bluuebunny/crossref_metadata_2025 huggingface dataset:
The safety and feasibility of colchicine uptitration in the management of idiopathic recurrent pericarditis
Authors: Peet C , Wood M , Hull D , Papadopoulou C , Lachmann H
Published: October 2024

Introduction

Colchicine is recommended first line in the management of idiopathic recurrent pericarditis (IRP) at low doses (0.5 - 1 mg/24h). In cases refractory to low dose colchicine, corticosteroid use is common, despite an increased risk of disease recurrence and the risk of complications resulting from corticosteroid dependence. Biologic agents that block interleukin-1, anakinra and rilonacept, are highly effective in IRP, but their use is limited by expertise and cost. Colchicine uptitration is recommended by consensus international guidance in familial Mediterranean fever, a disease characterised by recurrent serositis, and, hence, offers an accessible steroid sparing approach to the management of treatment-refractory idiopathic recurrent pericarditis

Purpose

To explore the safety and feasibility of colchicine uptitration in patients with IRP refractory to low dose colchicine (0.5-1 mg/24h).

Methods

Retrospective review of electronic medical records of all patients with IRP and familial Mediterranean fever reviewed at a tertiary centre 2013-2023. Treatment-refractory IRP cases were defined as active disease despite colchicine 1mg/24h or disease requiring other prophylactic drugs, and corticosteroid dependence as daily corticosteroid use for 6 months.

Results

Of 121 IRP cases, 77 (63.6%) were treatment refractory at first review. Median follow up was 24 months (IQR 6 – 36). Corticosteroid dependence complicated 34/77 (44.2%) cases. Of treatment-refractory cases without corticosteroid dependence, 42/43 (97.7%) were treated with colchicine uptitration and 4/43 (9.3%) with anti-interleukin-1 biologic(s); none became corticosteroid dependent. Of corticosteroid dependent cases, 30/34 (88.2%) were treated with colchicine uptitration and 13/34 (38.2%) with anti-interleukin-1 biologic(s). Corticosteroids were fully discontinued in 25/34 (73.5%): 8/25 (32.0%) weaned with colchicine uptitration alone, 14/25 (56.0%) with anti-interleukin-1 biologic(s) and 3/21 (14.3%) with azathioprine. Median corticosteroid duration was 17.5 months (IQR 13 - 44.25) and corticosteroid toxicity occurred in 8/34 (23.5%). Among the 76/77 cases (98.7%) treated with colchicine (median maintenance dose 2 mg/24h (IQR 1.5-2)), permanent discontinuation was uncommon (3/76, 3.9%) and due to gastrointestinal symptoms. Self-limiting liver transaminase elevation was common (29/76, 38.2%) but did not lead to discontinuation in any case. The prevalence of liver transaminase elevation among patients with familial Mediterranean fever on life long colchicine was 181/568 (31.9%).

Conclusions

In this treatment-refractory pericarditis cohort, colchicine uptitration enabled avoidance of new corticosteroid dependence, facilitated corticosteroid discontinuation and was well tolerated. This contrasts with the frequent toxicity seen with prolonged corticosteroid use and offers an accessible steroid sparing approach to IRP management that warrants prospective investigation.
Coronary atherosclerotic plaque burden and characterization by spectral computed tomography scan in patients with high lipoprotein a and non-hemodynamically significant stenosis
Authors: Martinez Vives P , Ramos-Cano P , Monteagudo-Ruiz J M , Piris A , Carrion-Sanchez I , Garcia-Sebastian C , Antonana S , Garcia-Martin A , Gonzalez A , Hinojar R , Casas Rojo E , Ayala Carbonero A M , Alarcon Rodriguez J J , Zamorano J L , Fernandez-Golfin C
Published: October 2024

Introduction

Atherosclerotic coronary disease increases morbidity and mortality worldwide. Lipoprotein A (LpA) has emerged as a cardiovascular risk marker, but little is known of its direct influence in plaque volume and composition. Spectral computed tomography (CT) technology allows to characterize coronary plaques with new promising tools.

Purpose

To evaluate the association of LpA with the extent and composition of non-significant coronary plaques producing stenosis <50%.

Methods

We prospectively recruited 109 patients referred for noninvasive CT angiography (November 2023-January 2024) with suspected coronary artery disease. 20 had totally/partially non-calcified, non-significant coronary plaques. Plaques were segmented and volume was measured. Their composition was stablished as calcified (>200 UH), lipidic (<60 UH) and fibrous (60-200 UH). Spectral data-based plaque parameters were analyzed, including radiological attenuation on polyenergetic images (CTPI), on virtual low/high monoenergetic images (CT40KeV and CT140KeV, respectively), variation in attenuation across monoenergetic levels (slope40-140 KeV) and Z-effective value.

CT scan images were acquired with a 128 detectors dual-layer spectral scan with prospective-retrospective/synchronization. Intravascular iodine-based contrast was administered. LpA was stablished as high (≥25 mg/dL) or low (<25 mg/dL).

Results

Mean age was 60 ± 11. Cardiovascular risk factor were equally distributed between groups.

We analyzed 33 plaques. Total plaque volume was significantly higher in high LpA patients (125.9 mm3 vs 62.1 mm3). There were no differences in plaque composition by LpA (Table). Additionally, spectral data showed significantly higher plaque attenuation on CT140KeV images in high LpA patients (36.07 vs 21.32 HU; p = 0.05). There were no differences for the rest of spectral parameters.

