bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between the elevation of biomarkers and incipient alterations in ventricular function in patients with Chagas disease without evidence of specific organ damage
Authors: Chirino D , Dizeo C , Volverg V , Toledo G , Vecchio V , Leonardi M.S , Calderon G 
Published: November 2020

Abstract

Background
Chagas disease (ChD) has a long asymptomatic period, where there is no evidence of myocardial damage. However, incipient alterations in ventricular systo-diastolic function have been described using echocardiography with Tissue Doppler and Strain. On the other hand, the presence of elevated higth-sensitivity T troponin (HS-TnT) and N-terminal pro B-type natriuretic peptide (NT-pro BNP) has been documented in the early stages of the ChD. The association between the elevation of both markers and incipient alterations in ventricular function in patients with ChD without evidence of heart damage has been poorly studied.

Purpose
The aim of this study is to evaluate the prevalence of elevation of both biomarkers (HS-TnT and NT-proBNP) and their association with insipients alterations in systo-diastolic function in patients with ChD without evidence of structural heart affection.

Materials and methods
Outpatients with stage 0 of ChD (positive serology, with normal electrocardiogram, holter and chest teleradiography) were included prospectively. They were divided in three groups according to the dosage of HS-TnT and NT-proBNP. Group 1: patients with both markers within normal values; group 2: patients with elevation of one of the markers (HS-TnT&gt;13 ng/L OR NT-proBNP&gt;125 pg/ml) and group 3: patients with elevation of both markers (HS-TnT&gt;13 ng/L AND NT-proBNP&gt;125 pg/ml). All of them underwent Doppler echocardiography with tissue Doppler.

Results
Two hundred and sixty-one patients were included, with 47±9 years old of age, 44% woman, 86.6% (n=226) in group 1, 9.6% (n=25) in group 2 and 3.8% (n=10) in group 3. Table 1 shows the main results.

Conclusions
Elevation of both markers was found in almost 4% of patients. This elevation was associated with a higher E/e' ratio, E/A ratio, Letf Atrial Area and a lower S'-wave lateral.

Funding Acknowledgement
Type of funding source: None
Hydroxychloroquine for colchicine-resistant glucocorticoid-dependent idiopathic recurrent pericarditis: an observational prospective study
Authors: Lazaros G , Antonopoulos A , Azzu A , Antonatou A , Skendros P , Ritis K , Hadziyiannis E , Lazarou E , Leontsinis I , Simantiris S , Vlachopoulos C , Tousoulis D , Vassilopoulos D 
Published: November 2020

Abstract

Background
Glucocorticoid (GC)-dependent, colchicine-resistant idiopathic recurrent pericarditis (IRP) remains a clinical challenge. We assessed for the first time the efficacy and safety of hydroxychloroquine (HCQ) in IRP.

Methods
This is a single center, post hoc analysis of prospectively collected data of 15 patients with refractory to standard therapy (colchicine plus either GC or anakinra) IRP (≥3 recurrences, disease duration ≥12 months and inability to wean off treatment) treated with HCQ (400 mg/day). These patients were matched 1:1 for age, sex, and treatment type to IRP patients receiving standard-of-care treatment (control group, n=15). Pericarditis recurrence, the time and C-reactive protein (CRP) levels at 1st flare, the % of patients able to achieve a ≥50% reduction of baseline GC dose and the % reduction of GC dose were compared between groups.

Results
Almost all patients (n=29) but one in the HCQ group (14/15) relapsed during follow-up. However, HCQ treatment was associated with an increased median time of flare-free survival (increase by 4 weeks compared to controls) and reduced hazard ratio for flare in survival analysis (HR=0.36, 95% CI 0.16–0.77, p=0.009). HCQ was also associated with a higher proportion of patients obtaining a ≥50% dose reduction of GCs (33.3% vs. 0% in the control group, p=0.037) and reduced GC dose (HCQ: −43.5% vs. control: −4.5%, p&lt;0.001). There were no signficant differences in CRP levels at flare between groups (p=0.615).

Conclusions
In this prospective study, HCQ use was associated with a GC-sparing effect and an increased flare-free survival period in patients with colchicine resistant GC-dependent IRP.

