bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of morbidity in patients with Ebstein anomaly: a two-country, population-based cohort study including 823 patients
Authors: Eckerstrom F , Dellborg M , Hjortdal V E , Eriksson P , Mandalenakis Z 
Published: October 2022

Abstract

Background
Burden of morbidity in patients with Ebstein anomaly (EA) is to a large extent undescribed.

Purpose
We conducted an extensive two-country register-based collaboration aiming to describe the burden of morbidity in patients with EA.

Methods
Patients born in the period 1930–2017 and diagnosed with EA were identified in Danish and Swedish nationwide medical registries and subsequently merged. Each EA patient was matched by birth year and gender with ten controls without congenital heart disease from the general population. Cox proportional hazard regression model was used to compute risk (hazard ratio (HR)) of morbidity (arrhythmia, heart failure, and stroke). Follow-up started at birth. Patients and controls became at risk at birth.

Results
We included 823 patients and 8,230 matched controls; median follow-up was 13.2 years (interquartile range: 3.5–20.9). In the total EA cohort, 44% (n=366) underwent cardiac surgery, predominantly EA-related surgery (81%) and other congenital cardiac surgery (15%). Approximately half of the cohort had an isolated EA (n=442) and 13% (n=108) had a concomitant atrial septal defect (ASD) only. Patients with non-operated isolated EA had a 9-fold increased risk of arrhythmia and a 5-fold increased risk of heart failure compared with the general population [HR for arrhythmia 9.4 (95% CI: 6.9–12.7) and HR forheart failure 5.2 (95% CI: 3.2–8.3)]. The risk of arrhythmia, heart failure, and stroke among patients with non-operated EA and concomitant ASD was 12.1 (95% CI: 3.0–48.8), 30.6 (95% CI: 3.2–295.2), and 8.2 (95% CI: 0.7–91.2), respectively. The risk of stroke in operated EA patients with concomitant ASD was 43.8 (95% CI: 17.5–109.7). Patients with operated isolated EA had a 25-fold increased risk of developing arrhythmia and 10-fold increased risk of heart failure compared with the general population [HR for arrhythmia 25.0 (95% CI: 17.7–35.3) and HR for heart failure 10.1 (95% CI: 6.0–16.9].

Conclusion
Patients with EA carries a substantial burden of arrhythmia, heart failure, and stroke compared with the general population irrespective of treatment pathway, necessitating meticulous follow-up in specialized adult congenital heart disease clinics to detect and possibly prevent or limit morbidity at an early stage.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Novo Nordic Foundation.
Candidacy for heart transplantation in adult congenital heart disease patients: a cohort study
Authors: D'Angelo E C , Angeli E , Ragni L , Gargiulo G G , Donti A , Potena L , Tonoli F , Bartolacelli Y , Bulgarelli A , Careddu L , Ciuca C , Zanoni R , Egidy Assenza G 
Published: October 2022

Abstract

Objective
The object of the present study is to evaluate factors precluding heart transplantation (HTx) in adult congenital heart disease patients (ACHD) with end-stage heart failure (HF) referred for HTx evaluation.

Methods
This retrospective cohort study enrolled consecutive ACHD patients considered for HTx in our institution between 2014 and 2020 and patients receiving HTx between 2001 and 2013. HTx refusal due to poor candidacy status for excess risk of mortality after transplantation, served as the main study outcome.

Results
Between 2014 and 2020, 46 ACHD patients were evaluated for HTx, 14 ACHD patients underwent HTx between 2001 and 2013. We compared clinical, anatomical and demographic data of 41 patients suitable for transplantation (including both listed/transplanted patients, not yet listed because too well and patients who chose to refuse transplantation) with 15 patients refused after screening (excluding 4 patients with ongoing screening). Risk factors for refusal were: multiple high risk features (odds ratio [OR]: 3.6; 95% confidence interval [CI]: 1.1 to 12.9; p 0.048); anatomical factors (OR: 14.5; 95% CI: 3.1 to 68.4; p 0.001), out-of-center ACHD/HTx program referral (OR: 5.3; 95% CI: 1.5 to 19.0; p 0.01). HTx refusal identifies a high risk ACHD patient subgroup (hazard ratio for overall mortality: 3.1; 95% CI: 1.1 to 8.3; p 0.02).

