bluuebunny/crossref_metadata_2025_split huggingface dataset:
T1 mapping in patients with Fabry disease predicts functional and morphological abnormalities in cardiac MRI
Authors: Gatterer C , Mundigler G , Graf S , Beitzke D , Sunder-Plassmann G 
Published: November 2020

Abstract

Introduction
About 50% of Fabry disease (FD) patients develop cardiac manifestation, also known as Fabry cardiomyopathy. Beside echocardiography, cardiac magnetic resonance imaging (CMR) is included in the regular assessment of these patients, allowing non-invasive tissue characterization via T1 Mapping but also evaluation of morphological and functional characteristics.

Purpose
Myocardial strain measured by feature-tracking CMR has been previously shown to be a sensitive indicator of mechanical dysfunction in different diseases. We therefore evaluated changes of these parameters over the time, potentially reflecting disease progression in patients with FD. Furthermore, we also assessed the association of T1 mapping with follow-up changes of myocardial strain. Thus, our data may provide novel insights about cardiac changes in the natural course of the disease and cardiac effects of specific therapies.

Methods
We used post processing software for CMR to analyze baseline and follow-up cardiac involvement in a cohort of FD patients who were enrolled in the KarMA study, which examines cardiac changes over time. We measured left ventricular mass (LVM), left ventricular end-systolic and end-diastolic volume (LVEDV, LVESV), left ventricular ejection fraction (LVEF), mean left ventricular T1 relaxation times (T1), global longitudinal strain (GLS), global regional strain (GRS) and global circumferential strain (GCS). Statistical analyses included T-test and Spearman's correlation.

Results
CMR Images of 33 Patients were analyzed (22 females; mean age 40.8±16.3 years; at baseline 17 were therapy naïve and 16 on ERT), of whom 31 underwent a second CMR. In 18 patients (10 females; 44.9±16.0 years) myocardial strain measurement by feature-tracking was possible in both examinations. T1, LVM, LVEDV and LVESV, LVEF as well as GLS, GRS and GCS showed no significant change during the mean follow-up period of 43 (±17) months in all patients. However, we found a significant correlation of baseline T1 (967±84.5ms) with follow up values of LVM (84.9±32.7 g/m2; p=0.02, ρ=−0.462), LVEDV (63.0±17.6 g/m2 p=0.049 ρ=−0.398) and GRS (70.2±14.2% p=0.011 ρ=−0.5). Baseline T1 also correlated with changes in LVM (p=0.036 ρ=−0.44) and changes of GCS (p=0.001 ρ=−0.858) from baseline to follow up. Differences in T1 from baseline to follow up correlated with follow-up values of GLS (−19.5±3.57 p=0.044, ρ=−0.414) and GRS (69.1±18.7 p=0.003, ρ=−0.588).

Conclusion
T1, reflecting glycosphingolipid accumulation might predict changes in LVM, LVEDV and strain. Moreover, changes in T1, reflecting myocardial remodeling, go in parallel with worse left ventricular function shown by more positive values of GLS, GCS and GRS. T1 mapping together with strain parameters are important markers for monitoring patients with FD.

Funding Acknowledgement
Type of funding source: None
Defining the prognostic value of [15O]H2O positron emission tomography derived myocardial ischemic burden
Authors: Van Diemen P.A , Wijmenga J.T , Driessen R.S , Bom M.J , Schumacher S.P , Stuijfzand W.J , Raijmakers P.G , Everaars H , De Winter R.W , Van De Ven P.M , Van Rossum A.C , Danad I , Knaapen P 
Published: November 2020

Abstract

Background
A myocardial ischemic burden (IB) of 10% is used to denote high-risk patients with coronary artery disease (CAD). This threshold has primarily been assessed by single-photon emission computed tomography. Differences in the pharmacokinetics of the utilized traces, higher resolution of positron emission tomography (PET), and lastly differences in assessment of IB might lead to a higher prognostic threshold for quantitative PET.

Purpose
To determine a [15O]H2O PET derived IB to identify low (annualized event rate (AER) &lt;1.0%) and high (AER ≥3%) risk CAD patients.

