bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombosis-related miR-16-5p predicts the disease severity in patients hospitalised for COVID-19
Authors: Keshwani D , Eyileten C , Wicik Z , Nowak A , Jakubik D , Simoes S N , Martins-Jr D C , Shahzadi A , Jarosz-Popek J , Wolska M , Siller-Matula J , Postula M
Published: October 2022

Introduction

SARS-CoV-2 tropism for the ACE2 receptor, along with the multifaceted inflammatory reaction, is likely to drive the generalized hypercoagulable state seen in patients with COVID-19.

Methodology

Using the original bioinformatic workflow and network medicine approaches we reanalyzed four coronavirus-related expression datasets and performed co-expression analysis focused on thrombosis and ACE2 related genes. We identified microRNAs (miRNAs) which play role in ACE2-related thrombosis in coronavirus infection and further, we validated the expressions of those miRNAs in 79 hospitalized COVID-19 patients and 32 healthy volunteers by PCR and monitored miRNAs patterns during the acute phase of COVID-19, as well as the prognostic potential of these miRNAs as biomarkers.

Results

We identified EGFR, HSP90AA1, APP, TP53, PTEN, UBC, FN1, ELAVL1 and CALM1 as regulatory genes which could play a pivotal role in COVID-19 related thrombosis. We also found miR-16-5p, miR-27a-3p, Let-7b-5p and miR-155-5p as regulators in coagulation and thrombosis process. We observed in separate cohort of COVID-19 patients and healthy controls that (i) expression of miR-16-5p, miR-27a-3p and miR-155-5p increased during observation, compared to the baseline measurement; (ii) a low baseline miR-16-5p expression presents predictive utility in assessment of the hospital length of stay or death in follow-up as a composite endpoint (AUC: 0.810, 95% CI, 0.71–0.91, p<0.0001); (iii) low baseline expression of miR-16-5p and diabetes mellitus are independent predictors of increased length of stay or death according to a multivariate analysis (OR: 9.417; 95% CI, 2.647–33.506; p=0.0005 and OR: 6.257; 95% CI, 1.049–37.316; p=0.044, respectively).

Conclusion

This study enabled us to better characterize changes in gene expression and signaling pathways related to COVID-19 thrombosis. In this study we identified, characterized and validated miRNAs which could serve as novel, thrombosis-related biomarkers of the COVID-19, can be used for early stratification of patients and prediction of severity of infection development in an individual.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Warsaw
Citrullination of histoneH3 in neutrophil via CXCL1 enhances neutrophil adhesion to femoral artery of LDLR−/− mice fed HFD
Authors: Osaka M , Yoshida M
Published: October 2022

Background

Vascular inflammation plays an important role in the development of atherosclerosis. Previously we have shown that a high-fat diet (HFD) increased neutrophil adhesion to the vascular intima in wild-type (wt) mice (Osaka M. Sci Rep. 2016). However, the involvement of neutrophils in atherosclerosis-related vascular inflammation is not well known.

Purpose

This study examined that neutrophil extracellular trap (NETs) or the hypercitrullination of histone H3 in neutrophils enhances neutrophil adhesion to atheroprone-arteries in LDL receptor null (LDLR−/−) mice.

Methods

We observed leukocyte adhesion in the femoral artery of LDLR−/− mice fed normal chow (NC) or HFD, and determined leukocyte subtype that adhered on vascular endothelium under neutrophil or monocyte depletion using intravital microscopy. Importantly, neutrophil adhesion was examined under the administration of TDFA which inhibits NETs and citrullination of histone H3, in LDLR−/− mice fed HFD. Furthermore, immunohistochemistry for citrullinated histone H3 in peripheral neutrophils of mice was examined. Comprehensive cytokine/chemokine analysis for a plasma of mice was performed to determine the factors citrullinating histone H3 in LDLR−/− mice. Moreover, these mice were treated with a novel specific PPARα agonist, to reduce the elevation of plasma triglyceride levels.

Results

Leukocyte adhesion in LDLR−/− mice fed HFD significantly increased compared to NC. More interestingly, it significantly enhanced compared to wt mice fed HFD. Furthermore, neutrophil depletion rather than monocyte depletion diminished leukocyte adhesion, suggesting that the leukocyte subtype that adhered in LDLR−/− mice fed HFD was neutrophil. Neutrophil adhesion in these mice significantly was reduced by the administration of TDFA, suggesting a pivotal role for histone H3 citrullination in neutrophil adhesion. Moreover, citrullination of histone H3 in neutrophils from LDLR−/− mice fed HFD but not from those without HFD was significantly enhanced. In addition, comprehensive cytokine/chemokine analysis revealed an increase of CXCL1 in plasma of LDLR−/− mice fed HFD. CXCL1 enhanced neutrophil adhesion to HUVECs, and the adhesion significantly decreased by the treatment of TDFA to neutrophil in vitro non-static adhesion assay. These results showed that CXCL1 enhanced neutrophil adhesion in LDLR−/− mice fed HFD through citrullination. Furthermore, when these mice were treated with PPARα agonist, observed histone citrullination, as well as neutrophil adhesion, was significantly reduced.

