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Objectives: Evaluation of in-stent restenosis (ISR), especially for small stents, remains challenging during computed tomography (CT) angiography. We used deep learning reconstruction to quantify stent strut thickness and lumen vessel diameter at the stent and compared it with values obtained using conventional reconstruction strategies. Methods: We examined 166 stents in 85 consecutive patients who underwent CT and invasive coronary angiography (ICA) within 3 months of each other from 2019–2021 after percutaneous coronary intervention with coronary stent placement. The presence of ISR was defined as percent diameter stenosis ≥ 50% on ICA. We compared a super-resolution deep learning reconstruction, Precise IQ Engine (PIQE), and a model-based iterative reconstruction, Forward projected model-based Iterative Reconstruction SoluTion (FIRST). All images were reconstructed using PIQE and FIRST and assessed by two blinded cardiovascular radiographers. Results: PIQE had a larger full width at half maximum of the lumen and smaller strut than FIRST. The image quality score in PIQE was higher than that in FIRST (4.2 ± 1.1 versus 2.7 ± 1.2, p < 0.05). In addition, the specificity and accuracy of ISR detection were better in PIQE than in FIRST (p < 0.05 for both), with particularly pronounced differences for stent diameters < 3.0 mm. Conclusion: PIQE provides superior image quality and diagnostic accuracy for ISR, even with stents measuring < 3.0 mm in diameter. Clinical relevance statement: With improvements in the diagnostic accuracy of in-stent stenosis, CT angiography could become a gatekeeper for ICA in post-stenting cases, obviating ICA in many patients after recent stenting with infrequent ISR and allowing non-invasive ISR detection in the late phase. Key Points: • Despite CT technology advancements, evaluating in-stent stenosis severity, especially in small-diameter stents, remains challenging. • Compared with conventional methods, the Precise IQ Engine uses deep learning to improve spatial resolution. • Improved diagnostic accuracy of CT angiography helps avoid invasive coronary angiography after coronary artery stenting. [ABSTRACT FROM AUTHOR]

To describe the updated coronary computed tomographic angiography (CCTA)-based coronary artery bypass graft (CABG) anatomic SYNTAX Score (aSS) and assess its utility and reproducibility for assessing the completeness of revascularization after CABG. The CCTA-CABG aSS is a visual assessment using CCTA post-CABG which quantifies the failure in effectively grafting stenotic coronary segments, and therefore assesses the completeness of surgical revascularization. It is calculated by subtracting the aSS of successfully anastomosed coronary segments from the aSS of the native coronary tree. The inter-observer reproducibility of the CCTA-CABG aSS was evaluated in 45 consecutive patients with three-vessel disease with or without left main disease who underwent a CCTA 30 days (± 7 days) after CABG. The CCTA-CABG aSS was evaluated in 45 consecutive patients with 117 bypass grafts and 152 anastomoses. The median native coronary aSS was 35.0 [interquartile range (IQR) 27.0–41.0], whilst the median CCTA-CABG aSS was 13.0 (IQR 9.0–20.5). The inter-observer level of agreement for the native coronary aSS and the CCTA-CABG aSS were both substantial with respective Kappas of 0.67 and 0.61. The CCTA-CABG aSS was feasible in all patients who underwent CABG for complex coronary artery disease with substantial inter-observer reproducibility, and therefore can be used to quantify the completeness of revascularization after CABG. [ABSTRACT FROM AUTHOR]

The diagnostic performance of the SYNTAX score 2020 (SS-2020) when calculated using CCTA remains unknown. This study aimed to compare treatment recommendations based on the SS-2020 derived from coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA). This interim analysis included 57 of the planned 114 patients with de-novo three-vessel disease, with or without left main coronary artery disease, enrolled in the ongoing FASTTRACK CABG trial. The anatomical SYNTAX scores derived from ICA or CCTA were evaluated by two separate teams of blinded core-lab analysts. Treatment recommendations were based on a maximal individual absolute risk difference in all-cause mortality between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) of 4.5% ([predicted PCI mortality] – [predicted CABG mortality]). The level of agreement was evaluated with Bland–Altman plots and Cohen's Kappa. The mean age was 66.2 ± 9.2 years and 89.5% of patients were male. Mean anatomical SYNTAX scores derived from ICA and CCTA were 35.1 ± 11.5 and 35.6 ± 11.4 (p = 0.751), respectively. The Bland–Altman analysis showed mean differences of − 0.26 and − 0.93, with standard deviation of 3.69 and 5.23, for 5- and 10-year all-cause mortality, respectively. The concordance in recommended treatment for 5- and 10-year mortalities were 84.2% (48/57 patients) and 80.7% (46/57 patients), with Cohen's κ coefficients of 0.672 and 0.551. There was moderate to substantial agreement between treatment recommendations based on the SS-2020 derived using CCTA and ICA, suggesting that CCTA could be used as an alternative to ICA when making decisions regarding the modality of revascularization. [ABSTRACT FROM AUTHOR]

The electrocardiogram (ECG) is a ubiquitous diagnostic modality. Convolutional neural networks (CNNs) applied towards ECG analysis require large sample sizes, and transfer learning approaches for biomedical problems may result in suboptimal performance when pre-training is done on natural images. We leveraged masked image modeling to create a vision-based transformer model, HeartBEiT, for electrocardiogram waveform analysis. We pre-trained this model on 8.5 million ECGs and then compared performance vs. standard CNN architectures for diagnosis of hypertrophic cardiomyopathy, low left ventricular ejection fraction and ST elevation myocardial infarction using differing training sample sizes and independent validation datasets. We find that HeartBEiT has significantly higher performance at lower sample sizes compared to other models. We also find that HeartBEiT improves explainability of diagnosis by highlighting biologically relevant regions of the EKG vs. standard CNNs. Domain specific pre-trained transformer models may exceed the classification performance of models trained on natural images especially in very low data regimes. The combination of the architecture and such pre-training allows for more accurate, granular explainability of model predictions. [ABSTRACT FROM AUTHOR]