Funding Acknowledgement
Type of funding source: None
Long-term natural history of transient constrictive pericarditis
Authors: Ramchand J , Chahine J , Alnajjar H , Chetrit M , Cremer P , Johnston D , Kwon D , Jellis C , Klein A 
Published: November 2020

Abstract

Background
In recent years, there has been increasing recognition of a potentially-reversible, transient/ subacute form of constrictive pericarditis (CP). To date, studies have been small with lack of long-term longitudinal follow-up.

Purpose
We aimed to elucidate the causes and natural history of subacute CP.

Methods
Patients were included if (1) they had a diagnosis of CP, (2) had cardiac magnetic resonance (CMR) within 12 months of symptom onset with evidence of pericardial delayed enhancement/ inflammation (Figure) (3) received anti-inflammatory medications.

Results
A total of 78 individuals were included, comprising 61 men (78%) with a mean age of 59±14 years. Causes of subacute CP included idiopathic/ viral pericarditis (58%), post-pericardiotomy (29%), autoimmune (6%), radiation therapy (3%) and others (4%). After median follow-up of 4.4 years, 31 (40%) required pericardiectomy. There were no deaths.
Patients who underwent pericardiectomy had longer duration of symptoms at presentation [6 (4–9) vs. 3 (2–5) months, P&lt;0.01], were more likely to be on diuretic therapy (87 vs. 45%, P&lt;0.001), had lower ultra-sensitive C-reactive protein [4.4 (2.6–13.1) vs. 11.95 (1.8–61.55) mg/dl, P&lt;0.001] and lower erythrocyte sedimentation rate [5 (2–10) vs. 25 (6–43 mm/hr), P=0.031] compared to those who were managed medically. There were no other significant differences in clinical characteristics or baseline anti-inflammatory therapy. The presence of elevated inflammatory markers (HR: 0.18; 95% CI: 0.06–0.58, P&lt;0.01) was an independent predictor of freedom from pericardiectomy after adjustment for relevant clinical and imaging parameters.

Conclusions
We present the original observations of the largest cohort of patients with transient CP to date and demonstrate that increased inflammatory markers were independently associated with long-term freedom from pericardiectomy. Our results suggest that a trial of anti-inflammatory therapy in the setting of elevated inflammatory markers may be appropriate prior to referral for surgery given the possible reversibility.
Pericardial delayed enhancement

Funding Acknowledgement
Type of funding source: None
Pretriscuspid shunt and Eisenmenger syndrome: a deadly combination
Authors: Playan Escribano J , Segura De La Cal T , Dos Subira L , Lazaro Salvador M , Barbera Mir J.A , Garrido-Lestache E , Otero Gonzalez I , Martinez-Quintana E , Lopez Ramon M , Martinez Menaca A , Molina Ferragut L , Suberviola V , Lopez Reyes R , Barrios Garrido-Lestache E , Escribano Subias P 
Published: November 2020

Abstract

Introduction
Pulmonary arterial hypertension (PAH) is a common comorbidity in congenital heart disease (CHD) and significantly affects prognosis. Our aim was to investigate how the location of the shunt influences the outcome of these patients.

Methods
The REHAP registry is a Spanish multicentre voluntary registry of patients over 14 years of age, which includes patients with congenital heart disease and PAH, starting in 2007. Baseline characteristics, functional class, right catheterization data, treatment and survival were compared. We performed a cox regression model for assessing the impact of the type of shunt on prognosis, after looking for confusing and effect modifying variables.

Results
664 patients were analyzed, their characteristics are detailed in the table. Mean follow up time was 10 years. We performed a survival analysis adjusted for the confounding variables: age (Hazard ratio (HR) 1.02 p&lt;0.001), functional class (HR 2.45 p 0.001) and clinical group. The clinical group was also an effect-modifying variable, which means there is no unique effect (HR) of the type of shunt, instead it depends on the clinical group. We did a multiple regression analysis, adjusting for the confounding variables, to calculate the HR for each clinical group: in patients with Eisenmenger syndrome, the HR is 0.27 (p&lt;0.001) for simple posttricuspid shunt and HR 0.38 (p&lt;0.001) for complex posttricuspid shunt (reference group: pretricuspid shunt). In the others clinical groups, the type of shunt did not reach statistical significance.

