bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late cardiac interventions in adults with congenital ventricular septal defects
Authors: Berglund E , Wikner A , Larsson L , Rinnstrom D , Christersson C , Dellborg M , Nielsen N.E , Sorensson P , Thilen U , Johansson B 
Published: November 2020

Abstract

Introduction
Ventricular septal defect (VSD) is one of the most common congenital heart lesions. Shunts with hemodynamic significance are usually closed early in life whereas small shunts are left without intervention. The need for late cardiac interventions in these populations is essentially unknown. The aim was to study the late cardiac interventions in adults with VSD.

Methods
The national register on congenital heart disease was searched for patients with VSD with or without associated simple cardiac defects but without complex lesions. For these patients, the last 10 years (over the age of 18) in the national patient register was searched for cardiac interventions.

Results
774 patients (mean age 39.0±14.7 years, women =50.6%), 224 (28.9%) with previous closure of VSD, were identified. The total observed time was 6920 patient years. There were 43 interventions in 41 patients (5.3%) of whom 12 had a previous closure of VSD. Twelve patients had isolated closure of VSD, 18 closure of VSD together with other cardiac surgery (one of these had repeated cardiac surgery) and 8 had only other cardiac surgery. In 4 cases, a pacemaker was implanted, of whom one together with cardiac surgery.

Conclusion
The need for cardiac interventions is relatively common in adults with a VSD, also in those without previous closure of their shunt. Our data suggests that most patients with a VSD, closed or not, should be offered periodic follow-up as approximately one out of 20 patients may encounter a complication within 10 years.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): The Swedish Heart-Lung Foundation
Differences in resting and ambulatory blood pressure data in coarctation of aorta vs idiopathic hypertension
Authors: Egbe A , Banala K , Vojjini R 
Published: November 2020

Abstract

Background
Ambulatory systolic blood pressure (SBP) is more sensitive than resting-SBP in detecting hypertension in patients with coarctation of aorta (COA) and patients with idiopathic hypertension. A recent study showed that compared to patients with idiopathic hypertension with similar resting-SBP, COA patients had lower arterial compliance, and hence experienced higher SBP per unit increase in stroke volume during exercise. The purpose of this study was to compare resting vs ambulatory-SBP relationship between COA patients and non-COA patients (with and without hypertension), and to determine if ambulatory-SBP had better correlation with left ventricular (LV) remodeling as compared to resting-SBP.

Methods
Case-control study of 106 COA patients and 106 patients with idiopathic hypertension (ControlHTN+ group) matched by age, sex, body mass index and resting-SBP. Resting/ambulatory BP relationship in COA patients and patients with idiopathic hypertension were also compared to that of 19 patients without hypertension (ControlHTN- group). LV remodeling was assessed using LV mass index, e', and E/e'.

Results
Although the COA and ControlHTN+ groups had similar resting-SBP (by design), the COA group had a higher ambulatory-SBP and a higher prevalence of masked hypertension (30% vs 12%, p&lt;0.001). There was a stronger correlation between ambulatory-SBP (as compared to resting-SBP) and LVMI (r=0.36 vs r=0.55, p=0.042), and average E/e' (r=0.42 vs r=0.59, p=0.046), in the COA group but not the ControlHTN+ group. There was no difference in the resting/ambulatory BP relationship between ControlHTN+ and ControlHTN- groups, but both groups were significantly different from the COA group.

Conclusion
These results highlight the unique differences in disease pathophysiology between hypertension in patients with COA and those with idiopathic hypertension, and also suggest that ambulatory-SBP may be a more accurate measure of LV pressure overload in COA patients. This underscores the potential limitations of relying on resting-SBP alone for clinical decision making.

Funding Acknowledgement
Type of funding source: None
Long-term outcome of adult patients with partial anomalous pulmonary venous connection treated surgically and conservatively: data from the SACHER registry and a French center
Authors: Touray M , Bouchardy J , Ladouceur M , Schwerzmann M , Greutmann M , Tobler D , Harald R , Engel R , Pruvot E , Blanche C , Sekarski N , Rutz T 
Published: November 2020

Abstract

Introduction
Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital heart disease, which is characterized by one or some but not all pulmonary veins anomalously connected to the right atrium or a systemic vein. PAPVC is either an isolated shunt lesion or associated with an atrial septal defect (ASD). The only curative treatment is surgery, however the indication for surgery can be challenging. This study compares the outcome of patients treated surgically with those clinically monitored.