Background: I-123 meta-iodobenzylguanidine (MIBG) imaging has long been employed to noninvasively assess the integrity of human norepinephrine transporter-1 and, hence, myocardial sympathetic innervation. Positron-emitting F-18 meta-fluorobenzylguanidine (MFBG) has recently been developed for potentially superior quantitative characterization. We assessed the feasibility of MFBG imaging of myocardial sympathetic innervation. Methods: 16 patients were imaged with MFBG PET (30-minute dynamic imaging of chest, followed by 3 whole-body acquisitions between 30 minutes and 4-hour post-injection). Blood kinetics were assessed from multiple samples. Pharmacokinetic modeling with reversible 1- and 2-compartment models was performed. Kinetic rate constants were re-calculated from truncated datasets. All patients underwent concurrent MIBG SPECT. Results: MFBG myocardial uptake was rapid and sustained; the mean standardized uptake value (SUV (mean ± standard deviation)) was 5.1 ± 2.2 and 3.4 ± 1.9 at 1 hour and 3-4-hour post-injection, respectively. The mean K1 and distribution volume (VT) were 1.1 ± 0.6 mL/min/g and 34 ± 22 mL/cm3, respectively. Both were reproducible when re-calculated from truncated 1-hour datasets (Intraclass Correlation Coefficient of 0.99 and 0.91, respectively). Spearman's ϱ = 0.86 between MFBG SUV and VT and 0.80 between MFBG PET-derived VT and MIBG SPECT-derived heart-to-mediastinum activity concentration ratio. Conclusion: MFBG is a promising PET radiotracer for the assessment of myocardial sympathetic innervation. [ABSTRACT FROM AUTHOR]

There have been no previous attempts to assess coronary plaque morphology in statin-treated patients with combined residual cholesterol and inflammatory risk. The aim of this study was to characterize the morphology using optical coherence tomography (OCT) and to investigate the underlying molecular mechanisms. Two hundred seventy statin-treated patients with stable coronary artery disease who underwent OCT imaging prior to elective percutaneous coronary intervention were included in this single-center retrospective analysis. Subjects were stratified into four groups based on low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) levels using 70 mg/dl and 2 mg/L as cut-offs, respectively. OCT images of the target lesions were assessed. For a subset of patients, peripheral blood mononuclear cells (PBMC) were isolated, and gene expression was characterized using microarray analysis. Patients with high LDL-C and high hs-CRP demonstrated a higher frequency of lipid-rich plaques (LRP) (91%, P = 0.03) by OCT. LRPs in these patients had a greater maximal lipid arc (186.6 ± 92.5°, P = 0.047). In addition, plaques from patients who did not achieve dual-target were less frequently calcified (P = 0.003). If calcification was present, it was characterized by a lower maximal arc (P = 0.016) and shorter length (P = 0.025). PBMC gene expression analysis demonstrated functional enrichment of toll-like receptors (TLRs) 1–9 to be associated with high LDL-C and hs-CRP. Obstructive coronary lesions in patients on statin therapy with combined residual cholesterol and inflammatory risk demonstrated a higher prevalence of LRP with greater maximal lipid arcs and more frequent spotty calcifications. PBMC from these patients revealed functional enrichment of TLR 1–9. [ABSTRACT FROM AUTHOR]

Patients with diabetes mellitus are at increased risk of cardiovascular events. We aimed to analyze the impact of serum HbA1c levels on coronary plaque characteristics in stable coronary disease. Two hundred sixty-one patients who underwent optical coherence tomography (OCT) examination before elective percutaneous coronary intervention for a de novo obstructive lesions were included in this single-center retrospective analysis. Patients were divided into tertiles according to HbA1c level (tertile 1: HbA1c < 6.3%, tertile 2: 6.3 ≤ HbA1c < 7.8%, tertile 3: HbA1c ≥ 7.8%) and OCT findings were compared. Fibrous cap thickness (FCT) was significantly thinner in tertile 3 compared to tertile 1 and tertile 2 (103.9 ± 48.2 µm [tertile 1] vs. 107.5 ± 60.6 µm [tertile 2] vs. 86.2 ± 35.8 µm [tertile 3], p = 0.03). Higher prevalence of thin-cap fibroatheroma (TCFA) was observed in tertile 3 vs tertile 1 and tertile 2 (19.5% [tertile 1] vs. 19.5% [tertile 2] vs. 33.3% [tertile 3], p = 0.04). HbA1c inversely correlated with FCT (beta coefficient - 4.89, 95% confidence interval - 8.40 to - 1.39, p < 0.01). The logistic regression model revealed that the probability of having TCFA was positively associated with HbA1c with a small change in the range of low and medium HbA1c and a big change in the range of high HbA1c. Furthermore, minimal lumen area and reference lumen area were smaller in tertile 3. In patients with stable coronary disease, high serum HbA1c levels are associated with higher plaque burden and thinner FCT on OCT, while low and medium HbA1c levels result in similar plaque vulnerability. [ABSTRACT FROM AUTHOR]

Background: Fluoride-18 sodium fluoride (18F-NaF) localizes in microcalcifications in atheroma. The microcalcifications may aggregate, passing the resolution threshold to visualize on computed tomography (CT). We evaluated serial NaF positron emission tomography (PET)-CT scans to determine the temporal relationship between vascular NaF uptake and CT evident calcification in the abdominal aorta.Methods: Prostate cancer patients who had at least 3 NaF PET-CT scans over at least 1.5 years were retrospectively enrolled. Regions of interest were traced in the abdominal aorta on both PET and CT images, excluding skeletal NaF activity. The maximum standardized uptake value (SUVmax) of NaF and the density and volume of calcium (exceeding 130 HU) were summed and divided by the number of slices to produce the SUVmax/slice and the mm3·slice-1 of calcium.Results: Of 437 patients, 45 patients met criteria. NaF uptake waxed and waned between scans, while the calcium volume plateaued or increased over time. NaF uptake correlated with calcium volume on the baseline scan (P = .60, < .0001†) and calcium volume increment, especially from 1.0 to 1.5 years (r = .79, P < .0001†). Patients with persistently high NaF uptake showed a higher calcium volume increment (0-1.5 years) than patients with low or transiently high NaF uptake.Conclusions: Abdominal aortic NaF uptake varied over time. NaF uptake on the baseline scans and high NaF uptake on the serial scans preceded an increase in calcium volume, especially by 1.0-1.5 years. Persistently high NaF uptake was associated with a greater increment in calcium volume than patients with transiently elevated or persistently low fluoride uptake. [ABSTRACT FROM AUTHOR]