Conclusion
The type of shunt significantly affects prognosis in Eisenmenger patients, with a much worse outcome for those with pretricuspid shunts. Functional class and clinical group are also closely related to outcome.

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): MSD, GSK
Transcatheter intervention of coarctation of the aorta (CoA): a multinational population-based registry – effect on hypertension
Authors: Eriksson P , Pihkala J , Jensen A.S , Dohlen G , Liuba P , Wahlander H , Sjoberg G , Hlebowicz J , Furenas E , Dellborg M , Settergren M , Kudsk-Nielsen J.E , Sondergaard L , Sinisalo J , Larsen S.H 
Published: November 2020

Abstract

Background
CoA is associated with hypertension caused by reduced wind kessel function in the aortic arch, general hypoplasia of the arch and/or essential hypertension. In patients with a native or recurrent/rest CoA, a gradient &gt;20 mmHg by non-invasive meassurement if associated with hypertension is an ESCguideline indication for intervention. We studied the persistence and presence of hypertension after transcatheter intervention of a CoA

Methods
All consecutive patients undergoing catheter interventions for CoA from 1st of January 2000 to 31st of December 2016 were identified by each of the particpating nine centers. The nine centers perform all catheter interventions for CoA for a complete population coverage of 25 millions inhabitants. A common protocoll was filled out from medical records. Hypertension was defined as a pre-intervention blood pressure above 140/80 or pharmacological treatment of hypertension. Exclusion criteria were weight less than 20 kg at the time of intervention or Norwood surgery

Results
590 interventions were performed on 520 patients: two interventions n=76, three: n=11, four n=2 and one patient underwent five interventions. Before intervention, 437 (74%) of the patients were hypertensive and 285 were on pharmacologocal treatment; 134 (48%) were treated with one drug, 79 patients (28%) with two drugs, 41 patients (15%) with three drugs and 14 (5%) with four drugs. After the intervention during follow up hypertension was present in 294 patients (50%, p&lt;0.001 vs pre) of whom 270 (46%) were on pharmacological treatment; with one drug, n=128 (48%), two drugs n=93 (34%), three drugs n=34 (13%) or 4 drugs n=7 (3%).

Conclusions
Catheter intervention of CoA reduced the presence of hypertension significantly from 74% down to 50% but many patients will remain hypertensive and in need for treatment. Life time follow up also after transcatheter CoA intervention seems warranted.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): ALF-LUA, Heart and Lung Foundation
The benefit of atrial septal defect closure in the elderly patients
Authors: Prochownik P.J , Przewlocki T , Sobien B , Gancarczyk U , Olszowska M , Podolec P , Komar M 
Published: November 2020

Abstract

Objective
Closure of the atrial septal defect in the elderly patients is controversial. The aim of the study was to evaluate the outcomes of transcatheter closure of secundum atrial septal defect (ASD) in elderly patients.

Methods
From a total of 650 pts with ASD who underwent transcatheter closure 120 pts over 60 years (70 F, 50 M) with a mean age of 66.7±18.1 (60–78) were analyzed. All patients had an isolated secundum ASD with a mean Qp:Qs: 2.79±1.8 (1.5–3.9). A symptom-limited treadmill exercise tests with respiratory gas exchange analysis and transthoracic color Doppler echocardiographic study as well as Quality of life (QoL) measured using the SF36 questionnaire (SF36q) were repeated in all pts before procedure and after 12 months of follow-up.

Results
The device was successfully implanted in all pts (procedure time 30.1±9.9 (10–59) minutes, fluoroscopy time 10.1±7.2 (6–40) minutes). There were no major complications. The defect echo diameter was 19.5±15.4 (12 - 34) mm. The mean balloon stretched diameter of ASD was 22.0±7.8 (14 - 36) mm. The diameter of the implanted devices ranged 16 - 38 mm. After 12 months of ASD closure, all the pts showed a significant improvement of exercise capacity parameters. Seven QoL parameters (except mental health) improved at 12 months follow up compared to their baseline data. The mean SF36q scale increased significantly in 96 (80.2%) pts of mean 41.6±26.1 (4–71). The right ventricular dimension decreased in 101 pts (84.2%) (Table 1).