Conclusion

These results suggest that HFD induced histone citrullination in neutrophils in LDLR−/− mice and PPARα agonist plays a role during hypertriglyceridemia-mediated vascular inflammation in atherosclerosis.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research(C)
The Calcium Score's power of zero in 82-Rubidium PET depending on age group and sex
Authors: Frey S , Clerc O F , Amrein M , Thommen K , Leu K , Caobelli F , Haaf P , Zellweger M J
Published: October 2022

Background

Coronary calcium score (CAC) is a well-validated method to detect coronary artery disease (CAD). A significant number of patients referred for functional ischaemia tests reveal a normal result. CAC could be a potential gatekeeper to reduce unnecessary testing.

Purpose

Study aims were to describe the frequency of zero calcium and its diagnostic power to exclude abnormal perfusion stratified by age and sex in a large cohort undergoing 82-Rubidium Positron Emission Tomography (PET).

Methods

All consecutive patients with suspected CAD who were referred for myocardial perfusion PET at our tertiary center between 2016 and 2021 were identified. Baseline and scan related data were extracted from the electronic database. Patients were included for this retrospective analysis if CAC and semi-quantitative analysis of perfusion study were available. Percentiles and test characteristics of zero calcium were calculated stratified by age and sex. Summed stress score (SSS) ≥4 on PET was considered abnormal.

Results

2640 patients were included. Mean age was 65±11 years; 54% were male. Angina and dyspnea were present in 39% and 60%, respectively. 21% (558/2640) of the scans were abnormal and median CAC was 62 [0–374]. 685 patients (26%) had no calcium. Stratified by age, the proportion of zero calcium was 89% (<40 years), 61% (40–49y), 40% (50–59y), 21% (60–69y), 14% (70–79y) and 6% (≥80y). CAC was higher in abnormal scans (median 561 vs. 27, p<0.001) and zero CAC was associated with a lower risk of abnormal PET (2.6% vs. 27.6%, p<0.001). The negative predictive value (NPV) of calcium zero to exclude abnormal PET was 97%, 96% and 98% for all patients, males and females, respectively. Test characteristics are displayed in Table 1. Percentiles of CAC according to scan result are depicted in Figure 1.

Conclusion

The proportion of zero calcium is frequent and declines with increasing age. The absence of coronary calcium is associated with less abnormal PET scans. Zero calcium to exclude an abnormal scan performed best in young patients (<50) with a NPV ≥98%. CAC could act as a gatekeeper. However, further studies including safety endpoints are needed.

The upper calcium score indicates the 90th percentile of patients with normal PET. The lower calcium score indicates the 5th percentile of patients with abnormal PET. Calcium scores within the white area are unlikely to be associated with abnormal PET (since this area includes only the 5% of abnormal PET scans). The dark grey area indicates patients with a high likelihood of positive PET. For better readability, different scales were used.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of coronary flow capacity derived from [15O]H2O positron emission tomography perfusion imaging
Authors: De Winter R W , Jukema R A , Van Diemen P A , Schumacher S P , Somsen Y B O , Van De Hoef T P , Van Rossum A C , Twisk J W , Maaniitty T , Knuuti J , Saraste A , Nap A , Raijmakers P G , Danad I , Knaapen P
Published: October 2022

Background

Coronary flow capacity (CFC) is a cross-modality framework integrating hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to quantify the physiological impact of coronary atherosclerotic disease on vasodilator capacity.

Purpose

This study explores the prognostic value of CFC derived from [15O]H2O positron emission tomography (PET) perfusion imaging in addition to traditional perfusion metrics.

Methods

Quantitative perfusion measurements were obtained from 1300 patients with suspected or known coronary artery disease who underwent [15O]H2O PET imaging. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC or normal flow using previously defined perfusion thresholds. The endpoint was a composite of death and non-fatal myocardial infarction (MI).

Results

The composite endpoint occurred in 153 (12%) patients during a median follow-up of 5.5 (interquartile range 3.7–7.8) years. Myocardial steal (HR 10.65, 95% CI 4.45–25.49, p<0.001), severely reduced CFC (HR 3.77, 95% CI 1.88–7.58, p<0.001), moderately reduced CFC (HR 2.03, 95% CI 1.25–3.29, p=0.004) and minimally reduced CFC (HR 1.72, 95% CI 1.05–2.81, p=0.030) were independently associated with worse outcome after adjusting for clinical risk factors. Similarly, increased resting MBF (HR 3.19, 95% CI 1.74–5.83, p<0.001), decreased hMBF (HR 0.72, 95% CI 0.57–0.90, p=0.004) and decreased CFR (HR 0.59, 95% CI 0.47–0.73, p<0.001) were significant prognostic factors for events. In a combined perfusion model, only resting MBF (p=0.018) and CFC (overall p=0.012) demonstrated independent prognostic value.

Conclusions

[15O]H2O PET-derived resting MBF, hMBF, CFR and CFC were prognostic factors for death and non-fatal MI. Notably, in a combined model including all perfusion metrics, only resting MBF and CFC were independently associated with adverse outcome.

Funding Acknowledgement

Type of funding sources: None.
Coronary microvascular health in patients with prior COVID-19 infection and no known CAD
Authors: Ahmed A I , Saad J M , Han Y , Alahdab F , Malahfji M , Nabi F , Mahmarian J , Cooke J P , Zoghbi W A , Al-Mallah M H
Published: October 2022

Introduction

Although most patients recovering from acute COVID-19 infection have complete resolution of symptoms, some have cardiopulmonary symptoms lingering long after the acute phase of the disease. One proposed mechanism involves chronicity of COVID-19 associated with myocarditis and endotheliopathy.

Purpose

To determine the coronary microvascular health of patients with prior COVID-19 and no known coronary artery disease (CAD) using positron emission tomography (PET).

