bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of scintigraphy with [99mTc]Tc-DPD for the detection of transthyretin cardiac amyloidosis. Reference centre experience in an endemic area
Authors: Orta Tomas N , Soledad Salomon C , Ripoll Vera T , Rubi Sureda S , Fortuny Frau E , Bosch Rovira M T , Losada Lopez I , Gonzalez Moreno J , Cisneros Barroso E 
Published: October 2024

Abstract

Background
Cardiac amyloidosis (CA) is an infiltrative disorder caused by protein deposition, being transthyretin amyloidosis (ATTR) and primary amyloidosis (AL) the most common forms of CA. ATTR can occur in a hereditary form (ATTRv) or wild-type (ATTRwt). Our area is endemic for ATTRv due to the Val30Met mutation.

Purpose
To analyse the usefulness of scintigraphy with [99mTc]Tc-DPD (DPD-CS) in an endemic area and its relationship with the diagnostic of CA.

Methods
We conduct a retrospective study (04/2013-12/2022) of DPD-CS performed for suspected/screening of CA. Our acquisition protocol consists of performing planar images after 3h p.i.(anterior, left anterior oblique and left lateral) +/- SPECT/CT. The assessment of myocardial uptake was evaluated using the Perugini scale (PS: 0-3), considering 2 and 3 as positive scans. DPD-CS results were classified based on the suspicion of CA, according to the 2021 ESC guidelines (we considered cardiomyopathy if: left ventricle hypertrophy ≥12 mm + ≥3 typical signs/symptoms), as well as according to their final diagnosis: ATTRv, asymptomatic carriers, ATTRwt, AL, AA and other non-amyloid (NA) causes. Clinical findings were correlated with the results of the DPD-CS.

Results
509 DPD-CS were performed in 478 patients (median age:73 years [22-95], 62% men). Median follow-up: 4.17 years. 127/478 patients were classified with cardiomyopathy (131/509 DPD-CS) and 351/478 without cardiomyopathy (378/509 DPD-CS).
115/509 positive DPD-CS (PS-2: 17, PS-3: 98): 113 had cardiomyopathy (55 ATTRv, 60 ATTRwt) and 2 without cardiomyopathy (1 ATTRv, 1 asymptomatic carrier). These latter two patients developed cardiomyopathy during the follow-up.
394/509 negative DPD-CS (PS 0: 387, PS 1: 7): 18 with cardiomyopathy (1 ATTRv, 1 carrier, 3 AL and 13 NA) and 376 without cardiomyopathy (30 asymptomatic carriers, 88 ATTRv, 2 AA, 9 AL and 247 NA). One patient with cardiomyopathy and ATTRv had initial negative DPD-CS, but became positive DPD-CS on follow-up. All ATTRv without cardiomyopathy presented polyneuropathy.
Final diagnoses (according to DPD-CS number): 143 ATTRv (140 Val30Met, 2 Val122Ile, 1 Glu495Gln), 32 carriers (29 Val30Met, 2 Val122Ile, 1 His51Asn), 61 ATTRwt,12 AL, 2 AA and 259 NA. The analysis obtained after correlating the results of the DPD-CS regarding the presence of cardiomyopathy was: sensitivity 86.25%, specificity 99.47%, PPV 98.26% and NPV 95.43%.

Conclusion
Our study reaffirms the usefulness of DPD-CS in the non-invasive diagnosis of transthyretin CA. DPD-CS has an additional value in endemic areas for the early detection of CA in asymptomatic patients.
Protosappanin a protects DOX-induced myocardial injury and cardiac dysfunction by targeting ACSL4/FTH1 axis-dependent ferroptosis
Authors: Cui J , Chen Y , Yang Q , Zhao P , Yang M , Wang X , Mang G , Yan X , Wang D , Tong Z , Wang P , Wang N , Liu M , Zhang M , Yu B 
Published: October 2024

Abstract

Background
Doxorubicin (DOX) is a breakthrough drug in cancer therapy that mediates irreversible dosedependent cardiotoxicity with poor outcomes.Cardiomyocyte ferroptosis plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC). Agents that block DOX-induced cardiomyocyte ferroptosis may have clinical utility in the treatment of DIC.

Purpose
We pursued the potential role of protosappanin A (PrA), an active constituent extract from traditional Chinese hematoxylin, on DOX-induced cardiac dysfunction.