Methods
623 patients who underwent [15O]H2O PET because of suspected CAD and in whom follow-up was obtained were included. The IB was defined as the percentage of myocardium with a hyperemic blood flow (hMBF) ≤2.3 ml/min/g and by a coronary flow reserve (CFR) of ≤2.5. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Time-dependent ROC curves were constructed for the prediction of the endpoint within the first 5-years, based on these curves thresholds were selected for which specificity was maximized and sensitivity was at least 80%. Patients were classified as having a high IB if their respective IBs were above the prognostic thresholds and as having a low IB if not.

Results
During a median follow-up of 6.7 years, 34 (6%) patients died and 28 (4%) experienced a MI resulting in 62 (10%) endpoints. An IB of 24% and 28% for hMBF and CFR, respectively, was found to be the optimal threshold to define prognosis. Patients with a high hMBF or high CFR IB had worse outcome compared to patients with a low IB (log-rank p&lt;0.001 for both), with AERs of 0.6% vs. 2.8%, and 0.6% vs. 2.4% (p&lt;0.001 for both), respectively. Patients with a concordantly high hMBF and CFR derived IB had the worst outcome (AER: 3.1%), whereas patients with a concordantly low or discordant IB result had a similarly low event rate of 0.5% and 0.9% (p=0.953), respectively (log-rank p=0.445). A concordantly high hMBF and CFR IB was an independent predictor of adverse outcome beyond clinical characteristics (adjusted hazard ratio: 3.52, p&lt;0.001).

Conclusion
An IB of 24% and 28% for hMBF and CFR was found to be the optimal prognostic threshold. Both measurements can be used to determine patients outcome. However combining hMBF and CFR IB results leads to a further refinement of risk-stratification allowing for the identification of low (concordant low or discordant IB result) and high (concordant high IB result) risk CAD patients.

Funding Acknowledgement
Type of funding source: None
Diagnostic accuracy of cardiac computed tomography and 18F-fluorodeoxyglucose with positron emission tomography/computed tomography in cardiac masses
Authors: D'Angelo E.C , Paolisso P , Foa A , Bergamaschi L , Magnani I , Toniolo S , Donati F , Rinaldi A , Lovato L , Fanti S , Leone O , Rucci P , Pacini D , Galie N , Pizzi C 
Published: November 2020

Abstract

Background
Understanding the nature of cardiac masses represents a challenge for clinicians in order to select the appropriate therapeutic strategies. The diagnostic accuracy of cardiac computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) with positron emission tomography/CT (PET/CT) in identifying the nature of cardiac masses has not been evaluated before in a large population.

Purpose
To assess the diagnostic value of CT and 18F-FDG PET/CT in defining the nature of cardiac masses, integrating morphologic features and metabolic activity.

Methods
Out of 223 we selected a final cohort 60 patients which underwent cardiac CT scan and 18F-FDG PET/CT. All masses had histological certain, apart from thrombi, in which was defined radiologic resolution after adequate anticoagulant treatment. For each mass, eight morphologic CT signs and standardized uptake value (SUVmax, SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in 18F-FDG PET, were evaluated.

Results
Twenty patients had benign cardiac masses and 40 patients malignant cardiac masses. Irregular tumour margins, pericardial effusion, invasions, solid nature of the mass, mass diameter, TC contrast up-take and pre-contrast characteristics were strongly associated with the malignant nature of cardiac masses (p&lt;0.001). Additionally, the presence of at least four CT signs was able to discriminate malignancies, withsensitivity of 95% and specificity of 95% (AUC=0.988, 95% CI 0.969–1). The mean value of SUVmax, SUVmean, MTV and TLG was significantly higher in malignant cardiac masses than in benign lesions (p&lt;0.001). ROC curve for diagnostic accuracy of 18F-FDG PET/CT parameters in detecting malignant lesions showed an excellent performance of SUV (AUC=0.948, 95% CI 0.891–1), MTV (AUC=0.928, 95% CI 0.841–1) and TLG (AUC=0.961, 95% CI 0.902–1).