Conclusions

Plaque volume was higher in patients with non-significant atherosclerotic disease and high LpA, but these plaques showed similar composition in high and low LpA patients. These patients might, therefore, respond to the same conventional treatment event though there is not specific treatment for high LpA yet. Additionally, spectral CT140KeV images could add more precision differentiating these plaques since radiological attenuation in these reconstructions is higher in patients with high LpA.TableFigure
Whole exome sequencing in patients with recurrent pericarditis
Authors: Collini V , Faletra F , Zucco J , Mio C , Carraro M , Gava A M , De Biasio M , Damante G , Imazio M
Published: October 2024

Background/Introduction

About 10% of patients with recurrences may have a family history of pericarditis suggesting a genetic predisposition, that has been confirmed in selected cases with idiopathic recurrent pericarditis with a focused analysis of genes involved in autoinflammatory diseases (TNFRSF1A, MVK, NLRP3 genes, and variants at the Interleukin 1 Gene Locus).

Purpose

Aim of the present paper is to describe the frequency of detected variants of causative genes by Whole Exome Sequencing (WES) in patients with idiopathic recurrent pericarditis.

Methods

This is an observational, cohort study including all consecutive adult patients (>18 years) with > 2 episodes of recurrent pericarditis. All patients performed WES. We analyzed the frequency of genetic variants in: 1) known or predicted to be at least likely pathogenic (LP) variants already related to recurrent pericarditis, 2) predicted at least of unknown significance in genes not yet associated with recurrent pericarditis. Moreover, we highlighted incidental findings.

Results

We studied 108 patients with recurrent pericarditis (median age of 32 years, IQR 18.5; 67.6% females, all Caucasian, idiopathic etiology in 71.1%). The median number of recurrences was 5 (IQR 2). Eleven gene variants related to recurrent pericarditis were detected by WES analysis in 11/108 patients (10.2%): 9 variants were pathogenic/likely pathogenic (P/LP) according the ACMG guidelines and involved NLRP3 and TNFRSF1A genes, 2 VUS associated with familial Mediterranean fever (gene MEFV) (figure 1). We also recorded 3 P/LP variants and 2 VUS related to the inflammatory response (IFIH1, NFKBIA, JAK1, NOD2 and ALPK1 genes); 7 P/LP variants and 3 VUS related to heart’s electrical system (SCN5A, CALM2, TRPM4, KCND2, KCNQ1 genes); 12 P/LP variants and 10 VUS related to heart structural genes (figure 2).

Conclusion(s)

A substantial proportion of patients with multiple recurrences of pericarditis carries LP or P variants suggesting the importance of genetic predisposition evaluation in this population.
Histological assessment of the shared vascular wall in anomalous aortic origin of coronary arteries with an interarterial course
Authors: Verheijen D B H , Borsboom T C , Kies P , Egorova A D , Wisse L J , Koolbergen D R , Hazekamp M G , Jukema J W , Accord R E , Vliegen H W , De Ruiter M C , Jongbloed M R M
Published: October 2024

Background

In anomalous aortic origin of a coronary artery (AAOCA) an intramural segment is present if the proximal AAOCA courses through the aortic wall. This is defined as a shared tunica media of the aorta and AAOCA in the ‘intramural septum’. This definition is based on autopsy studies of selected AAOCA patients who suffered sudden cardiac death and is difficult to apprehend on imaging modalities. Therefore, the aim was to identify the histological features and variants of the interarterial vascular wall in living adult patients, and correlate this to CT-angiography (CTA).

Methods

This prospective multicenter study included consecutive adult AAOCA patients who underwent surgical unroofing between 2021 to 2024. The excised interatrial vascular wall tissue was embedded, sectioned, and immunohistochemically stained for physiological components, e.g. smooth muscle cells and connective tissue, and pathological components such as fibrosis. Microscopic examination and quantification was performed by two independent observers and findings were correlated with CTA.

Results

Fifteen patients (mean age 42.9±14.0 years, 60% female) and 1 postmortem specimen were included. Fourteen (93%) had a right-AAOCA and 1 (7%) a left-AAOCA, with a mean intramural length of 8.4±4.1mm. Histopathologically, disorganized elastic lamellae with fragmentation, presence of fibrosis and loss of nuclei were observed. No vasa vasorum or nervi vasorum were identified. Post-sectioning virtual 3D reconstructions enhanced the spatial insight in correlation of histological sections with CTA.

Conclusion

This first study of the intramural septum in adults with AAOCA reveals the histological structure of the shared vascular wall between the aorta and AAOCA. Marked vascular wall abnormalities such as lack of vasa and nervi vasorum, fragmentation of elastic lamellae and fibrotic changes were observed. These findings support a propensity to local vascular wall pathology in patients with AAOCA. 3D reconstruction supported the translation of histological data to clinical imaging techniques.Central Figure
The ventricular septal defect in tetralogy of Fallot: A multi-centre morphological and statistical shape analysis study
Authors: Sabarigirivasan V , Sivera R S , Crucean A C , Cook A C
Published: October 2024

Background

Ventricular septal defects (VSDs) in Tetralogy of Fallot (TOF) are often thought to be ‘large and unrestricted’ but experience suggests they have a more heterogenous morphology. Understanding the morphological variations and dimensions is the first step in modifying surgical closure or optimising potential device design.

Purpose

The objective of this study was to perform a comprehensive multi-center morphological analysis of the characteristics of the VSD in TOF. Additionally, we sought to perform a preliminary 2D shape analysis and principal component analysis (PCA) on standardised photos of the VSDs. Through this multi-dimensional approach, we aim to elucidate the morphological variations and structural characteristics of the VSD in TOF as a basis for future 3D shape analysis.

