DM2 status.

Conclusions

Among a real-world cohort of ACS-patients, the coexistence of PVD and DM2 highlights the highest CV risk phenotype, being associated with significant increased rates of MACCE and all-cause of death. These observations might help clinicians to furtherly stratify the very high risk population and to identify patients who may derive the greatest benefit from more intense secondary prevention therapies.
P6443Late outcomes in patients undergoing PCI for ST elevation myocardial infarction with respect to diabetic status and completeness of revascularisation
Authors: Burgess S , Juergens C , Nguyen T , Leung M , Thomas L , Mussap C , Lo S , French J K
Published: October 2019

Objectives

This paper examines the degree to which the poor prognosis of ST elevation myocardial infarction (STEMI) patients with diabetes mellitus (DM) can be attributed to incomplete revascularization (ICR).

Background

Cardiovascular disease is the most common cause of death for patients with DM; patients with DM often have complex coronary disease and ICR. In STEMI the relative impact of DM and ICR is uncertain as these two factors frequently co-exist, the potential for confounding is high.

Methods and results

Of 589 consecutive STEMI patients, 22% had DM, who compared to patients without DM were of similar age (59 years), were more often female, had more hypertension and dyslipidaemia, but less often were smokers. A residual SYNTAX Score (rSS) >8, which defined ICR, occurred in 33%. Late cardiac death [median 3.5 years] was 4% among those without DM and 12% in those with DM (p=0.002) (p<0.001), and was 3% among 396 with rSS≤8 and 12% in 193 patients with rSS>8 (p<0.001). Patients with both ICR and DM accounted for only 8% of the STEMI population but 30% of all cardiac deaths. At final follow up (3.5 years) cardiac death rates (see Figure) were 22% in patients with both DM and ICR; these were significantly higher than rates in patients with ICR but no-DM (9%, p=0.034), and those with DM and rSS≤8 (6%, p<0.019). Multivariable analysis for cardiac death found a HR for ICR of 2.89 (95% CI 1.31–6.37; p=0.009) and a HR for DM of 5.18 (95% CI 2.45–10.97, p<0.001).

Diabetes, cardiac death & rSS

Conclusions

While ICR in DM patients with STEMI predicts a significantly poorer outcome, the poor prognosis seen in patients with DM is not explained by the degree of ICR alone. Both ICR and DM contribute independently to the risk of cardiac death in STEMI patients.
P6447Prediabetes versus diabetes mellitus in acute coronary syndrome patients: two sides of the same coin
Authors: Vila Cha Vaz Saleiro C , Lopes J , Teixeira R , Campos D , Sousa J P , Puga L , Ribeiro J M , Lourenco C , Costa M , Goncalves L
Published: October 2019

Background

Prediabetic patients are at increased risk of composite cardiovascular (CV) events and all-cause mortality. The impact of prediabetes diagnosis in the context of an acute coronary syndrome (ACS) remains to be determined.

Purpose

To assess the differences on long-term mortality between well controlled diabetic and prediabetic patients admitted with non-ST elevation ACS.

Methods

352 non-ST elevation ACS patients admitted to a single coronary care unit between 2009 and 2016 were included. Clinical, laboratorial and echocardiographic data were evaluated. Two groups were created based on the diabetic status and HBA1c level: Group A (prediabetic patients, HBA1c between 5.7–6.4%) N=229; Group B (diabetic patients, HBA1c ≤7%) N=123. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The mean time of follow up was 48±30 months.

Results

The groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, peak troponin I, left ventricular (LV) systolic function, multivessel disease and treatment option (PCI, CABG or OMT). On the contrary, well controlled diabetic patients had a higher prevalence of chronic kidney disease (CKD) (27.9% vs 39.0%, P<0.05), hypertension (82.5% vs 91.9%, P<0.05), higher body mass index (BMI) (23±4 vs 24±4 kg/m2, P<0.05) and previous coronary artery disease (37.1% vs 51.2%, P<0.05). 95 patients met the primary outcome. Kaplan-Meyer curves showed a tendency to decreased survival in the diabetic group (72.8% vs 66.4%, Log Rank P=0.09 – Figure 1). After adjustment for age, CKD, BMI (6 categories), heart failure diagnosis, peak troponin I and LV systolic function, controlled diabetes was not associated with increased death (HR 1.40, 95% CI 0.87–2.26). In this model, only age (HR 1.05, 95% CI 1.02–1.08), peak troponin (HR 1.01, 95% CI 1.00–1.01) and moderate to severely impaired LV function (HR 2.00, 95% CI 1.12–3.56) remained associated with the outcome.