Conclusions
In patients with cardiac masses, cardiac computed tomography and 18F-FDG PET/CT findings provide independent and incremental prognostic information regarding their nature. A systematic use of CT and 18F-FDG PET/CT is therefore useful for diagnostic and therapeutic purposes.
PET-CT evaluation of cardiac masses

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): S. Orsola Malpighi Hospital, University of Bologna
Prognostication of cardiac amyloidosis by pittsburgh b compound positron emission tomography
Authors: Maqsood H , Shakeel H.A , Khan M.D , Shoukat H.F , Shah S.A.Y 
Published: November 2020

Abstract

Introduction
Regardless of the underlying pathogenesis of amyloid production, cardiac involvement is the leading cause of morbidity and mortality in systemic amyloidosis. In the cardiac variant, there is an extracellular deposition of amyloid substance throughout the heart. The infiltrative process results in ventricular wall thickening with concentric hypertrophy and low cardiac output. The PiB compound has been promising for the detection of amyloid deposits in the brain but it remains unknown whether this noninvasive evaluation can predict the prognosis of patients with cardiac amyloidosis.

Purpose
This study sought to investigate the efficacy of 11C-Pittsburgh B (PiB) positron emission tomography for prognostication of cardiac amyloidosis by noninvasively imaging the myocardial amyloid deposition.

Methods
A total of 33 consecutive patients were enrolled in this prospective pilot study with suspected cardiac amyloidosis. The amyloid deposit was assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET.

Results
It was found that the degree of myocardial 11C-PiB PET uptake was significantly greater in the patients of cardiac amyloidosis compared with control group subjects and was parallel with the degree of amyloid deposit on histology (p&lt;0.001). When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial 11C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p=0.013). The clinical outcome was significantly predicted by the degree of myocardial PiB PET uptake on multivariate Cox regression analysis (adjusted hazard ratio: 1.191; 95% confidence interval: 1.062 to 1.340; p=0.005).

Conclusion
Our study concludes that the noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in cardiac amyloidosis patients.
11-C Pittsburgh B PET imaging

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): Self funding
Hybrid CMR- and FDG-PET-imaging gives new insights into the relationship of myocardial metabolic activity and fibrosis in patients with Becker muscular dystrophy
Authors: Florian A , Vehof V , Buether F , Stegger L , Yilmaz A 
Published: November 2020

Abstract

Background
Cardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course.

Purpose
Since the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach.

Methods
Hybrid CMR- and FDG-PET-imaging was performed in N=14 patients with BMD on a whole-body Biograph mMR system. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 minutes starting with tracer injection. Uptake values from 60 to 65 minutes p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake.

Results
In the total study group, mean left ventricular (LV) ejection fraction (EF) was 55±5% and there were 6/14 patients with a reduced LV-EF &lt;55%. A characteristic pattern of LGE in LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. Segmental FDG uptake was 88±6% in the LV lateral wall vs. 77±10% in the septal wall (p&lt;0.001). There was a rather inverse relationship between segmental FDG activity compared to segmental LGE extent (r=−0.33, p=0.089). There were N=6 patients (= ΔFDG-high) with a segmental difference in FDG uptake of &gt;15% in the LV lateral wall compared to the septal wall (lateral FDG = 91±3% vs. septal FDG = 69±8%; p&lt;0.001) while the remaining N=8 patients (= ΔFDG-low) showed a segmental difference in FDG uptake of ≤15% (lateral FDG = 85±7% vs. septal FDG = 83±5%; p=0.37). Patients in the ΔFDG-high group showed a similar LV lateral wall vs. septal wall LGE extent of 12±6% vs. 7±15%, respectively, while those patients in the ΔFDG-low group demonstrated a large difference in LV lateral wall vs. septal wall LGE extent of 33±24% vs. 4±6%, respectively.

Conclusions
Segmental FDG uptake – reflecting myocardial metabolic activity – is in principal higher in the LV free wall of BMD patients – possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsche Gesellschaft für Kardiologie (DGK)
Self-navigated MRI 3D whole heart sequence for non-enhanced aortic root measurement in transcatheter aortic valve intervention: comparison to cardiac CT
Authors: Holzknecht M , Pamminger M , Tiller C , Kranewitter C , Kremser C , Reindl M , Reinstadler S.J , Reiter G , Piccini D , Klug G , Bauer A , Metzler B , Mayr A 
Published: November 2020

Abstract

Purpose
To evaluate image quality, inter-observer reliability and diagnostic accuracy of self-navigated noncontrast 3D whole-heart magnetic resonance angiography (MRA) for transcatheter aortic valve intervention (TAVI) evaluation in comparison to standardized contrast-enhanced computed tomography angiography (CTA).

