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PubMed2026

Baseline Computed Tomography Coronary Angiography and Polygenic Risk Profiles in Adults With Type 2 Diabetes: A Cross-Sectional Analysis From the VOLTAIRE Study.

AIMS: To characterise baseline clinical, anatomical, and genetic cardiovascular risk profiles in participants enrolled in the VOLTAIRE (Evaluation of Polygenic Scores and CT Imaging in Risk Factor Modification in Patients with Type 2 Diabetes) study and examine concordance across these domains. METHODS: This analysis included adults with T2D who completed baseline computed tomography coronary angiography (CTCA) and polygenic risk score (PRS) assessment prior to randomisation in the VOLTAIRE study. Coronary atherosclerosis was evaluated using coronary artery calcium (CAC) score and CTCA-derived stenosis severity. Clinical risk was assessed using the New Zealand Society for the Study of Diabetes 5-year cardiovascular risk calculator. Polygenic risk for coronary artery disease was assessed using a genome-wide PRS and categorised into tertiles. RESULTS: Among 126 participants with T2D (mean age 57.5 ± 8.7 years; 62.7% male), coronary atherosclerotic burden was highly heterogeneous: 34.9% had CAC = 0, whereas 19.8% had CAC ≥ 400. Moderate-to-severe coronary stenosis (≥ 50%) was present in 40.5% of participants overall, including 20.4% of those classified as low clinical risk. PRS distribution was variable (low 37.3%, intermediate 35.7%, high 27.0%). Overlap between anatomical, genetic, and clinical domains was limited, with only 8.7% of participants classified as high risk across all three. CONCLUSIONS: Substantial heterogeneity and limited overlap exist between anatomical, genetic, and clinical cardiovascular risk measures in T2D. These findings support a multimodal approach to risk assessment integrating imaging and genetic profiling. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov; ID: NCT07091162.

Aged↗
PubMed2026

Comprehensive assessment of vasospastic angina using coronary computed tomography angiography: synergistic value of the presence of myocardial bridge, perivascular inflammation, and myocardial extracellular volume fraction.

AIMS: Coronary computed tomography angiography (CCTA) has evolved beyond anatomical assessment to include sophisticated tissue characterization. While an elevated perivascular fat attenuation index around the right coronary artery (FAI-RCA) is known to reflect coronary inflammation in vasospastic angina (VSA), recurrent vasospasms may also induce chronic subclinical myocardial injury and subsequent remodelling, potentially associated with an increased myocardial extracellular volume fraction (ECV). However, the diagnostic integration of ECV and FAI-RCA for identifying VSA in patients with angina with non-obstructive coronary arteries (ANOCA) remains to be elucidated. METHODS AND RESULTS: This study included consecutive ANOCA patients who underwent CCTA with a dedicated ECV protocol, followed by an invasive spasm provocation test. Comprehensive CCTA analysis quantified both FAI-RCA and the transmural ECV gradient (the difference between endocardial and epicardial ECV: ECVEndo - ECVEpi). Of the 100 patients analysed (mean age: 65.3 &#xb1; 11.8 years; 55% male), 27 were diagnosed with VSA. Multivariable logistic regression analysis identified transmural ECV gradient [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.01-1.25], presence of myocardial bridging (MB) (OR: 3.49, 95% CI: 1.25-9.74), and high FAI-RCA (> -70.95 Hounsfield units [HU]) (OR: 5.79, 95% CI: 2.06-16.30) as significant independent predictors of VSA (all P < 0.05). Notably, the integration of transmural ECV gradient provided incremental diagnostic value beyond FAI-RCA and MB, as assessed by the Net Reclassification Improvement and Integrated Discrimination Improvement. CONCLUSION: A multi-parametric CCTA approach potentially identifies patients at high risk for VSA. The significant association of the transmural ECV gradient with VSA suggests that myocardial remodelling imaging provides a novel diagnostic window into the cumulative myocardial impact of vasospasm, independent of active adipose tissue inflammation and the presence of MB.

