bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4639Plasma tissue factor coagulation activity in post-acute myocardial infarction patients
Authors: Lim X C , Yatim S M J M , Chong S Y , Wang X , Tan S H , Yang X , Chan S P , Richards A M , Charles C J , Chan M , Wang J W 
Published: October 2019

Abstract

Background
Coagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure.

Purpose
We aimed to evaluate the association of plasma tissue factor (TF) coagulation activity with LV remodeling prior to heart failure in post-AMI patients.

Methods
This study was conducted in 228 subjects from the Post-AMI Left Ventricular Remodeling Biomarker Analysis (PAMILA) study and 57 healthy subjects. The post-AMI patients were divided into two age- and sex-matched groups: patients with adverse LV remodeling defined as an increase in LV end systolic volume by ≥15% over 6 months and patients with reverse LV remodeling defined as an decrease in LV end systolic volume by ≥15% over 6 months. TF coagulation activity was determined using human coagulation factor Xa generation based TF chromogenic activity assay and converted into concentrations of active TF (pM). Sodium-citrate anticoagulated plasma was collected at baseline (within 3 days after revascularization), 30 days and 6 months post-AMI. Results are presented as mean±S.E.M. One-way or two-way repeated measures ANOVA or a multiple multi-level longitudinal data analysis with structural equation model was used to assess differences in coagulation activity. P<0.05 was considered statistically significant.

Results
Plasma from healthy subjects and post-AMI patients at baseline had similar concentrations of active TF (TFa): 29.0±1.4 versus 29.1±0.7 pM. Patients treated with warfarin (15 out of 228 patients) showed lower plasma levels of TFa (mean difference −15.2 pM, [95% CI: −18.7, −11.7], p<0.001). Compared to baseline, plasma levels of TFa in the patients was significantly lower at 30 days post-AMI (mean difference −6.9 pM, [95% CI: −4.8, −8.9], p<0.001) and 6 months post-AMI (mean difference −2.8 pM, [95% CI: −0.8, −4.8], p=0.003). Intriguingly, plasma levels of TFa tended to recover from 30 days to 6 months post-AMI (mean difference 4.1 pM, [95% CI: 2.8, 5.4], p<0.001) toward the baseline level and the level in healthy subjects. Similar trends of temporal changes of plasma TFa levels were observed in patients with adverse LV remodeling and those with reverse LV remodeling although TFa levels were slightly higher in patients with reverse LV remodeling (F(2,448)=3.112, p=0.045 for interaction). After adjusting for age, gender, ethnicity, medications, lipid profile and risk factors, the temporal changes of plasma TFa levels in patients remain significant, however, the difference between patients with adverse versus reverse LV remodeling was not significant.

Conclusion
Plasma TF coagulation activity decreased post-AMI but did not differ in patients with adverse versus reverse LV remodeling.

Acknowledgement/Funding
National University Health System Singapore (NUHS O-CRG 2016 Oct-23) to JW Wang
P4649Whole exome sequencing and whole genome sequencing improves genetic diagnosis of fetals with heterotaxy syndrome revealed by prenatal ultrasound
Authors: Yi T , Sun H , Fu Y , Wang J , He Y 
Published: October 2019

Abstract

Background
Heterotaxy (Htx) syndrome is an congenital disorders resulting from incorrectly establishment of left-right patterning during embryogenesis. Over 96% of patients with Htx exhibit some form of congenital heart disease (CHD),and has relatively poor survival. Multiple lines of evidence support genetic contributions to the etiology of Htx. As a specific genetic etiology is currently identifiable in only a minority of patients, there remains enormous potential for novel gene and pathway discovery.

Purpose
The aim of this study was to investigate the diagnostic yield of whole-exome sequencing (WES) and whole-genome sequencing (WGS) in fetuses with the pathogenesis of Htx, to explore candidate genes for Htx and to expand the clinical phenotype of known genetic conditions.

Method
WES and WGS were performed on specimens from 46 fetuses diagnosed with Htx and their parents. The single-nucleotide variants (SNVs) and copy-number variants (CNVs) were filtered and annotated by standard analysis process. All reported variants were classified according to he American College of Medical Genetics and Genomics guidelines.