Methods

Of 495 specimens analysed, 460 were included in the morphological analysis. Standardised protocol was applied to assess the characteristics of the VSD: basic measurements of the height, width, inferior limb, and length of the inferior fibrous rim (if perimembranous) were taken and indexed to ventricular length. The degree of aortic override and presence of aorto-mitral continuity were also documented with double outlet right ventricle (DORV) being defined as more than 50% of aorta supported by the right ventricle. Statistical analysis was performed to assess variations in TOF morphology across different age groups and disease phenotypes. Standardised photographs of 130 VSDs were taken from the right ventricle and traced for PCA, in order to assess shape variations among the VSDs.

Results

Both the length of the inferior limb of the PM VSD and the length of the fibrous rim increased with ventricular length but the rate of change was lower for the fibrous rim. A chi-square analysis comparing the presence of double outlet right ventricle and the presence of a fibrous continuity between the aortic and mitral valves showed no association between these features (p = 0.89). The results of PCA in the indexed datasets showed that the largest variation was in the size of the VSD and then from the shape of the VSD where two distinct morphologies emerged: a classic V-shaped VSD and wide but shallow variant.

Discussion

Our study challenges conventional definitions and assumptions regarding the morphological characteristics of the VSD in TOF and suggests that components may change size at differing rates. Our study conclusively shows that DORV and TOF can co-exist and the definition of DORV should be made independently of the presence of aorto-mitral continuity. Contrary to the traditional view of TOF featuring large unrestricted VSDs, our findings suggest wide shallow VSDs are common. These findings challenge paradigms and underscore a necessity for the continuing morphological re-evaluation of TOF utilising large datasets with a diverse phenotypic spread.
Risk factors of 30-day mortality following cardiac surgery in adults with congenital heart disease: analysis from the Japanese registry
Authors: Osawa T , Machino T , Saji M , Sumita Y , Kanaoka K , Kawamatsu N , Ishizu T
Published: October 2024

Background

With advancements in pediatric therapies, the adult congenital heart disease (ACHD) population has grown consistently. ACHD patients often face complications necessitating cardiac surgery, and understanding surgical risk factors is essential.

Purpose

This study aims to assess ACHD surgical risk factors using big data, addressing evidence gaps in previous research limited to univariate analysis due to few perioperative adverse events.

Methods

We analyzed the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database from April 2013 to March 2020. The JROAD-DPC database covers nearly all teaching hospitals with cardiovascular beds participation in JROAD. Our study included ACHD patients (>15 years) undergoing open-heart surgery. Our primary outcome was 30-day mortality. We assessed clinical backgrounds, admission status, treatment, and length of hospital stay.

Results

Out of 13,677 ACHD patients (mean age: 53 years, females 47%) undergoing cardiac surgery assessed for 30-day mortality, 13,516 (98.8%) patients were categorized into the survival group and 161 (1.2%) into the death group. Mortality rates varied by complexity of congenital heart disease (CHD): 0.8% for simple, 1.8% for moderate, and 0.9% for great. The figure shows that a significant increase in 30-day mortality rates with age was demonstrated in simple and moderate complexity (p<0.001 for trend analysis in both categories). In contrast, for cases of great complexity, the increase in 30-day mortality rates with aging was not statistically significant (p=0.443). The death group was significantly older and had higher rates of ambulance admissions, renal disease, and peripheral vascular disease. Intra-aortic balloon pumps (IABP), veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and dialysis during hospitalization were significantly higher among deceased patients. Length of ICU stay was significantly longer in the death group (median [IQR]; 3 [2-4] vs. 6 [3-11], p<0.001). Cox proportional-hazards model showed that age, moderate complexity, emergency admission, hospital bed counts, renal disease, and use of IABP and VA-ECMO were independently associated with 30-day mortality (Table).

Conclusions

The present study, which utilizes the nationwide administrative DPC database, demonstrates that surgical outcomes for patients with ACHD, as measured by 30-day mortality rates, are generally favorable. These outcomes significantly depend on factors such as age, complexity of CHD, emergency admissions, hospital capacity, renal disease, and use of mechanical circulatory support.
Transcranial doppler to detect high-risk PFO and predict decompression illness in divers
Authors: Lee H , Lim D S , Kang Y C , Lee J Y , Oh M Y , Lee D G , Park J S , Kim C H , Jung J H , Choi R K
Published: October 2024

Background

It has not yet been clearly demonstrated whether it is feasible to diagnose patent foramen ovale (PFO) using transcranial doppler (TCD) and to use it in strategies to prevent decompression illness (DCI) in self-contained breathing apparatus (SCUBA) divers.

Purpose

DIVER-PFO study confirmed that high-risk PFO is associated with an increased risk of DCI in SCUBA divers. In this prespecified post-hoc analysis, we aimed to prospectively evaluate the accuracy of TCD to diagnose high-risk PFO and to predict the occurrence of DCI.

Methods

Eighty-two consecutive divers (mean age; 41 years, male 80.5%) underwent transesophageal echocardiogram (TEE) and TCD with a saline bubble test to determine the presence of PFO and were subsequently divided into high-risk and low-risk groups by TEE findings. Divers in the high-risk PFO group included those with the following conditions: PFO with atrial septal aneurysm, hypermobility, PFO size ≥2 mm, or right to left shunt at resting state. The enrolled divers were then followed-up using a self-reported questionnaire through e-mail or telephone interview for 3 years, while they were blinded to their PFO status. The primary endpoint of the study was PFO-related DCI, comprising cases of cutaneous or neurologic DCI, DCI symptoms requiring hyperbaric chamber therapy, DCI symptoms within 30 minutes after surfacing, or unexplained death occurring within 2 weeks after diving.

