INTRODUCTION:A family history (FH) of premature coronary artery disease (CAD) is a major cardiovascular risk factor often underestimated by traditional scoring systems like SCORE2, which do not incorporate FH. The FAMILY trial (NCT07352111) is a prospective study investigating the role of cardiac CT (CCT) in identifying high-risk atherosclerosis in this specific population. RATIONAL AND OBJECTIVES:To enable personalized primary prevention, this study integrates genotypic and bio-humoral profiling with CCT plaque imaging in asymptomatic individuals with an FH of CAD. The primary objective of the study is to determine the prevalence of high-risk atherosclerosis in this specific cohort. METHODS:and Preliminary Data: We are prospectively enrolling asymptomatic first-degree relatives of patients with early-onset myocardial infarction (males <55, females <60 years). Participants undergo clinical evaluation, SCORE2 risk calculation, and advanced 256-slice CCT. High-risk atherosclerosis is defined by the presence of at least two high-risk plaque features and/or elevated volumes of low-attenuation/non-calcified plaque. A nested cohort (10-20%) of risk-reclassified patients will undergo comprehensive genetic profiling. Preliminary, data on the first 16 subjects enrolled (mean age 54 ± 6 years) were collected and analysed supporting the feasibility of the study. CONCLUSION:Traditional risk scores often underestimate CAD risk in individuals with a strong family history. By utilizing advanced CCT to detect high-risk atherosclerosis, the FAMILY trial aims to accurately reclassify patient risk and, potentially, guide early, targeted prevention. Feasibility data are presented but, given the limited size of this preliminary cohort, definitive conclusions await full enrolment.
BACKGROUND:The coronary artery calcium score (CACS) has strong prognostic value in stable chest pain patients. However, studies with follow-up beyond 5 years are scarce. We studied the long-term prognosis of CACS beyond pre-test probability (PTP) and single-photon emission computed tomography (SPECT) results for major adverse cardiac events (MACE). METHODS:We performed a retrospective cohort study among 6059 patients with non-acute chest pain, suspected of obstructive coronary artery disease who underwent clinically indicated SPECT/CT imaging with simultaneous CACS. Data on MACE, defined as cardiac death and non-fatal myocardial infarction, were collected during follow-up. The value of CACS in addition to PTP categories and SPECT results was studied using multivariable Cox analysis. RESULTS:During a median follow-up of 9.1 years (IQR 7.8-10.4), 6.1% (N = 365) of patients suffered from MACE. In CACS 0 (27% of all) annual MACE rates were 0.2-0.3% across PTP categories, and 0.2-0.6% across SPECT results. In CACS >1000 (10 % of all) annual MACE rates were 2.5-2.5% across PTP categories and 2.2-3.0% across SPECT results. High CACS (>1000 vs. 0, HR 4.14; 95%CI, 2.64-6.53) and abnormal SPECT (>10% ischemia vs. normal, HR 1.78; 95%CI, 1.27-2.46) predicted MACE. Compared to a model of PTP and cardiovascular risk factors (area under the ROC curve 0.72), adding SPECT improved discriminatory ability (0.73; p = 0.003), and adding CACS on top of SPECT improved performance further (0.75; p < 0.001). CONCLUSIONS:CACS adds incremental prognostic information to PTP and SPECT in stable chest pain patients. Absence of coronary calcium results in an excellent long-term prognosis regardless of PTP and SPECT result.
BACKGROUND:Non-calcified coronary atherosclerosis may be present despite a coronary artery calcium (CAC) score of zero, but its metabolic determinants are not well defined. This study investigated biomarker associations with non-calcified plaque and quantitative plaque characteristics in individuals with CAC = 0. METHODS:From a prospective registry of 860 adults underwent coronary CT angiography (CCTA) for suspected coronary artery disease, 418 individuals with CAC = 0 were analyzed. Clinical risk factors and biomarkers-including HbA1c, LDL-C, HDL-C, triglycerides, ApoA-I, ApoB, the ApoB/ApoA-I ratio, lipoprotein(a) [Lp(a)], hs-CRP, and creatine kinase-were assessed. Propensity score matching (PSM) balanced clinical risk factors (age, sex, body mass index, hypertension, hyperlipidaemia, diabetes, smoking, statin therapy, and glucose-lowering therapy) between patients with and without plaque. RESULTS:Non-calcified plaque was detected in 10.3% of CAC-zero individuals. Before matching, those with plaque were older (55.2 ± 10.3 vs 51.9 ± 10.5 yrs; p = 0.055) and had higher rates of hypertension, hyperlipidaemia, and diabetes, as well as higher HbA1c and Lp(a) levels. After PSM (n = 86; 43 with plaque and 43 without plaque), HbA1c remained significantly higher in individuals with plaque (39.76 ± 5.36 vs 37.60 ± 3.65 mmol/mol; p = 0.026), while other biomarkers were not significant. In exploratory analysis, elevated Lp(a) ≥50 mg/dL may be associated with greater total plaque volume (≥70 mm3) (OR 4.89, 95% CI 1.17-20.41; p = 0.03), and higher Lp(a) levels were observed in patients with low-attenuation plaque compared with those without low-attenuation plaque. CONCLUSION:Among individuals with CAC = 0, higher HbA1c was associated with non-calcified coronary plaque. Elevated Lp(a) may be associated with greater plaque burden and plaque characteristics. These findings suggest a potential role for metabolic factors and CCTA in detecting subclinical atherosclerosis beyond CAC scoring.