Conclusions
Closure of ASD in elderly patients caused a significant clinical and hemodynamic improvement after percutaneous treatment, which is maintained to long-term follow-up what justified this procedure in old age.

Funding Acknowledgement
Type of funding source: None
Mechanical-electrical interaction of the right ventricle in patients with repaired tetralogy of fallot: the next step towards resynchronization in congenital heart disease
Authors: Rodriguez Garcia J , Pijuan Domenech A , Perez Rodon J , Benito Villabriga B , Francisco Pascual J , Santos Ortega A , Dos Subira L , Subirana Domenech M , Miranda Barrio B , Gordon Ramirez B , Ferreira Gonzalez I , Rivas Gandara N 
Published: November 2020

Abstract

Introduction
Patients with repaired tetralogy of Fallot (rTF) and severe pulmonary regurgitation frequently progress to dilation and dysfunction of the right ventricle (RV). It has been documented in the literature that there is a correlation between the duration of the QRS in the surface electrocardiogram and the hemodynamic parameters of the RV of these patients, suggesting the presence of a mechanical-electrical interaction.

Purpose
To determine if there is an association between the contraction delay in certain areas of the RV measured in M-mode echocardiography and the delay in electrical activation measured in the electroanatomic map (EAM) of RV in patients with rTF.

Methods
Unicentric and observational study of all patients with rTF undergoing EAM, echocardiography with study of RV asynchrony and cardiac magnetic resonance imaging (MRI). Activation delay in the antero-basal area and in the RV outflow tract (RVOT) in the EAM were both analysed (Figure 1A). The shortening delay in the same areas in M-mode echocardiography was also evaluated (Figure 1B, C). MRI data regarding volume and ejection fraction was also collected.

Results
64 patients were included (36.7±10.6 years, 65% men). The mean total activation time of the RV (RV-TAT) was 127.3±42.4 ms. Activation mapping showed a recurrent pattern with beginning in the interventricular septum and ending in RV antero-basal region and/or RVOT. A linear positive correlation was observed between RV-TAT and the activation delay in both regions analysed (ρ=0.60 and ρ=0.52, respectively; p&lt;0.001) and also between the electrical and mechanical delay in the anterior wall (ρ=0.41; p=0.001). On the other hand, it was observed a negative correlation between RV ejection fraction (RVEF), measured on MRI, and the RV-TAT (ρ=−0.41, p=0.002) and also between RVEF and the activation delay in the RV antero-basal region and in the RVOT (ρ=−0.32, p=0.016 and ρ=−0.36, p=0.007, respectively).

Conclusions
There is a mechanical-electrical interaction in the RV of patients with rTF, with a negative correlation between the activation delay and RVEF and between mechanical and electrical activation delay in specific anatomical regions (regional mechanical-electrical interaction). These results may guide future studies on resynchronization in this heart disease.
Figure 1. EAM and echocardiographic measures

Funding Acknowledgement
Type of funding source: None
Contribution of peptidyl prolyl isomerase (Pin1) to development of pulmonary hypertension via pulmonary vascular endothelial cell dysfunction
Authors: Sakai S , Maruyama H , Ieda M 
Published: November 2020

Abstract

Background
Endothelial dysfunction is thought to be a major contributor to overall pathogenesis of vasculopathy seen in pulmonary hypertension (PH), which is manifested by the impaired release of nitric oxide (NO) generated through endothelial nitric oxide synthase (eNOS) in endothelial cells. Activation of human eNOS is regulated by phosphorylation at multiple sites including Thr33 and Ser114, which residues are followed by Pro. The peptidyl isomerase Pin1 specifically isomerizes the phospho-protein having Ser/Thr-Pro bond and regulates their activity. Pin1 is involved in proliferation, cell cycle, and apoptosis in cancer, by isomerizing some functional molecules such as JNK, JUN, cyclin D, BAX, etc. However, it is controversial whether direct interaction of Pin1 with eNOS and how eNOS activity is altered by Pin1, especially in PH.

Purpose
We aimed to clarify whether Pin1 contributes to the PH development using Pin1 knockout mice and Pin1 affects the expression of phosphorylated eNOS (p-eNOS) molecule and pulmonary arterial endothelial cell (PAEC) apoptosis.