Methods
We established acute DIC murine models to investigate the role of PrA in DOX-induced cardiotoxicity.In vivo, western blotting was performed to assess the levels of classical proteins associated with the iron death pathway, while Prussian blue staining and DHE staining were utilized to measure iron ion levels and reactive oxygen species respectively. In vitro, DOX-induced H9C2 cells model was established and the level of ferroptosis-related indicators were detected,such as iron, reactive oxygen species (ROS), and lipid peroxides. Proteome microarray, Molecular docking and Cellular thermal shift assay were used to identify the molecular targets (ACSL4 and FTH1) of PrA. Pull-down assay was used to validate the interaction of PrA with ACSL4 and FTH1 proteins in lysates from H9c2 cells, and explored theirs possible mechanism of action. Finally, we investigated the in vivo effect of PrA treatment in mice challenged with a myocardial ischemia-reperfusion mouse model.

Results
We report for the first time that PrA ameliorates myocardial damage and cardiac dysfunction in a mouse model of DIC. PrA improves DOX-induced ferroptotic phenotypes in cardiomyocytes, as demonstrated by reduced production of iron, reactive oxygen species (ROS), and lipid peroxides, thereby preserving mitochondrial homeostasis. PrA physically combines with the ferroptosis-related protein acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), thus conferring the following regulatory mechanisms: PrA inhibits ACSL4 phosphorylation and subsequent phospholipid peroxidation; PrA prevents FTH1 autophagic degradation and subsequent ferrous ions (Fe2+) release. Notably, the cardioprotective and antiferroptotic activities of PrA are verified in a myocardial ischemiareperfusion mouse model.

Conclusion
Our studies indicate for the first time that PrA has a superior protective effect against DOX-induced cardiotoxicity via inhibiting a dual ferroptosis-assistance mechanism of the ACSL4/FTH1-dependent axis. We unveil a novel pharmacological inhibitor that targets ferroptosis, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.
Incidence and risk factors for development of left ventricular hypertrophy in Fabry disease
Authors: Monda E , Bakalakos A , Lachmann R , Syrris P , Limongelli G , Murphy E , Hughes D , Elliott P M 
Published: October 2024

Abstract

Background
Left ventricular hypertrophy (LVH) is the principal cardiac manifestation of Fabry disease (FD). This study aimed to determine the incidence and predictors of LVH development in a contemporary cohort of patients with FD and no LVH at baseline evaluation.

Methods
Consecutively referred adult (age ≥16 years) patients with FD were enrolled into an observational cohort study. Patients were prospectively followed in a specialist cardiomyopathy centre and the primary endpoint was the first detection of LVH (left ventricular mass index (LVMi) ≥115 g/m2 in men and ≥95 g/m2 in women).

Results
From a cohort of 393 patients, 214 (age 35.8 ±13.8 years; 61 [29%] males) had no LVH at first evaluation. During a median follow-up of 9.4 years (interquartile range [IQR] 4.7-12.7), 55 patients (24.6%) developed LVH. The estimated incidence of LVH was 11.3% (95% confidence interval [CI] 6.5-16.1) at 5 years, 29.1% (95%CI 21.5-36.7) at 10 years, and 45.0% (95%CI 33.8-62.4) at 15 years of follow-up. On multivariable analysis, independent predictors for LVH development were age (hazard ratio [HR] 1.04 [95%CI 1.02-1.06] per 1 year increase, p-value &lt;0.001), male sex (HR 2.90 [95%CI 1.66-5.09], p-value &lt;0.001), and an abnormal ECG (HR 3.10 [95%CI 1.72-5.57], p-value &lt;0.001). The annual rate of change in LVMi was +2.77 (IQR 1.45-4.62) g/m2/year in males and +1.38 (IQR 0.09-2.85) g/m2/year in females (p-value &lt;0.001).

Conclusions
Approximately one quarter of FD patients developed LVH during follow-up. Age, male sex, and ECG abnormalities were associated with a higher risk of developing LVH in patients with FD.Central Illustration
Correlation of coronary and carotid atheroma volume in patients with severe and familial hypercholesterolemia (VOCCA-3D HF)
Authors: Fawaz S , Boulestreau R , Pucheu Y , Liegey J S , Gaufroy A , Broitman J , Ducos C , Bazin C , Sridi-Cheniti S , Coste P , Cochet H , Montaudon M , Couffinhal T 
Published: October 2024

Abstract

Background
Stratifying the risk of CV event of familial hypercholesterolemia (FH) patients is not always simple, as they usually are excluded from CV disease risk estimation scores. It has become increasingly clear over the last several years that the heterogeneity in risk among patients with FH is far greater than previously appreciated. To that end, not all patients with FH will require the use of PCSK9 inhibitors.

Aim
We described the type of coronary artery disease (CAD) in patients with severe and familial hypercholesterolemia and without known atherosclerotic cardiovascular disease and searched for the best determinants of CAD. We searched for correlation between epicardial adipose tissue and CAD.

