bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution analysis with multiphase computed tomography of the left atrio-ventricular junction in mitral annular disjunction
Authors: Jouan J , Masari I , Bliah V , Soulat G , Craiem D , Mousseaux E
Published: November 2020

Background

Mitral annular disjunction (MAD) has been associated with myxomatous mitral valve disease (MMVD) but functional analyses of the mitral annulus (MA) and the entire left atrio-ventricular junction (LAVJ) are lacking from high-resolution imaging to understand MAD physiopathology.

Purpose

Using multiphase cardiac computed tomography imaging (4D-MCCTI), we aimed at characterizing the morphological changes of MA and LAVJ throughout the cardiac cycle.

Methods

Volume imaging data sets through time were obtained from 4D-MCCTI of 2 groups of 10 patients as defined by echocardiographic diagnosis of MMVD and/or MAD: MMVD+MAD+, MMVD+MAD− and 20 case-controls without mitral regurgitation (MMVD−). Data were implemented in a custom software for 3D semi-automated delineation of 18 points around MA perimeter. Coordinates of these points in each of the 10 time-phases within an RR interval were used for MA reconstruction and calculation of areas, perimeters, 360°-diameters and parameters of planar/vertical deformation. Subsequently, left ventricle (LV) and left atrium (LA) inner contours were delineated.

Results

Groups were similar for age, body surface area and LV ejection fraction. Compared to the 2 other groups, MA expansion in MMVD+MAD+ started early after end-diastole, following LA expansion, and reached a maximum at end-systole (ES): 3D-area ES: 13.9±4.0cm2/m2, 3D-perimeterE S: 10.4±1.6cm/m2 versus respectively 8.8±3.0cm2/m2, 7.9±1.4cm/m2 in MMVD+MAD− (p<0.001) and 6.1±1.3cm2/m2, 7.0±1.1cm/m2 in MVVD− (p<0.001). However throughout the cardiac cycle, MA perimeter reduction was not altered in MMVD+MAD+: −14.0±6.3%, compared to MMVD+MAD−: −10.1±5.6% and MMVD−: −8.7±2.3% (p=0.09). MA shape modification was different in MMVD+MAD+ group, MA becoming more elliptical during systole, whereas MA reached a minimal eccentricity index (EcI) at ES in both MMVD+MAD− and MMVD− groups: EcIES = 0.63±0.09 versus 0.52±0.15 and 0.49±0.13 (p=0.04), respectively (Figure). Surprisingly, vertical deformation of MA increased during early systole in MMVD+MAD+ group when MA became more planar in the MMVD+MAD− and MMVD− groups.

Conclusions

MA function was globally preserved in MAD but was desynchronized with respect to LV contraction.

Eccentricity index of mitral annulus

Funding Acknowledgement

Type of funding source: None
The utility of coronary artery calcium in non-gated high resolution CT thorax scans in predicting cardiac events as compared to the Framingham risk score: a retrospective study
Authors: Saluja S , Contractor H , Daniells M , Sobolewska J , Khan K , Mitchell L , Saluja S , Jiang X , Anderson S.G
Published: November 2020

Background

There is existing evidence to suggest a correlation between coronary artery calcification (CAC) measured using ECG-triggered chest computed tomography and cardiovascular disease. Further evidence has emerged to suggest a correlation between CAC measured using non-gated CT scans and cardiovascular disease. Herein, we sought to ascertain the utility of incidental findings of CAC on non-triggered high resolution CT (HRCT) thorax used for patients undergoing lung cancer screening or follow-up for interstitial lung disease and Framingham risk score (FRS) in predicting cardiovascular events.

Methods

The Computerised Radiology Information Service (CRIS) database was manually searched to determine all HRCT scans performed in a single trust from 05/2015 to 05/2016. The reports issued by Radiologists and images of selected studies were reviewed. For patients with CAC, we calculated the calcium score for patients using the Agatston method. Clinical events were determined from the electronic medical record without knowledge of patients' CAC findings. For these patients, the Framingham Risk Score (FRS) was also calculated. The primary end point of the study was composite of all-cause mortality and cardiac events (non-fatal myocardial infarction, coronary revascularization, new atrial fibrillation or heart failure episode requiring hospitalization).