Saphenous veins (SVs) are frequently employed as bypass grafts. The SV graft failure is predominantly seen at the valve site. Avoiding valves during vein harvest would help reduce graft failure. We endeavored to detect SV valves, tributaries, and vessel size employing upright computed tomography (CT) for the raw cadaver venous samples and in healthy volunteers. Five cadaver legs were scanned. Anatomical analysis showed 3.0 (IQR: 2.0–3.0) valves and 13.50 (IQR: 10.00–16.25) tributaries. The upright CT completely detected, compared to 2.0 (IQR: 1.5–2.5, p = 0.06) valves and 9.5 (IQR: 7.5–13.0, p = 0.13) tributaries by supine CT. From a total of 190 volunteers, 138 (men:75, women:63) were included. The number of valves from the SF junction to 35 cm were significantly higher in upright CT than in supine CT bilaterally [upright vs. supine, Right: 4 (IQR: 3–5) vs. 2 (IQR:1–2), p < 0.0001, Left: 4 (IQR: 3–5) vs. 2 (IQR: 1–2), p < 0.0001]. The number of tributaries and vessel areas per leg were also higher for upright compared with supine CT. Upright CT enables non-invasive detection of SV valves, tributaries, and vessel size. Although not tested here, it is expected that upright CT may potentially improve graft assessment for bypass surgery. [ABSTRACT FROM AUTHOR]

Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells. Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells. Discussion The authors summarize that compared to FDG imaging, SSTR imaging with Dotatate may be less sensitive for the detection of myocardial inflammation in sarcoidosis. [Extracted from the article]

Myocardial perfusion imaging (MPI) using Single Photon Emission Computed Tomography has been established as a standard noninvasive tool for risk stratification of coronary artery disease (CAD). We evaluated the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR) in comparison with MPI using invasive fractional flow reserve (invasive FFR) as a gold standard. We enrolled 97 patients with suspected CAD. Diagnostic performance of CT angiography (CTA), and CT-FFR was compared in 105 lesions of 97 patients. Invasive FFR ≤ 0.8 was detected in 38 (36%) lesions. Diagnostic performance of CT-FFR was improved compared with CTA (AUC 0.83 vs. 0.60, p < 0.0001). The lesions with both CTA and MPI findings (n = 47), invasive FFR ≤ 0.8 was detected in 19 (40.4) lesions. CT-FFR (AUC 0.81, 95% CI 0.72–0.94) significantly improved diagnostic performance compared with CTA-50% (AUC 0.59, p = 0.00019) and MPI (AUC 0.64, p = 0.0082). In lesions with ≥ 50% on CTA (n = 42), diagnostic accuracy of CT-FFR (AUC 0.81) was significantly superior to MPI (AUC 0.64, p = 0.0239). In conclusions, CT-FFR improved diagnostic accuracy to detect invasive FFR ≤ 0.8 compared with luminal stenosis on CTA and ischemia on MPI. Patients with ≥ 50% stenosis on CTA would be the candidates for CT-FFR. [ABSTRACT FROM AUTHOR]

Background: Patients with normal myocardial perfusion imaging (MPI) have a good prognosis. However, pre-clinical coronary and extracoronary atherosclerosis may exist in the absence of myocardial ischemia.Methods: 154 Egyptian patients (mean age 53 years) underwent whole-body non-contrast CT following normal MPI.Results: Atherosclerosis in the form of calcification was observed in ≥1 vascular bed in 115 of 154 (75%) patients. This included the iliofemoral (62%), abdominal aorta (53%), thoracic aorta (47%), coronary (47%), and carotid (25%) vascular beds. Mean total body calcium score was 3172 ± 530 AU. Extracoronary atherosclerosis in patients with a zero coronary artery calcium (CAC) score was common, occurring in the above-listed beds 42%, 36%, 29%, and 7% of the time, respectively. CAC was rarely present without iliofemoral or abdominal aortic calcification.Conclusion: Quantitative assessment of calcification in different vascular beds demonstrates that extracoronary atherosclerosis is common in patients who have normal MPI. Atherosclerotic calcifications are most common in the iliofemoral arteries and abdominal aorta, which typically predate coronary calcifications. An imaging strategy to detect extracoronary atherosclerosis could lead to greater understanding of the natural history of atherosclerosis in its long pre-clinical phase and possibly to earlier preventive strategies. [ABSTRACT FROM AUTHOR]

South Asians (SAs) are at heightened risk for cardiovascular disease as compared to other ethnic groups, facing premature and more severe coronary artery disease, and decreased insulin sensitivity. This disease burden can only be partially explained by conventional risk factors, suggesting the need for a specific cardiovascular risk profile for SAs. Current research, as explored through a comprehensive literature review, suggests the existence of population specific genetic risk factors such as lipoprotein(a), as well as population specific gene modulating factors. This review catalogues the available research on cardiovascular disease and genetics, anthropometry, and pathophysiology, and cancer genetics among SAs, with a geographical focus on the U.S. A tailored risk profile will hinge upon population customized classification and treatment guidelines, informed by continued research. [ABSTRACT FROM AUTHOR]

The most numerous leukocytes that propagate inflammation in the heart are macrophages. Macrophages may play a reparatory role initially by modulating the number and function of the recruited fibroblasts and subsequently more directly by converting into fibroblast-like cells and depositing collagen and extracellular matrix[7],[8]. The most exciting applications for this modality will enable sampling two inflammation-related, orthogonal biomarkers, for instance the number of macrophages (using PET isotope labeled nanoparticles) and their predominant phenotype (using smart MRI agents such as MPO-Gd)[10]. [Extracted from the article]