Methods
We evaluated the atherosclerosis burden with a combination of calcium score (CAC), computed tomography angiography, and the quantification of coronary atheroma volume and the analysis of the composition of the plaques, alongside with the use of ultrasonography of supra-aortic trunks with 3D quantification of atheroma volume. We also evaluated epicardial adipose tissue volume with CT.

Results
We analyzed 89 individuals with LDL-c &gt; 190 mg/dL, with a mean age of 56,7 years. LDL-c burden was high (maximal LDL-c level across life of 2.77 g/L in mean, duration of hypercholesterolemia of 21.5 years in mean). Forty percent of the individuals had a CAC score of zero, and only one patient had non-calcified atheroma despite a CAC score of zero. Among patients with CAD, 50% had a CAC &gt; 100 AU, 9% had a stenosis &gt; 50%. Coronary atheroma volume amounted to a median of 50.9 mm3 in patients with CAD, representing 4% of the analyzed coronary lumen volume, and was mainly made of calcified and non-calcified fibrous plaques. At-risk plaques were not frequent (9% of low-attenuation plaques, 15.2% of positive remodeling and 2% of napkin-ring sign) in patients with CAD. Fifty percent of the individuals had no carotid plaque. Among various clinical and biological risk factors (LDL-year-score, age, blood pressure, smoking, familial history, diabetes), the carotid atheroma volume was the only variable to be independently correlated with both CAC (t=3.1, p=0.006) and coronary atheroma volume (t=4.9, p&lt;0.001). Epicardial adipose tissue was not associated with CAD.

Conclusion
A significant part of the patients with severe and familial hypercholesterolemia has no CAD, however half of the patients with CAD have an important atherosclerosis burden, which can be well predicted by the carotid atheroma volume. Such a screening could help identify the individuals who would benefit the most from intensive cholesterol-lowering drugs.CAC categoriesType of coronary plaques
New clinical staging proposal applied to a Fabry cardiomyopathy cohort
Authors: Oliveira C , Marques C , Santos J , Fortuna I , Santos L , Pinho A , Cabrita A , Oliveira J P , Martins E 
Published: October 2024

Abstract

Background
Fabry disease (FD) is a rare cause of hypertrophic cardiomyopathy (HCM), and early diagnosis is important considering the response to enzyme replacement or chaperone therapies. Recently, a practical clinical staging for Fabry cardiomyopathy was proposed by Olivotto et al 2023, considering several features, being potentially useful for standardizing the criteria for initiation and response assessment to therapy. Imaging characterization of hypertrophy and fibrosis are critical key items to determine stages. This new proposal suggested 4 main stages (0, I, II, III) according to these parameters. Stages 0 and I are further divided in 2 sub-stages according to minor findings and hypertrophy severity, respectively. Unfortunately, not all patients with Fabry cardiomyopathy are identified early in the disease, limiting the response to treatment.

Aim
Our study aimed to evaluate retrospectively the staging of Fabry cardiomyopathy at first imaging cardiac evaluation according to the recent proposal (1), in a cohort of 35 patients with FD at a reference centre of Fabry disease.

Results
At the first cardiac evaluation, the group of patients had a median age of 46 years (28-68 years), 69% were female and 5% were already under enzymatic therapy. The majority of Fabry patients (66%) were in non-hypertrophic stage 0: 4 patients in 0A with no detected cardiac involvement and 19 patients in 0B with subclinical cardiac findings (17% presenting diastolic dysfunction, 14% impaired global longitudinal strain, 6% hypertrabeculation, 6% reduced native T1, 3% short PR duration, 3% cardiac symptoms). In hypertrophic stage I, 14% of patients were classified according to the presence and severity of LVH: 3 in IA (12-15 mm) and 2 in IB (&gt;15mm). All patients (n=3, 9%) in hypertrophic fibrotic stage II presented non-extensive late enhancement (&lt; 3 LV segments) in the first CMR. Patients with overt dysfunction or stage III (n=4; 11%), presented diffuse myocardial fibrosis (&gt; 3 LV segments) or impaired systolic function (LVEF &lt; 50%).