Methods

Cases consisting of patients without known CAD but previous COVID-19 infection who had clinically indicated PET imaging were matched 1:4 on clinical and cardiovascular risk factors to controls having no prior COVID-19 infection. Myocardial blood flow (MBF) in ml/gm/min was obtained from dynamic images at rest and peak hyperemia. The coronary flow reserve (CFR) was calculated as the ratio of stress to rest MBF of the left ventricle. Coronary microvascular dysfunction (CMD) was defined as CFR<2.

Results

The study population consisted of 315 patients, 25% (n=80) of which had prior COVID-19 infection (mean±SD age 64±11 years, 46% men). The median (IQR) number of days between COVID-19 infection and PET imaging was 190 (85–268) days. After adjusting for age, gender and cardiovascular risk factors, patients with prior COVID-19 and no known CAD had a statistically significant higher odds of having a CFR <2 (OR 4.9, 95% CI 2.3–10.1 p<0.001) and CFR <2 normalized to patient's rate-systolic blood pressure product (OR 2.8, 95% CI 1.6–5.0 p=0.001). The annualized event rate for the composite outcome of all-cause death, myocardial infarction, admission for heart failure exacerbation and late revascularization was higher in cases vs controls and in those with CMD.

Conclusion

Our analysis showed that patients with prior COVID-19 and no known CAD had higher rates of CMD, and that the presence of CMD was associated with higher risk of incident cardiovascular events.

Funding Acknowledgement

Type of funding sources: None.
Exercise capacity as a predictor of coronary microvascular dysfunction
Authors: Saad J M , Ahmed A I , Alahdab F , Han Y , Alfawara M , Al-Mallah M
Published: October 2022

Introduction

Exercise capacity (EC) is an important prognostic test in patients with coronary artery disease (CAD). Positron-emission tomography (PET) is an important risk-stratifying tool to tailor management of patients with coronary artery disease.

Purpose

We aimed to assess EC in predicting positron emission tomography (PET) myocardial perfusion imaging (MPI) derived coronary flow reserve (CFR).

Methods

Consecutive patients who had clinically indicated PET MPI and EC were included. EC was defined based on peak metabolic equivalents (METS) achieved during exercise stress test. Myocardial blood flow (MBF) in ml/gm/min was obtained from dynamic PET MPI images at rest and peak hyperemia. The coronary flow reserve (CFR) was calculated as the ratio of stress to rest MBF of the left ventricle.

Results

The study population consisted of 511 patients who underwent PET MPI and EC testing (mean age 56 (±11), 71% male). Cardiovascular risk factors were prevalent (75% hypertensive, 82% dyslipidemic, 43% diabetics, 27% known CAD). Peak METS >6 was achieved in 81% of patients, and the CFR <2 was present in 27%. In multivariable logistic regression models adjusted for age, sex, cardiovascular risk factors (hypertension, diabetes, dyslipidemia) and medication use (angiotensin converting enzyme inhibitor/angiotensin receptor blocker, statins, beta-blockers), patients with peak METS >6 had a statistically significant lower odds of microvascular dysfunction (CFR <2: OR 0.43, 95% CI 0.26–0.71, p=0.001). Assessment of discrimination showed the model with CFR <2 had an incremental improvement of Harrell's C statistic over clinical variables (0.65 vs 0.69, p=0.02).

Conclusion

Our findings showed exercise capacity was a good predictor of CFR and microvascular coronary health over and above clinical variables. Further studies are needed to assess the prognostic interplay between EC and CFR.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of coronary flow reserve and coronary calcification in patients with suspected coronary artery disease
Authors: Alahdab F , Ahmed A I , Saad J M , Han Y , Alfawara M , Al-Mallah M H
Published: October 2022

Introduction

Current cardiac PET and computed tomography imaging allows the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.

Purpose

We aimed to evaluate the incremental prognostic value of coronary artery calcium (CAC) score and coronary flow reserve (CFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).

Methods

We included consecutive patients who underwent PET MPI and CAC score calculation at Houston Methodist Hospital between August 2019 and January 2022. MPI and CAC scores were obtained in the same setting. The primary endpoint of the study was MACE. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and CFR by sequentially adding the variables to a model that included clinical and PET variables.

Results

A total of 2,072 patients (mean age 65.7±11.6 years, 54.7% women) were included in the analysis. Risk factors were prevalent (86.1% hypertension, 75.2% dyslipidemia, 45.5% diabetes). In total, 25.3% of the cohort had a CAC score of 0, 38.1% had CAC ≥400, and 39.9% had CFR <2. Over a median follow up of 6.26 (IQR 1.7–12.4) months, 66 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CFR score added incremental prognostic value over clinical and perfusion variables alone (base model: c-index 0.75; Akaike information criterion [AIC]: 1,860.6; p<0.001; CFR model: c-index 0.78; AIC: 1,842.4; p=0.041). However, CAC score did not show an increased prognostic utility (CAC model: c-index 0.76; AIC: 1,854.8; p=0.087 vs. base model), and neither did the combined model of CAC and CFR scores (c-index 0.79; AIC: 1,839.4; p=0.366 vs. CFR model).

Conclusions

Among patients referred for PET MPI, CFR score added an increased prognostic value over clinical and MPI variables. However, when evaluating the prognostic utility of CAC alone, or of CAC and CFR combined, the multivariable model did not show any increased prognostic potential.