Humans↗
PubMed2025

Pitavastatin, Procollagen Pathways, and Plaque Stabilization in Patients With HIV: A Secondary Analysis of the REPRIEVE Randomized Clinical Trial.

IMPORTANCE: In a mechanistic substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) randomized clinical trial, pitavastatin reduced noncalcified plaque (NCP) volume, but specific protein and gene pathways contributing to changes in coronary plaque remain unknown. OBJECTIVE: To use targeted discovery proteomics and transcriptomics approaches to interrogate biological pathways beyond low-density lipoprotein cholesterol (LDL-C), relating statin outcomes to reduce NCP volume and promote plaque stabilization among people with HIV (PWH). DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the double-blind, placebo-controlled, REPRIEVE randomized clinical trial. Participants underwent coronary computed tomography angiography (CTA), plasma protein analysis, and transcriptomic analysis at baseline and 2-year follow-up. The trial enrolled PWH from April 2015 to February 2018 at 31 US research sites. PWH without known cardiovascular diseases taking antiretroviral therapy and with low to moderate 10-year cardiovascular risk were eligible. Data analyses were conducted from October 2023 to February 2024. INTERVENTION: Oral pitavastatin calcium, 4 mg per day. MAIN OUTCOMES AND MEASURES: Relative change in plasma proteomics, transcriptomics, and noncalcified plaque volume among those receiving treatment vs placebo. RESULTS: Among 558 individuals (mean [SD] age, 51 [6] years; 455 male [82%]) included in the proteomics assessment, 272 (48.7%) received pitavastatin and 286 (51.3%) received placebo. After adjusting for false discovery rates, pitavastatin increased abundance of procollagen C-endopeptidase enhancer 1 (PCOLCE), neuropilin 1 (NRP-1), major histocompatibility complex class I polypeptide-related sequence A (MIC-A) and B (MIC-B), and decreased abundance of tissue factor pathway inhibitor (TFPI), tumor necrosis factor ligand superfamily member 10 (TRAIL), angiopoietin-related protein 3 (ANGPTL3), and mannose-binding protein C (MBL2). Among these proteins, the association of pitavastatin with PCOLCE (a rate-limiting enzyme of collagen deposition) was greatest, with an effect size of 24.3% (95% CI, 18.0%-30.8%; P&#x2009;<&#x2009;.001). In a transcriptomic analysis, individual collagen genes and collagen gene sets showed increased expression. Among the 195 individuals with plaque at baseline (88 [45.1%] taking pitavastatin, 107 [54.9%] taking placebo), changes in NCP volume were most strongly associated with changes in PCOLCE (%change NCP volume/log2-fold change&#x2009;=&#x2009;-31.9%; 95% CI, -42.9% to -18.7%; P&#x2009;<&#x2009;.001), independent of changes in LDL-C level. Increases in PCOLCE related most strongly to change in the fibro-fatty (<130 Hounsfield units) component of NCP (%change fibro-fatty volume/log2-fold change&#x2009;=&#x2009;-38.5%; 95% CI, -58.1% to -9.7%; P&#x2009;=&#x2009;.01) with a directionally opposite, although nonsignificant, increase in calcified plaque (%change calcified volume/log2-fold change&#x2009;=&#x2009;34.4%; 95% CI, -7.9% to 96.2%; P&#x2009;=&#x2009;.12). CONCLUSIONS AND RELEVANCE: Results of this secondary analysis of the REPRIEVE randomized clinical trial suggest that PCOLCE may be associated with the atherosclerotic plaque stabilization effects of statins by promoting collagen deposition in the extracellular matrix transforming vulnerable plaque phenotypes to more stable coronary lesions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02344290.

Humans↗
PubMed2026

Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials.