Method
Clinical, surgical, imaging and invasive data were retrospectively reviewed from 7 centers from the Swiss Adult Congenital HEart Registry (SACHER) and a French center.

Results
A total of 168 patients with partial anomalous pulmonary venous connection were identified. The majority (77%) of patients underwent surgery and the remaining (23%) were treated conservatively with clinical monitoring. The operated group (OG) had a significantly higher proportion of associated ASD (N=106, 82%) (p&lt;0.001) and a higher prevalence of anomalous pulmonary veins leading to a mean Qp:Qs at 2.5±1.2 before surgery.
Latest follow-up was 12 years after surgery. Mean age was 40±17 years. Patients in the non-operated group (NOG) were significantly more dyspneic than the OG (p=0.002). However, the need for medical treatment did not differ between groups: 58% of the NOG and 48% in the OG (p=0.203).
Right ventricular (RV) ejection fraction did not differ between groups despite a significantly larger RV end-diastolic volume and a higher Qp:Qs on cardiac magnetic resonance (CMR) in the NOG (table).
On echocardiography, the NOG showed a significantly better right ventricular longitudinal function and a higher systolic pulmonary artery pressure than the OG (table). The prevalence of significant valvulopathies did not differ between groups (table).
Both groups had normal exercise capacity and with no differences between groups (table).
Eighteen (14%) OG patients required a re-intervention either for residual shunt and/or stenosis of the pulmonary veins, superior and inferior vena cava.

Conclusion
PAPVC patients after surgical correction, show a favorable outcome in terms of imaging parameters and exercise capacity, however, a significant number presents with symptoms. PAPVC patients treated conservatively with small left to right shunting, have similar outcome justifying a conservative approach.

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted grant from Actelion, Switzerland
The association between atrial fibrillation and pulmonary embolism
Authors: Svennberg E , Friberg L 
Published: November 2020

Abstract

Background and objectives
Previous studies have suggested that atrial fibrillation is a risk factor for pulmonary embolism. Oral anticoagulant therapy is the mainstay of treatment for atrial fibrillation and pulmonary embolism. We wanted to investigate if atrial fibrillation remained associated with the development of pulmonary embolism if oral anticoagulant treatment was accounted for.

Method
In this retrospective registry study a random sample of 20% of the adult Swedish population comprising approximately 1.5 million individuals were included during 2010–2017 in a cohort analysis. The endpoint was acute pulmonary embolism. In the cohort study, patients were analysed according to oral anticoagulant treatment and presence of atrial fibrillation at baseline.

Results
The group with atrial fibrillation was &gt;25 years older than the group without and had almost three times higher incidence of pulmonary embolism (2.91 vs 1.09 /1000 year at risk, p&lt;0.001). Individuals with atrial fibrillation on oral anticoagulant therapy had a lower risk of pulmonary embolism in multi-variable analysis (HR 0.59, CI 0.45–0.77). In the unadjusted analysis participants with atrial fibrillation without oral anticoagulant therapy showed an increased risk of pulmonary embolism (HR 3.33, CI 3.05–3.63). However, after multi-variable adjustment this association disappeared (HR 0.98, CI 0.89–1.07). In the entire atrial fibrillation cohort, no association was seen with the development of pulmonary embolism after multi-variable adjustment (HR 0.92, CI 0.84–1.01). The higher rate of pulmonary embolism among patients with atrial fibrillation can be fully explained by differences in age and co-morbidity.