Results

We selected 300 scans from a total of approximately 2000 scans performed over this time. Data at follow up was available for 100% of the patients, with a median duration of follow up of 1.6 years. Moderate to severe CAC was found in 35% of people. Multivariable analysis showed good concordance between CAC and FRS in predicting composite clinical end point. The Odds Ratio for cardiac events in patients with moderate to severe CAC was 5.3 (p<0.01) and for composite clinical end point was 3.4 (p<0.01). This is similar to the OR predicted by the FRS: 4.8; p<0.01 and 3.1; p<0.01 respectively. Only 6.2% of patients with moderate to severe CAC were currently statin treated.

Conclusion

In this retrospective study of patients with respiratory disease attending for HRCT scanning, co-incidentally detected CAC predicts cardiac events, with good concordance with the FRS. The incidental finding of CAC on non-gated CT scanning should be reported with Agatston score calculation allowing consideration of intervention to mitigate cardiovascular risk and optimize. Further multi-centre prospective studies of this strategy, with a larger patient cohort should be conducted to clarify the utility of CAC as a prediction tool to modify cardiac risk.

Funding Acknowledgement

Type of funding source: None
The painful chest pain history: improving risk stratification with coronary calcium score
Authors: Teo H.K , Lim L.M , Aurangzeb A , Koh S.Y , Huang Z.J , Ho J.S , Tan S.Y , Huang W.T
Published: November 2020

One of the commonest presentations to the Cardiology outpatient clinic is chest pain. Conventional risk scores for predicting coronary artery disease (CAD) depend greatly on chest pain histories which can be subjective and disadvantage individuals who present with less typical symptoms. The coronary calcium score (CACS) has a quick turnabout time and is an objective marker of atherosclerosis which can provide actionable information on presence of coronary artery disease.

This study aims to explore a) if CACS can be a surrogate for chest pain history to better manage patients with atypical presentations, and b) determine the feasibility of utilising CACS in a new risk model as a form of triage for chest pain in the outpatient specialist setting.

Two cohorts of patients who underwent CT Coronary angiogram (CTCA) were used: Asymptomatic patients with no obstructive coronary artery disease (CAD) and patients with symptomatic chest pain. The readouts of the CTCA include presence or absence of obstructive CAD (epicardial artery stenosis ≥50% on CTCA) and the CACS. In the asymptomatic cohort, we derived the formula for the median predicted CACS using latent class analysis and quantile regression with age and gender.

The symptomatic cohort was divided into derivation and validation groups. Multivariate logistic regression was used to select significant risk factors for CAD and develop the prediction model. The presence of a ≥10-point difference between the patient's actual CACS and predicted median CACS was established as a predictive parameter. Performance of the model was assessed and compared with the CAD I consortium score using area under the curve (AUC), net classification index and integrated discriminative index in the validation group.

In the asymptomatic cohort of 1911 persons, gender and age were significant factors used to calculate median predicted CACS. In the derivation cohort of 2345 patients, a CACS of 10-point difference between patient's CACS and predicted medium calcium score had a negative predictive value of 96.8%. Performance AUC (Figure 1) of the various models were: new model with chest pain history 0.887 (95% CI 0.858–0.916); without chest pain history 0.884 (95% CI 0.854–0.913); CAD I Consortium score 0.746 (95% CI 0.707–0.784). Both models performed significantly better than calcium score alone, p-value = 0.011.

Coronary calcium score is an objective measure of coronary atherosclerosis and appears to be a reliable surrogate for chest pain history. A new risk marker of positive 10-points difference between patient's calcium score and predicted median calcium score can potentially better risk stratify patients presenting with chest pain in the outpatient setting.

Funding Acknowledgement

Type of funding source: None
Downstream testing after an halted coronary CT angiography due to high coronary artery calcium score
Authors: Gama F , Rocha B , Freitas P , Ferreira A , Abecasis J , Guerreiro S , Saraiva C , Santos A.C , Andrade M.J , Ventosa A , Almeida M , Pintao S , Mendes M
Published: November 2020

Background and aim

In many centers, coronary artery calcium score (CACS) is performed immediately before coronary CT angiography (CCTA) in order to exclude heavy calcification that could hamper test performance. When high CACS values are found, CCTA is usually aborted and other tests suggested. However, there are no recommendations on which test to pursue, and little data on their diagnostic yield in this setting. The aim of this study was to assess the type and results of downstream testing among patients whose CCTA study was halted due to high CACS.