Conclusion
In our cohort patients, the new staging scheme allows us to identify and classify the different stages of FD cardiomyopathy. The majority of patients were unexpectedly identified in early disease stages, but that could be related to diagnosis in the context of familial screening.
This proposal seems useful for clinical staging standardization to facilitate the evaluation of responses to treatments and to predict outcomes, however, needs to be validated in larger and prospective studies.
A comprehensive evaluation of available evidence of mavacamten in obstructive HCM: a meta-analysis of randomised controlled trials
Authors: Ramadan S , Abdelaziz A , Husain M A , Mesbah S M , Elnady M I , Mohamed A E , Hafez A H , Ghaly R , Mostafa M , Abdelazeem B , Banour S , Lavie C J , Slipczuk L 
Published: October 2024

Abstract

Introduction
Obstructive hypertrophic cardiomyopathy (HCM) poses a significant clinical challenge, characterized by left ventricular hypertrophy and impaired cardiac function. mavacamten, a novel medication targeting the sarcomere protein myosin, has emerged as a promising therapeutic option for patients with symptomatic obstructive HCM. Despite its potential efficacy, the comparative effectiveness and safety of Mavacamten remain uncertain, necessitating a comprehensive evaluation of available evidence.

Purpose
We aimed to give a comprehensive appraisal on mavacamten as a treatment option for patients with obstructive HCM informing clinical decision-making.

Methods
We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until February 2024. We included randomised controlled trials (RCTs) comparing mavacamten versus placebo in patients with obstructive HCM. The primary outcomes were improvement in NYHA class, Change from baseline in KCCQ-CSS, and the incidence of atrial fibrillation. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data.

Results
Four randomised controlled trials involving 503 patients were included in the final analysis. the overall odds ratio demonstrated a substantial preference for Mavacamten in achieving more than a one-level improvement in NYHA functional class from baseline (OR: 3.83 (95% CI [2.54 to 5.77], P=0.0001). However, there was no significant difference in terms of KCCQ-CSS (MD= 1.06, 95% CI [ -0.03 to 2.15], P=0.06) or the incidence of atrial fibrillation (OR=1.27, 95% CI [0.51 to 3.14], P=0.60).

Conclusion
Mavacamten showed a significant improvement on NYHA functional class, with no observed significance in terms of reducing the incidence of AF, or improving the KCCQ-CSS score.KCCQ-CSSNYHA
Coronary CT angiography using photon counting CT for the detection of coronary artery stenoses and coronary atherosclerotic plaque: comparison of reconstructions with 0.2 mm and 0.4 mm slice thickness
Authors: Zuhair Kassem T , Achenbach S , Moshage M , Weidinger F , Jung S , Smolka S , Marwan M 
Published: October 2024

Abstract
Photon Counting CT allows the acquisition of high-resolution data sets with 0.2 mm reconstructed slice thickness. It is unknown whether the detection of coronary artery stenoses, of coronary plaque or of vulnerable plaque characteristics is improved in data sets that employ maximum resolution. We therefore compared the identification of above characteristics in data sets reconstructed with 0.2 mm and 0.4 mm slice thickness
In 30 patients with suspected coronary artery disease, sinus rhythm, a heart rate ≤65 beats/min, and body weight ≤ 100 kg, high-resolution data sets were acquired by photon counting CT (60 ml contrast i.v. at 6 ml/s) after s.c. application of nitrates in inspiratory breathhold. Data were reconstructed with 0.2 mm slice thickness at 0.1 mm increment and 0.4 mm slice thickness at 0.2 mm increment. Next to quantitative analysis of image quality parameters, all data sets were evaluated by two independent expert reviewers concerning subjective image quality as well as the ability to determine the presence of coronary artery stenoses, calcified and non- calcified plaque, as well as parameters of plaque vulnerability (positive remodeling, necrotic core, density &lt; 30 HU and napkin-ring sign) using a 5-point Likert scale (-2 to +2) and a dedicated 11-segment coronary model.
Of the 30 patients, 47% were male (mean age 58±12 years, mean heart rate 53±6 bpm, mean body weight 80±15 kg). The median dose length product was 508 mGy*cm. Mean image noise was 42±7 HU vs. 34±7 HU for 0.2 mm vs. 0.4 mm reconstructions (p &lt; 0.001). The median image quality score was significantly higher for 0.2 mm reconstructions (3.8±0.8 vs 3.6±0.7). Of 335 coronary segments, none were classified as "unevaluable" while 87% vs. 76% were classified as "perfect" in 0.2 mm vs. 0.4 mm reconstructions (p &lt; 0.001). Full confidence to rule-in or rule out significant coronary stenoses was achieved in 93% of segments in both reconstructions. The number of non-calcified plaques identified in 0.2 mm reconstructions was numerically higher than in 0.4 mm reconstructions (77 vs. 71, p = n.s.). On the Likert scale, the confidence to identify parameters of plaque vulnerability was significantly higher for 0.2 mm reconstructions (1.93 vs. 1.85, p &lt; 0.001). In a selected patient group, photon counting CT coronary angiography demonstrated excellent image quality and an extremely low rate of unevaluable coronary segments. High-resolution reconstructions improve subjective image quality as was as the assessment of vulnerable plaque characteristics.
Left ventricular apical aneurysms and outcomes in hypertrophic cardiomyopathy
Authors: Malcolmson J , Amarin M , Davies W , Husselbury T , Mezzanotte G , Learoyd A , Petersen S E , O'mahony C , Mohiddin S A 
Published: October 2024

Abstract

Background/Introduction
The presence of left ventricular apical aneurysm (LVAA) has been shown to be associated with increased risk of adverse events in patients with hypertrophic cardiomyopathy (HCM). However, the between LVAA size and outcomes is uncertain.