Conclusion

In the context of an ACS, prediabetics should be regarded as a high-risk group. This study raises the provocative question that prediabetics and diabetics patients should be approached in similar ways in terms of risk stratification and therapeutic options after an ACS. In these patients, age, peak troponin and impaired LV function appear to be the main contributors to decreased survival.
P6448Major cardiovascular events free survival in the long term follow up of “real world” diabetic patients with stable coronary artery disease at the beginning of the 21st century. The CICCOR Registry
Authors: Ruiz Ortiz M , Sanchez Fernandez J J , Ogayar Luque C , Romo Penas E , Delgado Ortega M , Mesa Rubio D , Rodriguez Almodovar A , Castillo Dominguez J C , Anguita Sanchez M , Mateos De La Haba L , Carrasco Avalos F , Lopez Aguilera J , Lopez Granados A , Arizon Del Prado J M , Pan Alvarez-Ossorio M
Published: October 2019

Background

Safety trials of antidiabetic drugs have included a main endpoint of cardiovascular morbidity and mortality. However, “real world” data on long term prognosis of diabetic patients with stable coronary artery disease (sCAD) are limited. This study aimed to assess long-term incidence of major cardiovascular events in this population and to identify clinical predictors of this end-point.

Methods

The CICCOR registry is a prospective, monocentric, cohort study. From February 1, 2000 to January 31, 2004, all consecutive patients with sCAD attended at two outpatient cardiology clinics in a city of the south of Spain were included in the study and prospectively followed. Patients with type 2 diabetes mellitus were selected for this analysis. None of these patients received sodium-glucose cotransporter-2 inhibitors at first visit, as they were not commercially available at that time. Survival free of major cardiovascular events (combined end-point: acute myocardial infarction, stroke, or cardiovascular death) and variables associated with this end-point were investigated.

Results

The study sample included 394 patients (mean age 68±9 years, 61% male). After up to 17 years of follow-up (median 9 years, IQR 4–14 years, only 2 patients lost in follow-up, with a total of 3517 patients-years of observation), 66 had an acute myocardial infarction, 55 had an stroke and 165 died for cardiovascular causes. Survival free of major cardiovascular events was 88%, 70%, 57%, 47% and 32% at 3, 6, 9, 12 and 15 years. Multivariate predictors of the combined end-point are shown in the table.

Predictors of major cardiovascular event Variable Hazard Ratio (95% CI) p value Age (year) 1.06 (1.04–1.08) <0.0005 Tobacco use 0.02 Never smoker 1 (reference) Ex-smoker 1.43 (1.02–1.99) 0.04 Active smoker 2.23 (1.16–4.30) 0.02 Functional Class ≥II (angina) 1.57 (1.14–2.16) 0.006 Resting heart rate (10 bpm increase) 1.12 (1.01–1.24) 0.04 Diuretic treatment at first visit 1.71 (1.26–2.30) 0.001

Conclusions

Probability of major event-free survival was only 47% at 12 years in this “real world” cohort of diabetic patients with sCAD followed in the first 17 years of this century in a single center in the south of Spain. Simple clinical variables can identify patients at higher risk of events.

Acknowledgement/Funding

This work has been partially financed by an investigational grant by Boehringher Ingelheim
P6453Activation of necroptotic pathway by downregulated caspase-8 expression is associated with progression of left ventricular remodeling in nonischemic dilated cardiomyopathy
Authors: Fujita Y , Yano T , Abe K , Nagano N , Kamiyama N , Fujito T , Mochizuki A , Koyama M , Kouzu H , Muranaka A , Naganara D , Tanno M , Miki T , Miura T
Published: October 2019

Background

Necroptosis, a form of programmed necrosis, has been suggested to be involved in the pathogenesis of various pathological conditions including heart failure. Protein expression of caspase-8, an endogenous inhibitor of necroptosis, is reported to be downregulated in human failing hearts, but its clinical significance remains unclear.