Background: Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion.Methods: Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion. Cardiac cell death was assessed by in vivo micro-SPECT/CT after injection of Indium-111-labeled 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (111In-GSAO). Thereafter, hearts were explanted for ex vivo imaging, γ-counting, and histopathological characterization.Results: Myocardial damage was visualized by micro-SPECT/CT imaging. Quantitative GSAO uptake (expressed as percent injected dose per gram, %ID/g) in the area at risk was lower in minocycline-treated animals than that in saline-treated control animals (0.32 ± 0.13% vs 0.48 ± 0.15%, P = 0.04). TUNEL staining confirmed the reduction of cell death in minocycline-treated animals.Conclusions: This study demonstrates cardioprotection by minocycline in a clinically translatable protocol. [ABSTRACT FROM AUTHOR]

Purpose: Arterial inflammation and vascular calcification are regarded as early prognostic markers of cardiovascular disease (CVD). In this study we investigated the relationship between CVD risk and arterial inflammation (F-FDG PET/CT imaging), vascular calcification metabolism (NaF PET/CT imaging), and vascular calcium burden (CT imaging) of the thoracic aorta in a population at low CVD risk. Methods: Study participants underwent blood pressure measurements, blood analyses, and F-FDG and NaF PET/CT imaging. In addition, the 10-year risk for development of CVD, based on the Framingham risk score (FRS), was estimated. CVD risk was compared across quartiles of thoracic aorta F-FDG uptake, NaF uptake, and calcium burden on CT. Results: A total of 139 subjects (52 % men, mean age 49 years, age range 21 - 75 years, median FRS 6 %) were evaluated. CVD risk was, on average, 3.7 times higher among subjects with thoracic aorta NaF uptake in the highest quartile compared with those in the lowest quartile of the distribution (15.5 % vs. 4.2 %; P < 0.001). CVD risk was on average, 3.7 times higher among subjects with a thoracic aorta calcium burden on CT in the highest quartile compared with those in the lowest two quartiles of the distribution (18.0 % vs. 4.9 %; P < 0.001). CVD risk was similar in subjects in all quartiles of thoracic aorta F-FDG uptake. Conclusion: Our findings indicate that an unfavourable CVD risk profile is associated with marked increases in vascular calcification metabolism and vascular calcium burden of the thoracic aorta, but not with arterial inflammation. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the impact of pregnancy and labor on left ventricular (LV) myocardial mechanics using speckle tracking echocardiography (STE). Pregnancy is characterized by profound hormonal and hemodynamic alterations that directly or indirectly influence cardiac structure and function. However, the impact of these changes on left ventricular (LV) myocardial contractile function has not been fully elucidated. In this prospective, longitudinal study, 35 pregnant women underwent serial clinical and echocardiographic evaluation during each trimester and at labor. Two dimensional STE was performed to measure global LV longitudinal, circumferential and radial strain (GLS, GCS and GRS, respectively). Similar data obtained from 20 nulliparous, age-matched women were used as control. All strain values during pregnancy were adjusted for age and hemodynamic parameters. There was a progressive increase in heart rate, systolic and diastolic blood pressure, cardiac output and LV stroke-work during pregnancy. LV end-diastolic and end-systolic volumes also increased progressively but LV ejection fraction remained unaltered, except for slight reduction during the second trimester. Compared to the controls, GLS and GCS were reduced in the first trimester itself (GLS -22.39 ± 5.43 % vs. -18.66 ± 0.64 %, P 0.0002; GCS -20.84 ± 3.20 vs. -17.88 ± 0.09, P < 0.001) and remained so throughout the pregnancy and labor. In contrast, GRS showed an increase during pregnancy which peaked during the second trimester (24.18 ± 0.39 % vs. 18.06 ± 8.14 % in controls, P < 0.001). Alterations in loading conditions during pregnancy are associated with counterbalancing changes in the myocardial mechanics. LV longitudinal and circumferential strain are reduced whereas radial strain is increased. These counterbalancing changes serve to maintain overall LV ejection performance within a normal range and enable the maternal heart to meet the hemodynamic demands of pregnancy and labor. [ABSTRACT FROM AUTHOR]

An editorial commentary with reference to the article within the issue by author L. Li and colleagues is presented with regard to the uptake of sodium fluoride (NaF) in unstable plaques formed as a result of coronary artery calcification. Topics discussed include conduction of F-NaF positron emission tomography (PET)-computed tomography (CT) imaging, characteristics of high-risk plaques and types of NaF uptakes in plaques.

Our goal was to construct three-dimensional (3D) virtual models to allow simultaneous visualization of the ventricles, ventricular septal defect (VSD) and great arteries in patients with complex intracardiac anatomy to aid in surgical planning. We also sought to correlate measurements from the source cardiac magnetic resonance (CMR) image dataset and the 3D model. Complicated ventriculo-arterial relationships in patients with complex conotruncal malformations make preoperative assessment of possible repair pathways difficult. Patients were chosen with double outlet right ventricle for the complexity of intracardiac anatomy and potential for better delineation of anatomic spatial relationships. Virtual 3D models were generated from CMR 3D datasets. Measurements were made on the source CMR as well as the 3D model for the following structures: aortic diameter in orthogonal planes, VSD diameter in orthogonal planes and long axis of right ventricle. A total of six patients were identified for inclusion. The path from the ventricles to each respective outflow tract and the location of the VSD with respect to each great vessel was visualized clearly in all patients. Measurements on the virtual model showed excellent correlation with the source CMR when all measurements were included by Pearson coefficient, r = 0.99 as well as for each individual structure. Construction of virtual 3D models in patients with complex conotruncal defects from 3D CMR datasets allows for simultaneous visualization of anatomic relationships relevant for surgical repair. The availability of these models may allow for a more informed preoperative evaluation in these patients. [ABSTRACT FROM AUTHOR]

