bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-risk plaque burdens myocardial flow reserve in intermediate coronary artery disease: hybrid analysis of 13N-ammonia PET and coronary CT angiography
Authors: Yamamoto A , Nagao M , Ando K , Nakao R , Sakai A , Watanabe E , Momose M , Sato K , Sakai S , Hagiwara N 
Published: November 2020

Abstract

Background
13N-ammonia PET (NH3-PET) can detect myocardial perfusion abnormalities in patients with coronary artery disease (CAD) and also obtain diagnostic quantitative values of absolute myocardial blood flow and myocardial flow reserve (MFR). Low MFR (MFR&lt;2.0) is an independent prognostic factor for major adverse cardiac event in patients with ischemic and non-ischemic heart disease. A feature of low attenuation plaque (LAP) on coronary CT angiography (CCTA) has been known as high-risk plaque (HRP) for acute coronary syndrome even if there is no significant coronary stenosis. The presence of HRP potentially adversely affects MFR, but the hypothesis has not been elucidated.

Purpose
We aimed to investigate the affect of LAP to MFR in intermediate CAD.

Methods
One hundred five patients (age 67±9 years, 65% male) with CAD underwent NH3-PET and CCTA within 6 months between April 2015 and March 2019 were enrolled. Based on the results of CCTA, mild and moderate stenosis were defined as 1% to 49% and 50% to 69% stenosis. Ischemic territories for major three vessels were identified by stress/rest NH3-PET images. Finally, 194 coronary arteries with mild to moderate stenosis corresponding to non-ischemic territory were analyzed in this study. LAP was defined as plaques containing CT value less than 90HU. Partially calcified plaques were included in LAP. Entirely calcification plaque without LAP was defined as calcified plaque. MFR for major three vessels were calculated from dynamic scan at stress/rest NH3-PET.

Results
CCTA showed 80 coronary arteries with LAP (41%), 104 coronary arteries with calcified plaque (54%), 102 vessels with mild stenosis (53%), and 92 vessels with moderate stenosis (47%). MFRs for coronary arteries with LAP were significantly lower than those without LAP (2.1±0.6 vs 2.5±0.6, p&lt;0.0001). The significant difference in MFR between with and without LAP was observed in both mild and moderate stenosis (mild: 2.0±0.6 vs 2.5±0.6, p=0.0015, moderate: 2.1±0.6 vs 2.5±0.6, p&lt;0.0001). In contrast, coronary arteries with calcified plaque had significantly higher MFR than those without (2.5±0.6 vs 2.1±0.6, p&lt;0.0001).
In 58 coronary arteries with MFR&lt;2.0, 71% (41/58) had LAP and 24% (14/58) had calcified plaque. In 136 coronary arteries with MFR≥2.0, 29% (39/136) had LAP and 66% (90/136) had calcified plaque. LAP was significantly more frequent in the former and calcified plaque was significantly more frequent in the latter.

Conclusion
The presence of LAP burdens MFR in mild to moderate CAD. On the other hand, calcified plaque alone had no adverse effect on MFR. LAP is an important sign in CAD risk assessment even without significant coronary stenosis.
MFR and stress MPI

Funding Acknowledgement
Type of funding source: None
Predicting cardiovascular risk traits from pet myocardial perfusion imaging with deep learning
Authors: Juarez-Orozco L , Yeung M.W , Knol R.J.J , Benjamins J.W , Ruijsink B , Martinez-Manzanera O , Knuuti J , Asselbergs F , Van Der Zant F.M , Van Der Harst P 
Published: November 2020

Abstract

Background and aim
Deep Learning has revolutionised image analysis and its implementation in cardiology is rapidly advancing. DL offers the possibility to abstract highly-complex patterns from any image in order to optimise classification and prediction tasks. At the same time, positron emission tomography (PET) represents the reference technique for quantitative evaluation of myocardial perfusion and is a powerful tool for the diagnosis of myocardial ischemia and infarction. Although pathological perfusion patterns in PET are easily recognised by expert clinicians, it is unclear whether PET images harbour complex patterns inherent to traditional cardiovascular risk traits (factors) recognisable in an individual-patient basis. Hence, we aimed to deploy Deep Learning in order to predict cardiovascular risk traits from individual quantitative PET myocardial perfusion images.