Methods and results
Wild (WT) and Pin1-deficient mice (KO) were exposed to hypoxia (10% O2) or normoxia for 3 weeks to generate hypoxia-induced PH. Hypoxia-inducible factor (HIF1α) expression in lungs was significantly enhanced in WT-hypoxia (WH, n=6) and KO-hypoxia (KH, n=6), suggesting that hypoxic response was certainly occurred in these mice. Pulmonary arterial pressure did not elevate in KH compared with KO-normoxia (KN, n=6) and WT-normoxia (WN, n=6), it was significantly increased only in WH (P&lt;0.01), indicating that KO did not develop PH by hypoxia. The gain of RV weight was parallel to the increase of pulmonary arterial pressure. Western blot showed that p-eNOS expression in lungs was significantly decreased in WH compared to WN, however, the expression was not different between KH and KN. It suggests that Pin1 plays a regulatory role in p-eNOS expression in hypoxic response. In cultured PAECs, the expression of p-eNOS and eNOS was markedly increased by siRNA-mediated Pin1 knockdown. Immunoprecipitation study showed the possibility of Pin1 binding to p-eNOS molecule. Apoptosis evaluated by caspase-3/7 activity by fluorescent assay and cleaved caspase-3 expression by Western blot was significantly increased by Pin1 overexpression in PAECs; however, it was significantly decreased by Pin1 knockdown. Moreover, the exaggeration of apoptosis induced by doxorubicin was markedly increased by Pin1 overexpression compared with control in PAECs; however, it was clearly suppressed by Pin1 knockdown.

Conclusion
This study suggests that endogenous Pin1 contributes to the development of PH partly via the dysfunction of PAECs, that is, by the interference with p-eNOS expression and by the increase of apoptosis inducibility to external stimuli.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI
Prognostic value of pulmonary artery diameter in patients with pulmonary arterial hypertension
Authors: Zuffa E , Dardi F , Saia F , Niro F , Palazzini M , Russo V , Taglieri N , Lovato L , De Lorenzis A , Pasca F , Guarino D , Magnani I , Marrozzini C , Manes A , Galie N 
Published: November 2020

Abstract

Background
Pulmonary artery (PA) dilation is common in pulmonary arterial hypertension (PAH) and may cause left main coronary artery (LMCA) compression. This complication have been sistematically evaluated in patients with angina but no evidence is available for patients asymptomatic for angina.

Purpose
To evaluate the prognostic value of PA diameter and the prevalence of LMCA compression in PAH patients with and without angina.

Methods
All patients with PAH and a baseline angio-CT scan were included. The last angio-CT scan performed was considered for PA diameter increase velocity calculation. Patients with angina or radiological signs of suspected LMCA compression underwent a coronary (cor)-CT scan. Patients with a not negative cor-CT underwent invasive coronary angiography. If clinically indicated invasive coronary angiography was performed without a preliminary cor-CT. To evaluate the predictivity for compression at coronary angiography the PA diameter at cor-CT or at the nearest angio-CT scan was considered.

Results
958 patients were included. PA diameter at baseline is higher in patients with congenital heart disease (CHD) and is not predictive of death. The velocity of PA diameter increase is lower in patients with connective tissue disease and is a risk factor for death in both overall population and different etiological subgroups except CHD and pulmonary veno-occlusive disease. 180 patients had angina and 50 had LMCA compression. 120 patients without angina underwent cor-CT and/or coronary angiography and 15 patients had LMCA compression. The best PA diameter cut-offs predicting LMCA compression in symptomatic/asymptomatic patients were, respectively, 40/42 mm (sensitivity and specificity, respectively, 80 and 72%/87 and 77%).

Conclusion
28% of patients with angina and 13% of patients without angina had LMCA compression. We found a similar PA diameter predicting LMCA compression in patients with or without angina. PA diameter, instead, was not predictive of prognosis (maybe because most deaths were related to heart failure and also because patients with LMCA compression were treated with stenting, possibly preventing sudden cardiac death). Eventually, PA diameter velocity increase is associated with prognosis but this may only reflect a severe disease refractory to medical therapy.

Funding Acknowledgement
Type of funding source: None