Conclusions
In our study risk factors for refusal from HTx are adverse anatomical features, multiple conventional HTx high risk factors and out-of-center referral. ACHD patients refused from HTx present shorter time to death. Efforts to increase HTx candidacy are strongly necessary for this growing population.

Funding Acknowledgement
Type of funding sources: None.
Long-term survival in patients with univentricular heart: a nationwide, register-based cohort study
Authors: Ozturk A G , Dellborg M , Giang K W , Dalen M , Sorensson P , Mandalenakis Z 
Published: October 2022

Abstract

Background
Univentricular heart (UVH) is a broad term that covers various cardiac structural abnormalities in which one ventricle is severely underdeveloped, or a ventricular septal wall did not form, leading to a functional single-ventricle physiology. Patients with UVH have a very limited life expectancy if not surgically treated. While the outcome in children with UVH have been extensively studied, data regarding the long-term outcomes in an unselected, nationwide cohort is still lacking.

Purpose
The aim of the present study was to determine long-term survival in patients with UVH compared to an age- and sex-matched control population without congenital heart disease in Sweden.

Methods
We linked data from the Swedish Patient and Cause of Death Register to identify patients with UVH that were born between 1970 and 2017. Each patient with UVH was matched with ten individuals without congenital heart disease for year of birth and sex. The mortality risk in patients with UVH compared with matched controls was analyzed using Cox proportional regression models and Kaplan-Meier survival analysis.

Results
Of a total of 5,075 patients with UVH and 50,620 matched controls, 1,992 (37.9%) and 485 (1.0%) died, respectively. The mean follow-up (standard deviation) was 15.7 (± 14.2) years. A total of 758 patients (14.9%) of the UVH population were diagnosed with hypoplastic left heart syndrome (HLHS). The mortality risk was 53.01 (95% CI, 48.0–58.6) times higher in UVH and 163.5 (95% CI, 124.3–215.2) times higher in HLHS compared to controls. According to birth period, highest mortality was found at the earliest UVH cohort (1970–1981) 59.8%, and decreased by later birth periods. The lowest mortality was in the latest birth period, 2006–2017 (16.3%).

Conclusions
In this nationwide, register-based cohort study, the overall risk of mortality was more than 50 times higher in patients with UVH compared to matched controls. However, an increased survival was observed over time and by later birth periods. Quadragenarians with UVH is still a rare group but are expected to increase during the next decades.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish heart lung foundation
Impact of left atrial size and strain on new atrial arrhythmias during a 5-year follow-up in adults with congenital heart disease
Authors: Nussbaumer C , Schwitz F , Elchinova E , Goulouti E , Wustmann K , Papa A , Schwerzmann M 
Published: October 2022

Abstract

Introduction
Atrial arrhythmias are a common and important cause of morbidity and mortality in adults with congenital heart disease (ACHD). In acquired heart disease, left atrial (LA) strain has been shown to predict supraventricular tachyarrhythmias (SVT). This study sought to investigate if LA strain is also a reliable predictor of SVT in the ACHD population.

Method
We retrospectively obtained baseline clinical and echocardiographic data, including LA function parameters and strain, in 206 ACHD patients. Only patients with sinus rhythm at baseline and 5-years follow-up were included (median age 29, IQR 22–41 years). 157 participants had a left heart defect (aortic stenosis or aortic coarctation, with or without correction) and 49 a right heart defect (Fallot physiology). Diagnosis of sustained SVT was determined from clinical reports during the follow-up period (standard 12-lead ECG, ECG Holter).

Results
During a median follow-up of 6.2 years, a new or recurrent sustained SVT occurred in 16 patients (7.8%). Patients baseline characteristics are depicted in Table 1. Patients who developed SVT were older, had larger LA dimensions and left ventricular mass, more likely diastolic dysfunction on echo, and a lower peak LA longitudinal strain (PALS). PALS was a good predictor of SVT risk in patients with left and right heart defects with an area under the receiver-operating-curve of 0.857. By Cox regression analysis, patient in the lowest quartile for PALS had a 16.7-fold higher hazard ratio of SVT (95% confidence interval, 4.7 to 59.0, p&lt;0.001) in comparison with the top three quartiles. Overall freedom from arrhythmia after 1, 3 and 5 years of follow-up was 98.1%, 96.1% and 94.2%, respectively. The freedom from SVT as a function of PALS quartiles is shown in Figure 1.