Methods
Data form 1180 patients evaluated through quantitative N13-ammonia PET-imaging for suspected myocardial ischemia was analysed. We implemented transfer learning with fine-tuning of individual concatenated instances of an ImageNet pre-trained convolutional neural network (ResNet-50). From each PET scan, the 3 standard quantitative polar maps (rest/stress/perfusion reserve) were used as network input. A 5-fold cross validation policy was applied to training and validation for hyperparameters optimisation. Deep Learning modelling was deployed to independently predict: sex, smoking, arterial hypertension, dyslipidemia and type 2 diabetes mellitus as cardiovascular risk traits. Final model performance was evaluated through AUC and accuracy (with associated standard deviations [SD]) on a hold-out test set of 104 scans. Deep Learning-based heat maps were generated to identify regions of interest in PET imaging related to each of the predicted risk trait

Results
Deep Learning was able to strongly predict sex (0.87±0.04, 78%±4) and diabetes mellitus (0.75±0.13,71%±8), while its performance was only discrete for smoking (0.63±0.11, 85%±2), hypertension (0.61±0.06,58%±3) and dyslipidemia (0.59±0.05,57%±3), albeit all statistically significant (p&lt;0.01).

Conclusion
Deep Learning is able to significantly predict cardiovascular risk traits from individual quantitative PET myocardial perfusion images. This suggests the existence of complex high-dimensional and localised features within cardiac imaging that relate to cardiovascular risk factors at the individual level, which definitely warrants further research.

Funding Acknowledgement
Type of funding source: None
The effects of chemotherapy on arterial inflammation assessed by 18 FDG PET-CT in patients with Lymphoma
Authors: Solomou E , Koutagiar I , Ioakimidis N , Terentes-Printzios D , Georgakopoulos A , Pouli A , Sioni A , Karakitsios I , Kafouris P , Gaitanis A , Pianou N , Aggeli C , Tousoulis D , Vlachopoulos C , Anagnostopoulos C 
Published: November 2020

Abstract

Introduction
Anti-cancer treatment can lead to increased cardiovascular morbidity among lymphoma survivors. This may be the result of direct effect of treatment on heart function, or indirect acceleration of atherosclerosis. 18F-fluorodeoxyglucose (FDG) uptake is a sensitive and robust marker for assessment of atherosclerotic inflammation.

Purpose
To investigate the effects of chemotherapy on arterial inflammation using FDG-PET CT in patients with lymphoma.

Methods
Fifty nine (mean age 58±17 years) patients with Hodgkin (n=39) or non-Hodgkin lymphomas (n=20) underwent 18FDG PET-CT imaging at baseline, interim and after completion of chemotherapy as part of their routine protocol. Arterial inflammation was assessed by arterial target to background ratio (TBR) of the aortic wall along the entire aorta. The index vessel TBR (the vessel with the higher value at baseline) was used for assessment of arterial inflammation. Patients with Hodgkin Lymphomas (HL) underwent therapy with Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim of their treatment was set at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non Hodgkin Lymphomas (NHL) underwent therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone+rituximab (R-CHOP). The interim of their treatment was set at 2 weeks post the 4th chemotherapy cycle. All patients we reassessed 6 weeks after chemotherapy completion.