Methods

Single-centre retrospective study of consecutive patients undergoing CCTA for suspected obstructive coronary artery disease (CAD). A CACS threshold of >400 was generally used to cancel CCTA. Downstream testing and its results were assessed using electronic medical records. A group of consecutive patients with CACS <400 who underwent CCTA was used for comparison.

Results

Of the 795 patients who performed CCTA for suspected CAD, 86 (10.8%), had their test halted due to high CACS (57 men, mean age 71±11 years). In this subgroup, the median pre-test probability for CAD was 27% (interquartile range 25) and the median CACS was 983 (interquartile range 930). Compared to patients who underwent CCTA, those who saw their tests cancelled were older, more frequently male, and had higher prevalence of cardiovascular risk factors and higher pre-test probability for CAD.

Patient's downstream testing is illustrated in Figure. From the 86 patients enrolled, 12 are currently waiting for downstream tests and were excluded from further analysis. Overall, 35 patients ended up performing invasive coronary angiography (ICA, 47.3%) of whom 19 (54.3%) had significant CAD. Among those who underwent non-invasive testing (N=19, 25.7%), 10 (52.6%) had significant ischemia and 4 (21%) underwent additional testing with ICA. In 24 patients (32.4%), no downstream testing was pursued. Finally, 17 (22.3%) patients underwent coronary revascularization, either percutaneous (N=10, 13.5%) or surgical (N=7, 10.8%).

Conclusion

Invasive coronary angiography is the most frequently used downstream test when CCTA is halted due to high CACS values, and shows significant CAD in roughly half of the cases. Considering the high prevalence of significant CAD, direct referral for ICA (with the possibility of invasive functional testing) seems a reasonable approach.

Funding Acknowledgement

Type of funding source: None
Association of coronary high-intensity plaque on T1-weighted magnetic resonance imaging and circulating malondialdehyde-modified low-density lipoprotein levels with cardiac events
Authors: Hiraya D , Sato A , Hoshi T , Watabe H , Ieda M
Published: November 2020

Background

Although elevated oxidized low-density lipoprotein could play critical roles in vulnerable plaque, there are no studies that compared coronary high-intensity plaque (HIP) on non-contrast T1-weighted magnetic resonance imaging (T1WI_MRI) and circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels for the prediction of cardiac events.

Methods and results

A total of 139 patients with coronary artery stenosis (>70%) were examined with non-contrast T1WI using a 1.5-T MRI (HIP: n=63, non-HIP: n=76). Scheduled percutaneous coronary intervention (PCI) for culprit lesions was performed within 48 h after MRI. HIP was defined as a signal intensity of coronary plaque to cardiac muscle ratio (PMR) of ≥1.4. At admission, circulating levels of MDA-LDL and other lipid-related markers were measured. We evaluated the subsequent cardiac events, which were defined as major adverse cardiac events (MACE; cardiac death, myocardial infarction, and/or ischemia-driven PCI) during follow-up periods (5.6±1.3 years). Circulating MDA-LDL levels were significantly higher in patients with HIP than in those without HIP (p<0.0001). MDA-LDL levels were significantly correlated with PMR (r=0.490, p<0.0001). In multivariable logistic regression analysis, MDA-LDL levels were independently associated with the presence of HIP (OR 1.05; 95% CI, 1.02–1.08, p<0.0001). The incidence of MACE was significantly higher in patients with HIP (27%) than in those without HIP (5%; p=0.011 by the log-rank test). In the multivariable Cox proportional hazard analysis, the MDA-LDL levels (HR 1.03; 95% CI:1.01–1.05, p=0.007) and PMR (HR 2.39; 95% CI:1.19–4.65, p=0.016) were significantly associated with MACE. For MACE prediction, the C-statistic values for MDA-LDL, PMR, and PMR+MDA-LDL were 0.724, 0.791, and 0.800, respectively. Compared with MDA-LDL alone, the addition of PMR to MDA-LDL increased the net reclassification improvement by 0.78 (p=0.012).

Conclusions

MDA-LDL levels might be associated with the presence of HIP in patients with coronary artery disease. Furthermore, adding PMR to MDA-LDL levels markedly improved MACE prediction.

