bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positron emission tomography/computed tomography perfusion imaging with myocardial blood flow has diagnostic and prognostic value for cardiac allograft vasculopathy
Authors: Abadie B , Chan N , Sharalaya Z , Bhat P , Harb S , Jacob M , Tang W H , Cremer P , Jaber W 
Published: October 2022

Abstract

Background
Cardiac allograft vasculopathy (CAV) is a leading cause of morbidity and mortality in patients with orthotopic heart transplantation (OHT). Invasive coronary angiography is the traditional method of screening for and diagnosing CAV. Alternative non-invasive modalities have been sought to screen for CAV. A small, single-center study utilizing Positron Emission Tomography/Computed Tomography Perfusion Imaging (PET/CT) with stress myocardial blood flow (MBF) demonstrated good diagnostic and prognostic value for CAV.

Purpose
The purpose of this study was to validate the proposed algorithm for diagnosing and prognosticating CAV by PET/CT with stress MBF in a large and contemporary series.

Methods
Patients with a history of OHT with no prior revascularization in the transplanted heart who underwent PET/CT with MBF were included in the prognostic portion of the study. For the diagnostic value of PET/CT with MBF, only patients who had a PET/CT within 12 months of coronary angiography were included. The diagnostic accuracy of PET/CT was compared to the most recent coronary angiogram. A composite outcome of death, heart failure hospitalization, acute coronary syndrome, revascularization, and re-transplantation was used to validate the prognostic ability of PET/CT with MBF.

Results
450 PET/CT scans with MBF were performed and included in the prognostic portion of the study. 78 patients had PET/CT within 12 months of coronary angiography and were included in the diagnostic portion. Normal perfusion with normal myocardial blood flow had a 100% negative predictive value for moderate-severe CAV by angiography. PET/CT CAV 2/3 had a positive predictive value of 69% for moderate-severe CAV. Over 24 months, there were 20 events in the 39 patients with a PET CAV grade of 2/3 versus 21 events in the 411 patients with a PET CAV grade of 0/1 with a hazard ratio 13.3 (p&lt;0.001).

Conclusions
The current proposed algorithm for diagnosing CAV by PET/CT with stress MBF has excellent negative predictive value along with good positive predictive value for detecting moderate-severe CAV by coronary angiography. A PET/CT with stress MBF with CAV classification of 2/3 is associated with a poor prognosis.

Funding Acknowledgement
Type of funding sources: None.
AD-9308 ameliorates the impacts of 4-HNE on the progress of pulmonary arterial hypertension in aldehyde dehydrogenase 2*1*2 knock-in mice
Authors: Chou Y H , Lee Y N , Su C H , Yeh H I , Wu Y J 
Published: October 2022

Abstract

Endothelial dysfunctions play a critical role on the development of pulmonary arterial hypertension (PAH). It has been reported that the one-year mortality rate is still up to 15% even with PAH-targeted therapy, implying that there may be untargeted pathways. 4-hydroxynenonal (4-HNE), an unsaturated aldehyde, is highly induced in the lungs of PAH animals and its serum levels were also reported to be higher in PAH patients. 4-HNE is metabolized by mitochondrial aldehyde dehydrogenase (ALDH2), which is dysfunctional in near 40% of East Asian people. Currently, the impacts of 4-HNE on endothelial dysfunctions in the development of PAH are unclear. In terms of translational medicine, we proposed that modulation of 4-HNE level may alleviate the progress of PAH patients with ALDH2 deficiency.
We found that 4-HNE alone was not sufficient to induce pulmonary artery endothelial cell (PAEC) functional changes, including proliferation, migration and tube formation, whereas their effects emerge from the depletion of ALDH2. We further mimicked human ALDH2 functional deficiency by using daidzin (DZN), an inhibitor which is able to block the substrate binding site of ALDH2. ALDH2 functional inhibition alone did not induce any PAEC functional change, while an add-on of 4-HNE impaired PAEC functions. In addition, 4-HNE significantly reduced eNOS activity with combined DZN treatment. Consistent with the mechanism of ALDH2 activity-mediated angiogensis, ALDH2 enhancers Alda-1 and AD-5591 completely reverse the anti-angiogenic effects of 4-HNE in the presence of DZN. To further confirm whether ALDH2 functional deficiency impact on PAH development in mammals, heterozygous ALDH2*1/*2 transgenic and wild-type mice were subjected to chronic hypoxia to induce PAH. ALDH2*1/*2 transgenic mice had similar right ventricular systolic pressure (RVSP) as wild-type mice. However, after exposure to chronic hypoxia, ALDH2*1/*2 transgenic mice indeed developed a significantly higher RVSP than that in wild-type mice. Furthermore, we demonstrated that 4-HNE expression was profoundly enhanced in ALDH2*1/*2 transgenic mice by chronic hypoxia-induced PAH with pulmonary artery smooth muscle cell hyperplasia. More importantly, we found that AD-9308, an enhancer of ALDH2 significantly decreased hypoxia-induced RVSP elevation in heterozygous ALDH2*1/*2 transgenic mice.
Taken together, our data demonstrate that 4-HNE and ALDH2 functional deficiency potentially contribute to PAH development and worsening, and that ALDH2 enhancers may be promising as a PAH adjunct therapy, particularly for patients with ALDH2 nonfunctional alleles.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Science and Technology, Taiwan
Focused ultrasound stimulation of the inflammatory reflex at the spleen ameliorates pulmonary arterial hypertension in rodents
Authors: Zafeiropoulos S , Ahmed U , Giannakoulas G , Puleo C , Zanos S 
Published: October 2022