Results
There were no differences in age and atherosclerotic risk factors (hypertension, diabetes, dyslipidemia and smoking), between the two groups (all P&gt;0.05). Similarly, there were no differences in mean (±SD) index vessel TBR between HL and NHL patients (2.4±0.7 vs 2.7±0.9, respectively, P=0.65). In the whole study population the index vessel TBR progressively decreased after the end of therapy (by 0.53±0.11, from baseline to 6 weeks following the end of therapies) (F=10.94, P&lt;0.001, ANOVA). The index vessel TBR decreased in both HL and NHL patients at 6 weeks after therapy compared to baseline level (all P&lt;0.01, ANOVA, figure). The decrease at the interim scan was more pronounced in NHL compared to HL patients, however at 6 weeks after chemotherapy completion the index vessel TBR decreased further in patients with HL, while it increased slightly compared to interim levels in NHL patients (figure 1).

Conclusion
Arterial inflammation is reduced during and post-chemotherapy in patients with lymphoma. The index vessel TBR changes at the interim phase and 6 weeks after therapy completion indicate a different effect of specific treatment regimes in arterial inflammation between HL and NHL patients.
Figure 1

Funding Acknowledgement
Type of funding source: None
Left atrial late gadolinium enhancement is associated with atrial fibrillation as detected by continuous monitoring
Authors: Bertelsen L , Diederichsen S.Z , Haugan K.J , Brandes A , Graff C , Krieger D , Kronborg C , Kober L , Peters D.C , Olesen M.S , Hojberg S , Vejlstrup N , Svendsen J.H 
Published: November 2020

Abstract

Background
Left atrial late gadolinium enhancement (LA LGE) measured with cardiac magnetic resonance (CMR) imaging is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures. However, the prognostic value of LA LGE for incident AF remains unknown.

Methods
CMR including measurement of left ventricular (LV) and LA volumes and function, as well as LV extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received and implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists.

Results
Patients were monitored for AF with implantable loop recorder during a median of 41 [36; 43] months. AF episodes lasting ≥6 minutes were detected in 32 patients (47%) and 16 patients (24%) experienced AF episodes lasting ≥5.5-hour. In Cox regression analyses adjusted for sex, age and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratio for time to AF episodes lasting ≥6 minutes and ≥5.5 hours were 1.40 (1.03, 1.89) per 10 cm2 increase (p=0.03) and 1.63 (1.11, 2.40) per 10 cm2 increase (p=0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value.

Conclusions
Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark [no grant number]
Predictors for rapid progression of coronary calcification: an optical coherence tomography (OCT) study
Authors: Nakajima A , Araki M , Kurihara O , Minami Y , Soeda T , Higuma T , Kakuta T , Lee H , Malhotra R , Nakamura S , Jang I.K 
Published: November 2020

Abstract

Background
The natural progression of coronary calcification has not been systematically studied. In vivo coronary calcium can be evaluated by OCT.

Purpose
To identify the incidence and predictors for rapid progression of coronary calcification.

Methods
Patients with serial OCT imaging at baseline and at 6 months were selected from our database. Changes in calcium index during 6-month follow-up and predictors for progression of calcification were studied. Calcium index was defined as the product of the mean calcium arc and calcium length. Rapid progression of calcification was defined as an increase in calcium index above the median value.

Results
Among 187 patients who had serial OCT imaging, 235 calcified plaques were identified in 108 patients (57.8%) at baseline with median calcium index of 132.0 (Interquartile range 58.5–281.2). After 6 months, the calcium index increased in 95.3% of calcified plaques from 132.0 to 178.2 (p&lt;0.001). In multivariable analysis, diabetes mellitus (DM), chronic kidney disease (CKD), lipid-rich plaque, and macrophages were found to be independent predictors for rapid progression of coronary calcification (table). Interestingly, rapid progression of calcification was associated with a significant reduction of inflammatory features (thin-cap fibroatheroma [TCFA]; baseline 21.2% vs. follow-up 11.9%, p=0.003, macrophages; baseline 74.6% vs. follow-up 61.0%, p=0.001).

Conclusions
This study demonstrated that DM, CKD, lipid-rich plaque, and macrophages were independent predictors for rapid progression of coronary calcification. High level of vascular inflammation may stimulate rapid progression of calcification.