Results

PFO was detected in 47 (57.3%) and 59 (72.0%) divers by TCD and TEE, respectively. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of TCD were 68.3%, 67.8%, 69.6% 85.1%, and 45.7% for the diagnosis of PFO, and 65.9%, 82.8%, 56.6%, 51.1% and 85.7% for the diagnosis of high-risk PFO, respectively. PFO-related DCI occurred in 9 divers in the PFO group (PFO vs non-PFO: 6.4 vs 0.7 incidences per 10,000 person dives; p=0.03) during a mean follow-up of 25.6 months. Integrated time-dependent Area Under the Curves for TCD and TEE to predict DCI occurrence using Cox’s proportional hazards regression model were 0.714 and 0.675, respectively.

Conclusions

TCD was moderately accurate to diagnose high-risk PFO in divers. However, it predicted DCI as much as TEE.Study flowIncidence of DCI in the PFO vs No PFO
Machine learning prediction for prognosis and long-term effectiveness for transcatheter ventricular septal defect closure: a 5-year single center experience
Authors: Li Z F , Li W C , Kong P X , Feng S Y , Li Y H , Li J , Liu Z Y , Zhang F W , Wang S Z , Fang F , Ouyang W B , Hu X P , Xie Y Q , Pan X B
Published: October 2024

Background

Transcatheter therapy, with minimal invasiveness and rapid recovery advantages, has emerged as the primary choice for treating perimembranous ventricular septal defect. However, patients receiving transcatheter occlusion may confront conduction abnormalities due to the occluder's proximity to the cardiac conduction bundle during implantation. Few have assessed the risks of postoperative conduction block (CB) via robust machine learning models.

Purpose

The purpose of this study was to evaluate our long-term follow up results of pmVSD occlusion and establish a prediction model to identify risk predictors of conduction abnormalities via robust machine learning methods.

Methods

Five methods including logistic regression with a stepwise selection of variables, lasso regularization; random forest; gradient descent boosting (GBM); and support vector machine, were used to train models for predicting risks of late-onset and persistent conduction block through 5 years of follow-up and were validated using 5-fold cross-validation. Receiver-operating characteristic curves and Brier scores were utilized to evaluate model discrimination and calibration, respectively. The top prediction variables were identified by using the best performing models, using the relative influence score of each variable in 5-fold cross-validation.

Results

The GBM model performed the best with an AUC of 0.82 (95% confidence interval [CI]: 0.75 to 0.89) for predicting late-onset CB (Brier score: 0.0204), and 0.70 (95% CI: 0.62 to 0.78) for persistent CB (Brier score: 0.0003) over entire study period. Conduction block on admission, advanced age and aortic regurgitation before discharge were strongly associated with late-onset CB, whereas decreased left ventricular ejection fraction, enlarged left ventricle end diastolic diameter at 1-month follow-up were the most significant predictors of persistent CB.

Conclusions

These models predict the risks of temporary and persistent postoperative conduction block in patients with pmVSD occlusion and shed light on preventing long-term complications.Study FlowchartCentral Illustration
Sex differences in outcomes among patients undergoing transcatheter atrial septal defect closure: Do they benefit equally?
Authors: Schrutka L , Abrahamyan L , Vishwanath V , Flores-Umanzor E , Asghar A , Benson L , Osten M , Horlick E
Published: October 2024

Background

Although sex differences in congenital heart disease are prevalent and relevant, there is limited research on their role in atrial septal defect (ASD) closure. We aimed to investigate sex differences in baseline characteristics, procedural and long-term outcomes of patients with transcatheter ASD closure.

Methods

Data from adult patients undergoing ASD closure between 2005-2016 were retrospectively analyzed.

Results

Of the 853 patients included, 281 (32.9%) were male and 572 (67.1%) were female. Females were more symptomatic at presentation than males (p < 0.001). Males had a higher frequency of cardiovascular comorbidities than females (p < 0.001). Although echocardiographic right ventricular (RV) diameter relative to body surface area was equal in males and females (2.49 cm/m2 versus 2.57 cm/m2; p = 0.072), males had more RV dysfunction (12.1% versus 7.6%; p = 0.028). In contrast, females had higher RV systolic pressures (39.71 mmHg versus 37.23 mmHg; p = 0.025), and were more likely to have moderate to severe tricuspid regurgitation (15.4% versus 8.9%; p = 0.007). Males had larger defects with use of larger implants (p < 0.05). Procedure-related complications were rare and did not differ by sex. At 12-month follow-up, both male and females showed comparable decreases in RV diameter (-0.57 cm versus -0.59 cm; p = 0.751), RV systolic pressure (-4.57 mmHg versus -6.31 mmHg; p = 0.094), and severity of tricuspid regurgitation (p = 0.173; Figure). After a mean follow-up of 3 years (SD = 5), no significant differences were observed in the incidence of death (incidence rate ratio (IRR) = 0.49 [95% CI 0.27-0.83]; p = 0.402), new onset atrial fibrillation (IRR = 3.22 [95% CI 2.57-3.99]; 0.063), cardioversion or ablation (IRR = 0.40 [95% CI 0.20-0.71], p = 0.335), stroke/TIA (IRR = 0.29 [95% CI 0.12-0.56]; p = 0.745), and pacemaker implantation (IRR = 0.29 [95% CI 0.12-0.57], p = 0.728).

Conclusions

Although patient profiles differed by sex, procedural and long-term outcomes were comparable, suggesting that transcatheter ASD closure can be safely performed in both males and females.Figure.Sankey Plot
Different microRNA expression in the right ventricular outflow tract myocardium of tetralogy of Fallot
Authors: Kotani Y , Suzuki H , Yamazaki S , Shishido T , Shimizu S , Kasahara S
Published: October 2024

Background

When repairing tetralogy of Fallot (TOF), there are two surgical options according to the size of the pulmonary valve: transannular patch repair and valve-preserving repair. Since the development of the pulmonary valve depends on the degree of obstruction of the right ventricular outflow tract (RVOT), molecular profiles of the RVOT muscles may be associated with the surgical decision. As a recent study shows altered microRNA expression of the right ventricular myocardium even in TOF patients, microRNA expression of the RVOT infundibular muscle may be different between the two procedures.