BACKGROUND: Coronary artery disease (CAD) polygenic risk scores (PRS) may identify individuals at elevated genetic risk "flying under the radar" in contemporary practice. The aims of the PROACT (Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis) trials are to prospectively identify these individuals, quantify subclinical coronary plaque, and slow its progression with pharmacologic interventions. OBJECTIVES: The aim of this study is to report interim feasibility and implementation findings from PROACT, a genotype-first, biobank-enabled trial, characterizing eligibility yield, callback engagement, and subclinical coronary atherosclerosis on coronary computed tomographic angiography among individuals with high CAD PRS. METHODS: Within a hospital-based biobank, adults 40 to 75 years of age with high CAD PRS, without cardiovascular disease, and not on lipid-lowering therapy were invited. The authors characterize 2,495 eligible individuals with high CAD PRS, report on the feasibility and early operational outcomes of a genotype-first callback strategy for a clinical trial in the first 1,314 invited, and describe plaque prevalence by age and sex in the first 204 participants using coronary computed tomographic angiography. RESULTS: Among 64,092 genotyped participants, 2,495 (3.9%) were eligible and had high CAD PRS despite low clinical risk (median 10-year pooled cohort equations risk for atherosclerotic cardiovascular disease 3%; Q1-Q3: 1%-8%). Recruitment showed high engagement: among 1,314 invited individuals, 283 (21.5%) opted in, and 204 (15.5%) completed baseline imaging. Compared with participants who did not opt in, those who opted in had higher specialty care engagement and lived closer to the study site. Analysis of the first 204 participants enrolled by January 31, 2025 (mean age 56.3 &#xb1; 8.5 years, 69% women), showed that despite the low clinical risk and favorable cardiovascular health (mean Life's Essential 8 score 73.3 &#xb1; 11.5 vs the U.S. average of &#x223c;65), one-half the participants (102 of 204) had subclinical plaque. Subclinical plaque prevalence was 76.2% in men and 38.3% in women and was high across age groups. CONCLUSIONS: These exploratory findings highlight the feasibility of implementing genotype-first recruitment for prevention trials and reveal a large proportion of "silent" high-genetic risk individuals with subclinical plaque for whom pharmacotherapy could be beneficial but who remain undetected by standard clinical assessments. (Polygenic Risk Based Detection of Subclinical Coronary Atherosclerosis and Change in Cardiovascular Health [PROACT 1], NCT05819814; Polygenic Risk Based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine [PROACT 2], NCT05850091).

Adult↗
PubMed2025

Cardiac CT fractal analysis of LV noncompaction and common cardiomyopathies.

BACKGROUND: Left ventricular noncompaction (LVNC), or hypertrabeculation, is a myocardial condition that remains challenging to diagnose and differentiate from other cardiomyopathies. This study evaluated the ability of cardiac CT to differentiate between LVNC, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and controls using fractal analysis of LV trabeculae. METHODS: Subjects with LVNC, HCM, DCM, as well as controls, who underwent coronary CT angiography were included. LV trabecular structure was quantified using fractal analysis on a stack of 15 short-axis CT images. For each subject, maximum (FDmax) and average (FDglobal) fractal dimensions were reported. A subset of subjects also had clinically acquired cardiac MRI (CMR) exams for comparison. One-way ANOVA, Pearson correlation, and Bland-Altman analysis were used for statistical analysis. RESULTS: The study included 313 subjects (median age: 58.8 [48.1-68.0] years, 153 male) categorized into Control (89), LVNC (46), HCM (106), and DCM (72) cohorts. FDmax was significantly higher in LVNC (1.379 &#x200b;&#xb1; &#x200b;0.047) than in Control (1.305 &#x200b;&#xb1; &#x200b;0.033), HCM (1.321 &#x200b;&#xb1; &#x200b;0.040), and DCM (1.344 &#x200b;&#xb1; &#x200b;0.054) cohorts; all p &#x200b;< &#x200b;0.001. Similarly, FDglobal was significantly higher in LVNC (1.279 &#x200b;&#xb1; &#x200b;0.041) than in the other cohorts; all p &#x200b;< &#x200b;0.05. In a subset of 132 subjects with both CT and CMR exams, fractal dimensions from the two modalities were strongly correlated (r &#x200b;= &#x200b;0.63, p &#x200b;< &#x200b;0.0001), with CT-derived values being higher (1.337 &#x200b;&#xb1; &#x200b;0.049 vs. 1.262 &#x200b;&#xb1; &#x200b;0.045, p &#x200b;< &#x200b;0.0001). CONCLUSIONS: CT-derived fractal dimensions of LV trabecular structure were significantly higher in LVNC compared to control subjects, HCM, and DCM. CT-derived fractal dimensions strongly correlated with, but were higher than, those from cardiac MRI in the same subjects.

