bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.