Abstract

Background
Inflammation is a major contributor in pulmonary arterial hypertension (PAH) pathogenesis. Non-invasive, focused ultrasound stimulation (FUS) of the spleen activates the neuroimmune inflammatory reflex (IR) and suppresses systemic inflammation [1].

Purpose
We aimed to explore whether daily FUS of the spleen improves haemodynamics and biomarkers by modulating the IR, in a rat model of PAH.

Methods
Sprague-Dawley rats (n=12) were injected s.c. with Sugen5416 (VEGF receptor inhibitor) and then, were placed in a hypoxic chamber (FiO2=10%) for 21 days, followed by 14 days of re-exposure to normoxia (FiO2=10%). At day 21, rats were randomized to either FUS (n=6) or sham-stimulation of the spleen (n=6). Each FUS- or sham-stimulation session consisted of 12 minutes. After 14 days of treatment, in a terminal experiment, right ventricular systolic pressure (RVSP) and arterial pressure were measured invasively, as well as biomarkers, in each animal (Figure 1A).

Results
FUS significantly reduced RVSP compared with the sham-stimulation (Mean±SEM, 50.83±3.57 mmHg vs 72.50±5.81; p=0.009), resulting in a 30% relative reduction (Figure 1B). Mean systemic arterial pressure was similar in the 2 groups (Mean±SEM, 79.83±3.73 mmHg vs. 87.00±2.95; p=0.137) (Figure 1C), as was the change in heart rate between day 1 and day 14 of treatment period (−19.53±5.36% vs. −16.79±3.1, p=0.61) (Figure 1D). Consistently, plasma brain natriuretic peptide (BNP) levels are reduced in the FUS group (119.45±19.93 ng/μl vs. 319.39±91.85; p=0.019), indicative of reduced myocardial wall stress in the FUS group (Figure 1E).

Conclusion
Non-invasive FUS of the spleen reduced RVSP by ∼30% and BNP without significantly affecting systemic pressure or heart rate, in rats with severe PAH. Non-invasive FUS, by modulating the IR, may exert an anti-inflammatory effect in PAH. FUS of the spleen is noninvasive, safe, widely available and easy to perform, and should be further explored as a possible therapeutic option in PAH.

Funding Acknowledgement
Type of funding sources: Private hospital(s). Main funding source(s): Northwell Health
Incremental prognostic value of coronary flow reserve derived from SPIM digital positron emission tomography
Authors: Ahmed A I , Saad J M , Alahdab F , Han Y , Alfawara M , Nabi F , Mahmarian J , Al-Mallah M H 
Published: October 2022

Abstract

Introduction
Positron emission tomography (PET) myocardial perfusion imaging (MPI) is an established test in the diagnosis and prognosis of patients with cardiac diseases. Silicon photomultiplier (SiPM) digital PET is the latest advancement in this technology with improved detector sensitivity, coincidence time resolution, and spatial resolution, allowing for Sub-milliSievert cardiac PET MPI.