Methods

Endomyocardial biopsy specimens were obtained from patients with nonischemic dilated cardiomyopathy (n=57, 56.2±14.5 years old, 70% male). The area stained with antibodies against caspase-8 and phospho-MLKL-Ser358 was calculated using an image analyzer, and fibrotic and cardiomyocyte areas were determined by Masson's Trichrome staining. Using a level of median caspase-8 expression (6.04% of the area of the myocardium with caspase-8 signal), patients were classified into a high caspase-8 expression group (H-cas8) and a low caspase-8 expression group (L-cas8).

Results

Caspase-8 signals were detected in cytoplasm and intercalated disks of cardiomyocytes. Patients in the L-cas8 group was younger (51.3±13.1 vs. 61.2±14.3 years old) and had larger left ventricular end-diastolic volume (LVEDV: 174±49 vs. 131±41 ml), larger left ventricular end-systolic volume (LVESV: 123±51 vs. 87±39 ml), and higher ratio of mitral peak velocity of early filling to late diastolic filling (E/A: 1.94±1.48 vs. 1.12±0.66) compared with the H-cas8 group. Caspase-8 expression level was positively correlated with age (r=0.34, p=0.01) and negatively correlated with LVEDV (r=−0.47, p<0.01), LVESV (r=−0.40, p<0.01), and E/A (r=−0.39, p<0.01) in simple linear regression analysis. The extent of myocardial fibrosis was not correlated with caspase-8 expression level. Multiple regression analysis indicated that LVEDV, LVESV, and E/A were independent explanatory factors of caspase-8 expression level after adjusting age and sex. Phospho-MLKL signals, an index of activation of necroptotic pathway, were frequently observed in cytoplasm, intercalated disks, and nuclei in the L-cas8 group but not in the H-cas8 group.

Conclusion

Lower caspase-8 expression in cardiomyocytes was associated with increased phosphorylation of MLKL and larger left ventricular volume, suggesting that downregulated caspase-8 may contribute to progression of myocardial remodeling via activation of MLKL in human dilated cardiomyopathy.
P6465Are we calculated enough? Glomerular filtration rate as a predictor of intra-hospital prognosis in patients with pulmonary embolism
Authors: Salinger-Martinovic S , Dimitrijevic Z , Stanojevic D , Subotic B , Dzudovic B , Stefanovic B , Matijasevic J , Miric M , Markovic-Nikolic N , Nikolic M , Miloradovic V , Kos L J , Kovacevic-Preradovic T , Srdanovic I , Obradovic S
Published: October 2019

Background

Pulmonary embolism (PE) can lead to multi-organ damage including an acute renal dysfunction which is associated with adverse events and high long-term mortality rate.

Purpose

The aim of our study was to investigate the predictive role of renal dysfunction on intrahospital mortality risk in patients hospitalized due to PE. The study was performed in intensive care units of six university hospitals.

Methods

The prospective cohort study comprised 665 consecutive patients with acute PE which was confirmed using MDCT. All patients underwent echocardiography examination on admission and blood samples were collected for troponin I (TnI), B-type natriuretic peptide (BNP) and routine laboratory analyses.

