bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of right ventricular dysfunction in patients with TTR amyloidosis
Authors: Istratoaie S , Al Wazzan A , Antonelli J , Oger E , Donal E 
Published: October 2024

Abstract

Background
Transthyretin amyloidosis (ATTR) is increasingly recognized as a cause of heart failure (HF) that now benefits from effective treatment. While the role of right ventricular (RV) systolic dysfunction has been widely accepted as an independent predictor of poor prognosis in HF patients, its implications in ATTR remain poorly understood. Right ventricular free wall strain (FWS) over pulmonary arterial systolic pressure (PAsP) has been recently proposed as an accurate and sensitive tool to evaluate RV function and its coupling to the afterload.

Purpose
Our study sought to analyze whether indexing FWS to PASP should integrate the set of fundamental data we have to assess the prognosis of ATTR patients.

Methods
191 consecutive patients diagnosed with ATTR were enrolled. A comprehensive echocardiographic examination was part of the systematic evaluation. The primary outcome was a composite of cardiovascular mortality and hospitalization caused by heart failure worsening.

Results
After a median follow-up of 24 months, among patients with ATTR [median age 82 (77, 85), 89.5% male], the primary composite outcome occured in 26%. Cardiovascular mortality rate was 7.3% and the hospital event rate was 18.8%. Tricuspid annular plane systolic excursion (TAPSE), FWS, TAPSE/PAsP and PAsP were univariately significant risk factors for adverse outcome.
In multivariate Cox regression analysis, after adjustment of confounding factors, FWS/PASP emerged as an independent predictor of the composite endpoint of cardiac death and rehospitalization (HR 1.61, 95% CI 1.07-2.42, p=0.021). Based on receiver-operating characteristic analysis, the optimal FWS/PASP cut-off value for event prediction was 42.5% (area under the curve = 0.749, p = 0.001).

Conclusion
Right ventricular function assessed with speckle-tracking echocardiography is an independent prognostic marker for cardiac mortality and heart failure hospitalization in patients with ATTR. FWS/PAsP should be integrated into regular clinical practice for a better evaluation and follow-up of ATTR patients.
Cardiac transthyretin amyloidosis in patients with conduction system disease
Authors: Pudich J , Seleng J , Syler J , Palickova N , Kapsova E , Drienikova D , Musiolova K , Pudichova H , Plasek J , Vaclavik J 
Published: October 2024

Abstract

Background/Introduction
Cardiac amyloidosis (CA) is characterized by extracellular deposition of misfolded proteins in the heart. The data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. More than 98% of currently diagnosed cardiac amyloidosis result from fibrils consisting of monoclonal immunoglobulin light chains (AL) or transthyretin (ATTR). The natural history of ATTR cardiomyopathy commonly includes both the conduction system disease and arrhythmias, which may occur years before the onset of heart failure. Conduction abnormalities are commonly encountered among patients with CA and constitute an important cause of morbidity and mortality. Most reports agree that pacemakers are most common in wild type ATTR-CA, followed by hereditary ATTR-CA and, finally, AL-CA.

Purpose
As unexplained LV wall thickness ≥ 12 mm is a screening sign of possible cardiac ATTR, systematicscreening for CA in patients requiring permanent pacemakers with unexplained LV wall thickness of ≥ 12 mm seems to be rational and could possibly lead to early diagnosis of cardiac ATTR. To the best of our knowledge, the usefulness of such screening has not been investigated before. This project, therefore, aims to determine the prevalence of cardiac ATTR and its subtypes in this preselected group, and to propose the most suitable battery of diagnostic procedures for this purpose.

Methods
Population to be tested: Consecutive patients ≥50 years referred for permanent pacemaker implantation with unexplained LV wall thickness ≥12 mm determined by echocardiography. The research protocol was that of an open-label prospective study. Biochemistry samples including serum troponin I and NT-proBNP were collected before pacemaker implantation. All patients were screened for ATTR-CA according to the recommendations of the Position statement of the ESC Working group on myocardial and pericardial diseases. Tc-DPD scintigraphy scan served as a gold standard for determining the diagnosis of cardiac ATTR.

Results
Out of 100 consecutive patients meeting inclusion criteria, 15 % suffered from amyloidosis (12 patients were diagnosed with ATTR and 3 with AL cardiac amyloidosis). Table 1 shows a variety of parameters, many of which differed between patient groups with and without amyloidosis, confirming the wide range of parameters significantly associated with cardiac amyloidosis; our ongoing research in this field could lead to the development of a scoring system for detection of cardiac amyloidosis.

Conclusions
The prevalence of cardiac amyloidosis in the investigated group was 15 %. Systematic screening for ATTR in patients with unexplained LV wall thickness ≥ 12 mm requiring permanent pacemaker implantation seems to be rational and could possibly lead to an earlier diagnosis of cardiac amyloidosis, especially ATTR.
Characterizing the progression of subclinical cardiac amyloidosis through artificial intelligence applied to electrocardiographic images and echocardiograms
Authors: Oikonomou E K , Sangha V , Coppi A , Krumholz H M , Miller E J , Khera R 
Published: October 2024

Abstract

Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) follows an indolent course and may remain undiagnosed for many years before resulting in clinical disease.

Purpose
To assess the utility of scalable artificial intelligence (AI) methods applied to electrocardiographic (ECG) images and echocardiograms in detecting longitudinal changes that precede the clinical diagnosis of ATTR-CM.