We previously reported that serial coronary computed tomography angiography (CTA) had a potential to evaluate the interval change of plaque morphology of coronary arteries. The aim of this study was to evaluate variables associated with the plaque progression by serial CTA. We included 148 patients (age 66.3 ± 9.8 years, male 81.1 %, median scan interval 12 months) with coronary artery disease undergoing serial CTA. Each coronary artery was compared visually between baseline and follow-up CTA to detect plaque progression. Baseline characteristics between progression and nonprogression patients did not demonstrate any significant differences. Logistic analysis revealed that only low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dl at follow-up was associated with plaque progression (odds ratio 2.59, 95 % confidence interval 1.12-6.34, P = 0.0263). Cutoff value of LDL-C for plaque progression at follow-up was 103.0 mg/dl based on receiver-operator characteristic curves analyses. Of the 36 progressive lesions in 32 patients, plaque composition at baseline included 13 lesions (36.1 %) of noncalcified plaque, 1 lesion (2.8 %) of calcified plaque, 12 lesions (33.3 %) of partially calcified plaque, and the remaining 10 lesions (27.8 %) had no plaque at baseline and revealed de novo plaques at follow-up. There were 9 lesions (25 %) with high-risk plaque (HRP) characteristics at baseline and 18 lesions (50 %) with HRP at follow-up. Plaque progression of coronary arteries by serial CTA was associated with LDL-C ≥100 mg/dl at follow-up regardless of baseline LDL-C level. There was no specific finding to predict plaque progression on the baseline plaque characteristics. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of mortality worldwide and also exerts a significant economic burden, especially in low- and middle-income countries (LMICs). Detection of subclinical CVD, before an individual experiences a major event, may therefore offer the potential to prevent or delay morbidity and mortality, if combined with an appropriate care response. In this review, we discuss imaging technologies that can be used to detect subclinical atherosclerotic CVD (carotid ultrasound, coronary artery calcification) and nonatherosclerotic CVD (echocardiography). We review these imaging modalities, including aspects such as rationale, relevance, feasibility, utilization, and access in LMICs. The potential gains in detecting subclinical CVD may be substantial in LMICs, if earlier detection leads to earlier engagement with the health care system to prevent or delay cardiac events, morbidity, and premature mortality. Thus, dedicated studies examining the feasibility, utility, and cost-effectiveness of detecting subclinical CVD in LMICs are warranted. [ABSTRACT FROM AUTHOR]

Acute insult to the myocardium is associated with substantial loss of cardiomyocytes during the process of myocardial infarction. In this setting, apoptosis (programmed cell death) and necrosis may operate on a continuum. Because the latter is characterized by the loss of sarcolemmal integrity, we propose that an appropriately labeled tracer directed at a ubiquitously present intracellular moiety would allow non-invasive definition of cardio-myocyte necrosis. A trivalent arsenic peptide, GSAO (4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid), is capable of binding to intracellular dithiol molecules such as HSP90 and filamin-A. Since GSAO is membrane impermeable and dithiol molecules abundantly present intra-cellularly, we propose that myocardial localization would represent sarcolemmal disruption or necrotic cell death. In rabbit and mouse models of myocardial infarction and post-infarct heart failure, we employed In-111-labelled GSAO for noninvasive radionuclide molecular imaging. 111In-GSAO uptake was observed within the regions of apoptosis seeking agent- 99mTc-Annexin A5 uptake, suggesting the colocalization of apoptotic and necrotic cell death processes. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate the performance of the built-in MR-based attenuation correction (MRAC) included in the combined whole-body Ingenuity TF PET/MR scanner and compare it to the performance of CT-based attenuation correction (CTAC) as the gold standard. Methods: Included in the study were 26 patients who underwent clinical whole-body FDG PET/CT imaging and subsequently PET/MR imaging (mean delay 100 min). Patients were separated into two groups: the alpha group (14 patients) without MR coils during PET/MR imaging and the beta group (12 patients) with MR coils present (neurovascular, spine, cardiac and torso coils). All images were coregistered to the same space (PET/MR). The two PET images from PET/MR reconstructed using MRAC and CTAC were compared by voxel-based and region-based methods (with ten regions of interest, ROIs). Lesions were also compared by an experienced clinician. Results: Body mass index and lung density showed significant differences between the alpha and beta groups. Right and left lung densities were also significantly different within each group. The percentage differences in uptake values using MRAC in relation to those using CTAC were greater in the beta group than in the alpha group (alpha group −0.2 ± 33.6 %, R = 0.98, p < 0.001; beta group 10.31 ± 69.86 %, R = 0.97, p < 0.001). Conclusion: In comparison to CTAC, MRAC led to underestimation of the PET values by less than 10 % on average, although some ROIs and lesions did differ by more (including the spine, lung and heart). The beta group (imaged with coils present) showed increased overall PET quantification as well as increased variability compared to the alpha group (imaged without coils). PET data reconstructed with MRAC and CTAC showed some differences, mostly in relation to air pockets, metallic implants and attenuation differences in large bone areas (such as the pelvis and spine) due to the segmentation limitation of the MRAC method. [ABSTRACT FROM AUTHOR]

Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because mannose is an isomer of glucose that is taken up by macrophages through glucose transporters and because mannose receptors are expressed on a subset of the macrophage population in high-risk plaques, we applied 18F-labeled mannose (2-deoxy-2-[18F]fluoro-D-mannose, [18F]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [18F]FDM and [18F]FDG in atherosclerotic lesions in a rabbit model; [18F]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[14C]carbon-D-glucose ([14C]2DG) support at least 35% higher [18F]FDM uptake by macrophages in cell experiments. We also demonstrate that FDM restricts binding of anti-mannose receptor antibody to macrophages by approximately 35% and that mannose receptor targeting may provide an additional avenue for imaging of plaque inflammation. [ABSTRACT FROM AUTHOR]