Results

Based on estimated glomerular filtration rate (GFR), patients were divided into three groups: first with the GFR <30ml/min, second with GFR 30–60 ml/min, and third with GFR >60 ml/min. During hospitalization in the first group the overall incidence of death was recorded in 28 (45.9%), in the second in 42 (18.9%), and in the third in 30 (7.9%) patients (p<0.0001). Pulmonary embolism as a cause of death was recorded in the first group in 18 (29.5%) patients, in the second in 25 (11.3%) and in the third in 17 (4.5%) patients (p<0.0001). Fatal bleeding was recorded in the first group in 1 (1.6%), in the second in 1 (0.5%) and in the third group in 3 (0.8%) patients (p<0.05). There were no significant differences regarding major bleeding frequency among the groups. Multivariate analysis showed that age, comorbidities, hemodynamic status, TnI, and GFR were strongly associated with an overall mortality rate and with death due to PE, while the use of anticoagulation therapy influenced the fatal bleeding rate. After controlling for age, we found that GFR on admission had a significant effect on in-hospital survival. Compared with patients in the third group, those from the second group had more than 2 fold increased mortality risk [OR 2.17 (CI 1.301–3.625), p=0.001], and patients in the first group had 6 fold higher risk of mortality [OR 6.006 (CI 3.487–6.006)]. In the ROC analysis GFR showed significant predictive value for intra-hospital mortality risk in PE patients [AUC= 0.725, 95% CI (0.68–0.78), p<0.001]. The highest sensitivity (64%) and specificity (70%) had GFR “cutoff” value of 59.12/min.

Conclusion

Renal dysfunction, on admission, in patients with acute PE is strongly associated with high intrahospital mortality risk and fatal bleeding. The estimation of GFR in these patients is important not only for prediction of the outcome but also for the prevention of bleeding complications, regarding the optimal dosage of anticoagulants. Even though it seems that GFR calculation is not still the clinical routine in PE.
P6467Pressure-mediated changes in the ventricular septum shape during exercise in patients with pulmonary hypertension: a 3-d echocardiography study
Authors: D'Alesio G , Migliavacca F , Rodriguez Matas J F , Bandera F , Losito M , Alfonzetti E , Guazzi M
Published: October 2019

Background

The role of interventricular (IV) septum in mediating the mechanical interaction between the two ventricles is well recognized. This interaction is promoted by several structural and hemodynamic determinants. We aimed at assessing the geometrical RV changes in patients with pulmonary hypertension (PH) compared to normal, evaluating RV curvature at rest and during stress testing addressing the specific role of pressure-induced changes in IV septum curvature.

Methods

Thirty-four subjects (15 controls; 19 PH patients) underwent RV real-time 3D full volume acquisition at rest and during exercise-echo. The 3D data were analysed off-line using the 4D RV TomTec software. The 3D mesh of the RV model was post-processed using a custom developed software. The value of mean regional curvature was assessed for the interventricular septum (IVS) at end-diastole (ED) and at end systole (ES).

Results

In controls the IVS curvature, assessed at end-diastole (ED) and end-systole (ES), was significantly (p<0.001) more concave (at rest −0.31±0.06 at ED, and −0.29±0.06 at ES; during exercise −0.28±0.09 at ED, and −0.28±0.08 at ES) than in PH patients (at rest −0.09±0.14 at ED, and −0.09±0.11 at ES ; during exercise −0.05±0.18 at ED, and −0.02±0.18 at ES). There was no significant variation in any of RV IVS curvatures between rest and exercise or between ES and ED. In PH subjects, IVS curvature at ES weakly increased from −0.09±0.11 (SD) at rest to −0.02±0.18 during exercise (p=0.179).Nonetheless, the degree of IVS curvature was strongly related to systolic pulmonary artery pressure (PASP), both at rest (r=0.743 at ES, p<0.01; r=0.794, p<0.001 at ED) and during exercise (r=0.823 at ES, p<0.0001; r=0.812 at ED, p<0.0001).

Conclusions

These data provide new perspectives on how the interventricular septum morphology adapts during exercise in PH patients vs controls. Changes in IVS curvature are linearly related to pulmonary pressure changes and occur with different slope (rest-exercise) in PH vs controls.
P6474Hidden in plain sight: diastolic blood pressure, resting heart rate and physical examination are independent predictors of mortality in chronic aortic regurgitation
Authors: Yang L.-T , Enriquez-Sarano M , Pellikka P A , Scott C G , Mankad S V , Schaff H V , Michelena H I
Published: October 2019

Background

In patients with hemodynamically-significant chronic aortic valve regurgitation (AR), the prognostic significance of routinely-measured diastolic blood pressure (DBP), resting heart rate (RHR) and physical examination signs of heart failure (HF), is unknown.

Purpose

To investigate the association of DBP, RHR and HF signs, with all-cause mortality.