Results
In the 46 fetuses, the detection rates of pathogenic and likely pathogenic variations were21.7% (10/46) and 10.9% (5/46) respectively. Ten pathogenic variations were identified on genes of CCDC114, DNAH11, ARMC4, STRA6, PQBP1 (hemizygote), HYDIN, RAI1 (Alagille Syndrome), ZFMP2 and Del(22q11.2) Syndrome. Five likely pathogenic variation were on DNAAF1 (Holshner syndrome), NF1, NEXN, NOTCH3 and FOXC1. Of 30 fetuses with prenatally diagnosed right atrial isomerism (RAI), the main intracardiac anomalies were atrioventricular canal (AV canal), isomerism of right atrial appendages, pulmonary stenosis or atresia (PS & PA) and right aortic arch. In 16 fetuses diagnosed left atrial isomerism (LAI) the main intracardiac anomalies were isomerism of left atrial appendages, interrupted IVC and azygos vein continuation. Of the 10 positive cases, 8 fetus were diagnosed of RAI and 2 were diagnosed of LAI by prenatal ultrasonic examination or fetal autopsy. The detection rate was 8/30 (26.7%) for RAI and 2/16 (12.5%) for LAI.

Conclusion
This study outlines the way for a substantial improvement in the diagnostic yield of prenatal genetic disorders in Htx through WES and WGS. Our experience also expanded the knowledge of the clinical phenotype of known genetic conditions. Our results indicate that the proportion of SNV in Htx of prenatal cases was significantly higher than that in patients with other congenital heart abnormalities, and the recessive inheritance occurred in a higher proportion in Htx. Our results have important implications for clinical management and genetic counseling of Htx.

Acknowledgement/Funding
Ministry of Science and Technology of the People's Republic of China
P4650Sex differences in clinical presentation and in hospital outcomes among myocarditis and peri-myocarditis patients
Authors: Younis A , Matetzky S , Masalha E , Chernomordik F , Afel Y , Fardman A , Goitein G , Ben-Zekry S , Grupper A , Segev A , Beigel R 
Published: October 2019

Abstract

Background
Data are scarce regarding sex differences among patients with myocarditis and peri-myocarditis. Our aim was to define the sex differences in clinical characteristics as well as in-hospital outcomes in a cohort of consecutive patients hospitalized due to myocarditis and peri-myocarditis.

Methods and results
We analyzed data of 322 consecutive patients between January 2007 and October 2017 who were hospitalized with the diagnosis of myocarditis or peri-myocarditis at our medical center. Eighty-four percent of the patients were males. Both males as well as females had similar rates of chronic medical conditions. However, males were more likely to present with ST elevation (75% vs. 44%. P<0.001) as well as PR depression in ECG compared to women and have higher admission troponin levels (7.6±11 vs. 2.3±4, P<0.001). Women were older (45±17 vs. 36±14, P<0.001) and tended to present with a rather normal ECG. There were no differences in the incidence of in-hospital mortality or the need for escalation therapy between male and female patients. However, males were more likely to have ventricular arrhythmias (7% vs. 0%, P=0.05). no differences in long term mortality were observed among males and females.
Variable Male (N=272) Female (N=50) P-value Age 36±14 45±17 <0.001 Cardiology Department 243 (90%) 39 (78%) 0.03 Dyspnea 63 (23%) 22 (44%) 0.002 Pericardial chest pain 94 (35%) 20 (40%) 0.52 Admission SBP (mmhg) 122±16 116±16 0.02 Admission HR (b/min) 82±16 89±21 0.04 Normal ECG 37 (14%) 12 (24%) 0.06 ST elevation 204 (75%) 22 (44%) <0.001 LVEF <50% 215 (80%) 45 (90%) 0.08 LGE 176 (88%) 20 (69%) 0.009 Albumin 4±0.3 3.6±0.4 <0.001 Troponin admission 7.6±11 2.3±4 <0.001

Conclusions
Male patients, which constitute the majority of patients. Admitted with myocarditis are younger, with higher troponin levels at admission, are more likely to present with ST elevation, and have a higher rate of ventricular arrythmias when compared to women. However, there are no differences in early as well as long term mortality rates between men and women.
P4657Cardiac myxomas: are we dealing with distinct clinical entities?
Authors: Sa Mendes G , Abecasis J , Ferreira A , Ribeiras R , Reis C , Nolasco T , Gouveia R , Abecasis M , Mendes M , Ramos S , Neves J 
Published: October 2019

Abstract

Background
Cardiac myxomas are rare, despite being the most common primary cardiac tumours. A significant number of myxomas are discovered accidentally in asymptomatic patients (pts), as there is increased use of non-invasive cardiac imaging. Our aim was to describe the experience of a cardiac surgery centre managing cardiac myxomas during the last 28 years.

Methods
Single-center retrospective study of consecutive pts admitted with the diagnosis of a cardiac myxomas between 1990 and 2018. Registry data concerning clinical presentation, non-invasive imaging assessment and definitive histopathology were collected.