Funding Acknowledgement

Type of funding sources: None.
Visualization of macrophage inflammatory activity on visceral obesity in high-fat diet-induced obese mice by 18F-FDG PET/CT
Authors: Pahk K , Kwon H W , Kim S
Published: October 2022

Background

Obesity induced inflamed visceral adipose tissue (VAT) secretes pro-inflammatory cytokines thereby promoting systemic inflammation and insulin resistance which further exacerbate obesity-related cardiovascular disease (CVD). Macrophages are the key players in the development of obesity-associated VAT inflammation. Extensive clinical studies have reported that 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can be used to evaluate the macrophage inflammatory activity on VAT in human beings. However, due to difficulty in human VAT biopsy, pathologic correlations were lacking and there was a few study on preclinical animal models.

Purpose

Here, we investigated whether 18F-FDG PET/CT could reflect the macrophage inflammatory activity on VAT in high-fat diet-induced obese mice.

Methods

Obese animal models were induced by a high-fat diet (60% fat) for 20 weeks using the male C57BL/6 mice. Insulin tolerance test was performed to evaluate the status of insulin resistance and C-reactive protein (CRP) was measured to assess the status of systemic inflammation. All animals underwent 18F-FDG PET/CT before sacrifice. Macrophage inflammatory activity was evaluated using the maximum standardized uptake value (SUVmax). Flow cytometry-, histological-, and molecular analyses were performed on harvested VAT.

Results

All obese animals showed insulin resistance which resembled the human metabolic syndrome, a key pathophysiological process that contributes to increase CVD risk. VAT SUVmax was increased in obese mice and significantly correlated with the levels of CRP. Furthermore, VAT from obese mice showed increased macrophage infiltration, compared to normal mice.

Conclusions

18F-FDG PET/CT could visualize and evaluate the macrophage inflammatory activity on obesity-driven inflamed VAT in obese mice model. Our preclinical study strongly supports the clinical application of 18F-FDG PET/CT in the assessment of VAT inflammation to patients who are vulnerable to CVD.

Funding Acknowledgement

Type of funding sources: None.
The automatic identification of left ventricular chambers and quantification of ejection fraction using a novel artificial intelligence-based system – a validation against cardiac magnetic resonance
Authors: Dindane Z , Sveric K , Winkler A , Botan R , Mierke J , Svitil J , Heidrich F M , Ulbrich S , Linke A
Published: October 2022

Background/Introduction

Cardiac magnetic resonance imaging (CMR) is regarded as the reference method in assessing left ventricular (LV) ejection fraction (EF). However, 2-dimensional echocardiography (2D-Echo) is the most frequently used technique due to availability and practicability. The interpretation of 2D-Echo examinations depends on the user's expertise and may vary between different operators. A novel vendor-independent software based on artificial intelligence (AI) performs both, automated evaluation of 2D-Echo exams and calculations of LV EF in one workflow.

Purpose

We sought to assess the ability of the AI to automatically identify appropriate LV 4- and 2-chamber views (4CV) (2CV) from 2D-Echo exams and validate the resulting EF with CMR.

Methods

We consecutively enrolled 128 patients who underwent clinically indicated CMR examinations and performed a standard 2D-Echo at the same day. The server-based AI solution recognized the optimal LV 4CV and 2CV from 2D-Echo according to quality and depth criteria and automatically performed calculation of biplane EF by endocardial borderline detection. LV EF from CMR and AI were supervised by independent cardiologists blinded to the mutual results. Pearson's correlation (R) and Bland-Altman analysis with limits of agreement (LOA) were performed in order to assess bias between the two methods. Significance was defined as a 2-tailed P value <0.05.

Results

CMR was performed and LV EF was measured in all 128 patients. The median age was 60 years [20–86], 65% were males and CMR was performed due to coronary artery diseases (33%), suspected/florid myocarditis (20%) or further diagnosis of non-ischemic heart failure (47%). Eleven cases (9%) did not pass AI's criteria due to impaired acoustic window or poor 2D-Echo images. The AI system detected either 4CV or 2CV (ratio 1.2) in 13 patients (10%), and both 4CV and 2CV in 104 patients (81% overall feasibility) with a correct classification of 100%. For these 104 patients, excellent correlation was found for AI's biplane LV EF and LV EF from CMR with r=0.91 (p<0.001) (Figure 1, left). However, the absolute mean bias between AI and CMR was 3.5% (p<0.001) and LOAs were −10.6 and +17.5% (Figure 1, right).

Conclusion

The results provided by the AI-based software showed good capabilities and a perfect classification rate to identify 4CV and 2CV. In addition, the LV EF results were excellent compared to CMR, especially since our study did not include “echocardiographically” pre-selected patients. However, differences between AI and CMR measurements are not negligible and warrant further investigation.

Funding Acknowledgement

Type of funding sources: None.
Novel echocardiography-based algorithms to identify severe aortic or mitral regurgitation by cardiac magnetic resonance imaging: a prospective multi-modality imaging study
Authors: Wang T K M , Grimm R A , Popovic Z B , Rodriguez L L , Bolen M A , Chann N , Moennich L A , Rutkowski K , Griffin B P , Flamm S D , Kwon D H
Published: October 2022

Background

Magnetic resonance imaging (MRI) has shown incremental prognostic value to transthoracic echocardiography (TTE) for valve diseases, however TTE remains more widely available and utilized. We sought to develop TTE-based algorithms that best identify severe AR and MR by MRI in a prospective study.