Purpose
We aimed to assess the independent and incremental prognostic value of SiPM digital PET derived coronary flow reserve (CFR) to clinical and nuclear variables.

Methods
Consecutive patients who had clinically indicated digital Rubidium PET MPI were included. Rubidium dose was 10–20 mCi according to patient's weight. Patients were followed from the date of imaging to incident major adverse cardiovascular event (MACE: inclusive of all-cause death, myocardial infarction, admission for heart failure and late revascularization – percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) &gt;90 days after imaging).

Results
The study population consisted of 2,893 patients with clinically indicated PET MPI (mean age 67 (±12), 53% male, 41% Caucasian). Cardiovascular risk factors were prevalent (88% hypertensive, 80% dyslipidemic, 47% diabetics, 18% ever smoking). After a mean follow-up of 8±7 months, 250 patients (8.6%, 10.7 per 1000 person-year) experienced MACE (90 D / 38 MI / 51 PCI / 11 CABG / 113 HF). In nested multivariable cox models, CFR was independently associated with incident MACE (HR 0.38, 95% CI 0.29–0.51, p&lt;0.001) and incrementally improved risk prediction (Harrell's C=0.77, p=0.002).

Conclusion
Our findings showed that a Sub-milliSievert SiPM digital PET-derived CFR provided incremental value in risk-stratifying patients and identifying those at increased risk of incident outcomes.

Funding Acknowledgement
Type of funding sources: None.
Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19
Authors: Solomou E , Terentes-Printzios D , Gardikioti V , Katsaounou P , Exarchos D , Economou D , Christopoulou G , Kalkinis A D , Kafouris P , Antonopoulos A , Kotanidou A , Datseris I , Tsioufis K , Anagnostopoulos C D , Vlachopoulos C 
Published: October 2022

Abstract

Aim
Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19.

Methods
Between November 2020 and May 2021, in this pilot, case-control study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59±12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20–120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR.

Results
There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40–1.57] vs. 1.43 [1.32–1.70], respectively, p=0.422 and IAS-TBR: 1.60 [1.50–1.67] vs. 1.50 [1.42–1.61], respectively, p=0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho=−0.528, p=0.017 and Spearman's rho=−0.480, p=0.032, respectively), Figure 1. Patients who were scanned less than or equal to 60 days from admission (n=11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42–1.60] vs. 1.40 [1.33–1.45], respectively, p=0.016 and IAS-TBR: 1.64 [1.51–1.74] vs. 1.52 [1.46–1.60], respectively, p=0.038). There was a significant difference in IAS-TBR between patients scanned ≤60 days and controls (1.64 [1.51–1.74] vs. 1.50 [1.41–1.61], p=0.036), Figure 2.

Conclusion
This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post-COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

Funding Acknowledgement
Type of funding sources: None.
Exploring macrophage mannose receptor expression after myocardial infarction by Al[18F]F-NOTA-DCM positron emission tomography
Authors: Andriana P , Lijenback H , Iqbal I , Palani S , Makrypidi K , Virta J , Herre E A , Jalkanen S , Knuuti J , Pirmettis I , Li X G , Saraste A , Roivainen A 
Published: October 2022

Abstract

Introduction
Mannose receptor (CD206) is primarily expressed on the surface of alternatively activated macrophages that are involved in resolution of inflammation after myocardial injury [1]. The purpose of this study was to evaluate mannose receptor targeting positron emission tomography (PET) tracer Al[18F]F-NOTA-DCM consisting of dextran backbone with cysteine-mannose moieties for imaging of experimental acute myocardial infarction (MI) [2].

Methods
First, ALEXA-488 fluorophore-labelled DCM was used for specificity studies using flow cytometry of M1 and M2 polarized macrophages derived from human blood monocytes. Secondly, Sprague-Dawley rats were studied on day 3 and day 7 after permanent ligation of left coronary artery or after sham-operation. [18F]FDG PET (35 MBq, 10 min static scan) was performed to visualize myocardium and on the next day, 60 min dynamic PET was performed after injection of 50 MBq of Al[18F]F-NOTA-DCM. Then, rats were euthanized for biodistribution study by gamma counting followed by digital autoradiography and histology (H&E, CD206 staining) of left ventricle cryosections. In vitro Al[18F]F-NOTA-DCM blocking study was performed on left ventricle cryosection with molar excess of unlabelled DCM.