Purpose

To evaluate differences in microRNA expression levels of RVOT infundibular muscles between the transannular patch repair and valve-preserving repair groups.

Methods

Surgically resected infundibular muscles from TOF patients are frozen in liquid nitrogen and stored in our hospital biobank. Nine samples collected between August 2020 and July 2022 were used in this study. Five patients underwent a valve-preserving repair and the others underwent a transannular patch repair. Six patients were female and mean age at operation was 453 ± 240 days. These samples were homogenized and total RNA including microRNAs were extracted. MicroRNA expression levels were measured using a microRNA array capable of detecting over 2000 microRNAs simultaneously.

Results

1171 microRNAs were detected in all nine samples. The expression levels of 22 microRNAs were significantly different between the transannular patch repair group and the valve-preserving repair group (P<0.05). The expression levels of 19 microRNAs were significantly higher in the transannular patch repair group and the others were significantly higher in the valve-preserving repair group. More than 2-fold changes were observed in 2 microRNAs between the transannular patch repair and valve-preserving repair groups.

Conclusion

MicroRNA expression of RVOT infundibular muscle differs between the transannular patch repair and valve-preserving repair groups. Therefore, microRNA analysis will be useful to evaluate the pathophysiology of TOF. In addition, microRNAs may become a useful biomarker for surgical decision making in TOF.
Long-term heart failure risk after atrial septal defect closure in elderly
Authors: Ho C B , Ng P K , Lun W C , Kwok W Y , Leung C Y , Ko H Y , Kwan C M , Ho M H , Chim M Y , Yeung Y K , Leung C , Chui S F , Chan K C , Wong C Y , Lee K Y
Published: October 2024

Background

There is concern that atrial septal defect (ASD) closure will unmask underlying diastolic dysfunction or left heart disease in elderly causing heart failure. It is controversial whether fenestrated devices should be used in elderly patients.

Purpose

To assess the long-term heart failure risk after ASD closure in elderly and risk factors associated with heart failure hospitalization in a single centre.

Method

From 2003-2023, all elderly patients aged more that 60 years old who had ASD closure performed successfully in this centre were retrospectively studied. Baseline demographics, underlying risk factors and survival without heart failure hospitalization were analyzed.

Result

From 2003-2023, 73 patients aged more than 60 years old underwent successful ASD closure in our centre. None of these patients had balloon occlusion test for assessment of left atrial pressure. Median age was 66 years old (60-84) at operation and 27 (37.0%) of them were male. Common risk factors included diabetes (n=9, 12.3%), hypertension (n=31, 42.5%) and ischaemic heart disease (n=8, 11%). Thirty-nine (53.4%) patients had pre-existing atrial fibrillation and 17 (23.3%) of them had moderate to severe left sided valvular lesions. Heart failure symptoms were present in 31 (42.5%) of them (Figure 1). During a median follow-up time of 4 years (1-15 years), 80.8% of patients did not experience heart failure hospitalization (Figure 2). Pre-existing atrial fibrillation and left-sided valvular lesions were associated with higher risk of heart failure hospitalization (OR 4.06, 95% CI 1.03-16.06 p=0.036 and OR 4.9, 95% CI 1.41-17.09 p=0.009).

Conclusion

In a median follow-up time of 4 years, patients aged more than 60 years old had low rate of heart failure hospitalization after ASD closure. Pre-existing atrial fibrillation and left-sided moderate to severe valvular lesions were associated with higher risk of heart failure admission. Further studies should be conducted on ASD closure in these group of patients.Figure 1Figure 2
E-selectin and asymmetric dimethylarginine plasma levels in adult cyanotic congenital heart disease patients: relation to biochemical parameters, vascular function, and clinical status.
Authors: Nartowicz S , Miechowicz I , Szczepaniak-Chichiel L , Bartczak-Rutkowska A , Gabriel M , Lesiak M , Trojnarska O
Published: October 2024

Background and Aim

Patients with cyanosis secondary to congenital heart disease (CHD) are characterized by erythrocytosis and increased blood viscosity, which contributes to endothelial dysfunction, increased arterial stiffness, and impaired vascular function, which may affect the final clinical presentation. Asymmetric dimethylarginine (ADMA) and e-selectin (e-sel) are valuable biomarkers for prognosis of endocardial dysfunction and vascular damage. Their concentration levels in blood serum have the potential to be a rapid and easily accessible tool that reflects the severity of the disease. We aimed to assess e-sel and ADMA levels, their relationship with clinical status, as well as endothelial and vascular function.

Methods

A cross-sectional study including 36 adult CHD cyanotic patients [(17 males)(42.3 +/- 16.3 years)] with arterial blood oxygen saturation less than 92% and 20 healthy controls [(10 males)( 38.2 +/- 8.5 years)] was performed. All patients underwent clinical examination, blood testing, and cardiopulmonary tests. Endothelial function was assessed using intima-media thickness and flow-mediated dilatation (FMD). Vascular function using applanation tonometry methods was completed while considering aortic systolic pressure, aortic pulse pressure (AoPP), augmentation pressure (AP), augmentation index (AI), pulse pressure amplification (PPampl), and pulse wave velocity (PWV).