Methods

Patients with >moderate-to-severe AR (n=101) and MR (n=71) undergoing both TTE and CMR within 3-months (median 1 day) were prospectively studied. Correlation analyses were performed, and TTE-based decision tree regression algorithms were derived to best identify CMR-defined severe AR and MR (regurgitant fraction >40% and >33% respectively).

Results

Mean regurgitant volumes/fractions by TTE were 15 mL/18% and 13mL/18% higher than CMR in AR and MR respectively. Decision-tree analyses found regurgitant volume >50 mL and left ventricular end-systolic volume indexed >38 mL/m2 by TTE to best identify CMR-derived severe AR, and regurgitant fraction >50% and left ventricular stroke volume indexed >39 mL/m2 by TTE to best identify CMR-derived severe MR (Figure 1). Their areas under curve compared with current guidelines criteria were 0.75 versus 0.63 (P=0.038) for severe AR, and 0.80 versus 0.67 (P=0.017) for severe MR.

Conclusion

Novel TTE-based algorithms were devised to identify severe MRI-derived AR and MR, superior to the more complex multi-parametric criteria of current TTE guidelines.

Funding Acknowledgement

Type of funding sources: None.
Myocardial scarring and recurrence of ventricular arrhythmia in patients surviving a ventricular fibrillation out of hospital cardiac arrest
Authors: Thomsen A F , Winkel B G , Jons C , Bertelsen L , Bhardwaj P , Stampe N K , Kober L , Engstrom T , Vejlstrup N G , Jacobsen P K
Published: October 2022

Introduction

Prediction of ventricular arrhythmia recurrence in survivors of ventricular fibrillation out of hospital cardiac arrest (VF-OHCA) is important, but currently difficult. Risk of recurrence may be related to presence of myocardial scarring and dedicated late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) software allows for characterization of left ventricular scarring, including differentiation between core, border zone (BZ) and BZ channels that represent potential electrical circuits of slow conductivity responsible for ventricular arrhythmic events.

Purpose

Our study aims to characterize myocardial scarring as defined by LGE-CMR in survivors of a VF-OCHA and investigate its potential role for the risk of new ventricular arrhythmia.

Methods

Between 2018 and 2021, a total of 130 VF-OHCA patients had CMR, of which we included 28 patients with LGE-CMR before ICD implantation for secondary prevention. A total of 15 (54%) patients had signs of acute or chronic ischemic heart disease (IHD); and 13 (46%) patients had arrhythmogenic cardiomyopathy (ACM). Scar tissue including core, BZ and BZ channels were automatically detected by specialized investigational software. To differentiate BZ from healthy tissue and BZ from core, thresholds of 40% ± 5% and 60% ± 5% of the maximum signal intensity were applied. A BZ channel in the LGE-CMR reconstruction was defined as a continuous corridor of BZ between 2 core areas or between a core area and a valve annulus (Figure 1A+B).

Results

The median age was 56 years; 86% were men and the median left ventricular ejection fraction was 50±11%. A total of 16 (57%) patients had an inferior scar on LGE-CMR, and 8 (29%) patients with IHD were incompletely revascularized. After a median follow-up of 98 days, 9 (32%) patients (6/9 with IHD, including 5/6 incompletely revascularized; 3/9 with ACM) had recurrence of ventricular arrhythmia (6/9 monomorphic ventricular tachycardia (VT)). A significantly higher number of patients with BZ channels had recurrence of ventricular arrhythmia compared with patients without BZ channels (7/11 vs. 2/17; P=0.01) (Figure 2). The number of BZ channels (3±1 vs. 2±1; P=0.13); scar mass (21±8g vs. 14±11g; P=0.21); core mass (7±4g vs. 4±5g; P=0.14); and BZ mass (11±5g vs. 9±7g; P=0.42) were insignificantly higher in patients with recurrent ventricular arrhythmia compared with patients without.

Conclusion

Borderzone channels analyzed by LGE-CMR were associated with subsequent recurrence of ventricular arrhythmia in patients with out of hospital cardiac arrest caused by ventricular fibrillation.

Funding Acknowledgement

Type of funding sources: None.
Higher triglyceride level is associated with the higher prevalence of layered plaque in nonculprit coronary plaques
Authors: Asakura K , Minami Y , Nagata T , Katamine M , Katsura A , Kinoshita D , Ako J
Published: October 2022

Background

The impact of the high triglyceride (TG) level on the characteristics of coronary plaque in nonculprit lesion remains to be elucidated.

Purpose

To clarify the association between the TG level and the characteristics of nonculprit coronary plaque in patients with stable coronary disease using optical coherence tomography (OCT).

Methods

A total of 531 consecutive patients who underwent OCT imaging of the nonculprit lesion were included. Patients were classified into either the higher TG group (non-fasting TG ≥150 mg/dL, n=197) or the lower TG group (non-fasting TG <150 mg/dL, n=334). The morphologies of nonculprit plaque assessed by OCT were compared between the two groups.

Results

The median (interquartile range) of TG in the two groups was 193.0 (168.0–244.0) mg/dL and 95.0 (75.0–120.0) mg/dL, respectively. The prevalence of layered plaque was significantly higher in the higher TG group than the lower TG group (40.1 vs. 27.5%, p=0.004), whereas the prevalence of other plaque components was comparable between the two groups (Figure 1). The prevalence of layered plaque was significantly higher in the higher TG group than in the lower TG group among patients with diabetes mellitus (DM) (44.2 vs. 28.7%, p=0.037) although it was comparable between the two groups among patients without DM (Figure 2).