Methods

This retrospective cohort study included all consecutive patients with moderately-severe or severe AR within a tertiary-referral center from 2006–2017. Patients with ≥moderate aortic stenosis and those with ≥moderate mitral stenosis/regurgitation were excluded.

Results

Of 820 patients (age 59±17 years; 82% men) with DBP 64±13mmHg and RHR 64±12bpm, followed for 5.5±3.5 years, 104 died under medical management and 400 underwent aortic valve surgery (AVS). In multivariable analysis, DBP (adjusted-hazard ratio [HR] 0.82 [0.68–0.98] p=0.031, per 10mmHg increase), RHR (adjusted HR 1.2 [1.01–1.41] p=0.034 per 10bpm increase), and any HF signs (adjusted HR 1.66 [1.04–2.61] p=0.032) were associated with all-cause death independently of demographics, comorbidities, and guideline-derived surgical triggers. Mortality increased in a J-curve fashion for DBP starting at 70 mmHg and peaking at 55 mmHg (Fig A,C), and in a linear fashion for RHR starting at 60bpm (Fig B, D). The association persisted after additional adjustment for medications, presence of hypertension and time-dependent AVS. A clinical score combining DBP, RHR and any HF signs increased the mortality risk-discrimination of demographics and comorbidities from 74% to 79% (p=0.01), and from 79% to 82% after addition of surgical triggers (p=0.04).

Figure. Risk of death by DBP and RHR

Conclusions

In patients with AR, routinely-measured vital signs and physical examination are strongly associated with all-cause mortality; lower DBP, higher RHR and any HF signs are independent predictors of mortality, and provide incremental mortality risk-discriminating value to baseline demographics, comorbidities and guideline-derived surgical triggers. These findings represent a clinical paradigm shift and have guideline implications.
P6482Stress echocardiography in the assessment of long-term outcomes results of aortic valve replacement with mechanical prostheses of small size
Authors: Nikityuk T G , Ivanova L N , Ivanov V A , Ivanova E V
Published: October 2019

Relevance

Evaluation of the function of aortic mechanical prostheses of small size in the long-term period is an topical problem, due to the fact that a narrow fibrous ring occurs in 20–35% of cases of patients with aortic stenosis.

Objective

To study clinical and hemodynamic parameters of small size aortic prostheses using stress echocardiography in the long-term period after valve replacement

Materials and methods

The study included 89 patients (54 women, 35 men) who underwent aortic valve replacement with a landing diameter of 21 mm or less.

The average was 48,1±11,3 years. BSA of 1,8 m2 (1.3 to 2.2). The following models of prostheses were used: On-X, ATS-AP, Carbomedics, St. Jude Medical. All patients after surgical correction in the long-term period (an average of 5,9±3,3 years from 1 to 11 years) underwent a comprehensive clinical and instrumental examination, including an ECG and stress - echocardiography with bicycle exercise.

Results

In the long-term period after aortic valve replacement of mechanical prostheses of small size, the ECG showed regression of hypertrophy and overload of the left ventricle.

According to stress-echocardiography, there was a significant increase in load tolerance. At the peak of the load, the following were recorded: improvement of the pumping function and cardiac performance (stroke volume, cardiac output, cardiac index), improvement of myocardial work index (Tei - index), increase in speed parameters on the aortic valve prosthesis no more than 30% of the initial values.

In repose, the maximum and mean pressure gradients were 26.3±9 mm Hg and 14.3±5.4 mm Hg, effective orifice area (EOA) 1,7±0,3 cm2, index effective orifice area (EOAi) 0,93±0,2 cm2/m2. When the submaximal load levels were reached, the maximum and mean pressure gradients were 33,5±6,0 mm Hg and 17,1±4,0 mm Hg, EOA - 1,5±0,4 cm2, EOAi - 0,79±0,6 cm2/m2.