Results

Concentrations of e-sel and ADMA were significantly higher in patients with CHD than in controls (56.3 ± 13.6 ng/mL vs. 15.5 +/- 8.6 ng/mL, p<0.001) and (1.48 ± 0.48 ng/mL vs. 0.46 ± 0.1 ng/mL, p<0.001) respectively. E-sel levels correlated with gender, blood oxygen saturation, red blood cell, hemoglobin concentration, hematocrit, augmentation pressure, forced expiratory one second volume, forced vital capacity, and oxygen uptake. ADMA levels were found to correlate with age only.

Conclusions

E-sel level, unlike ADMA concentration, reflects the degree of severity of erythrocytosis and hypoxia and, thus, the physical status of patients with cyanotic CHD. E-selectin predicts increased augmentation pressure.Figure 1.A) ROC analysis for e-selectin
Variability in patient-reported outcomes among different congenital heart defects: a comparative analysis of 7,498 patients from 32 countries
Authors: Moons P , Kovacs A H , Goossens E , Luyckx K , Van Bulck L
Published: October 2024

Background

Patient-reported outcomes (PROs) may not always correlate with the complexity of congenital heart defects (CHDs), as significant variation has been observed between CHDs within complexity levels. Accurate comparisons across various types of CHDs necessitate large sample sizes.

Purpose

The objective of this study was to compare PROs across different CHDs in a large international sample.

Methods

‘Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease – International Study II’ (APPROACH-IS II) was an international cross-sectional investigation, in which 8,415 patients from 32 countries in 6 continents were enrolled (20 high; 7 upper-middle; 4 lower-middle; and 1 low income). For the comparison across different CHDs, conditions with at least 50 patients were included in the analysis. Hence, the sample consisted of 7,498 patients (median age=33y; 53.1% women). Patients completed questionnaires to measure perceived health status (RAND-12 Health Survey; EuroQOL-5D Visual Analog Scale); depressive symptoms (Patient Health Questionnaire-8); anxiety (General Anxiety Disorder-7) and quality of life (Linear Analog Scale). Generalized linear mixed models (GLMMs) were performed with center as random effect.

Results

Cyanotic heart defects were associated with the lowest scores for physical functioning, mental health, self-rated health, and quality of life (see Figure). Other CHDs found to be associated with poor PRO scores encompassed unrepaired secundum atrial septal defect, Ebstein anomaly, single ventricle, and truncus arteriosus. Conversely, the most favorable scores for all PROs, except for anxiety, were observed with isolated pulmonic stenosis. Other CHDs with favorable PRO scores comprised coarctation of the aorta, isolated small ventricular septal defect, congenital aortic valve disease, and repaired ventricular septal defect. Adjusted for sociodemographic and physiological factors, GLMMs revealed significant differences across defects, using the best score for each PRO as the reference (see Figure).

Conclusion

Substantial variation in PROs was observed among different types of CHDs. Interestingly, some complex heart defects demonstrated relatively good PRO scores, comparable to some simple defects. On the other hand, unrepaired simple defects or those with residual lesions, were associated with worse PROs.
Effects of pulmonary hypertension targeted therapy on haemodynamics in pulmonary arterial hypertension associated with adult congenital heart disease: a meta-analysis
Authors: Tsigkriki L , Ntiloudi D , Papanastasiou C , Varrias D , Giannakoulas G
Published: October 2024

Background

Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. There is growing evidence that PAH drugs lead to improved hemodynamics, exercise capacity, quality of life and survival in patients with PAH.

Purpose

The aim of this systematic review and meta-analysis is to evaluate the effects of pulmonary hypertension (PH) medical therapy on the haemodynamic parameters as well as exercise capacity in adult patients with PAH-CHD.

Methods

PubMed and the Cochrane Library databases have been systematically searched. Meta-analysis was conducted using STATA and Review Manager.

Results

Fourteen studies including 575 patients were analyzed. Pulmonary haemodynamics improved in patients receiving PH-targeted therapy. The weighted mean reduction in mean pulmonary arterial pressure (mPAP) was -5.8mmHg (I2=0%, 95% CI [–7.55, –4.06], p<0.001).The weighted mean reduction in right atrial pressure (RAP) was -5.81mmHg (I2=0%, 95% CI [-7.55, - 4,07], p<0.001). The weighted mean reduction in pulmonary vascular resistance (PVR) was 358.5dynes/sec/cm-5 (I2 51%, 95% CI [-566.55, -150.46] and p<0.001). Cardiac index was increased by 0.61L/min/m2 (I2=6%, 95% CI [0.23,1.00], p=0.002). Six-minute walking distance increased by 47.26m, (I2=0%, CI [38.36, 56.16], p<0.001).

Conclusions

PH-targeted therapy improves pulmonary haemodynamics and exercise capacity in adult patients with PAH-CHD.
Ventriculo-arterial coupling parameters by cardiac magnetic imaging are associated with outcome in patients with a systemic right ventricle
Authors: Wustmann K , Burkhardt B , Ruperti-Repilado J , Greutmann M , Schwerzmann M , Rutz T , Bouchardy J , Tobler D , Gabriel H , Stambach D , Schwitter J , Valsangiacomo Buechel E
Published: October 2024

Introduction

Invasive studies have shown that patients with a systemic right ventricle (sRV) due to congenitally corrected transposition of the great arteries (TGA) or complete TGA after atrial switch procedure possess impaired ventriculo-arterial coupling (VAC) parameters. The randomized, placebo-controlled, double-blinded, multi-centre SERVE trial investigated the effect of phosphodiesterase-5 inhibitor tadalafil in sRV patients on RV endsystolic volume (RVESV), with negative results. Aim of this sub-analysis was to evaluate changes of non-invasively assessed VAC parameters over time and for treatment effect. We prospectively analysed whether VAC parameters predict clinical outcome in sRV patients.