Conclusion
Atrial fibrillation does not appear to be a clinically relevant risk factor for pulmonary embolism. Oral anticoagulant therapy protects against the development of pulmonary embolism in patients with atrial fibrillation.
Associations with pulmonary embolism

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): The main author has received funding from Stockholm County Council (Clinical postdoctorial appointment)
Endothelial cell premature senescence exacerbates pulmonary arterial hypertension through contact-mediated interaction with vascular smooth muscle cells
Authors: Ramadhiani R , Ikeda K , Miyagawa K , Ryanto G.R.T , Tamada N , Suzuki Y , Hirata K , Emoto N 
Published: November 2020

Abstract

Introduction
Pulmonary arterial hypertension (PAH) is characterized by remodelling and stenosis of the pulmonary arteries, ultimately leading to the right heart failure and death. Endothelial cell (EC) dysfunction is thought to play a central role in the pathogenesis of PAH by mediating the structural changes in pulmonary vasculatures. Various stresses promote premature senescence in EC, which may modify vascular disorders; however, the role of EC senescence in the development of PAH remains poorly understood.

Purpose
We aimed at investigating the potential role of EC premature senescence in the development of PAH.

Methods
We recently generated EC-specific progeroid mice in which ECs specifically undergo premature senescence by overexpressing the dominant-negative form of telomere repeat-binding factor 2 (published in Nat Commun 2020). These EC-specific progeroid mice were exposed to hypoxia (10% O2 for three weeks) to induce pulmonary hypertension. Also, we prepared premature senescent ECs using human pulmonary artery ECs (hPAECs) and explored their interaction with human pulmonary artery smooth muscle cells (hPASMCs) in two different conditions; direct and indirect interactions. For indirect coculture, hPASMCs were seeded onto the culture insert, while hPAECs were plated on the culture plate, and they were cocultured in the same well and medium so that secreted factors derived from senescent ECs could access to SMCs through the insert pores. For direct coculture, hPAECs were seeded onto the bottom side of the insert, while hPASMCs were cultured on the top side of the same insert, so that cell-to-cell contact could be made through the pores.

Results
After chronic hypoxia exposure, the EC-specific progeroid mice showed higher right ventricular systolic pressure and increased right ventricular mass as compared to wild-type (WT) mice, indicating exacerbated pulmonary hypertension. Histological analysis of the lung revealed a significantly enhanced muscularization in the small pulmonary arteries in EC-specific progeroid mice compared to WT mice. Mechanistically, we identified that direct coculture with premature senescent hPAECs enhanced proliferation and migration in hPASMCs, while no such effects were detected in indirect coculture condition.

Conclusion
To our knowledge, this is the first report that reveals a crucial role of EC premature senescence in the development of PAH. Our in vitro studies suggest that contact-mediated interaction between premature senescent ECs and SMCs is critically involved in its underlying mechanism. Therefore, EC premature senescence is a novel attractive pharmacotherapeutic target for the treatment of PAH.

Funding Acknowledgement
Type of funding source: None
Renal function improves mortality prediction in acute pulmonary embolism: results of a multicentre cohort study with external validation in the RIETE registry
Authors: Chopard R , Jimenez D , Serzian G , Ecarnot F , Falvo N , Kalbacher E , Bonnet B , Capellier G , Schiele F , Bertoletti L , Monreal M , Meneveau N 
Published: November 2020

Abstract

Background
Renal dysfunction may influence outcomes after pulmonary embolism (PE). We determined the incremental value of adding renal function impairment (estimated glomerular filtration rate, eGFR &lt;60 ml/min/1.73m2) on top of the 2019 ESC prognostic model, for the prediction of 30-day all-cause mortality in acute PE patients from a prospective, multicenter cohort.

Methods and results
We identified which of three eGFR formulae predicted death most accurately. Changes in global model fit, discrimination, calibration and net reclassification index (NRI) were evaluated with addition of eGFR. We prospectively included consecutive adult patients with acute PE diagnosed as per ESC guidelines. Among 1,943 patients, (mean age 67.3±17.1, 50.4% women), 107 (5.5% (95% CI 4.5–6.5%)) died during 30-day follow-up. The eGFRMDRD4 formula was the most accurate for prediction of death. The observed mortality rate was higher for intermediate-low risk (OR 1.8, 95% CI 1.1–3.4) and high-risk PE (OR 10.3, 95% CI 3.6–17.3), and 30-day bleeding was significantly higher (OR 2.1, 95% CI 1.3–3.5) in patients with vs without eGFRMDRD4 &lt;60 ml/min/1.73m2. The addition of eGFRMDRD4 information improved model fit, discriminatory capacity, and calibration of the ESC models. NRI was significantly improved (p&lt;0.001), with 18% reclassification of predicted mortality, specifically in intermediate and high-risk PE. External validation using data from the RIETE registry confirmed our findings (Table).