Conclusion

A higher TG level was associated with a higher prevalence of layered plaque in nonculprit plaques in patients with stable coronary disease, particularly in patients with DM. The present results may partly explain the impact of TG on the progression of coronary plaque and the increased incidence of recurrent events in patients with coronary artery disease.

Funding Acknowledgement

Type of funding sources: None.
Diagnosis of coronary layered plaque by deep learning
Authors: Park S , Arakai M , Nakajima A , Lee H , Ye J C , Jang I K
Published: October 2022

Background/Introduction

Healed coronary plaques, morphologically characterized by a layered pattern, are signatures of previous plaque disruption and healing. Recent optical coherence tomography (OCT) studies showed that layered plaque is associated with vascular vulnerability and rapid plaque progression. However, the diagnosis of layered plaque requires expertise in OCT image interpretation and is susceptible to interobserver variability.

Purpose

We aimed to develop a deep learning (DL) model for an accurate diagnosis of layered plaque.

Methods

We developed a Visual Transformer (ViT)-based DL model emulating the cardiologists who review consecutive OCT frames to make a diagnosis (Figure 1), and compared it to the standard convolutional neural network (CNN) model. We used 302,415 cross-sectional OCT images from 873 patients collected from 9 sites: 237,021 images from 581 patients for training and internal validation from 8 sites, and 65394 images from 292 patients collected from another site for external validation.

Results

Model performances were evaluated using the area under the receiver operating characteristics (AUC). In the five-fold cross validation, the ViT-based model showed better performance than the standard CNN-based model with AUC of 0.886 (95% confidence interval [CI], 0.882–0.891) compared with 0.797 (95% CI, 0.790–0.804). The ViT-based model also outperformed the standard CNN-based model in the external validation, with an AUC of 0.857 (95% CI, 0.849–0.864) compared to 0.806 (95% CI, 0.797–0.815) (Figure 2).

Conclusion(s)

The ViT-based DL model will help cardiologists to make an accurate diagnosis of layered plaque, which might help to stratify the risk of future adverse cardiac events.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Mrs. Gillian Gray through the Allan Gray Fellowship Fund in Cardiology
Warranty period of normal CCTA and [15O]H2O PET in chest pain patients
Authors: Jukema R , Maaniitty T , Van Diemen P , Berkhof H , Raijmakers P , Sprengers R , Planken R , Knaapen P , Saraste A , Danad I , Knuuti J
Published: October 2022

Background

Normal coronary computed tomography angiography (CTA) and positron emission tomography (PET) are associated with an excellent prognosis. Hitherto, data on the warranty period of normal coronary CTA and normal myocardial blood flow (MBF) by PET are scarce.

Purpose

To determine the event-free period after normal coronary CTA and PET results. In addition, to determine whether PET MBF imaging confers additional prognostic value beyond coronary anatomy in symptomatic patients.

Methods

Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD or obstructive CAD. A hyperemic MBF <2.3 ml/min/g was considered abnormal and indicative for ischemia. A cumulative risk below 5% against death and myocardial infarction (MI) was used to define the warranty period.

Results

Of 2575 included patients (mean age 61.4±9.9 years, 41% male) 1319 (51.2%) underwent coronary CTA only, 1237 (48.0%) underwent both coronary CTA and PET and 19 (0.74%) patients underwent PET imaging only. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients without any CAD was >10 years. Patients with non-obstructive CAD had a 5 year warranty period. In patients with no, non-obstructive or obstructive CAD on CTA, normal PET extended the warranty period with ≥2 years. The warranty period of patients with non-obstructive CAD or normal perfusion varied between 2.5 and >10 years for patients with or without clinical risk factors.

Conclusions

As standalone imaging, the warranty period for a normal coronary CTA is >10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Independent of coronary anatomy normal perfusion imaging has additional prognostic value and extends the warranty period by ≥2 years.

Funding Acknowledgement

Type of funding sources: None.
QFR vs. perfusion imaging to predict abnormal FFR in patients with prior coronary artery disease
Authors: Van Diemen P A , De Winter R W , Raijmakers P G , Maaniitty T , Robbers L F , Von Bartheld M B , Demirkiran A , Van Rossum A C , Reiber J H , Underwood S R , Knuuti J , Nagel E , Knaapen P , Driessen R S , Danad I
Published: October 2022

Background

In patients with suspected obstructive coronary artery disease (CAD) and a high pre-test probability, myocardial perfusion imaging (MPI) or referral for invasive coronary angiography (ICA) are viable diagnostic strategies. The present study compared the diagnostic performance of quantitative flow ratio (QFR) and MPI by single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR).

Methods

In this PACIFIC-II substudy, 189 patients with prior MI/PCI who were suspected of having symptoms related to myocardial ischemia and underwent SPECT, PET, and CMR before ICA were evaluated for inclusion. ICA was obtained with (109 patients) and without (80 patients) adherence to a QFR acquisition protocol. All major coronary arteries were interrogated by FFR, except for vessels with a subtotal/total occlusion. An FFR ≤0.80 was used to define significant epicardial CAD. QFR analyses (v2.0) were performed based on ICA by a corelab in vascular territories (N=487) in which FFR was obtained. MPI modalities were assessed for presence of ischemia by corelabs, uninterpretable scans were omitted from the diagnostic comparison analyses.