Humans↗
PubMed1978

Quantitative imaging of the structure and function of the heart, lungs, and circulation.

A 28-x-ray-source, cylindrical-scanning, transaxial tomographic x-ray-imaging system is in the process of being fabricated. This system will scan synchronously up to 250 parallel transverse cross sections of the human body over an axial range of 25 cm within 0.01 second at a maximum rate of 60 scans per second. The system will provide numerous variations of scanning configurations to permit quantitative assessment of the relative importance of transverse section thickness, image contrast, spatial and temporal resolution, and related computerized algorithms and display techniques. Synchronous imaging at high temporal resolution of a three-dimensional volume--for example, the heart--eliminates the need for successive periods of breath-holding and gated imaging techniques and is essential for quantitation of cardiovascular and pulmonary function and structure in intact animals or humans. Initial clinical applications are expected to be in the early detection of lung cancer and the diagnosis of the nature and degree of congenital and acquired cardiovascular disabilities.

Animals↗
PubMed1979

High speed synchronous volume computed tomography of the heart.

A new generation, fully electronic high-speed whole-body computed tomography system is being developed to provide accurate dynamic visualization and measurement of the vital functions of the heart based on rapid changes in its shape, dimensions, and perfusion. This Dynamic Spatial Reconstruction System (DSR) will provide stop-action (1/100 sec.), rapidly sequential (60/sec.) synchronous volume (240 simultaneous, 1mm-thick cross sections) reconstructions and display of the full anatomic extent of the internal and external structures of the heart throughout successive cardiac cycles, and will permit visualization of the three-dimensional vascular anatomy and circulation throughout the myocardium.

Animals↗
PubMed1978

[Clinical signs and therapy of the abdominal aortic aneurysm (author's transl)].

The abdominal, infrarenal aneurysm of the aorta shows a very unfavorable spontaneous outcome. Therefore, every patient should be operated on without delay. The surgical procedure consists of a partial resection of the aneurysm and the reconstruction of the vascular flow by means of a synthetic prosthesis. The most dangerous complication of the aneurysm is its rupture. Emergency surgery of a ruptured aneurysm is accompanied by essentially higher risks: The mortality rate lies between 34 and 90%. The prognosis of the operation varies with the patient's age, coronary sclerosis, and renal insufficiency. The diagnosis of the aneurysm can clearly be made with sonography, angiography, and computer tomography. In the case of a ruptured aneurysm, clinical signs are of primary importance. Angiography is not indicated here. From May 1969 until November 1976, 41 patients were operated on in our clinic: 23 electively and 18 after rupture. The mortality rate of the elective cases amounted to 17% and that of the ruptured to 72%.

Aged↗
PubMed1979

[Aortocoronary bypass permeability explored by tomodensitometry. Preliminary study].

The patency of 24 aorto-coronary grafts was studied by tomodensitometry. --16 out of the 18 bypasses examined within the two weeks following surgery were seen. --4 older bypasses were not visible, either by scanner or by angiography and were therefore occluded: two more, performed more than a year previously, were patent on tomodensitometric examination. The interpretation of the results, discussed taking into account the small number of angiographic check ups does not permit any formal conclusion as to the validity of the procedure. The results of this technique seem satisfactory and quite comparable with other non invasive methods used in the study of aorto-coronary grafts.

Adult↗
PubMed1979

Gated cardiac scanning: canine studies.

Retrospective electrocardiograph gating of data from a rotating detector fan beam computed tomography system was employed to produce end systolic and end diastolic images of the beating heart in a series of normal and experimentally infarcted canines. The gating window was typically less than 20% of the cardiac cycle, and the gated images showed superior spatial resolution compared with ungated images of the same cross section. Comparison of the scans of the normal and of the infarcted animals shows abnormal contrast enhancement of the myocardium in the region of the infarct, and the gating studies demonstrate dyskinetic behavior of the infarct zone.