Despite the exponential growth in medical knowledge, cardiovascular diseases (CVDs) contribute to more than one-third of worldwide morbidity and mortality. A range of therapies already exist for established CVDs, although there is significant interest in further understanding their pathogenesis. The urocortins (Ucns) are peptide members of the corticotrophin-releasing factor family, a group of evolutionary conserved peptides with homologues in fish, amphibians and mammals and considered to play a pivotal role in energy homeostasis and local tissue repair. A number of preclinical studies in vitro, in-vivo and ex-vivo have defined a multifaceted effect of Ucns on the cardiovascular system. Different G-protein coupled signaling and protein-kinase pathways have been shown to be activated by Ucns, together with different transcriptional and translational effects, all of which preferentially converge on the mitochondria, where the modulation of apoptosis is considered their principal action. It has been demonstrated in experimental models, and consequentially suggested in human diseases, that Ucn-mediated inhibition of apoptosis can be exploited for the improvement of both therapeutic and preventative strategies against CVDs. Specifically, some unavoidable iatrogenic ischemia/reperfusion (I/R) injuries, e.g. during cardiac surgery or percutaneous coronary angioplasty, may greatly benefit from the anti-apoptotic effect of Ucns. However, few studies on the topic have been employed in humans to date. Therefore, this review will focus on the different intra-cellular mechanisms of action of Urocortins, and detail the different Ucn-mediated pathways identified so far. It will also highlight the limited evidence already existing in human clinical and surgical settings, as well as emphasize the potential uses of Ucns in human cardiac pathology. [ABSTRACT FROM AUTHOR]

Computed tomography angiography (CTA) is commonly employed for exclusion of coronary artery disease and demonstration of the extent of coronary vascular involvement. It has been recently proposed that coronary artery plaques could be visualized noninvasively. This review article focused on the high risk plaque detected by CTA. Plaque characteristics of acute coronary syndrome (ACS) was compared to sable angina pectoris (SAP). The presence of positive remodeling (ACS 87 %, SAP 12 %, p < 0.0001), low attenuation plaque (LAP) (ACS 79 %, SAP 9 %, p < 0.0001), and spotty calcification (ACS 63 %, SAP 21 %, p = 0.0005) were significantly more frequent in the culprit ACS lesions. Furthermore, in asymptomatic patients, presence of positively remodeling and LAP portends a greater risk for development of acute coronary events (hazard ratio = 22.8, CI = 6.9-75.2, p < 0.001). Possibility of drug intervention to high risk plaque was also reported. Serial CTA assessment allows for evaluation of interval change in morphological plaque characteristics and can be employed for assessment of efficacy of therapeutic intervention. Use of statin results in substantial reduction in LAP volume (follow-up: 4.9 ± 7.8 versus baseline: 1.3 ± 2.3 mm, p = 0.02) forwards stabilization of plaques. Although not recommended currently as a population-based strategy, CT angiographic examination may help identify very high risk asymptomatic subjects. [ABSTRACT FROM AUTHOR]

Background: The Seattle Heart Failure Model (SHFM) is a multivariable model that uses demographic and clinical markers to predict survival in patients with heart failure. Inappropriate activation of the sympathetic nervous system, which contributes to the progression of heart failure and increased mortality, can be assessed using iodine-123 meta-iodobenzylguanidine (MIBG) cardiac imaging. This study investigated the incremental value of MIBG cardiac imaging when added to the SHFM for prediction of all-cause mortality. Methods: Survival data from 961 NYHA II-III subjects in the ADMIRE-HFX trial were included in this analysis. The predictive value of the SHFM alone and in combination with MIBG heart-to-mediastinum ratio (H/M) was compared for all-cause mortality (101 deaths during a median follow-up of 2 years). Results: The addition of H/M to the SHFM in a Cox model significantly improved risk prediction ( P < .0001), with a greater utility in higher risk SHFM patients. The observed 2-year mortality in the highest-risk SHFM subjects (rounded SHFM score of 1) was 24%, but varied from 46% with H/M <1.2 to 0% with H/M >1.8. Net reclassification improvement was 22.7% ( P < .001), with 14.9% of subjects who died reclassified into a higher risk category than suggested by SHFM score alone ( P = .01) and 7.9% of subjects who survived reclassified into a lower risk category ( P < .0001). The 2-year integrated discrimination improvement (+4.14%, P < .0001) and the 1-year area under the receiver-operator characteristic curve (+0.04, P = .026) both showed significant improvement for the combined model with H/M compared to the SHFM alone. Conclusion: The addition of MIBG imaging to the SHFM improves risk stratification, especially in higher risk patients. MIBG may have clinical utility in higher risk patients who are being considered for devices such as ICD, CRT-D, LVAD, and cardiac transplantation. [ABSTRACT FROM AUTHOR]

The aims of this study were (1) to evaluate the prognostic value of negative wall motion (WM) and myocardial perfusion during contrast-dobutamine stress echocardiography (DSE), (2) to determine whether WM-myocardial contrast echocardiography (MCE) had incremental prognostic value over just WM during DSE in patients with chest pain in the emergency room (ER), and (3) to compare the prognostic value of negative DSE-WM, and DSE-WM-MCE to nuclear-myocardial perfusion imaging (N-MPI) in a similar patient population over the same time period. We retrospectively studied 569 patients with real time contrast DSE, and 147 patients underwent N-MPI for evaluation of chest pain. Follow-up for cardiac events was obtained between 12 and 25 months. The cumulative cardiac event-free survival was 94.5% in negative DSE-WM, 97.1% in negative DSE-WM-MCE and 96.7% in negative N-MPI group. Cardiac event-free survival of the negative DSE-WM-MCE group was significantly higher than the DSE-WM group (log rank P < 0.01), and similar in the DSE-WM-MCE group compared to the N-MPI group. Combined WM and perfusion during DSE was the strongest independent predictor for cardiac events. The negative predictive power of DSE-WM-MCE is superior to that of just negative DSE-WM and is comparable to that of N-MPI. Myocardial perfusion and WM analysis during DSE provide independent information for predicting cardiac events in patients with chest pain syndrome in the ER. [ABSTRACT FROM AUTHOR]

The authors reflect on the modulation of myocardial menu for imaging inflammation in proximal coronary vasculature. They state that the inflammation can be conformable to molecular imaging strategies. They relate that the positron-labeled fluorodeoxyglucose (FDG) must focus on the site of inflammation to allow visualization on positron emission tomography (PET) images since the metabolic demand of lesional macrophages was fulfilled by exogenous glucose spreading into the lesion from the blood.