Purpose
To explore associations between baseline LVAA diameter and progressive changes in LVAA size over time and poor outcomes in HCM patients.

Methods
Our HCM multimodality imaging database (transthoracic echocardiography (TTE) or cardiac magnetic resonance (CMR)) was retrospectively assessed for studies reporting LVAA, defined as one or more akinetic or dyskinetic apical segments. LVAA size (widest systolic diameter in millimetres in the transverse plane) was recorded at two time points: earliest identification and most recent imaging, with LVAA size progression (mm/year) calculated. Patients’ electronic records were reviewed for composite outcome including stroke, apical thrombus, death, and appropriate therapy from implantable cardioverter defibrillator (ICD). Continuous variables are presented as mean ± standard deviation (SD), categorical data numerically or as percentages. Comparisons between groups were made using Wilcoxon ranks sum and Fischer exact test for continuous and binary variables, respectively. Cox regression was used to assess independent associations with composite outcomes. A p value of &lt;0.05 was considered statistically significant.

Results
A total of 106 patients were identified with LVAA and clinical follow-up (mean age 64.7±11.4 years, 70% male). Mean follow-up duration was 6.5±3.0 years. Baseline LVAA was confirmed by CMR and TTE in 70 and 30% of cases respectively. Mean LVAA size at baseline was 16.2±7.6 mm (range 6-56 mm). During multivariate Cox analysis, baseline LVAA size in mm was independently associated with the composite outcome (HR 1.04, 95% CIs 1.0 to 1.08, p=0.04). Mean duration between baseline and maximal LVAA size scan was 5.4±3.0 years. Median progression in LVAA size was 1.0 (IQR 0.6 to 1.8) mm per annum (range 0.0 to 8.1 mm). During multivariate analysis, LVAA progression rate in mm per year was independently associated with the composite outcome (HR 1.4 95% CIs 1.11 to 1.7, p=0.002).

Conclusion(s)
These data support the association between LVAA size and poor outcomes in HCM patients. We also demonstrate the progressive nature of LVAAs and indicate those more rapidly increasing in size are at highest risk of adverse events, with potential implications for management strategies.
Phenotypic and clinical evaluation of hypertrophic cardiomyopathy caused by the deep intronic variant MYBPC3:c.2308+227G&gt;A
Authors: Gallego Delgado M , Rodriguez Diego S , Lorenzo Hernandez S M , Diez Pelaez E , Rincon Diaz L M , Heredero Jung D , Merino A M , Roldan A , Mayorga A , Garcia Salgado M J , Ruiz Olgado M J , Perdiguero Martin P D , Garcia Berrocal B , Sanchez P L , Villacorta E 
Published: October 2024

Abstract

Introduction
Deep intronic variants can be the cause of hypertrophic cardiomyopathy (HCM), although these regions of the genome are not always sequenced in genetic studies. It is unknown if there are differences in phenotypic expressivity and prognosis compared to other forms of HCM.

Objective
to describe the phenotypic and clinical characteristics of a cohort of probands with HCM due to the variant MYBPC3:c.2308+227G&gt;A and compare whether there are differences with other HCM groups.

Methods
Retrospective observational study of the clinical and imaging data of patients with HCM evaluated in a reference center for Inherited Cardiovascular Disease. Probands carrying the MYBPC3:c.2308+227G&gt;A variant, other pathogenic or likely pathogenic variants in MYBPC3 and those with a negative genotype (NGS sequencing) were included.

Results
151 probands with HCM (70% males; age of diagnosis 56±14) were included, 26 carrying MYBPC3:c.2308+227G&gt;A (figure). No significant differences were found between the three groups in terms of baseline characteristics, phenotypic features or risk profile. In the survival curves, the subgroup with the variant had a earlier tendency to events, particularly for heart failure (figure).

Conclusions
HCM associated with MYBPC3:c.2308+227G&gt;A variant does not have differential characteristics in its phenotypic and clinical expression, having a similar prognosis to other HCM in our cohort.