Conclusion
Addition of eGFRMDRD4-derived renal dysfunction on top of the ESC prognostic algorithm yields significant reclassification of risk of death in intermediate and high-risk PE. Impact on therapy remains to be determined.

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): BMS-Pfizer Alliance, Bayer Healthcare
Lowering of mean pulmonary arterial pressure is a prognostic marker in pulmonary hypertension patients treated with subcutaneous treprostinil
Authors: Sadushi-Kolici R , Shafran I , Skoro-Sajer N , Campean I.-A , Lang I.M 
Published: November 2020

Abstract

Background
Treprostinil (TRE), a prostacyclin analog, is effective for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that change of hemodynamics is of prognostic value. In our prospective registry we evaluated effects of first-line subcutaneous (sc) TRE in patients with severe pulmonary hypertension (PH) and analyzed the prognostic value of hemodynamic changes from baseline on long-term follow-up.

Methods
Data was collected from patients with pre-capillary PH in WHO functional class III or IV, mean right atrial pressure of ≥10mmHg, and/or cardiac index ≤2.2 liters/min/m2. Patients received first-line scTRE. Dose adjustments were performed individually according to clinical symptoms and side effects.

Results
Between 1999 and 2018 138 patients were treated. Of these, 18 (13%) patients underwent double lung transplantation, and 59 (42.8%) died of any cause. Overall survival rates at 1, 5, 10, and 15 years were 91%, 57%, 31% and 29%. The strongest predictor of outcome was change in mPAP after one year of scTRE. Change in mPAP (−18.4±7.9 mmHg) was associated with the best subsequent survival of 12.7±1.5 years.

Conclusion
The data suggest that patients benefit from aggressive lowering of mPAP in the first year of treatment.

Funding Acknowledgement
Type of funding source: None
Usefulness of peripheral-pressure-directed balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension
Authors: Nagamatsu Y , Inami T , Nakata C , Takeuchi K , Kikuchi H , Goda A , Soejima K , Satoh T 
Published: November 2020

Abstract

Background
Balloon pulmonary angioplasty (BPA) in expert center may be considered in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are technically non-operable for pulmonary endarterectomy. BPA based on objective quantitative methods has not been established. The endpoint at BPA sessions has not been clarified yet.

Objectives
The purpose of this study was to investigate the usefulness of BPA according to peripheral pressure measured by pressure wire or catheter.

Methods
This study included consecutive 143 CTEPH who underwent cardiopulmonary exercise test with right heart catheterization after BPA. All patients were divided into 2 groups such as angio-guided (n=47) group or pressure-guidedgroup (n=96). In pressure-guided group, the pulmonary arterial pressure (PAP) proximal and distal to the target lesion and the ratio of the 2 pressures were measured by the pressure wire or catheter. the endpoint was determined to when the pressure ratio of distal to proximal pressures was &gt;0.7 to 0.8 finally. The dilation was stopped when the distal mean PAP after each dilation reached 35 mm Hg and when the baseline mean PAP was &gt;35 mm Hg. Changes of hemodynamic parameters such as PAP and pulmonary vascular resistance (PVR) from baseline, and mean PAP and PVR at peak oxygen consumption, and pulmonary arterial pressure – cardiac output (PA-CO) slope were compared between two groups. All data except changes of hemodynamics from baseline were expressed by median [25th percentile-75th percentile]. Changes of hemodynamics from baseline were expressed by average [95% confidence interval]