Methods
Across 5 hospitals of a large U.S.-based hospital system, we identified a total of 234 patients (age 79 [IQR:70-85] years, n=56 (23.9%) women) with ATTR-CM, defined by the presence of a positive bone scintigraphy scan (or pharmacotherapy with an approved transthyretin stabilizer) between 2015 and 2023. Using 10:1 age- and sex-matched controls, we independently trained convolutional neural network algorithms to discriminate ATTR-CM from controls using i) ECG images (AUROC 0.915) or ii) echocardiographic studies by incorporating all available views (AUROC 0.93). In a leave-out testing set of n=82 individuals with serial ECGs and n=49 individuals with serial echocardiograms we characterized longitudinal patterns in the evolution of the AI ECG and echo-based scores, and estimated the percentage of individuals that would have screened positive across distinct time intervals.

Results
In the leave-out testing set 52.4% and 34.7% of all individuals who went on to receive a diagnosis of ATTR-CM would have screened positive by AI deployed to ECGs and echocardiograms, respectively, 1 to 3 years before their confirmatory testing, with the percentage increasing to 75.6% and 69.4% in the 12 months before their eventual diagnosis (A). Across both modalities, there was a longitudinal increase in AI predictions when comparing the median of all studies performed more than a year before diagnosis versus the median of any studies performed within 12 months of diagnosis (AI-Echo: 0.20 [IQR: 0.04-0.35] to 0.49 [0.24-0.59] & AI-ECG: 0.07 [0.02-0.20] to 0.32 [0.11-0.49], p&lt;0.001 for both) (B), consistent with evolution in the ECG and echocardiographic signature of ATTR-CM before its clinical diagnosis.

Conclusions
We demonstrate that AI applied directly to ECG images and echocardiography may enable scalable monitoring of subclinical ATTR-CM progression.
Coronary plaque volume burden and composition in patients with non-hemodynamically significant coronary artery plaques and systemic inflammation
Authors: Martinez Vives P , Ramos-Cano P , Monteagudo-Ruiz J M , Piris A , Garcia-Sebastian C , Carrion-Sanchez I , Antonana S , Hinojar R , Garcia-Martin A , Gonzalez A , Jimenez-Nacher J J , Arribas Marcos A , Fernandez Mendez M A , Zamorano J L , Fernandez-Golfin C 
Published: October 2024

Abstract

Introduction
Atherosclerotic coronary disease is a leading cause of morbidity and mortality worldwide. Systemic inflammation can affect plaque composition and thus increase cardiovascular risk. Identifying plaque characteristics in these patients could be useful to learn how inflammation (identified by easy to access parameters, like high ferritin and CRP) affects plaque composition in these challenging patients.

Purpose
We aimed to evaluate the association of systemic inflammation identified by high ferritin and/or high C-reactive protein (CRP) with coronary plaque volume and composition in patients with non-hemodynamically significant coronary artery plaques (stenosis &lt;50%).

Methods
We prospectively recruited 109 patients referred for noninvasive CT angiography (from November 2023 to January 2024) with suspected coronary artery disease. 20 had totally/partially non-calcified, non-significant coronary plaques (stenosis &lt;50%). Plaque volume was measured. Plaque components were stablished as calcified (&gt;200 UH), lipidic (&lt;60 UH) and fibrous (60-200 UH). Systemic inflammation was identified when ferritin was &gt;300 ng/mL and/or C-reactive protein CRP was &gt;5 mg/L, according to our laboratory high normal limits. CT scan images were acquired with a 128 detectors dual-layer CT scan with prospective-retrospective/synchronization. Intravascular iodine-based contrast agent was administered.

Results
Mean age was 60 ± 11 years old and 75% of patients were men. 55% had high blood pressure, 65% were current or previous smokers and 40% had dyslipidemia (35% received statins). 10% were diabetic. There were no difference between groups for these characteristics.
We analyzed 33 plaques. Fibrous plaque volume was found to be significantly higher in patients with high ferritin (66.9 vs 32.5 mm3; p = 0.04) and in patients with high CRP (78.7 vs 36.4 mm3; p = 0.05). The percentage of fibrous plaque tended to be higher in patients with higher ferritin and CRP (54.9 vs 38.9; p = 0.06 and 60.6 vs 40.7%; p = 0.07, respectively).

Conclusions
Systemic inflammation affecting coronary plaque composition in non-hemodynamically significant coronary atherosclerotic disease can by identified by high ferritin and high CRP levels. It is associated with higher fibrous plaque volumes. This finding suggest that systemic inflammation can associate more vulnerable plaques and might benefit from more aggressive management of non-hemodynamically significant atherosclerosis.TableFigure
Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis
Authors: Moreno De Redrojo Cortes L , Gallego Delgado M , Eiros Bachiller R , Canadas Salazar J , Garcia Berrocal B , Perez Sanchez P , Sanchez Puente A , Rincon Diaz L M , Garcia Monsalvo M , Laffond Elvira A , Hernandez Martos A , Bracho Bracchitta D , Alvarez Martinez C , Sanchez Fernandez P L , Villacorta Arguelles E 
Published: October 2024

Abstract

Introduction and purpose
transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding.

Methods
a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed.

Results
184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale.

Conclusions
bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.
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

Abstract

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

Abstract

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 &lt;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 (&gt;200 UH), lipidic (&lt;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 (&lt;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

Abstract

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 (&gt;18 years) with &gt; 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

Abstract

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