Conclusion
PALS provides predictive information about the occurrence of SVT in the ACHD population, regardless of the type of the lesion. Including the measurement of LA strain in the follow-up of these patients may permit to better identify patients at risk of future atrial arrhythmias.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Universitätsklinik für Kardiologie, Inselspital Bern
Clinical and cardiovascular magnetic resonance predictors of early and long-term clinical outcome in acute myocarditis
Authors: Bohbot Y , Garot J , Hovasse T , Unterseeh T , Di Lena C , Boukefoussa W , Tawa C , Renard C , Limouzineau I , Duhamel S , Garot P , Tribouilloy C , Sanguineti F 
Published: October 2022

Abstract

Background/Introduction
The natural history of acute myocarditis (AM) remains partially unknown and predictors of outcome are debated.

Purpose
We sought to assess the impact of various cardiac magnetic resonance (CMR) parameters on early and long-term prognosis in a population of patients with AM.

Methods
In a two-centre longitudinal study, we included consecutive patients with diagnosis of AM based on CMR and without haemodynamic compromise. The primary endpoint was the occurrence of an event in the acute phase (≤15 days). Secondary endpoints were the occurrence of major adverse cardiac events (MACE) and recurrence of AM during follow-up.

Results
Three hundred and eighty-eight patients were included (mean age 38.5 years, 77.3% male, mean ejection fraction [EF]:56%) of which 82% (317) presented with chest pain. CMR was performed 4±2 days after index presentation. Overall, 38 patients (9.8%) had an event at the acute phase, 41 (10.6%) presented at least one MACE during follow-up (median 7.5 years, 6.6–8.9) and 30 (7.7%) experienced a recurrence of AM. By multivariate analysis, the independent predictors of initial complications were absence of chest pain (OR [95% CI] = 0.35 [0.15–0.82]), presence of syncope/pre-syncope (OR [95% CI] = 3.56 [1.26–10.02]), lower EF (OR [95% CI] = 0.94 [0.91–0.98] per %), myocardial extent of late gadolinium enhancement (LGE) (OR [95% CI] = 1.05 [1.002–1.100] per %) and absence of edema (OR [95% CI] = 0.44 [0.19–0.97]). Only age (HR [95% CI] = 1.021 [1.001–1.041] per year) and an initial alteration of EF (HR [95% CI] = 0.94 [0.91–0.97] per %) were associated with MACE during follow-up. Factors independently associated with AM recurrence were myocarditis prior to the index episodes (HR [95% CI] = 5.74 [1.72–19.22]) and viral syndrome at the index episode (HR [95% CI] = 4.21 [1.91–9.28]).

Conclusion
In routine consecutive hemodynamically stable patients with diagnosis of AM based on CMR, absence of edema, reduced EF, and extent of LGE were associated with early adverse outcome. Only age and EF were associated with long-term events.

Funding Acknowledgement
Type of funding sources: None.
Outcome of device atrial septal defect closure in different age groups: a nationwide cohort study
Authors: Muroke V , Jalanko M , Pihkala J , Hartikainen J , Tahvanainen A , Airaksinen J , Ukkonen H , Kervinen K , Ylitalo K , Sinisalo J 
Published: October 2022

Abstract

Background
Catheter based ASD closure has been a mainstay therapy for secundum type ASD for over 20 years and up to 80–90% of defects are deemed eligible for catheter closure. We are starting to get long term results for the outcome of the procedure. Numerous studies have reported excellent prognosis and low complication rates in patients with TC closed defects. However, little is known about the disease burden in the long run after the closure.

Objectives
This nationwide cohort aimed to evaluate long-term outcome of transcatheter closed atrial septal defects (ASD) by evaluating 1) hospitalisations and disease burden, 2) complications and 3) echocardiographic changes.

Material and methods
We gathered every transcatheter ASD closure done in Finland during 1999–2019. Mean follow-up time was 6.8 years (SD 5.1). We used hospital discharge register to study the incidence of new onset atrial fibrillation, stoke and migraine after the closure. Closure complications and echocardiographic changes were gathered from the electronic health records.