Funding Acknowledgement
Type of funding source: None
Beneficial electrophysiologic effects of sacubitril in different arrhythmia syndromes
Authors: Frommeyer G , Dimanski D , Ellermann C , Wolfes J , Eckardt L 
Published: November 2020

Abstract

Background
Previous studies report conflicting data regarding anti- or proarrhythmic effects of sacubitril. The aim of the presents study was to assess the impact of sacubitril in different arrhythmia models.

Methods and results
In 12 isolated rabbit hearts, sacubitril was infused in rising concentrations (3, 5, 10μM) after obtaining baseline data. In 12 further hearts, erythromycin was administered to simulate long QT syndrome-2 (LQT2). Other 12 hearts were perfused with veratridine to mimic long QT syndrome-3 (LQT3). Both LQT groups were treated with sacubitril (5μM). Ventricular vulnerability was assessed by a pacing protocol. AV-blocked bradycardic hearts were perfused with a hypokalemic solution to trigger torsade de pointes (TdP). In further 13 hearts, AF was induced by a combination of acetylcholine and isoproterenol (ACH/ISO) and sacubitril (5μM) was added afterwards. With sacubitril, action potential duration (APD) was abbreviated whereas spatial dispersion of repolarization (SDR) remained stable. In both LQT groups, APD and SDR were increased. Infusion of sacubitril reduced APD and SDR in the LQT2-group (APD: −21 ms, p&lt;0.05; SDR: −8 ms, p=ns) and did not alter APD but reduced SDR in the LQT3-group (APD: +2 ms, p=ns; SDR: −9 ms, p&lt;0.05). Ventricular vulnerability was not altered by sacubitril. No TdP were observed with sacubitril treatment or under baseline conditions in any group. Erythromycin provoked 43 episodes of TdP (p&lt;0.05). Additional treatment with sacubitril significantly suppressed TdP (3 episodes, p&lt;0.05). With veratridine, 16 episodes of TdP (p=0.07) occurred. Further treatment with sacubitril did not reduce TdP (10 episodes, p=ns) significantly. Infusion of ACH/ISO led to an increased inducibility of atrial fibrillation (31 vs. 7 episodes). Additional infusion of sacubitril increased atrial ERP (+21ms, p&lt;0.05) and reduced inducibility of AF (9 episodes).

Conclusion
Sacubitril abbreviated APD and was not proarrhythmic. SDR is a major pathomechanism of TdP and was reduced by sacubitril in both LQT groups. Thereby, sacubitril exhibits antiarrhythmic effects in LQT2 and may be beneficial in LQT3. Furthermore, sacubitril suppressed AF by prolonging aERP. Our results indicate beneficial effects of sacubitril on cardiac electrophysiology.

Funding Acknowledgement
Type of funding source: None
Splice site mutation of LMNA causes severe dilated cardiomyopathy via strong dominant reduction of total lamin expression
Authors: Kato K , Ohno S , Sonoda K , Makiyama T , Ozawa T , Horie M 
Published: November 2020

Abstract

Objective
LMNA is a known causative gene of dilated cardiomyopathy (DCM) and familial cardiac conduction disturbance (CCD). Genetic variants affecting the pre-mRNA splicing process often lead to premature stop codons and result in nonsense-mediated mRNA decay (NMD), followed by degradation of mutated alleles. The misssense variant LMNA c. 936G&gt;C was previously reported in a French family affected by muscular dystrophy, CCD, and DCM, but no detailed analysis has been performed. We so far identified the same variant in two Japanese families affected by CCD and DCM. In this study, we investigated the molecular consequences of the variant located at the last codon of LMNA exon5 to demonstrate its pathogenicity.