Methods
Whole-heart 1.5 T MRA was performed in 33 patients (aged 84 years [IQR 79–86], 48% male) for aortic root sizing and measurements of coronary ostia heights. A subgroup of 18 (55%) patients underwent additional CTA as gold standard for TAVI measurements. Image quality was assessed by a 4-point Likert scale, continuous MRA and CTA measurements were compared with regression and Bland-Altman analysis, valve sizing by kappa statistics.

Results
Median image quality of MRA as rated by two observers according was 1.5 [IQR 1.5–2.5]. In 4 patients (12%) one coronary ostium each (right coronary artery 3, left main artery 1) was not clearly definable on MRA. Inter-observer correlation was substantial to excellent (r=0.61 to 0.92) with a bias of 19 mm2 for annulus area (lower limit of agreement −59 mm2, upper limit of agreement 98 mm2; p=0.009). Aortic root and ostia height measurements by MRA and CTA showed substantial to excellent correlation (r=0.65 to 0.90) with no significant bias (all p≥0.333). Mean annulus area for MRA was 414±71 mm2 and for CTA 422±80 mm2 (r=0.9) with a bias of −8 mm2 (lower limit of agreement −79 mm2, upper limit of agreement −62 mm2; p=0.333). Regarding prosthetic valve sizing there was complete consistency between MRA and CTA-based decisions (κ=1).

Conclusion
Self-navigated noncontrast 3D whole-heart MRA enables reliable aortic root TAVI measurements without significant difference to standardized CTA. Prosthesis sizing by MRA measurements would completely match to CTA-based choice. However, in some cases coronary ostia may be difficult to define.

Funding Acknowledgement
Type of funding source: None
Impact of stress myocardial blood flow as an important predictor for major adverse cardiac and cerebrovascular event in hemodialysis patients, even in patients without myocardial perfusion abnormality
Authors: Umemoto N , Imaoka T , Inoue S , Oshima S , Itou R , Sakakibara T , Shimizu K , Ishii H , Murohara T 
Published: November 2020

Abstract

Background
In the clinical setting, ischemic heart disease (IHD) is a major problem not only in general patients but also in regular hemodialysis (HD) patients. Positron emission tomography (PET) is becoming a reliable modality for detecting coronary artery disease. Of course, PET illustrates myocardial perfusion (MP), PET also measures myocardial blood flow (MBF) directly. We have reported stress MBF is an independent predictor in HD population. Although some prior studies show CFR is an independent predictor for their prognosis in patients without MP abnormality, there is limited data about the predictability of stress MBF in HD patients without MP abnormality.

Methods
A total 438 of HD patients who undergone 13NH3PET for suspected IHD were enrolled. All patients were undergone13NH3PET at Nagoya Radiological Diagnosis Foundation. After we excluded patients whose summed stress score (SSS) &lt;4, we identified 182 eligible patients. Patients were divided into two group according to the median value of CFR levels; low stress MBF group (≤2.56) and high stress MBF group (&gt;2.56). We followed up them up to 4.2 years (median 2.4 years) and collected their data. We evaluated their major adverse cardiac cerebrovascular event. We performed Kaplan-Meyer analysis and multivariable cox regression models. Furthermore, we evaluated the incremental value with C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) when CFR added into a model with established risk factors.

Result
There were intergroup difference in baseline characteristics: age, gender, prior CVD and diabetes. Kaplan-Meyer analysis shows statistically intergroup difference [log rank p=0.013, hazard ratio (HR) 0.413, 95% confidential interval (CI) 0.220–0.775]. Multivariable cox regression model for MACCE shows CFR is an independent risk factor (p=0.004, HR 0.311, 95% CI 0.137–0.684). As regarding model discrimination, all of C-index (0.832 vs 0.796, p=0.15), NRI (0.513, p=0.008) and IDI (0.032, p=0.033) were greatest in a predicting model with established risk factors plus stress MBF.

Conclusion
The low stress MBF group has poor prognosis in MACCE comparing to the high stress MBF group. Stress MBF is an independent risk factor for MACCE. Adding stress MBF on conventional risk factors could more accurately predict MACCE in HD patients, even in patients without MP abnormality.