Results
Overall transcatheter ASD closure was performed for 1000 patients (68.5% females) during the study period. ASD patients had increased risk for new-onset atrial fibrillation (RR 2.55, 95% CI: 1.94–3.36), migraine (RR 3.41, 95% CI: 2.40–4.84) and heart failure. Stroke risk was not increased during the follow-up (p=0.19). Hospitalisations were more common in the ASD group in the following 12 months after the closure (RR 2.52, 95% CI: 2.14–2.98). Adverse events occurred in 6.9% (n=69) of the patients, including 4 erosions and 10 device embolisations.
Right heart size was enlarged in 83.9% of the patients before the closure and in 24.4% after the closure. Rate of mild mitral regurgitation increased 21.2% vs. 27.6%, p=0.005) and rate of sever to moderate tricuspid regurgitation decreased (9.4% vs. 5.6%, p=0.009) during the follow-up.

Conclusion
Catheter based Atrial septal defect closure is a safe procedure with low complication rates. TC closed ASD patients had more new-onset atrial fibrillation, heart failure and migraine during the follow-up.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Emil Aaltonen Foundation, Tampere, Finland
Percutaneous interventions in Fontan circulation
Authors: Marschall A , Alvarez-Fuente M , Garrido-Lestache E , Tellez L , Sanchez I , Toledano M , Molina I , Rivero N , Garcia-Ormazabal I , Tamariz R , Del Cerro M J 
Published: October 2022

Abstract

Background
In light of increased survival of patients with Fontan circulation, percutaneous interventions in these patients have become growingly significant in the recent years. Percutaneous treatments in patients with univentricular physiology can optimize the short term hemodynamics in these patients. However, information on long term outcomes is scarce.

Purpose
To present the cumulative work experience in percutaneous interventions of a tertiary center in the past 12 years in patients that have undergone total cavopulmonary deviation (TCD) and to investigate long term outcomes.

Methods
In this retrospective study, all patients with TCD that underwent follow-up in our specialized department of congenital heart disease in the past 12 years, were eligible for chart-review. Cardiac catheterization was performed by experienced interventional cardiologists, specialized in structural interventions in congenital heart disease. All catheterizations were performed under general anesthesia and mechanical ventilation. All patients underwent Fontan pressure measurements and cardiac output estimation with Fick method.

Results
A total of 80 patients, with a mean follow-up time of 24 (±7.1) years, were included in the study. Details on baseline characteristics are depicted in Table 1. Fifty-two (65%) patients underwent percutaneous intervention during follow-up, and 33% (n=17) of these patients required multiple interventions. Angioplasty with stent implantation of the Fontan conduit or the pulmonary arteries was the most common intervention (30 (58%) and 8 (15%) patients, respectively), followed by embolization of collaterals (11 (21%) patients). Patients with right systemic ventricle physiology needed more interventions and had a shorter time-to-first-intervention period. (Figure 1) Pacemaker implantation was required in a total of 15 patients, being significantly more frequent in patients with atriopulmonary connection than in patients with lateral tunnel or extracardiac conduit (11 (36%) vs 4 (11%), p&lt;0.01). Overall long-term outcome (with regards to mortality) was good (4 (0.5%) patients). Patients that required percutaneous structural interventions showed a tendency towards a higher mortality than those not in need of intervention (4 (8%) vs 0 (0%), respectively, p=0.14).

Conclusions
During long-term follow-up of patients with Fontan circulation, almost two thirds of the patients required percutaneous intervention. Patients with right systemic ventricle physiology were in greater need of intervention. Patients that required intervention had a tendency towards a worse clinical outcome.

Funding Acknowledgement
Type of funding sources: None.
Percutaneous edge-to-edge repair for systemic tricuspid valve regurgitation in patients with congenital heart disease: the first descriptive cohort
Authors: Guerin P , Jalal Z , Cueff C , Hascoet S , Bouvaist H , Levy F , Hugues N , Ladouceur M , Malekzadeh-Milani S G , Iriart X , Silini A , Karam N , Iserin L , Le Gloan L , Thambo J B 
Published: October 2022