Results
From 154 pts with the diagnosis of cardiac tumours, we identified 106 (68.8%) myxomas (67% females; mean age at diagnosis 61,5±13,1 years). Myxoma diagnosis increased throughout the 3 decades (27 cases until 2000; 26 cases in the second decade; 52 cases from 2010 until present). 30% of the pts were asymptomatic at diagnosis. Obstructive symptoms (heart failure and syncope) and embolic events were the most common complaints among symptomatic pts. Transthoracic echocardiography firstly identified the tumours in 88% of the cases. Cardiac magnetic resonance and computed tomography were performed for further investigation in 7% of the cases. Presumptive pre-operative diagnosis was correct in 83.8% pts.
Surgical excision was successfully achieved in all cases. 89% of the tumours were located in the left atrium with inter-atrial septum implantation (13 in right chambers; 1 valvular tumour). There were 10 multifocal tumours.
At histopathology myxomas were grossly described as mucous jelly appearance (80%), solid (15%) and mixed type lesions (5%). Rare histologic findings were described in 30% of the cases (8 tumours with bone tissue; 1 with forming bone marrow; 4 with endocrine type glandular epithelium; 16 with lympho-plasmocytic infiltrates; 3 with high mitotic grade; 5 with concomitant thrombus).
For a median follow up of 86 [31–214] months there were 15 deaths (2 of them with tumour related deaths). There were 3 recurrences (2 with high mitotic grade histology), mostly occurring 3 years after the first intervention.

Conclusion
In this case series cardiac myxomas are the most common cardiac tumours, with a significant proportion of asymptomatic lesions. Clinical heterogeneity followed polymorphic histology, with recognized differences when compared to classical descriptions of this kind of tumour.
P4676Experience of three years of balloon pulmonary angioplasty in a single centre: safety and short term results
Authors: Gotti E , Palazzini M , Saia F , Dardi F , Rinaldi A , Zuffa E , Guarino D , De Lorenzis A , Pasca F , Rotunno M , Magnani I , Manes A , Marzocchi A , Galie' N 
Published: October 2019

Abstract

Background
Balloon pulmonary angioplasty (BPA) has recently been developed as an alternative and less-invasive treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH) but therapeutic efficacy and technical safety of the technique have to be established.

Purpose
To examine the effects of BPA on patients with inoperable disease or residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA).

Methods
From June 2015 to January 2019 we enrolled symptomatic (WHO-FC ≥II) inoperable CTEPH patients and patients with residual PH after PEA. At baseline and after 3 months after last BPA session all patients underwent clinical evaluation, six-minute walking distance (6MWD) and right heart catheterization. For comparisons Friedman test (with Bonferroni post-hoc pairwise analysis) was used.

Results
Forty-one patients [male 49%, median age 65 (52–75) years, 34 inoperable and 7 with residual PH after PEA] were treated for a total of 111 sessions (median number of sessions for each patient: 2); during each session we treated 2 (2.0–2.5) vessels. Results are shown in the Table. Forty patients were treated with medical therapy before BPA (16 with combination therapy). Four pulmonary artery dissection and 2 haemoptysis with clinical impairment were documented during the procedures; 27 patients had lung injury (radiographic opacity with/without hemoptysis and/or hypoxemia), none had renal dysfunction, 6 patients had access site complications. Five patients died during follow-up (none within 30 days from the procedure) because of sepsis (1), heart failure (1), cancer (1), arrhythmic storm (1) and sudden death in a patients with severe coronary atherosclerosis (1).
Table 1 Median (interquartile range) Baseline Baseline ÷ Pre-BPA Pre-BPA Pre-BPA ÷ Post-BPA Post-BPA Global (n=41) 8 (3–49) months (n=41) 10 (6–18) months (n=32) p-value WHO-FC III-IV (%) 88 N.S. 83 <0.05 42 <0.001 6MWD (m) 430 (346–560) N.S. 425 (357–500) <0.05 450 (375–605) <0.001 RAP (mmHg) 6 (5–8) N.S. 6 (5–8) N.S. 6 (4–8) 0.023 mPAP (mmHg) 46 (40–52) <0.05 43 (33–50) <0.05 36 (28–41) <0.001 CI (l/min/m2) 2.6 (2.2–3.0) N.S. 2.7 (2.2–3.0) <0.05 3.1 (2.6–3.5) 0.004 PVR (WU) 7.5 (5.6–11.5) <0.05 6.5 (4.7–10.3) <0.05 4.1 (3.3–5.9) <0.001 PA O2 Sat (%) 69 (63–71) N.S. 69 (63–72) N.S. 69 (63–73) 0.002 CI, Cardiac Index; mPAP, mean Pulmonary Arterial Pressure; PVR, Pulmonary Vascular Resistance; PA O2 Sat, Pulmonary Artery Oxygen Saturation; RAP, Right Atrial Pressure; 6MWD, 6 Minute Walking Distance; WHO-FC, World Health Organization Functional Class.