Methods

Volumetric RV parameters and aortic flow were assessed by cardiac magnetic resonance (CMR) and analysed (blinded for patient and assessment time and treatment) at baseline, after 3 years, or after 1 year if the study drug was withdrawed. Parameters were compared with clinical outcome at each visit. Effective arterial elastance Ea was calculated as RV endsystolic pressure (RVesp) / aortic forward flow, with RVesp defined as 0.9 x systolic blood pressure. Right ventricular endsystolic elastance Ees was calculated by RVesp / RVESV, and RV VA-coupling ratio was expressed as Ea/Ees. Treatment effect was analysed using ANCOVA with baseline values and FU-time as covariates. Values of > 4th quartile were used as cut-off for Kaplan-Meier analysis on the primary outcome, defined as a composite of all-cause death, clinically relevant arrhythmias and hospitalisation for heart failure.

Results

CMR exams were available for 78 patients at baseline (40±11 years, 33% females) and for 71 patients at follow-up (FU). No effect of tadalafil compared to placebo was evident for effective arterial elastance Ea (p=0.35), ventricular endsystolic elastance Ees (p=0.11), VAC Ea/Ees (p=0.82), RVESVi (p=0.63) and RV ejection fraction (RVEF, p=0.6). Over the 3 years FU-time, Ea (p=0.24) and RVEF (p=0.11) did not change, whereas Ees mildly decreased (p=0.0052, fig. 1 A) and Ea/Ees increased (p=0.013, fig. 1 B). During FU, 14 patients experienced a clinical event. An Ees <0.73 mmHg/ml and an Ea/Ees ratio of >1.94 were associated with adverse clinical outcomes (for both p=0.004, fig. 2).

Conclusion

In sRV patients, treatment with tadalafil had no effect on VAC parameters compared to placebo. CMR-derived ventricular endsystolic elastance (Ees) and Ea/Ees ratio changed over the FU of 3 years and were associated with adverse clinical outcome.Figure 1Figure 2
Cardiovascular comorbidities and risk stratification in normotensive acute pulmonary embolism patients with right ventricular dysfunction and normal cardiac troponin: insights from a regional registry
Authors: Dzudovic B , Djuric I , Subotic B , Matijasevic J , Kovacevic-Preradovic T , Neskovic A , Mitevska I , Miloradovic V , Bozovic B , Obradovic S
Published: October 2024

Background

Acute pulmonary embolism (PE) management guidelines categorize normotensive patients with right ventricle dysfunction (RVD) and normal cardiac troponin (cTn) as intermediate low risk. This study explores the prevalence of cardiovascular comorbidities and their impact on risk stratification in this specific cohort.

Purpose

To investigate the characteristics of normotensive acute PE patients with RVD and normal cTn, emphasizing the role of pre-existing cardiovascular diseases in determining the intermediate-low risk status.

Methods

A total of 1675 PE patients from a regional registry were screened, excluding high-risk and intermediate-high-risk cases. Among the remaining 400 normotensive patients with RVD, 353 with echocardiography and normal cTn were included. Patients were categorized into low or intermediate-low risk based on RVD presence. Cardiovascular comorbidities were assessed, and logistic regression analyzed their association with intermediate-low risk.

Results

Intermediate-low-risk patients (n=137) exhibited significantly higher rates of chronic heart failure, arterial hypertension, coronary artery disease, diabetes, and atrial fibrillation compared to low-risk patients (n=216). A substantial 77.4% of intermediate-low-risk patients had at least one cardiovascular comorbidity, significantly elevating the risk of RV dysfunction (adjusted OR 2.954, p<0.001). The all-cause hospital mortality was 5.1% in intermediate-low-risk and 1.4% in low-risk PE.

Conclusions

Normotensive acute PE patients with RVD and normal cTn are predominantly burdened with chronic cardiovascular conditions. The majority of intermediate-low-risk patients have at least one cardiovascular comorbidity, indicating an increased risk of death during hospitalization compared to low-risk patients. This study underscores the necessity for nuanced risk stratification considering pre-existing cardiovascular diseases for tailored and effective management. These findings have important implications for optimizing treatment strategies and improving outcomes in this high-risk population.
Diagnostic performance of computed tomography-derived fractional flow reserve in patients with severe aortic stenosis
Authors: Kido S , Okayama H , Kurokawa T , Kazatani T , Aono T , Matsuda K , Kawamura G , Kawada Y , Hiasa G , Yamada T
Published: October 2024

Background

Computed tomography-derived fractional flow reserve (FFR-CT) is a clinical modality for assessing coronary artery disease; however, its use has not been validated in patients with severe aortic stenosis (AS).

Purpose

This study assessed the diagnostic performance of FFR-CT in patients with severe AS.

Methods

Retrospectively recruited patients with severe AS underwent standard-protocol invasive fractional flow reserve (FFR) and coronary CT angiography. The FFR-CT values were compared with the invasive FFR values (ischemia defined as invasive FFR ≦0.80).

Results

Among 46 patients (105 vessels), the mean age was 82.8 ± 5.9 years (37% male). Mean invasive FFR and FFR-CT values were 0.86 ± 0.11 and 0.83 ± 0.10, respectively. In a per-vessel analysis, there was a positive correlation between invasive FFR and FFR-CT values (Pearson correlation coefficient, R= 0.64; P<0.0001). In addition, the sensitivity, specificity, positive predictive, and negative predictive values were 100%, 86%, 43%, and 100% with 88% diagnostic accuracy, respectively. The Bland-Altman plot showed that the mean bias between invasive FFR and FFR-CT values was 0.031 (-0.146 to 0.209). The per vessels area under the receiver-operating characteristic curve analysis was 0.97 (95 % CI: 0.94-1.00, P<0.0001). Importantly, among another 58 patients who deferred invasive coronary angiography (ICA) because the FFR-CT value was negative (> 0.80), none experienced deterioration of condition during transcatheter aortic valve replacement (TAVR) or major adverse cardiac events (all-cause death, myocardial infarction, and unplanned hospitalization with urgent revascularization) within 30 days after TAVR.