Conclusions

The findings suggest that modern models of aortic prostheses with an increased effective orifice area provide good clinical results in the long term. Stress echocardiography is a necessary and highly informative method for assessing the parameters of mechanical aortic prostheses and heart function.
P6487Sequential combination of different thrombolytic therapy regimens in the management of patients with prosthetic valve thrombosis and stuck valves
Authors: Kalcik M , Guner A , Bayam E , Kalkan S , Yesin M , Gursoy M O , Karakoyun S , Gunduz S , Karavelioglu Y , Ozkan M
Published: October 2019

Introduction

Prosthetic valve thrombosis (PVT) is serious complication among patients with prosthetic heart valves. Recently, thrombolytic therapy (TT) regimens with low-dose, slow and ultra-slow infusions of tissue type plasminogen activator (tPA) has been widely used as a first-line treatment for PVT. PVT with stuck valves is a special entity which deserves particular management. In our study, we aimed to investigate the effectiveness and safety of sequential combination of different TT regimens in the management of patients with PVT and stuck valves.

Methods

The study included 52 patients with PVT and stuck valves [female: 34 (65.4%), mean age: 47.5±12.4] who underwent TT with sequential combination of slow (25mg/6 hours) and ultra-slow (25mg/25 hours) infusion of low dose t-PA regimens which was mainly based on the New York Heart Association functional class of the patients according to a previously established algoritm. All patients were evaluated by cinefluoroscopy, transthoracic and transesophageal echocardiography (Figure 1).

Results

The median number of TT sessions with slow and ultra-slow infusion of tPA were 1 (0–2.75) and 3 (1.25–5) respectively. Total tPA dose was 120 (96–175) mg and TT was successful in 46 (88.4%) patients. There were 3 major complications (cerebrovascular accident: 1, intracranial bleeding: 1, gastrointestinal bleeding requiring transfusion: 1) and 6 minor complications. The in-hospital mortality rate was 1.9%. Increased thrombus area was found to be the only independent predictor of both failed TT and adverse events. Thrombus area above 1.45 cm2 predicted failed TT with a sensitivity of 83% and a specificity of 70% (AUC: 0.871; 95% CI: 0.752–0.991; p=0.003) and predicted adverse events with a sensitivity of 77% and a specificity of 73% (AUC: 0.854; 95% CI: 0.747–0.961; p=0.001). There was a moderate positive correletion between thrombus area and total tPA dose used (r=479; p<0.001).

Figure 1

Conclusion

This study demostrated that TT with sequential combination of slow and ultra-slow infusion of low dose t-PA regimens may be useful for the treatment of patients with PVT and stuck valves with acceptable success and complications rates.
P6489Preoperative determination of artificial chordae length by transesophageal echocardiography
Authors: Pitsis A , Tsotsolis N , Theofilogiannakos E , Boudoulas H , Boudoulas K
Published: October 2019

The use of artificial chordae is one of the main techniques used in mitral valve repair to treat prolapsing leaflets, especially in anterior and bileaflet prolapse. With the use of PTFE sutures to replace elongated or ruptured chords mitral valve repair rates have significantly improved. The main difficulty with this technique is to determine the optimal length of the artificial chordae. Intraoperative transoesophageal echocardiography (TOE) is mandatory in mitral valve repair in order to determine the type of lesion of the mitral valve but also to evaluate the quality of the repair. We examined the accuracy of preoperative prediction of artificial chordae length by the preoperativeTOE.

Patients and methods

Twenty-one consecutive patients (7 females) underwent mitral valve repair with artificial chordae for significant mitral valve prolapse in our department during the last year. The median age of the patients was 62 y. (range 25 - 87) and the mean EuroSCORE II 3,36% (SD 4,61%). During the prep TOE we determined the predicted length of the required replacement chordae for the repair using mainly the 4 chamber view to calculate the distance between the tip of the papillary muscle and the coaptation point of the two leaflets and we subtracted 5mm which is the minimum of the desired coaptation length (top right part of the Figure). All the patients underwent totally endoscopic mitral repair through a 3 cm right periareolar incision. 14,3% of the patients had anterior leaflet (AML) prolapse, 23,8% bileaflet and 61,9% posterior (PML). The appropriate length of the required chordae was measured intraoperatively.