BACKGROUND:Motion artifacts limit coronary CT angiography (CCTA) when mid-diastolic quiescence is short. RR-PQ estimates the low-motion interval available for reconstruction, whereas motion correction may improve image quality without changing cardiac physiology. PURPOSE:To primarily evaluate the incremental effect of Clear Motion Cardiac (CMC) compared with half-scan reconstruction and secondarily characterize the probability of diagnostic image quality across RR-PQ values and derive candidate operational RR-PQ values on a 0.24-s/rotation 320-detector row CT system. METHODS:In 1012 consecutive CCTA examinations, paired half-scan and CMC series were reconstructed from identical raw data. Motion was graded A-D (A/B diagnostic). McNemar tests compared paired rates; logistic models estimated diagnostic probability and candidate RR-PQ values. RESULTS:Diagnostic image quality increased from 841/1012 (83.1%) with half-scan to 939/1012 (92.8%) with CMC (p < 0.0001). Of 171 half-scan failures, 101 were rescued; degradation occurred in 3/1012. Benefit increased with heart rate and was greatest at ≥70 bpm. RR-PQ was strongly associated with the probability of diagnostic image quality; candidate values at 95% probability were 807 ms for half-scan and 739 ms for CMC. CONCLUSION:CMC improved diagnostic image quality, especially at higher heart rates and shorter RR-PQ. The derived values may aid workflow planning but are platform- and cohort-specific.
BACKGROUND:Coronary computed tomography angiography (CCTA) is an alternative to single-photon emission computed tomography (SPECT) for evaluating intermediate-risk chest pain in the emergency department, offering rapid assessment and potentially less unnecessary invasive testing. Despite guideline support, real-world comparative data remain limited. METHODS:We retrospectively studied adults presenting with chest pain or angina-equivalent symptoms to emergency departments within the HCA Healthcare (United States) from January 2017 to June 2024 who underwent CCTA or SPECT at the index encounter. The primary outcome was invasive coronary angiography (ICA) during the index hospitalization. Secondary outcomes were length of stay (LOS), 30-, 60-, and 90-day all-cause readmissions, in-hospital mortality, and renal replacement therapy (RRT). Regression models adjusted for age, sex, diabetes, hypertension, and hyperlipidemia. RESULTS:Among 22,195 patients, 2827 (12.7%) underwent CCTA and 19,368 (87.3%) SPECT. ICA occurred in 15.2% of CCTA versus 24.6% of SPECT patients (adjusted odds ratio [OR] 1.75 for SPECT vs CCTA, 95% confidence interval [CI] 1.56-1.95; p < 0.0001). LOS and readmissions did not differ significantly, but RRT was more frequent with SPECT (OR 2.28, 95% CI 1.44-3.62; p = 0.0004). In-hospital mortality was rare; mortality comparison was underpowered. CONCLUSION:In this multicenter cohort, CCTA was associated with lower downstream ICA utilization and lower RRT incidence than SPECT, without extending LOS or increasing readmissions. These associations are directionally consistent with the 2021 AHA/ACC Chest Pain Guidelines. Given substantial baseline imbalance between cohorts and likely residual confounding, the findings are hypothesis-generating and require prospective validation before informing practice.
PURPOSE:To compare coronary artery calcium (CAC) scores from ultra-low-dose true non-contrast (TNC), virtual non-contrast (VNC), and virtual non-iodine (VNI) images with standard TNC on a dual-source photon-counting detector CT (PCD-CT). METHODS:In this prospective single-center study (January 2025-March 2026), patients underwent standard TNC (sequential, 120 kVp), ultra-low-dose TNC (high-pitch helical, tin-filtered 100 kVp), and coronary CT angiography (CCTA); VNC and VNI images were generated from CCTA. CAC scores and burden categories were evaluated. Correlation and agreement with standard TNC were assessed using Pearson coefficients with Williams' test, Bland-Altman plots, and weighted Cohen's kappa. RESULTS:Seventy-one patients (median age, 75 years; 52 men) were evaluated. Median dose-length product was 7.98, 71.8, and 428 mGy cm for ultra-low-dose TNC, standard TNC, and CCTA, respectively. Ultra-low-dose TNC showed the strongest correlation with standard TNC (r = 0.996), superior to VNI (r = 0.976, P < 0.001) and VNC (r = 0.900, P < 0.001). Agreement in CAC burden categorization was excellent for ultra-low-dose TNC (κ = 0.932) and good for VNI (κ = 0.827), whereas VNC showed moderate agreement (κ = 0.424). VNI had minimal bias (mean difference, -3.9) but wider limits of agreement than ultra-low-dose TNC (-356.5 to 348.6 vs. -163.2 to 105.9). VNC underestimated CAC scores (mean bias, -442.0). CONCLUSION:Ultra-low-dose TNC with dual-source PCD-CT showed excellent agreement with standard TNC while reducing radiation by nearly 90%. VNI was acceptable but less robust, whereas VNC substantially underestimated CAC scores. Ultra-low-dose TNC is a reliable, dose-efficient alternative to standard TNC for CAC scoring.