Funding Acknowledgement

Type of funding source: None
Left ventricular septal convexity in differentiating hypertrophic cardiomyopathy from hypertensive heart disease – cardiac MRI study
Authors: Tarkiainen M , Sipola P , Jalanko M , Helio T , Jaaskelainen P , Magga J , Peuhkurinen K , Husso M , Kivela K , Laine M , Lauerma K , Kuusisto J
Published: November 2020

Background

Subjects with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) have left ventricular hypertrophy (LVH). It is a common clinical problem to distinguish HCM from HHD. Septal convexity (SC) into the left ventricle is increased in subjects with hypertrophic cardiomyopathy (HCM)-causing mutations with and without LVH.

Purpose

Our objective was to study if SC by cardiac magnetic resonance (CMR) differentiates between HCM and HHD.

Methods

We measured SC in 29 subjects with hypertension and LVH (left ventricular maximal wall thickness (LVMWT) ≥13 mm), in 49 subjects with HCM (LVMWT ≥13 mm) caused by the D175N mutation in the alpha-tropomyosin (TPM1) or the Q1061X mutation in the myosin binding protein C (MYBPC3) genes, and in 20 healthy controls with no LVH. SC into the LV was measured in end-diastolic 4-chamber images as the maximal distance between LV septal endocardial border and a line connecting septal mid-wall points at the level of tricuspid valve insertion and at the level of apical right ventricular insertion on the LV.

Results

Subjects with HCM had significantly increased septal convexity compared to subjects with HHD both in non-indexed and in BSA-indexed measurements (10.7±4.0 mm vs 4.9±2.7 mm, P<0.001 and 5.5±2.1 mm/m2 vs 2.4±1.3 mm/m2, P<0.001). To differentiate between HCM and HHD, septal convexity cutoff value of 7.85 mm performed best with sensitivity of 77% and specificity of 90%. BSA-indexed SC cutoff value of 3.68 mm differentiated between HCM and HHD with sensitivity of 81% and specificity of 86%.

Conclusions

CMR derived septal convexity is easily measured and is useful in discriminating between HCM caused by sarcomere mutations versus HHD.

Measurement of septal convexity

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Foundation of Cardiovascular Research, the special governmental subsidy for health sciences research of the University Hospital of Kuopio
In-depth phenotyping of cardiac diseases by MRI in HIV-positive people reveals diverse and independent forms of myocardial involvement
Authors: Arendt C , De Leuw P , Haberl A , Stephan C , Vasquez M , Arcari L , Zhou H , Zainal H , Albrecht M , Vogl T , Zeiher A , Nagel E , Puntmann V
Published: November 2020

Background

It is increasingly recognised that non-ischaemic and ischaemic myocardial involvement represent important drivers of cardiac diseases in people living with HIV (PLWH). Non-invasive measurements with cardiac magnetic resonance (CMR) directly inform on the type of myocardial damage.

Purpose

To screen for the prevalence and type of cardiovascular disease (CVD) in PLWH using stress CMR in a cohort with highly active antiretroviral therapy (HAART).

Methods

This prospective cross-sectional study enrolled consecutive PLWH undergoing standardised evaluation for CVD using imaging. All participants underwent a standardised CMR protocol in a 3 Tesla scanner for function and volumes (cine), stress perfusion (regadenosone), scar (late gadolinium enhancement (LGE)), diffuse fibrosis (native T1-mapping) and oedema (native T2-mapping). Blood samples were additionally collected prior to CMR.

Results

141 participants were identified (n=32 in category C/AIDS). 16 patients had previously documented (n=23) myocardial diseases: myocarditis, n=1 non-obstructive coronary artery disease (CAD), n=8 myocardial infarction, n=3 congestive heart failure, n=3, and arrhythmia, n=8. Mean value for hs-cTnT, CRP and NT-proBNP was 9±18ng/l, 0.3±0.6mg/l and 104±229ng/l. 14 subjects had impaired LV-EF (<50%) and 35 presented borderline LV-EF (50–55%). Myocardial LGE was present in 28 patients: non-ischemic pattern, n=16, ischemic pattern, n=11, and both patterns, n=1. Two patients had relevant inducible ischaemia, whereas a pattern of microvascular disease (MVD) was found in 26 patients. 72 subjects had diffuse fibrosis and 25 had active inflammation. Elevated native T1/T2 was significantly associated with low (<350/μl), current, and initial CD4-count (χ2=5.317, p=0.021; χ2=3.841, p=0.050), just as with category C/AIDS (χ2=4.949, p=0.026). Native T2 showed a significant correlation with initial CD4-count (r=−0.252, p=0.008) and current NT-proBNP (r=0.190, p=0.030), but not with other laboratory values.