Animals↗
PubMed1979

Myocardial imaging with 134mCesium. Comparison of scintigraphic and cineradiographic results.

Thirty-four patients had noninvasive myocardial perfusion imaging at rest using 134mCs. The results were compared with the results of coronary cineangiography and left ventriculography. All 21 patients who had abnormal left ventriculograms had corresponding myocardial imaging defects. This group included 14 patients with electrocardiographic evidence of either an old inferior, anteroseptal, anterior, or anterolateral myocardial infarction. Thirteen patients had normal left ventriculograms: this group included 6 patients with 75% or greater obstruction of one or more coronary arteries and 7 patients with normal or insignificantly diseased vessels. Only 2 of these patients had abnormal myocardial images: both had severe obstruction of the proximal left anterior descending artery without collateral filling of this vessel. In the resting patient who has 134mCs myocardial imaging, we concluded that we primarily are visualizing varying degrees of scarred myocardium rather than reversibly ischemic myocardium.

Adult↗
PubMed1979

CT demonstration of cardiac structures.

Cross-sectional cardiac anatomy was studied by computed tomography (CT) in normal patients and in patients with well documented cardiac pathology. Specific cardiac chambers, aortic and pulmonary artery enlargement, ventricular aneurysms, coronary artery, and intracardiac calcifications were demonstrated using a 3 sec scan time with and without intravenous iodinated contrast media. Although CT imaging of the heart is in its infancy, the clarity with which cardiac chambers and other structures were visualized is encouraging and suggests the potential value of CT scanning for detecting significant intracardiac pathology on routine thoracic CT scans.

Aortography↗
PubMed1979

Display and visualization of three-dimensional reconstructed anatomic morphology: experience with the thorax, heart, and coronary vasculature of dogs.

A new method, termed reprojection, is used to visualize anatomic morphology contained within three-dimensional reconstructions made up of images of multiple parallel cross sections. This method involves the projection, either orthographically into a plane or radially onto a cylinder, of the volume picture elements (voxels) of the reconstruction. Orthographic reprojection images, formed by mathematically summing the magnitudes of the voxels along selected parallel paths through the reconstructed volume, are analagous to conventional radiographs formed by the passage of an X-ray beam through the volume. The reprojection image is a two-dimensional array of picture elements that is displayed on a television monitor using a digital-to-video scan converter. Also described are the techniques of noninvasive selective tissue dissolution and numerical dissection, whereby obscuring portions of the reconstructed volume are either partially "dissolved" or totally eliminated before reprojection. Utilizing these methods, anatomic information present in a three-dimensional reconstruction but not clearly seen in a reprojection image is rendered visible after removal of superposed structures. The usefulness of these methods is demonstrated utilizing three-dimensional reconstructions of the thorax, heart, and coronary arteries of dogs.

Animals↗
PubMed1978

[Risks in modern diagnosis].

The first principle in diagnosis, as in treatment, is: nil nocere. Modern methods of diagnosis are becoming more and more technical. They often create physical and mental stress to the patient, and have undesirable side-effects of varying kinds and degrees. To be aware of contra-indications is important not only for the doctor but also for the patient, who must be informed of the risk of a diagnostic procedure. The data presented gives statistical information from which the doctor can see the number likely to be at risk from his diagnostic methods. The most common methods and their adverse effects are mentioned: intravenous use of X-ray contrast media, invasive tests (peripheral, cerebral, coronary, renal angiographs), laparoscopies with and without liver biopsies, kidney biopsies, endoscopies (oesophago-gastro-duodenoscopy, colonoscopy, retrograde cholangio-pancreatography), percutaneous lung biopsy and mammography. Although the mortality rates of all methods of diagnosis, even the most hazardous ones, are relatively low, all techniques create a stress to which not every patient is accustomed; they all demand considerable co-operation for which not every patient is prepared. There is now a trend towards non-invasive diagnostic techniques, creating little or no stress, but which nevertheless give at least a comparable level of diagnostic efficiency (e.g. ultrasonics, isotopes and computer tomography).

Biopsy↗