Conclusions
BPA is a safe and effective treatment able to improve symptoms and hemodynamic profile in inoperable CTEPH patients and in patients with residual PH after PEA.

Acknowledgement/Funding
None
P4678The hemodynamic improvement with balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension depends on the lesion location
Authors: Nishihara T , Shimokawahara H , Matsubara H , Hayashi K , Tsuji M , Naito T , Shigetoshi M , Tabuchi I , Ogawa A , Munemasa M 
Published: October 2019

Abstract

Background
Pulmonary endarterectomy (PEA) is a treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Patients with proximal pulmonary artery disease are considered to be good candidates for PEA because of their generally excellent outcomes. However, not all patients can be operated because of patients' advanced age, comorbidities and poor general condition. Balloon pulmonary angioplasty (BPA) has become an alternative treatment for CTEPH patients especially whose lesions locate in the distal site. The effectiveness of BPA in patients who have lesions in the proximal pulmonary arteries but cannot be a candidate for PEA remains unclear.

Purpose
The aim of this study was to investigate the outcome of BPA in CTEPH patients whose lesions appears operable but ineligible for PEA.

Methods
A total of 370 patients who underwent BPA in our institute from November 2004 to January 2018 were enrolled. All the patients were divided into operable group and inoperable group according to the difference of lesion location based on the findings of perfusion scintigraphy, computed tomography and pulmonary angiography. Hemodynamic effects of BPA in both groups were investigated. We also conducted survival analyses using the Kaplan-Meier method with the log-rank test.

Results
Among 370 patients, 90 patients deemed operable. The main reasons why not operated in the PEA operable group were patient's refusal (44%), advanced age (14%), and comorbidities (27%). There were no baseline characteristic differences between two groups except for the history of acute pulmonary embolism. Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) equally improved after BPA in both groups (operable: 38.2±10.8 mmHg to 21.5±4.7mmHg, inoperable: 42.4±11.3 mmHg to 21.8±4.8 mmHg, p<0.001, operable: 8.0±4.2 wood unit to 3.5±1.5 wood unit, inoperable: 9.1±4.6 wood unit to 3.4±1.3 wood unit, p<0.001). Furthermore, five-year cumulative survival rates were not different between two groups (inoperable vs. operable: 93% vs. 88%, p=0.23, median follow-up period was 23.0 months (range: 5–136 months)). Meanwhile, the absolute change of mPAP and PVR in inoperable group were greater than those in operable group (inoperable: 20.7±11.2 mmHg, operable: 16.6±11.0 mmHg, p=0.010, inoperable: 5.6±4.4 wood unit, operable: 4.5±3.9 wood unit, p=0.015).

Conclusions
Although the outcome of BPA for CTEPH patients with operable lesions appears acceptable, absolute change in hemodynamics was lower than that of the patients with inoperable lesions. CTEPH with proximal lesions should be treated with PEA rather than BPA.
P4684Differential right ventricular adaptation patterns to chronic pressure overload
Authors: Garcia Lunar I , Pereda D , Ascaso M , Jorda P , Galan C , Solanes N , Santiago E , Sanchez J , Rigol M , Fuster V , Ibanez B , Garcia-Alvarez A 
Published: October 2019

Abstract

Background
Right ventricular (RV) dysfunction is the most important prognostic factor in chronic pulmonary hypertension (PH), but its underlying mechanisms are unknown. Clinical observation and prior experimental work suggest that RV pressure overload is not the only cause since the degree of RV adaptation varies with similar RV end-systolic pressures.

Purpose
Our aim was to characterize serial RV adaptation by cardiac magnetic resonance (CMR) in 3 different experimental large-animal models of increased afterload: a model of chronic postcapillary PH, a model of PH secondary to systemic-to-pulmonary shunt and a model of mechanical RV pressure overload (generated by pulmonary artery [PA] banding).

Methods
Four-week old piglets underwent pulmonary vein banding surgery to generate the chronic postcapillary PH model (n=20), aorto-pulmonary shunt (n=6), PA banding (n=7) or sham operation (n=7). They were followed up monthly with CMR and right heart catheterization (RHC). All procedures followed the “Principles of laboratory animal care”. Comparison of continuous variables among groups was performed with Mann-Whitney U test.