Conclusions

CMR in PLWH reveal high prevalence of cardiac involvement, which is predominantly non-ischaemic inflammatory in origin. MVD is a major presentation compared to relevant ischaemia due to epicardial CAD. Individual cardiovascular risk assessment in PLWH using CMR may bear a potential for personalised treatment.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The German Centre for Cardiovascular Research (DZHK)
Right ventricular functional changes detected by CMR during ajmaline challenge in patients with Brugada syndrome
Authors: Tondi L , Mecarocci V , Sturla F , Pica S , Giannelli L , Ciconte G , Camporeale A , Santinelli V , Lombardi M , Pappone C
Published: November 2020

Background

3D echocardiography has recently revealed alterations of right ventricular (RV) function in Brugada syndrome (BrS) during ajmaline challenge (AC). Cardiac magnetic resonance (CMR) is the gold standard for functional and anatomical RV assessment. CMR feature-tracking (FT) analysis is able to detect subtle functional changes in the underlying myocardial substrate.

Purpose

To investigate RV functional changes during AC in BrS patients using CMR-FT analysis.

Methods

24 consecutive BrS and 28 matched controls underwent CMR. CMR protocol included paraxial and parasagittal cine bSSFP sequences, acquired before and 2÷5 minutes after ajmaline infusion (1 mg/kg in 5 minutes), to obtain a comprehensive evaluation of the RV free wall. All patients were closely monitored with ECG. Semi-automatic threshold-based quantification of ventricular volumes, function and mass was performed in QMass. CMR-FT analysis of RV function was performed in QStrain. Values of longitudinal strain (LS) and transverse displacement (TD) of the RV wall before and after AC were compared in BrS patients and in the control group.

Results

AC induced Type 1 ECG pattern in all BrS patients and no ECG changes in controls. In BrS patients TD of the RV free wall was significantly reduced (P≤0.003) at peak ajmaline effect; controls reported sub-millimetric TD changes. LS of the RV wall was significantly impaired in BrS patients (P<0.0001) on both b SSFP sequences; LS remained comparable (P=0.62) in controls on the parasagittal sequence; minor but not negligible (P=0.01) LS changes were noticed on the paraxial stack. (Table 1)

Conclusions

In patients with BrS CMR-FT analysis during AC unveils dysfunctional RV wall mechanics in areas generally associated with abnormal electrical activity.

TD and LS in a Brs patient post AC

Funding Acknowledgement

Type of funding source: None
Reproducibility of left atrial assessment in cardiac magnetic resonance imaging
Authors: Alfuhied A , Marrow B , Gulsin G , Steadman C , McCann G.P , Singh A
Published: November 2020

Background

Left atrial (LA) volume and strain are recognised as predictors of adverse outcomes in cardiovascular disease. We aimed to determine the test-retest reproducibility of LA assessment derived from cardiac MRI in subjects with and without cardiovascular disease.

Methods

38 participants had two MRI scans a week apart: aortic stenosis (n=16); type 2 diabetes (n=16) and healthy volunteers (n=6). Images were analysed by a single trained observer using Medis v3.1, medical imaging system, Leiden, Netherlands. LA strain and strain rate were assessed with Feature Tracking (QStrain v2.0), corresponding to LA reservoir, conduit, and contractile function. LA ejection fraction (LAEF) was calculated using biplane area-length method (QMass v8.1). Both were assessed on 4- and 2-chamber long-axis standard steady-state free precession cine images, and average values calculated.

Results

As shown in the table, the test-retest reproducibility for strain and strain rate was moderate for reservoir phase (CoV 25–28%, ICC ∼0.70) and poor for conduit and contraction phases (CoV>40%). The test-retest repeatability for LA volumes and LAEF was good (CoV 16–29%, ICC≥0.70).

Conclusion

LA strain assessment using feature tracking is a poorly reproducible technique on CMR. However, good test-retest reproducibility for LA volumes and EF.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
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

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

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) <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<0.001 for both), with AERs of 0.6% vs. 2.8%, and 0.6% vs. 2.4% (p<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<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

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<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<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

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<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

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 <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<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 >15% in the LV lateral wall compared to the septal wall (lateral FDG = 91±3% vs. septal FDG = 69±8%; p<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

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

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) <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 (>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

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

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