Results
Flow cytometry confirmed that ALEXA-488-DCM bound specifically to M2 macrophages. In rats, the infarcted area was clearly detected in vivo with Al[18F]F-NOTA-DCM PET and its SUV was significantly higher than that of remote area or myocardium of sham-operated rats both on day 3 (SUV 0.78±0.18 vs. 0.47±0.13 vs. 0.43±0.07, p&lt;0.005) and day 7 post-MI (SUV 0.64±0.10 vs. 0.47±0.12 vs. 0.51±0.07, p&lt;0.05). Autoradiography confirmed increased uptake in the infarcted area compared to the remote area or to the myocardium of sham-operated rats on day 3 (PSL/mm2 141.21±46.06 vs. 49.76±20.37 vs. 57.97±6.77, p&lt;0.005) and day 7 (PSL/mm2 139.22±19.44 vs. 55.38±28.83 vs. 60.83±7.63, p&lt;0.0001). In vitro blocking study indicated that the tracer binding in infarcted area was specific. The area-% of CD206-positive staining in the infarcted area was significantly higher on day 3 post-MI than on day 7 (p&lt;0.05), and higher at both time points than in remote area or myocardium of sham-operated rats (p&lt;0.0001). Area-% of CD206 staining in the MI area positively correlated with Al[18F]F-NOTA-DCM uptake and MI size (p&lt;0.05 and p&lt;0.01, respectively).

Conclusions
Al[18F]F-NOTA-DCM PET detects overexpression of mannose receptor after ischemic myocardial injury and may be a suitable biomarker for early detection of the inflammation resolution process after MI.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Jane and Aatos Erkko FoundationSigrid Juselius FoundationFInnish Foundation for Cardiovascular Research
Epicardial adipose tissue in patients with systemic sclerosis
Authors: Wang X , Butcher S , Myagmardorj R , Liem S , Vries-Bouwstra J , Delgado V , Bax J , Marsan N 
Published: October 2022

Abstract

Background
Cardiac involvement is a major cause of death in patients with systemic sclerosis (SSc). Epicardial adipose tissue (EAT) has recently emerged as a mediator between systemic inflammatory disorders and cardiovascular disease, and may therefore play a role in the pathophysiology of cardiac involvement in SSc.

Purpose
To assess the correlation between EAT mass and left ventricular (LV) function, and to determine the prognostic value of EAT in patients with SSc.

Methods
Consecutive patients with SSc who underwent non-contrast thorax computed tomography and echocardiography were included. EAT mass was quantified using dedicated software (Figure A). The study endpoint was all-cause mortality.

Results
A total of 230 SSc patients [age 53±15 years, 14% male] were included. The median value of EAT mass was 67g (IQR: 45–101g). Patients with increased EAT mass (≥67g) showed specifically more impaired LV diastolic function as compared to patients with less EAT mass (&lt;67g). After adjusting for age and comorbidities, EAT remained independently associated with LV diastolic function parameters including left atrial volume index (B=0.031, P=0.025), LV mass index (B=0.139, P=0.036), E/E$'$ (B=0.025, P&lt;0.001) and E' (B=−0.012, P&lt;0.001). During a median follow-up of 8 years 42 patients died, and by Kaplan-Meier analysis patients with increased EAT mass showed higher all-cause mortality rate as compared to patients with less EAT mass (log-rank p&lt;0.001, Figure B). On multivariate analysis, EAT mass was independently associated with all-cause mortality (HR: 1.006; 95% CI: 1.001–1.010; p=0.010).

Conclusion
In patients with SSc, EAT mass is independently associated with LV diastolic dysfunction and higher mortality rate.

Funding Acknowledgement
Type of funding sources: None.
Is cardiac magnetic resonance of additional help in premature ventricular contraction work-up?
Authors: Richard M , Pop A , Hager H , Leven F , Mansourati J 
Published: October 2022

Abstract

Background
Premature ventricular contractions (PVCs) are common in routine medical practice. PVCs are commonly asymptomatic but can also result in palpitations, dyspnea, presyncope or PVC-induced cardiomyopathy that may lead to sudden death. Cardiovascular magnetic resonance (CMR) provides morphological, functional, and tissue characterization in a single setting. CMR imaging proved to reliably identify fibrotic lesions and, hence, has developed into a valuable tool for etiological orientation in patients with PVCs.