Results

QFR analysis success rate was higher (81%) among vessels acquired using the QFR acquisition protocol compared to vessels obtained without the protocol (52%, p<0.001). Overall, a QFR result was available in 334 (69%) vessels. Among these vessels, QFR had a higher sensitivity (72%) and accuracy (84%) compared to SPECT (46%, p=0.001 and 66%, p<0.001), PET (58%, p=0.032 and 65%, p<0.001), and CMR (33%, p<0.001 and 72%, p<0.001). Whereas specificity of QFR (87%) was similar to CMR (83%, p=0.123) but higher than that of SPECT (71%, p<0.001) and PET (67%, p<0.001). Lastly, QFR exhibited a higher area under the receiver operating characteristic curve (0.89) than SPECT (0.57, p<0.001), PET (0.66, p<0.001), and CMR (0.60, p<0.001).

Conclusions

Provided QFR was analyzable (69% of the vessels), QFR correlated better with FFR (both as measures of epicardial CAD) than MPI as reflected in the diagnostic performance measures for detecting vessels-specific significant epicardial CAD as defined by FFR.

Funding Acknowledgement

Type of funding sources: None.
Functional heart and brain changes in acute coronary syndromes
Authors: Williams M G L , Thai N J , Liang K , De Garate E , Hartley-Davies R , Lawton C B , Langley C , Hinton E , Bucciarelli-Ducci C
Published: October 2022

Aims

To investigate whether there are functional brain differences, or differences in global network measures, between patients with acute coronary syndrome (ACS) and non-obstructive coronary arteries and patients with an ST-elevation myocardial infarction (STEMI) and healthy controls.

Methods and results

In this single centre, prospective cohort study, all patients <80 years who presented to a tertiary cardiac centre with a suspected acute coronary syndrome and who had non-obstructive coronary arteries on invasive angiography were approached for inclusion. Age and sex matched patients presenting with a STEMI and a further group of healthy volunteers were recruited as control groups. All patients received routine clinical care and investigations and underwent additional psychological questionnaires, cardiac magnetic resonance imaging and functional brain imaging within 14 days of admission. Image pre-processing and analysis was undertaken in a blinded fashion.

72 participants, in addition to 27 STEMI controls and 28 healthy controls, were recruited. Median age in the participant group was 57 years (IQR 47–66 years) and patients were scanned 6 days (IQR 3–8 days) from admission. Patients with ACS and non-obstructive arteries had increased functional connectivity in the default mode network and reduced connectivity in the central executive network compared to controls (Figure 1). They also had higher anxiety scores compared to STEMI and healthy controls and higher depression and stress scores compared to healthy controls (Figure 2). There was no difference in any global network measure between participants and age and sex matched controls however high anxiety or stress scores were associated with lower global efficiency in patients with ACS and non-obstructive coronary arteries but not in controls (Figure 2).

Conclusion

Patients with ACS and non-obstructive coronary arteries are distinct from both the STEMI and healthy population in terms of their psychological and neurofunctional state and this may have important future therapeutic implications for patients.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): James Tudor FoundationRosetrees Trust
Trajectory of pulmonary congestion by lung ultrasound in patients with acute myocardial infarction and association with cardiac structure and function
Authors: Platz E , Claggett B , Jering K S , Kovacs A , Cikes M , Winzer E B , Rad A , Lefkowitz M , Gong J , Kober L , McMurray J J V , Solomon S D , Shah A
Published: October 2022

Background

The PARADISE-MI trial examined the efficacy of sacubitril/valsartan in patients with acute myocardial infarction (AMI) complicated by reduced left ventricular ejection fraction (LVEF), pulmonary congestion or both. Little is known about the trajectory and echocardiographic correlates of pulmonary congestion in this population.

Purpose

We sought to assess the trajectory of pulmonary congestion using lung ultrasound (LUS) and its association with cardiac structure and function in a subset of patients enrolled in PARADISE- MI.

Methods

Participants underwent 8-zone LUS at baseline and 8 months. B-lines were quantified offline, blinded to treatment group, clinical findings, timepoint and outcomes by a core laboratory. Paired t-tests, chi-squared tests, and linear regression analyses were conducted.

Results

Among 152 patients (median age 65 years, 32% women, 35% obese, mean LVEF 41%), any B-lines were detectable in 87%, the median sum of B-lines in 8 zones was 4 [IQR 2–8], and 67% had ≥3 B-lines indicative of congestion. Greater number of B-lines at baseline was associated with larger left atrial (LA) size, higher E/e' and E/A ratios, greater degree of mitral regurgitation, worse right ventricular (RV) systolic function, and higher tricuspid regurgitation velocity (P trend <0.05 for all) (Figure 1). Among 115 patients with 8-month LUS data, there was a significant decline in number of B-lines from baseline (mean ± SD: −1.6±7.3; p=0.018). Adjusted for baseline, B-lines at follow-up were on average 6 (95% CI: 3, 9) higher in a patient who experienced an intercurrent heart failure (HF) event than a non-HF patient (p=0.001). Among 75 patients with ≥3 B-lines at baseline, a decrease in B-lines to <3, indicating decongestion, occurred in 37% and was similar in the sacubitril/valsartan and ramipril groups (36% vs. 39%, p=0.83).