Results

We used on average 3 loops of artificial chordae size 23,3 mm (SD 1,15mm) to treat the AML prolapse, 5 loops size 23,2 mm (SD 2,28mm) to treat the bileaflet prolapse and 2,23 loops size 18mm (SD 2mm) to treat the PML prolapse (bottom part of the figure). The predicted size of the artificial chordae had a positive correlation to the length used (Pearson correlation, p<0,001) as demonstrated in the top left part of the Figure. An annuloplasty band was implanted to all the patients. All the patients had no mitral regurgitation in the postoperative TOE. The mean valve area was 3,54cm2 (SD 0,57) and the mean peak gradient 5,6 mmHg (SD 1,82). There was no mortality.

Chordae length predicted by echo

Conclusion

The length of artificial chordae can be predetermined with great accuracy with the use of TOE, making TOE an important tool not only for the determination of the mitral lesion and quality of the repair but also for the planning of the operation.
P6493Syk activation is a defense mechanism in murine model of aortic dissection
Authors: Hashimoto Y , Aoki H , Majima R , Hayashi M , Ito S , Ohno-Urabe S , Furusho A , Nishida N , Hirakata S , Fukumoto Y
Published: October 2019

Background

Aortic dissection (AD) is a serious clinical condition with unknown etiology that frequently results in fatal outcome. Recent studies showed essential role of inflammatory response both in promoting AD and aortic aneurysm (AA). However, the difference of the molecular pathogenesis between AD and AA is unclear. Previously, we reported that Syk, a tyrosine kinase that regulates differentiation and activation of inflammatory cells, promotes AA formation in a mouse model.

Objective

In the current study, we investigated the role of Syk in AD.

Methods and results

A mouse AD model was created by continuous infusion of beta-aminopropionitrile (125 mg/kg/day) and angiotensin II (1,000 ng/min/kg) (BAPN+AngII), which caused AD in approximately 80% of mice within 14 days. Immunohistochemical staining for activated (phosphorylated) Syk (pSyk) revealed that Syk was inactive in normal mouse aorta, but was activated in the aortic walls after AD development. Double immunofluorescence staining for pSyk and smooth muscle alpha actin showed that Syk was active not only in the infiltrating inflammatory cells, but also in smooth muscle cells in AD tissue. Western blot analysis revealed that BAPN+AngII treatment caused Syk activation at 3 days before AD development, followed by transient suppression, and reactivation at 14 days after AD development. We examined the significance of Syk activation in AD by treating mice with fostamatinib, a specific Syk inhibitor, before and during BAPN+AngII infusion. Notably, fostamatinib-treated group developed more severe AD compared to the vehicle-treated group. The AD lesion length was 3.80±0.86 mm for vehicle group and 8.87±1.69 mm for fostamatinib group (P<0.05, n=12 for each group). In addition, fostamatinib significantly worsened the mortality of mice due to the rupture of the aorta from 0% to 42% (P<0.05, n=12 for each group). Transcriptome analysis revealed that fostamatinib suppressed both positive and negative regulators of immune response, defense response and inflammatory response.

Conclusions

These findings uncovered the previously unrecognized role of Syk for protecting the aortic tissue in AD pathogenesis, and suggested fundamentally different disease mechanisms of AD and AA.
P6497Loeys-Dietz syndrome-5: phenotypic spectrum of TGFB3 mutations in an international cohort and first report of a homozygous patient
Authors: Marsili L , Overwater E , Hanna N , Baujat G , Baars M J H , Brehin A C , Gerard M , Gouya L , Houweling A C , Vanlerberghe C , Voorhoeve E , Van Tintelen J P , Maugeri A , Arnaud P
Published: October 2019

Background

Mutations in TGFB3 cause Loeys-Dietz syndrome-5 (LDS5), an autosomal dominantly inherited connective tissue disorder. LDS5 is characterized by aortic aneurysms and dissections associated with systemic features mainly involving the ocular and skeletal systems. Precise delineation of LDS5 phenotype is difficult because of the small number of identified cases.

Purpose

The purpose of this study was to further define LDS5 with an emphasis on cardiologic features by describing the genotype and phenotype in an international cohort of patients.

Methods

We performed a retrospective cross-sectional multicentre study. Genetic testing was performed as a part of standard medical care. Clinical data were collected by means of an anonymized questionnaire, which was sent to the referent physicians.