Methods
Genomic DNA and total RNA were isolated from patients' peripheral blood lymphocytes or cardiac tissue. LMNA-coding exons were screened by direct sequencing. Complementary DNAs (cDNAs) were generated by reverse transcription PCR from RNA. Quantitative PCR (qPCR) was performed to quantify the LMNA cDNA amount by using specific primers for lamins A and C. The protein expressions of both isoforms were analyzed by western blotting.

Results
We detected the heterozygous LMNA c.936 G&gt;C (p. Q312H) variant at the end of exon 5 by genomic DNA sequencing in two unrelated Japanese families (figure. pedigree) affected by DCM and CCD. In a genomic database survey, we did not find the variant in either gnomAD, TogoVar, or the Human Genetic Variation Database. The two commonly used splice site predictor tools, NetGene2 and FSPLICE, estimated that this site was a splice donor site. Sequencing of cDNA demonstrated that the mutated allele was absent. By qPCR assay, we confirmed a 90% reduction in LMNA cDNA. Western blot analysis revealed that lamin A and C expression was reduced far more than 50% (figure. western blot).

Conclusions
We report a LMNA missense mutation found in two families, which disrupts a normal splicing site, leads to NMD, and resulted in severe cardiac laminopathy. The drastic reductions of lamin expression at the cDNA and protein levels suggested that other co-existing mechanisms may also have suppressed the expression of the healthy wild type allele.
Pedigree and western blot assay

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science KAKENHI
The repolarization pattern of ARVC patients, healthy gene carriers and controls as analyzed with a 252-leads Body Surface Mapping Vest
Authors: Kommata V , Elshafie M.I , Perez M , Augustine R , Blomstrom-Lundquist C 
Published: November 2020

Abstract

Background
Repolarization abnormalities have a central role on the diagnosis of ARVC according to recent HRS consensus document from 2019 stating that T wave inversion in the right precordial leads is a major criteria if it appears in V1-V3 or a minor criteria if it appears in only V1-V2.

Purpose
The aim of our study was to investigate whether repolarization patterns as recorded by a Body Surface Mapping (BSM) system consisting of a vest with 252 ECG leads, could differentiate ARVC patients and even gene carriers from normal individuals. Our hypothesis is that the method can potentially identify repolarization disturbances earlier or better than conventional 12-lead ECG.

Method
12 definite ARVC patients, 20 healthy gene carriers and 8 family members who tested negative for the family mutation (controls) were included. All patients underwent 12-lead ECG, including right precordial leads (V4R) and BSM recordings. Repolarization (T-wave polarity and concordance with QRS complex vector) was analyzed qualitatively in all BSM recordings, the results of which were displayed on a color code map (fig.1).

Results
The mean age was 49.6, 43.6 and 38.8 years in ARVC patients, healthy gene carriers and controls, respectively. The number of males in the three groups were 8/12, 8/20 and 5/8, respectively.
All 8 controls had similar repolarization patterns with negative and concordant T waves on the right back panel, and T waves that successively changed from negative concordant (green) to positive disconcordant (red) and finally positive concordant (blue) on the left front panel (pattern 1). All 12 ARVC patients had different repolarization patterns as compared to the controls. Two of these patients had no apparent repolarization changes on conventional 12 lead ECG. The pattern type 2 repolarization, as defined by same pattern as the controls at the right back panel but different pattern at the front left panel was seen in 3/12 ARVC patients. The remaining 9 ARVC patients had different repolarization patterns both on the front and on the back panel (pattern 3). Among gene carriers, 15 had a normal repolarization pattern (pattern 1) and 5 demonstrated an abnormal repolarization pattern (4 had pattern type 2 and one pattern 3) despite normal surface ECG.

Conclusions
Using BSM recordings, abnormal repolarization patterns can be detected in all ARVC patients, even in those without repolarization changes on conventional surface ECG. The observation that 25% of gene carriers had divergent repolarization patterns, may indicate an early stage of the disease, and be used as an early diagnostic marker of the disease. Further and larger studies are warranted to confirm these observations.
Repolarisation patterns recorded by BSM

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Selanders Stiftelse