Results
Animals with either postcapillary PH or PH secondary to aorto-pulmonary shunt presented significant RV dilatation, hypertrophy and dysfunction that was maintained during follow-up (median RV end-systolic volume [RVESV]=32.6 ml/m2 for postcapillary PH and 32.6 ml/m2 for shunt vs. 16.1 ml/m2 in sham controls; median RV ejection fraction [RVEF]=61.5% for postcapillary PH and 60.5% for shunt vs. 69.6% in sham controls at the end of follow-up). Animals with PA banding also presented with significant RV dilatation and hypertrophy at the first month follow-up, but unlike all other groups, they developed reverse RV remodeling from the second month onwards and maintained normal RV volumes and RVEF values until the end of follow-up despite having severe RV hypertrophy (RV mass 22.6 g/m2 in PA banding vs. 16.1 g/m2 in controls at the 4th month follow-up; Figure).
CMR parameters (median values).

Conclusion
In PH there is a maladaptive RV hypertrophy that is not present in a model of progressive RV pressure overload without alterations of the pulmonary circulation. Increased RV pressure overload alone does not fully explain PH-associated RV dysfunction. Further research is needed to clarify the underlying mechanisms of adaptive and maladaptive hypertrophy in PH.

Acknowledgement/Funding
The CNIC is supported by the Ministerio de Ciencia, Innovaciόn y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence
P4686Multimodal assessment of right ventricular-arterial coupling allows better prognostication in pulmonary arterial hypertension patients
Authors: Kazimierczyk R , Malek L A , Szumowski P , Blaszczak P , Jurgilewicz D , Hladunski M , Sobkowicz B , Mysliwiec J , Grzywna R , Musial W J , Kaminski K A 
Published: October 2019

Abstract

Background
The concept of coupling mainly refers to the relationship between ventricular contractility and afterload. Together, strictly related parameters may provide a more accurate estimation of the RV performance status. Indexing RV function, assessed by CMR feature tracking analysis, with a pulmonary artery systolic pressure (PASP) obtained from right heart catheterization (RHC) allows estimation of ventricular-arterial coupling and could help in prognostic stratification of pulmonary arterial hypertension (PAH) patients.

Aim
To verify the prognostic value of multimodal approach to estimate RV ventricular-arterial coupling in PAH patients.

Methods
Twenty-six stable PAH patients (mean age 49.92±15.94 years) and twelve healthy subjects (control group, 44.75±13.51 years) were enrolled into the study. CMR feature tracking analysis of the RV was performed for generation of RV global longitudinal strain (RV GLS); RV ejection fraction was also obtained by CMR. Right heart catheterization was carried out only in the PAH group with a standard technique.RV- arterial coupling was evaluated by the ratio of RV GLS/PASP. Mean follow-up time of this study was 16.6±7.5 months and the clinical end-point (CEP) was defined as death or clinical deterioration.

Results
In study group, RV GLS significantly correlated with hemodynamic parameters from RHC – mean pulmonary artery pressure, mPAP (r=0.53, p=0.04) and pulmonary vascular resistance, PVR (r=0.57, p=0.002). Mean RV GLS/PASP ratio in PAH group was (−)0.24±0.15%/mmHg.
Patients who reached CEP (n=15) had a significantly higher RV GLS and RV GLS/PASP ratio (−13.3±7.9% vs −20.4±6.2%, p=0.01 and −0.15±0.09%/mmHg vs −0.36±0.19%/mmHg, p=0.005, respectively). However, ROC analysis revealed higher area under curve (AUC) of RV GLS/PASP in predicting CEP than of RV GLS alone (0.82 (95% CI 0.64–1) vs 0.77 (95% CI 0.58–0.96), p<0.0001). Interestingly, at univariate analysis only RV GLS/PASP (HR: 0.89; 95% CI: 0.79–1.08; p=0.03), together with mPAP were all significantly associated with CEP. Patients with RV GLS/PASP cut-off value (ROC analysis) higher than (−)0.29%/mmHg had worse prognosis, log-rank test, p=0.01 (Figure 1).
Figure 1

Conclusions
Combining CMR and hemodynamic measurements via catheterization offers the potential for more comprehensive assessment of pulmonary vascular load and right heart function, as required for evaluation of the hemodynamic state in patients with PAH.

Acknowledgement/Funding
This work was supported by National Center for Science in Poland [“Preludium” grant 2017/25/N/NZ5/02689 to R.K.]