Funding Acknowledgement
Type of funding source: None
Preservation of the microtubule network to beat atrial fibrillation: role of SR-mitochondrial contacts
Authors: Li J , Brundel B.J.J.M , Zhang D 
Published: November 2020

Abstract

Background
Atrial fibrillation (AF), the most common tachyarrhythmia, is a progressive disease characterized by electrophathology, which is defined as the structural remodeling of atrial cardiomyocytes that underlies electrophysiological remodeling and contractile dysfunction and consequently AF progression. We recently discovered that disruption of microtubule network, by HDAC6 activation, is a key factor underlying structural remodeling and AF promotion in experimental models for AF and patients with AF. However, the molecular mechanism how microtubule disruption induces contractile dysfunction in AF is unclear. Sarcoplasmic reticulum (SR) and mitochondria are the central organelles for normal cardiomyocyte contraction by controlling the Ca2+ and energy (ATP) homeostasis. The crosstalk between SR and mitochondria via contacts, termed SR-mitochondria contacts (SMCs), is essential for normal mitochondrial and cardiac function. Interestingly, functional SMCs are highly dependent on intact microtubule network. This study aims to whether preservation of microtubule protects against AF via SMC pathway.

Methods and results
Tachypacing of HL-1 cardiomyocytes significantly impaired calcium transient (CaT) amplitude compared to normal paced cardiomyocytes. Pretreatment with microtubule stalilizer taxol and acetyl-CoA inducer β-hydroxybutyrate (βOHB) significantly protected against tachypacing-induced CaT loss. Moreover, by using immunoflurecent staining, mitochondrial associated membrane isolation and seahorse, we showed that tubacin, Taxol and βOHB also significantly inhibited the SMC reduction, attenuated tachypacing-induced mitochondrial dysfunction. Consistently, these microtubule stabilizer drugs also prevented tachypacing-induced contractile dysfunction in the Drosophila model for AF.

Conclusions
Preservation of microtubule network prevented the reduction of SMCs and the consequent mitochondrial and contractile dysfunction in HL-1 cardiomyocytes and Drosophila models for AF. Therefore, the microtubule-SMC pathway is a novel central therapeutic target for AF.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Dutch Heart Foundation
Rare SCN10A variants associated with cardiac conduction system diseases
Authors: Hayashi K , Fujino N , Furusho H , Usui S , Sakata K , Kato T , Tsuda T , Niwa S , Takeuchi K , Kawashiri M , Takamura M 
Published: November 2020

Abstract

Background
The genetic bases of cardiac conduction-system disease (CCSD) range from ion channelopathies to mutations in many other genes. Genome-wide association studies have shown common variants in SCN10A influence cardiac conduction. However, it has not yet to be determined whether vulnerability to CCSD is associated with rare coding sequence variation in the SCN10A gene.

Purpose
We sought to determine the clinical impact of rare variants in SCN10A in patients with CCSD and classified the variants according to the 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines.

Methods
We performed screening for rare variants (minor allele frequency ≤0.001) in SCN10A in CCSD patients with an onset at a young age under 65 or those who had a family history of pacemaker implantation (PMI) (n=40; 18 female; mean age, 41±18 years). We transiently expressed engineered variants in ND 7/23 cells, and conducted whole-cell voltage clamp experiments to clarify the functional properties of the Nav1.8 current.

Results
We identified nine rare variants in SCN10A in 7 patients. Two patients were carriers of two rare variants in SCN10A and 5 were carriers of one rare variant in SCN10A. Four patients were affected with sinus node dysfunction, 1 were atrioventricular block, and 2 were both dysfunctions. We performed electrophysiological study for 8 of 9 rare variants. It demonstrated that 2 rare variants showed gain-of-function, and 3 rare variants showed loss-of-function. We finally determined 5 likely pathogenic variants in SCN10A in 5 patients (12.5%) according to the ACMG standards and guidelines. All 5 patients underwent a pacemaker implantation at an average age of 43±16.

Conclusions
These results demonstrate that SCN10A variants play a pivotal role in enhanced susceptibility of CCSD. We suggest the importance for screening SCN10A variants in clinical settings.

Funding Acknowledgement
Type of funding source: None