Abstract

In patients with congenital heart diseases (CHD) systemic tricuspid regurgitation (STR) is frequent.
Here, we report our experience with percutaneous edge-to-edge repair (PETER) in a series of 12 CHD patients with STR using the MitraClip system.
Twelve patients (median age = 35 years, 83% males) with severe STR (ccTGA (n=5), asTGA (n=3), SV (n=4)), at high-risk for surgical treatment, gave informed consent for treatment using PETER. The XTR MitraClip device (Abbott, Santa Clara, CA) was used. At baseline, 7/12 patients were in NYHA functional class ≥ III. Standard femoral venous access was successfully used in 10/12 patients. In SV patients, the systemic valve was accessed directly through the right atrium (n=2), after a Fontan conduit puncture (n=1), or after direct atrial surgical access (n=1). In TGA patients, either transseptal (ccTGA patients, n=4) or transbaffle (asTGA patients, n=3) puncture was performed (4).
Mitraclip devices were successfully implanted in 11/12 patients (Figure 1). One procedural complication was reported for a patient with SV in whom a septal leaflet rupture occurred following clip release, leading to severe STR; the patient died from refractory cardiac failure one week later. Peri-procedural complications included one case of left femoral vein injury and one case of atrial flutter treated by catheter ablation. After a median follow-up of 12-months (range 1–25) following device implantation, no death had occurred. The patients had significant reduction in STR (from severe to moderate in 10/11 patients) and clinically improved (10/11 patients were in NYHA class I or II).
To conclude, percutaneous edge-to-edge therapy of STR in CHD patients is feasible, safe and effective to reduce STR and SRV dilatation. This reduction is associated with a significant clinical improvement.

Funding Acknowledgement
Type of funding sources: None.
Patent foramen ovale (PFO) and migraine: role of platelet Tissue Factor expression and oxidative stress. The LEARNER study
Authors: Camera M , Brambilla M , Canzano P , Becchetti A , Conti M , Teruzzi G , Porro B , Muratori E , Tedesco C , Montorsi P , Bartorelli A , Tremoli E , Trabattoni D 
Published: October 2022

Abstract

Background
Migraine is a chronic neurovascular disorder with a multifactorial aetiology. A strong relationship links migraine with aura (MHA) and patent foramen ovale (PFO), with migraine regression after PFO closure. Increased platelet aggregation and oxidative stress were documented in migraineurs. Current guidelines suggest the use of aspirin or P2Y12-antagonists. To date, however, no clear mechanisms connecting MHA to PFO has been demonstrated.

Purpose
To perform a comprehensive analysis of platelet activation, inflammation and oxidative stress status in 78 aspirin-treated MHA-patients before (T0) and 6-months after (T1) PFO closure (LEARNER Study-NCT03521193-clinicaltrials.gov). Primary endpoint was migraine regression rate in relation to these parameters.

Methods
P-selectinpos-, activated-glycoproteinIIbIIIa (aGPIIbIIIa)pos-, Tissue Factor (TF)pos-, reactive oxygen species (ROS)pos-platelets, platelet-leukocyte aggregates (PLA) and microvesicles (MVs) were evaluated by flow cytometry; thrombin generation (TG) by Calibrated Automated Thrombogram (CAT) assay; oxidative stress status by mass spectrometry. Twelve aspirin-treated-healthy subjects (HS) were enrolled for comparison. To test the effect of PFO patients' plasma on platelet activation, blood from HS was plasma-depleted and replaced with a pool of plasma from PFO patients.

Results
Migraine resolution occurred in 69.7%, significant reduction in 27%, while no effect was observed in 2 patients (3.2%). Only ROSpos-platelets, and TFpos-platelets and -MVs were significantly higher at T0, sustaining a TG capacity that was associated with an altered blood GSSG/GSH (Oxidized/Reduced Glutathione) ratio. This phenotype reverted to HS levels at T1 (Fig. 1). MHA-PFO plasma, added to HS blood, mirrored the in vivo platelet activation and N-acetylcysteine blunted it. In vitro GSSG treatment of HS platelets reproduced the in vivo condition. Aspirin had little effect on the platelet prothrombotic phenotype which was effectively inhibited by a P2Y12-antagonist (Fig.2).

Conclusions
MHA-PFO patients show a platelet-associated prothrombotic phenotype, characterized by a marked thrombin generation capacity sustained by an elevated number of platelets and MVs expressing a functionally active Tissue Factor and sustained by altered oxidative stress status. This phenotype, not fully controlled by aspirin but by P2Y12-antagonism, reverted after PFO closure together with a complete migraine remission.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health