Conclusions

FFR-CT values were significantly correlated with invasive FFR values and had a high negative predictive value in patients with severe AS. Patients with a negative FFR-CT value and deferred ICA had an excellent short-term prognosis after TAVR. FFR-CT is expected to serve as a gatekeeper for unnecessary ICA prior to TAVR.
Impact of new definition on the prognosis of patients with pulmonary hypertension compared to classic definition
Authors: Lee S , Jung H
Published: October 2024

Background

The recent European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 pulmonary hypertension (PH) guidelines have updated the definition of PH from a mean pulmonary arterial pressure (mPAP) ≥ 25mmHg to > 20mmHg, and the pulmonary vascular resistance (PVR) threshold for pre-capillary PH (Pre-PH) from > 3 wood units (WU) to > 2 WU. Little is known regarding the implication of this new criteria in all PH subgroups in Asia.

Purpose

In this study, we aim to evaluate the impact of the new PH definition on the prevalence and prognosis of PH subgroups in as Asian cohort.

Methods

A retrospective analysis of a single-center RHC registry (April 2016 - July 2023) was conducted. 314 patients (median age 62.5, 50.3% men) were included. Patients were categorized into PH subgroups as defined by both the classic and new criteria. The primary outcome included cardiovascular mortality or heart failure hospitalizations, assessed over a maximum follow-up period of 5 years. Clinical outcomes of different PH subgroups using the classic and new definitions were compared using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models. Continuous parameters were analyzed using restrictive cubic splines within Cox models.

Results

Based on the new cutoffs (mPAP > 20mmHg, PVR > 2 WU), 76 patents (24.2%) were reclassified. PH increased to 233 (+ 41, +13.1%), Pre-PH increased to 92 (+ 30, +9.6%), Ipc-PH decreased to 27 (- 21, -6.7%), and Cpc-PH increased to 108 (+33, +10.5%). Over a median follow-up of 238.5 days, 65 primary outcomes occurred. Under the new PH definition, 5-year survival rates for Pre-PH, Ipc-PH, and Cpc-PH are 73.2%, 57.5%, and 47.0%, improved from 67.0%, 53.3%, and 44.3% in the classic definition. In the Cox regression analysis, using the Non-PH as a reference, the risk of primary outcome for PH subgroups was lower in the new definition compared to the classic definition (Table 1). Using the classic mPAP cut-off [<25 vs. ≥25 mmHg], patients with PH had a significantly higher risk for primary outcome (HR 2.25, 95% CI 1.26-4.00, p=0.006) compared with patients without PH. However, using the new mPAP cut-off [<20 vs. ≥20 mmHg], it didn’t show significant difference between two groups (HR 1.62, 95% CI 0.86-3.04, p=0.132). Spline analyses suggested a linear relation between the risk of primary outcome and mPAP considering mPAP between 20 and 45mmHg, and a plateau of events for mPAP values over 45mmHg. In patients with PVR > 2 WU, we observed a linear relation between PVR and events for values and a plateau of events for PVR values over 7.5 WU (Figure 1).

Conclusion

The new definition increased the diagnosis of PH, particularly in Pre-PH and Cpc-PH. This definition faciliates earlier diagnosis, encompassing milder disease states, and demonstrated better prognosis in PH subgroups. However, it dose not identify additional patients at increased risk of primary outcomes.Table 1Figure 1
Efficacy of specific drug class therapy in pulmonary arterial hypertension associated with HIV, portal hypertension or both: a single Center experience
Authors: Dardi F , Cennerazzo F , Guarino D , Ballerini A , Magnani I , Salvi M , Donato F , Bertozzi R , Manes A , Palazzini M , Galie' N
Published: October 2024

Background

Pulmonary arterial hypertension (PAH) is a rare complication of both HIV infection (HIV-PAH) and portal hypertension (Po-PAH); it can occur in patients with both diseases (HIV/Po-PAH). The use of the PAH-specific drug classes (prostanoids, endothelin-1 receptor antagonists [ERA] and phosphodiesterase-5 inhibitors [PDE5-i]) is largely justified by retrospective and observational case reports since, to date, there are no randomized clinical trials except for the PORTICO trial which demonstrated the efficacy of macitentan in Po-PAH.

Purpose

the aim of the study was to evaluate the efficacy of PAH-specific drugs, both monotherapy and dual oral upfront therapy (ERA + PDE5i started within 1 month apart), in patients with Po-PAH, HIV/Po-PAH and HIV-PAH.

Methods

Between 1998 and 2023 we enrolled patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to our Center and undergoing monotherapy with prostanoid, ERA and PDE5-I or dual upfront oral therapy. The efficacy of the drugs was assessed by comparing clinical parameters (NYHA functional class), exercise capacity (six-minute walking test) and hemodynamic parameters at baseline and after a treatment period of 3-6 months. The data are expressed as mean and standard deviation and were compared with Student's t-test for paired data.

Results

128 patients were enrolled (83 Po-PAH, 23 HIV/Po-PAH and 22 HIV-PAH). 20 were treated with ERA monotherapy, 90 with PDE5-I, 13 with prostanoids and 5 treated with dual oral upfront therapy.

Conclusions

Prostanoids, ERAs and PDE5-Is, both in monotherapy and as dual upfront oral therapy, are associated with a significant improvement in functional class, exercise capacity and hemodynamic parameters. The effect of such drugs is similar to patients suffering from other forms of PAH.