Background: Cardiologists are often confronted with patients presenting with chest pain, in whom clinical risk profiling is required. We studied four frequently used risk scores in their ability to predict for coronary artery disease (CAD) and major adverse cardiovascular events in patients presenting with stable chest pain at the cardiology outpatient clinic. Methods and Results: We enrolled 1,296 stable chest pain patients, who underwent cardiac computed tomographic angiography (CCTA) to assess CAD (any, significant: stenosis ≥50%). Framingham (FRS), PROCAM, SCORE risk score, and Diamond Forrester pre-test probability were calculated. All patients were followed up for a mean 19 ± 9 months for all cardiovascular events (mortality, acute coronary syndrome, revascularization >90 days after CCTA). In ROC-analysis for prediction of significant CAD, the areas under the curve for FRS; 0.68 (95% confidence interval: 0.64-0.72) and for SCORE; 0.69 (95% confidence interval: 0.65-0.72) were significantly higher than for PROCAM; 0.64 (95% confidence interval: 0.61-0.68; P ≤ .001), as well as marginally higher than for Diamond Forrester; 0.65 (95% confidence interval: 0.61-0.68; P ≤ .05). Low FRS category showed the lowest number of patients with significant CAD, compared to patients with low risk using PROCAM, SCORE or Diamond Forrester ( P < .001). Also, low FRS category showed less events (compared to PROCAM and SCORE; P < .001, for Diamond Forrester; P = .14). Conclusion: Our data show that in a stable chest pain population, the ability of FRS and SCORE to predict for CAD was similar and better compared to PROCAM and Diamond Forrester. The number of low risk patients showing significant CAD or events was lower using FRS. Consequently, risk categorization using FRS seems to be safest to stratify stable chest pain patients prior to CCTA. [ABSTRACT FROM AUTHOR]

Stem cell therapy promises to open exciting new options in the treatment of cardiovascular diseases. Although feasible and clinically safe, the in vivo behavior and integration of stem cell transplants still remain largely unknown. Thus, the development of innovative non-invasive imaging techniques capable of effectively tracking such therapy in vivo is vital for a more in-depth investigation into future clinical applications. Such imaging modalities will not only generate further insight into the mechanisms behind stem cell-based therapy, but also address some major concerns associated with translational cardiovascular stem cell therapy. In the present review, we summarize the principles underlying three major stem cell tracking methods: (1) radioactive labeling for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging, (2) iron particle labeling for magnetic resonance imaging (MRI), and (3) reporter gene labeling for bioluminescence, fluorescence, MRI, SPECT, and PET imaging. We then discuss recent clinical studies that have utilized these modalities to gain biological insights into stem cell fate. [ABSTRACT FROM AUTHOR]

Objectives: To compare the ability of Tc-labeled broad-based matrix metalloproteinase inhibitor (RP805) (MPI) and Tc-annexin V to identify more advanced atherosclerotic disease in apolipoprotein E-null (apoE) mice. Background: Both MMP expression and apoptotic cell death occur in both early and in advanced atherosclerotic plaques. Methods: Eight 6-9-week-old apoE mice, 10 apoE mice at 20 weeks, and 12 apoE at 40 weeks were injected with both tracers in alternating sequence separated by 48 h, underwent planar imaging and were killed. Radiotracer uptake was quantified from the scans as percent whole body and from tissue as percent injected dose per gram (%ID/g). Quantitative immunohistopathology of the aorta and carotids for macrophages, MMPs, and caspase was performed. Results: At 6 weeks, mice showed no tracer uptake in the chest or neck and had minimal lesion. At 20 weeks, uptake of annexin V as %ID was borderline higher than MPI (1.10 ± .48% vs .77 ± .31%, P = .09), between 20 and 40 weeks aortic lesion area increased from 37.4 ± 12.0% to 46.2 ± 7.4% and at 40 weeks MPI was significantly greater than annexin V uptake (1.11 ± .66% vs .70 ± .16%, P = .05). On histology there were greater increases in % MMP-2 and -9 than % caspase positive cells. Carotid uptake of MPI was greater than annexin V at both 20 and 40 weeks (1.25 ± .48% vs .78 ± .25%, P = .02 and 3.70 ± 1.45% vs 2.25 ± .66%, P = .005). The carotid lesion area at 40 weeks was 74 ± 9% with greater % cells positive for MMP's than caspase. %ID/g annexin V correlated significantly with % macrophages and with caspase-3 positive cells and %ID/g MPI correlated significantly with % macrophages and with MMP-2 and -9 positive cells. Conclusions: In apoE mice, MMP expression is greater than apoptosis as the disease progresses and MPI may be a better imaging agent for more advanced disease. [ABSTRACT FROM AUTHOR]

Introduction: The clinical feasibility of noninvasive imaging of interstitial alterations after myocardial infarction (MI) was assessed using a technetium-99m-labeled RGD imaging peptide (RIP). In experimental studies, RIP has been shown to target integrins associated with collagen-producing myofibroblasts (MFB). Methods and Results: Ten patients underwent myocardial perfusion imaging (MPI) within the first week after MI. At 3 and 8 weeks after MI, RIP was administered intravenously and SPECT images acquired for interstitial imaging. RIP imaging was compared to initial MPI and to the extent of scar formation defined by late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) imaging 1 year after MI. RIP uptake was observed in 7 of the 10 patients at both 3 and 8 weeks. Although, RIP uptake corresponded to areas of perfusion defects, it usually extended beyond the infarct zone to a variable extent; 2 of 7 patients showed tracer uptake throughout myocardium. In all positive cases, RIP uptake was similar to the extent of scar observed at 1 year by LGE-CMR imaging. Conclusion: This study demonstrates that RGD-based imaging early after MI may predict the eventual extent of scar formation, which often exceeds initial MPI deficit but colocalizes with LGE in CMR imaging performed subsequently. [ABSTRACT FROM AUTHOR]