Conclusions

In this post-AMI cohort, sonographic B-lines, indicating pulmonary congestion, were common at baseline and were significantly higher at follow-up in those who developed HF. Worse pulmonary congestion at baseline was associated with prognostically important echocardiographic markers of LV filling pressure, pulmonary pressure, and RV function.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Novartis
Sex-based differences on adverse left ventricular remodeling and clinical outcomes after an ST-segment elevation myocardial infarction in the PCI era
Authors: Alonso Tello A , Sambola A , Valente F , Sao A , Rello P , Maymi M , Barrabes J , Otaegui I , Garcia Del Blanco B , Gavara J , Marcos-Garces V , Ferreira I , Ortiz J T , Bodi V , Rodriguez-Palomares J F
Published: October 2022

Background

There is conflicting evidence regarding sex-based differences in myocardial salvage and clinical outcome in patients after an ST-segment elevation myocardial infarction (STEMI) in the contemporary era of primary percutaneous coronary intervention (PCI) and optimal medical treatment.

Adverse left ventricular remodelling (LVR) after a STEMI worsens outcomes, however, the influence of sex is not yet clear.

Aim/Purpose

To analyze whether there are sex differences in clinical outcomes and adverse LVR in patients after a STEMI.

Methods

Patients with STEMI who underwent primary PCI were included and a cardiac magnetic resonance (CMR) was performed during hospitalization (6.2±2.6 days) and after 6 months (6.1±1.8 months). LVR, myocardial salvage (MS), infarct size (IS), microvascular obstruction (MVO), and area at risk (AAR) were quantified. Adverse LVR was defined as a 15% increase in LV end-diastolic volume and a relative fall in LV ejection fraction of 3% at 6 months. The primary outcome was a composite of cardiovascular death, admission for heart failure, or ventricular arrhythmia.

Results

A total of 1046 patients were included (mean age: 59.8±9 years; 16.6% women), and a second CMR was completed in 589 patients. Women were older (58.8±8 years vs 65.0±10 years, p<0.0001) and presented more cardiovascular risk factors (Table). The primary outcome occurred in 310 patients during follow-up of 75 months (range: 36–112 months) and was more frequent in women than in men (35.8% vs 22.3%, p<0.001). After adjusting for baseline differences (age, diabetes, hypertension, Killip class, and time to reperfusion), female sex was not an independent predictor of major adverse cardiac events (Fig. 1A & B).

Although adverse LVR was a strong independent predictor for the primary outcome, no interaction was present between sex and LVR (women 6.4% vs men 8%, p=0.46) (Fig 1B), nor did we find significant differences between sex and other CMR derived variables such as MS, IS, MVO and AAR.

Conclusions

After a STEMI, women present worse clinical outcomes than men. However, these differences are related to their clinical characteristics and higher incidence of cardiovascular risk factors, and not to a higher incidence of adverse left ventricular remodeling.

Funding Acknowledgement

Type of funding sources: None.
Multimodality coronary imaging to predict non-culprit territory unrecognized myocardial infarction assessed by cardiac magnetic resonance in non-ST-elevation acute coronary syndrome
Authors: Hoshino M , Sugiyama T , Kanaji Y , Hada M , Misawa T , Nagamine T , Ueno H , Matsuda K , Sayama K , Yonetsu T , Sasano T , Kakuta T
Published: October 2022

Objectives

This study sought to assess the predictors of coherence tomography (OCT) and coronary computed tomography angiographic (CCTA) findings for non-infarct-related (non-IR) territory unrecognized myocardial infarction (UMI) in patients with first non-ST-elevation acute coronary syndrome (NSTE-ACS) presentation.

Background

UMI detected by cardiac magnetic resonance (CMR) is associated with adverse outcomes in patients with both acute coronary syndrome and chronic coronary syndrome. However, the association between the presence of UMI and findings of multimodality coronary imaging remains unknown.

Methods

We investigated 69 patients with a first clinical episode of NSTE-ACS, who underwent pre-PCI 320-slice CCTA, uncomplicated urgent percutaneous coronary intervention (PCI) with OCT assessment within 48 hours of admission, and post-PCI CMR. UMI was assessed on late gadolinium enhancement (LGE-CMR) by identifying regions of hyperenhancement with an ischemic distribution pattern in non-IR territories (non-IR UMI).

Results

Non-IR UMI was detected in 11 patients (15.9%). ROC analysis revealed the optimal cut-off value of PCATA in culprit vessel for predicting the presence of non-IR UMI were −71.3. Lower ejection fraction, higher Gensini score, high pericoronary inflammation (>−71.3), OCT-defined culprit lesion plaque rupture (OCT-PR), and OCT-defined culprit lesion cholesterol crystal (OCT-CC) were significantly associated with the presence of non-IR UMI (Figure 1A). OCT findings are shown in Figure 1B. Patients with non-IR UMI had a higher prevalence of OCT-PR and OCT-CC than those without. Compared with patients without non-IR UMI, the prevalence of high pericoronary inflammation was higher in patients with non-IR UMI (Figure 1C). When the total cohort was divided into four groups according to the numbers of aforementioned OCT-derived risk factors and PCATA, patients with all of these UMI risk factors showed 46.2% (6/13) prevalence of non-IR UMI, whereas none of 15 patients without these factors showed non-IR UMI (Figure 1D).

Conclusions

When culprit lesion showed OCT-PR, OCT-CC, and high PCATA, about half of these patients are likely to have non-IR UMI. The integrated CCTA and OCT assessment may help identify the presence of non-IR UMI, potentially providing prognostic information in first NSTE-ACS patients.

Funding Acknowledgement

Type of funding sources: None.