Results
The median age and male were 66 [56–72] years old and 35. There were no significant differences in number of sessions and dilated vessels between two groups (Angio-guided group vs. Pressure-guided group: 4 [3–6] vs. 4 [3–5], P&gt;0.05; 19 [12–22] vs. 17 [13–22], P&gt;0.05). Changes of PAP and PVR from baseline in pressure-guided group was significantly higher than in angio-guided groups (Angio-guided group vs. Pressure-guided group; ΔPAP: −19 [−20 to −17] vs. −20 [−21 to −20], P&gt;0.05; ΔPVR: −6.0 [−6.3 to −5.7] vs. −6.6 [−6.8 to −6.3], P&lt;0.01). Mean PAP and PVR at peak oxygen consumption (VO2) and PA-CO slope in pressure-guided group were significantly lower than in angio-guided group (Angio-guided group vs. Pressure-guided group; PAP at VO2: 43 [36–50] vs. 39 [34–43], P&lt;0.05; PVR at VO2: 2.7 [1.9–4.5] vs. 2.2 [1.6–2.9], P&lt;0.01; PA-CO slope: 3.8 [2.1–5.2] vs. 2.9 [1.9–4.0], P&lt;0.05).

Conclusions
Peripheral-pressure-directed BPA can improve hemodynamics at rest and exercise more effectively.

Funding Acknowledgement
Type of funding source: None
Efficacy of interventional treatment for patients with chronic thromboembolic pulmonary hypertension with microvasculopathy
Authors: Onishi H , Taniguchi Y , Miwa K , Sumimoto K , Matsuoka Y , Izawa Y , Tsuboi Y , Otake H , Kobayashi S , Emoto N , Hirata K 
Published: November 2020

Abstract

Background
The existence of microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH) had been suggested. However, the impact of microvasculopathy for pathophysiology had been unknown. Recently dual-energy computed tomography (DECT) can produce a sensitive iodine distribution map in lung fields to quantify lung perfusion, which may indicate the existence of microvasculopathy according to poor subpleural perfusion.
This study aimed to examine the therapeutic efficacy of interventional treatment (pulmonary endarterectomy or/and balloon pulmonary angioplasty) in CTEPH with microvasculopathy.

Methods
We retrospectively reviewed poor subpleural perfusion (defined as subpleural spaces either not or minimally perfused in all segments) and hemodynamics of 70 consecutive CTEPH patients who underwent DECT before and after interventional therapy from January 2014 to January 2020.
Patients were divided according to poor subpleural perfusion in DECT images before treatment: a microvasculopathy group (MV group, n=37) or a non-microvasculopathy group (Non-MV group, n=33).
We evaluated clinical parameters as WHO functional class (WHO-Fc), 6-min walk distance, respiratory function test, cardiopulmonary exercise test, hemodynamic parameters, and DECT parameters at baseline and after the treatments. DECT parameters as quantitative evaluation of pulmonary blood volume (PBV) calculated as the average of entire lung iodine density.

Results
After interventional treatments, WHO-Fc improved in 33 patients in MV group, and 27 patients in Non-MV group (p=0.50).
In MV group, baseline mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and VE/VCO2 slope were higher (38.3±9.3 vs. 33.2±10.8 mmHg p=0.04, 818±394 vs. 539±289 dyne*sec/cm5 p&lt;0.01 and 43.7±11.3 vs. 35.2±6.9 p&lt;0.01, respectively) and PBV were lower (43.7±11.3 vs. 35.2±6.9 Hounsfield Unit p&lt;0.01) After the treatments, mPAP, PVR, VE/VCO2 slope and PBV showed almost equivalent between the groups (19.5±4.1 vs. 20.6±5.1 mmHg p=0.35, 272±111 vs 251±109 dyne*sec/cm5 p=0.42, 29.2±6.3 vs. 26.0±6.1 p=0.06 and 27.1±6.6 vs. 29.6±6.6 Hounsfield Unit p=0.13).
Diffusing capacity for carbon monoxide (%DLCO/VA) did not improve after treatment in both groups (MV group: 59.5±13.1 to 58.8±11.9% p=0.43. Non-MV group: 77.8±13.4% to 70.5±10.8% P&lt;0.01).

Conclusion
Hemodynamics, pulmonary perfusion, exercise capacities significantly improved after the treatments in spite of the existence or absence of microvasculopathy. However, DLCO which might indicate the existence of microvasculopathy did not improve. Interventional treatments could not improve microvasculopathy because of their limit of accessibilities.

Funding Acknowledgement
Type of funding source: None