CT angiography is commonly used for exclusion of coronary artery disease and demonstration of the extent of coronary vascular involvement. It has been recently proposed that definition of vessel wall characteristics at the site of luminal stenosis may serve as a useful prognostic tool. Presence of positively remodeled plaques with low attenuation portends a greater risk for development of acute coronary events. Although not recommended currently as a population-based strategy, CT angiographic examination may help identify very high-risk asymptomatic subjects. [ABSTRACT FROM AUTHOR]

The article discusses the use of imaging techniques to help identify the type of plaque especially for asymptomatic patients. Computed tomography (CT) angiography helps identify morphological characteristics of plaque, while positron emission tomography (PET) helps assess plaque inflammation while contrast-enhanced ultrasound helps check for adventitial vascularity and intimal demarcation in symptomatic carotid disease. Overview of cases illustrating examples of plaque inflammation, intraplaque hemorrhage, and neovascularization are also provided.

Background: Macrophage apoptosis and MMP activity contribute to vulnerability of atherosclerotic plaques to rupture. By employing molecular imaging techniques, we investigated if apoptosis and MMP release are interlinked. Methods: Atherosclerosis was produced in rabbits receiving high-cholesterol diet (HC), who underwent dual radionuclide imaging with Tc-labeled matrix metalloproteinase inhibitor (MPI) and In-labeled annexin A5 (AA5) using micro-SPECT/CT. %ID/g MPI and AA5 uptake was measured, followed by histological characterization. Unmanipulated animals were used as disease controls. Correlation between MPI and AA5 uptake was undertaken and relationship confirmed in culture study of activated THP-1 monocytes. Results: MPI and AA5 uptake was best visualized in HC diet animals (n = 6) and reduced significantly after fluvastatin treatment (n = 4) or diet withdrawal (n = 3). %ID/g MPI (.087 ± .018% ) and AA5 (.03 ± .01% ) uptake was higher in HC than control (n = 6) animals (.014 ± .004%, P < .0001; .0007 ± .0002%, P < .0001), and reduced substantially after diet or statin intervention. There was a significant correlation between MPI and AA5 uptake (r = .62, P < .0001), both correlated with pathologically verified MMP-9 activity, macrophage content, and TUNEL staining. In vitro studies demonstrated MMP-9 release in culture medium from apoptotic THP-1 monocytes. Conclusions: The present study suggests that apoptosis and MMP are interrelated in atherosclerotic lesions and the targeting of more than one molecular candidate is feasible by molecular imaging. [ABSTRACT FROM AUTHOR]

To prevent progression of heart failure (HF), it is necessary to understand the cellular and molecular processes that precede more irreversible stages. Molecular imaging of HF has hitherto focused on myocytic and neuronal components. More recently, interstitial changes, particularly interstitial fibrosis, have been targeted both for diagnostic and therapeutic purposes. Molecular imaging of interstitial changes may identify patients at risk to develop HF, before adverse remodeling has occurred. In addition, it may also serve as a surrogate endpoint for the assessment of treatment efficacy. [ABSTRACT FROM AUTHOR]

Sudden cardiac death and acute myocardial infarction often occur as the first manifestation of coronary artery disease. Otherwise asymptomatic individuals with subclinical atherosclerosis almost always have a classic risk-factor profile and it is essential that they are identified before the occurrence of an acute coronary event. The ability to recognize such individuals requires the development of strategies that can localize unstable atherosclerotic lesions. Plaques that are vulnerable to rupture demonstrate distinct histological characteristics, including large plaque and necrotic core volumes, extensive remodeling of the vessel at the lesion site, and attenuated fibrous caps. Precise metrics of typical vulnerable atherosclerotic plaque dimensions will need to be defined to facilitate their identification by noninvasive imaging modalities. [ABSTRACT FROM AUTHOR]

Utilization of molecular imaging has significantly advanced the field of cardiovascular medicine. In addition to the targets currently in use, novel targets are being developed, including those involved in the processes of myocardial metabolism, myocardial injury, cardiac neurotransmission, and interstitial dysregulation. Further development of these imaging targets may lead to improved characterization of disease processes and guide provision of individualized therapies. [ABSTRACT FROM AUTHOR]

Cardiac myocytes die through apoptosis, oncosis, and autophagy. Apoptosis affects single cells and is morphologically characterized by nuclear fragmentation with generation of apoptotic bodies that can be seen either within dying cells or free in the interstitial spaces. Dead myocytes are removed by macrophages through phagocytosis without triggering inflammation. The circulating markers of myocyte necrosis are not increased by apoptosis. The morphologic changes of the induction and early execution phases are seen at electron microscopy while late fragmentation is visible on both light and electron microscopy. Immunoelectron microscopy provides combined functional and structural information showing cytochrome c immuno-labelling release from mitochondria, TUNEL labelling of apoptotic nuclei, annexin V translocation in the outer plasma cell layer. Oncosis is characterized by specific morphologic features that may coexist with apoptosis, especially in ischemic myocardium. Autophagy is a defense process that is associated with significant myocardial damage and necrosis when removal of the lysosomal content is impaired. Morphological features of apoptosis, oncosis, and autophagocytosis may coexist at the same time. Although dead myocytes showing characteristics of autophagy and apoptosis are rarely observed in human decompensated hearts, autophagic vacuoles, and early apoptotic changes may be seen more often in morphologically viable myocytes. Such features may occur in failing hearts of both ischemic and non-ischemic etiology. The shared mode of cardiac myocyte death in failing human hearts of different etiologies suggests that preservation of myocyte integrity may be possible by similar therapeutic strategies. [ABSTRACT FROM AUTHOR]