Results

Ten (7 novel) TGFB3 mutations were identified in 31 patients (16 index patients). The mean age at last evaluation was 32 years (range 4–60 years). Aortic root dilatation, varices, and mitral valve insufficiency were the most common cardiovascular findings, reported in 28%, 22%, and 21% of patients, respectively. Higher incidences (40%, 29%, and 25%) of these findings were observed in the index patients. Four patients (8%) underwent aortic surgery, all after age 40. Abdominal aortic aneurysms were reported in 2/26 (8%) patients. Extra aortic artery disease included iliac artery aneurysm (one index patient) and tortuosity of the internal carotid and vertebral arteries (one index patient and one relative). The most frequently reported systemic features were high-arched palate, arachnodactyly, pes planus, pectus deformity, and joint hypermobility. Interestingly, we identified an homozygous TGFB3 mutation in a patient who presented with aortic dilatation at age 17, splenic torsion, severe myopia, cleft palate, and other skeletal features. Her heterozygous parents, brother, and sister displayed signs of the disease, but to a milder degree. To the best of our knowledge, this is the first identification of homozygous TGFB3 mutation.

Conclusions

Our data are in line with previous research, showing that aortic root dilatation is the main cardiovascular feature of LDS5. No deaths related to cardiovascular events were reported in any of the presented families. The cardiovascular phenotype of LDS5 appears to be milder compared to other vascular connective tissue disorder, such as Marfan syndrome, although our findings suggest that homozygosity is associated with a more severe and early-onset phenotype.
P6499Genetic screening in 109 adult Chinese patients with thoracic aortic aneurysm and dissection
Authors: Li J , Wu B , Wang Y , Sun Y P , Liu D , Zhai J , Lai H , Sun Y X , Wang C
Published: October 2019

Background

Thoracic aortic aneurysm and dissection (TAAD) comprises a heterogenous group of cardiovascular urgencies, which could be further categorized into syndromic and non-syndromic entities. The accurate and timely identification of culprit genetic variants is of grave importance for TAAD patients, since different genetic defects have been associated with different risks for aortic dissection, thus different thresholds for preventive aortic intervention.

Purpose

With the advent of next-generation sequencing (NGS) techniques, accumulating records of rare variants have been found in TAAD patients, while inadequate functional validation also makes it difficult to give proper counsel for individual TAAD patients. Therefore, it is necessary for us to start re-evaluating clinical applications of genetic screening strategies in specific patient populations.

Methods

From June 2016 to July 2017, genetic screening using an NGS-based panel of 18 candidate genes (FBN1, FBN2, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3, COL1A1, COL3A1, COL5A2, COL5A1, PLOD1, ACTA2, MYH11, MYLK, PRKG1, MFAP5, and SKI) was applied in 109 adult TAAD patients from our institution. Patients with bicuspid aortic valve disease, complex congenital cardiac defect, aortic root infection, aortitis, pregnancy, and an age older than 70 years were excluded from the present study.

Results

Among 109 TAAD patients, 36 harboured an FBN1 variant, including 2 splicing site, 6 frame shift, 5 non-sense, and 23 mis-sense variants. The pathogenicity of mis-sense variants was further categorized into 10 disease-causing variants via database survey, 5 disease-causing variants via family survey, and 8 variants of uncertain significance (VUS). On the other hand, 25 patients harboured a non-FBN1 variant, including 3 established pathogenic variants on TGFBR1, TGFB2, and ACTA2 genes, as well as 22 VUS. Patients with an FBN1 variant displayed younger age, lower rate of hypertension, higher rate of aortic root aneurysm, and more frequent mitral valve prolapse, while an extreme male predominance (24/25) was observed in patients with a non-FBN1 variant.

Conclusion

In an adult Chinese TAAD cohort, disease-causing genetic variants were found in 28.4% (31/109) of patients, with FBN1 mutations still being the single leading cause of disease. The present study advocated a genetic screening strategy emphasizing the detection of FBN1 mutations in adult Chinese TAAD patients, and further studies should address the pathogenicity and clinical relevance of non-FBN1 VUS in TAAD patients.