Objectives
The aims of this study were: 1) to evaluate which ventricular arrythmia (VA) characteristics predicted CMR abnormalities and 2) the diagnostic yield and the impact in the management of CMR-based imaging versus non-CMR-based imaging in patients referred for PVCs.

Methods
This monocentric retrospective study was conducted in patients with PVCs referred for CMR imaging. Their baseline interview and characteristics, physical examination, surface electrocardiogram (ECG) analysis, ambulatory monitoring, echocardiography and treadmill exercise test data were collected when they were available. The CMR (1,5 T and 3.0 T) protocol included cine imaging and late gadolinium enhancement (LGE) using standard cardiac geometries.

Results
We analyzed 168 patients (65% males, mean age 54.2±16.8 years) referred to our center for PVCs over a two-year period. CMR reported abnormal findings in 73 patients (43.5%) with the diagnosis of structural heart disease (SHD) in 46 patients (27.4%). Left-ventricular late gadolinium-enhancement was documented in 43 patients with abnormal CMR. Using a multivariate analysis, age (p=0.026), sustained ventricular tachycardia (p=0.002) and presence of cardiomyopathy on echocardiography (p&lt;0.001) significantly predicted the presence of abnormal findings on CMR. Compared to non-CMR-based imaging, CMR had a diagnostic yield, by modifying the presumed diagnosis or by finding abnormalities requiring follow-up in 73 patients (43.5%).

Conclusions
Age, sustained ventricular tachycardia and presence of cardiomyopathy on echocardiography were the strongest predictors of positive CMR imaging results. Although echocardiography is generally used in first intention for the diagnosis of cardiomyopathy in patients with PVCs, this study showed that CMR-based imaging has a robust diagnostic yield in this indication.

Funding Acknowledgement
Type of funding sources: None.
Long-standing persistent atrial fibrillation with low coronary flow reserve is associated with unnecessary coronary angiography
Authors: Daniels F , Elvan A , Beemsterboer I T A , Mouden M 
Published: October 2022

Abstract

Background/Introduction
Atrial fibrillation (AF) is associated with an increased risk of myocardial infarction. Myocardial perfusion imaging (MPI) is well-established for the diagnosis of coronary artery disease (CAD) and risk-stratification in sinus rhythm (SR) patients.

Purpose
The aim of this study was to determine the impact of AF and coronary flow reserve (CFR) on revascularization in patients undergoing positron emission tomography (PET) MPI.

Methods
680 patients without a known history of CAD were included. 226 paroxysmal AF (PAF) and 114 long-standing persistent AF (LSPAF) patients were identified from a single-center prospective PET MPI registry and propensity matched in a 1:1 ratio to SR patients. The main indications for PET MPI were chest pain and dyspnea. Follow-up was obtained for downstream referral for invasive coronary angiography (CAG) and the occurrence of myocardial infarction (MI) or coronary revascularization.

Results
Compared with PAF, LSPAF patients were older (p=0.011) and more frequently male (p=0.031), with no significant differences in prior medical history and cardiac risk factors. The number of abnormal scans (infarction or ischemia) did not differ significantly between SR and AF, respectively 22.1% and 18.5% (p=0.253). The frequency of downstream CAG was comparable between the groups (p=0.298), with a significantly higher yield of obstructive CAD in the SR group as compared to PAF and LSPAF groups (63% vs 42% vs 36%, p=0.007). A low CFR (defined as CFR below the median of 2.4) in patients with SR showed significantly more revascularization compared with PAF and LSPAF (p&lt;0.001), although more patients with LSPAF and low CFR underwent CAG (p&lt;0.001). In patients with low CFR referred for CAG, the overall prevalence of obstructive coronary artery disease on CAG was 62%, with 30% for LSPAF, 52% for PAF and 78% for SR. There were no significant differences between SR, PAF and LSPAF in the occurrence of MI during a mean follow-up of 36 months (p=0.256).

Conclusion
A low CFR was only associated with a higher incidence of revascularization in patients with SR. Among patients with low CFR, LSPAF patients have the highest number of unnecessary CAGs as compared with SR and PAF.

Funding Acknowledgement
Type of funding sources: None.