Coronary Artery Calcium Research Articles

Defining high risk in the cardiovascular-kidney-metabolic syndrome and associated cardiovascular disease outcomes

Abstract Background The American Heart Association (AHA) recently developed the cardiovascular-kidney-metabolic (CKM) syndrome construct with stages 0-4 to comprehensively characterize the spectrum of cardiovascular disease (CVD) risk [1]. CKM Stage 3 is defined by subclinical CVD or high (≥20%) estimated 10-year CVD risk according to the newly-derived PREVENT models [2]. However, within CKM Stage 3, the burden of subclinical atherosclerosis equivalent to a ≥20% estimated CVD risk, and long-term CVD outcomes associated with CKM Stage 3, are not known. Purpose To (1) characterize the distribution of subclinical atherosclerosis by coronary artery calcium (CAC) according to PREVENT estimated CVD risk categories, and (2) quantify long-term CVD risk associated with CKM Stage 3, in two international cohorts of adults without prior CVD. Methods In participants of the Multi-Ethnic Study of Atherosclerosis (MESA, age 45-84 years) and the Rotterdam Study (age ≥55 years), the burden of CAC was calculated across estimated 10-year CVD risk (low, 0 to <5%; borderline 5 to <7.5%; intermediate, 7.5 to <20%; high, ≥20%). Participants were categorized into CKM stages according to CVD risk factors (body mass index, waist circumference, glycemic status, blood pressure, lipids, kidney function), estimated 10-year CVD risk (by AHA PREVENT model), and presence of CAC. The association of CKM syndrome stage with fatal or nonfatal CVD outcomes was evaluated with covariate-adjusted proportional hazards regression. Results Among 6,123 MESA participants (52% female, mean age 61.4 years) and 1,691 Rotterdam Study participants (46% female, mean age 67.1 years), the distribution of CAC across absolute 10-year CVD risk categories is shown in Figure 1. In high (≥20%) CVD risk adults, CAC score ≥100 was present in 50% of MESA participants and 48% of Rotterdam Study participants. Most participants were classified as CKM Stage 3 (53% in MESA, 83% in Rotterdam). Over a median follow-up of 17.5 years in MESA, CVD events occurred in 5% of CKM Stage 0, 6% of Stage 1, 9% of Stage 2, and 26% of Stage 3 participants. Over a median follow-up of 10.2 years in the Rotterdam Study, CVD events occurred in 0% of CKM Stage 0 and 1, 8% of Stage 2, and 17% of Stage 3 participants (Figure 2). The risk of total CVD was significantly higher in CKM Stage 3 participants relative to CKM Stage 0-2 (MESA: adjusted HR 2.74, 95% CI 2.32, 3.23; Rotterdam: adjusted HR 2.18, 95% CI 1.34, 3.54). Conclusions In an international, multi-ethnic sample of middle-aged adults, adults with high (≥20%) absolute 10-year CVD risk by PREVENT had substantial burden of CAC. Adults in CKM Stage 3 had approximately 2.2- to 2.7-times higher risk for CVD, compared with adults in lower CKM stages. Accounting for estimated CVD risk and burden of cardiovascular, kidney, and metabolic risk factors informs prevention of subclinical and clinical CVD.

Validation of quantitative aortic valve calcification assessment by photon-counting computed tomography from contrast-enhanced data sets using virtual non-contrast reconstructions

Abstract Background The spectral information of photon-counting computed tomography (PCCT) permits the reconstruction of energy-selective images. Purpose We evaluated two methods for the reconstruction of virtual non-contrast-enhanced images from contrast-enhanced CT angiographic data sets regarding their ability to quantify aortic valve calcification. Results were validated by comparison to non-enhanced computed tomography. Methods A total of 100 subjects with severe aortic valve stenosis who underwent ECG-synchronized cardiac photon-counting CT for diagnostic workup prior to transcatheter aortic valve implantation (TAVI) were included in the current analysis. A standard true non-contrast acquisition was performed for aortic valve calcium quantification in each subject. In addition, two virtual non-enhanced data sets were reconstructed from contrast-enhanced CT angiographic data: a calcium-specific image ("pure calcium scan", PCS) and a virtual non-contrast (VNC) scan by subtraction of iodine. The PCS algorithm separates calcium and iodine in spectral PCCT images, creating a non-calcium mask for denoised spectral input and preserving calcium contrast in final material decomposition. Iodine extraction is achieved by measurement of the iodine content and its differentiation from native soft tissue attenuation. The Agatston Score was assessed in each of the three image data sets using semi-automated software. Results The mean age of the subjects was 78 ± 7 years, 66% were male. Mean EUROSCORE II was 4 ± 4%, mean STS Score for morbidity and mortality was 16 ± 11%. In the true non-contrast scan used for validation, the mean Agatston Score was 3028 ± 1820. The mean Agatston Score obtained from the PCS data set was 3004 ± 2042 and did not differ significantly from true non—contrast image sets (p=0.716). In the VNC data sets, the mean Agatston score was 1726 ± 1288, significantly lower than in the true non-contrast and the PCS data sets (both <0.001). Both, PCS and VNC data showed a significant correlation with true non-contrast scans (correlation coefficient PCS: 0.978, VNC scan: 0.975, both p<0.001). Conclusion In conclusion, the current results show the possibility to reliably quantify the Agatston Score of larger cardiac calcifications in virtual non-contrast data sets – however, there is substantial influence of the algorithm that is used so that validation of new techniques is of key importance.

AI-enabled automated cardiac chambers volumetry in non-contrast ECG-gated cardiac scans vs. non-contrast non-gated lung scans

Abstract Introduction We have developed an AI-enabled automated volume measurement of cardiac chambers (AutoChamber) that works on ECG-gated coronary artery calcium scans and correlates well with contrast enhanced coronary CT angiography scans. We have recently reported that increased left atrial volume measured by AutoChamber is a strong predictor of new onset atrial fibrillation (AF) in asymptomatic individuals of Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we compare the volumetry results in ECG- gated CAC scans with those of non-gated full-chest lung cancer screening scans in the same individuals. Methods We have studied 169 cases of paired ECG-gated cardiac CT scans and non-gated lung scans obtained from Harbor UCLA. Mean±SD for age was 62.1±10.0 years with 52% female participants. All cases were asymptomatic and were scanned for preventive health assessment. AutoChamber was run on all cases by an independent operator who was not involved in data analysis. P value was calculated using a two-tailed test of significance with α=0.05. Results AutoChamber in cardiac scans vs lung scans reported volume (Mean±SD) for left atrium (LA) was 63.8 ± 18.5 vs. 65.5 ± 19.4, left ventricle (LV) 102.8 ± 25.3 vs. 105.5 ± 25.2, right atrium (RA) 81.9 ± 20.5 vs. 85.7 ± 21.9 right ventricle (RV), 140.7 ± 34.2 vs. 134.2 ± 33.7, left ventricle wall (LVW) 113.0 ± 26.6 vs. 109.7 ± 27.0 respectively (P < 0.0001). Strong correlation was shown between cardiac and lung scans for each cardiac chamber: LA (R = 0.92), LV (R = 0.93), RA (R = 0.91), RV (R = 0.92), and left ventricular wall (LVW) R = 0.95. Conclusions AutoChamber volumetry results are similar in ECG-gated cardiac scans vs non-gated full-chest lung scans. This AI-enabled automated tool is promising as it can provide added value to patients undergoing coronary calcium and lung cancer screening scans flagging enlarged cardiac chambers at risk of AF and heart failure.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography

Abstract Background There are sex differences in the extent, severity, and outcomes of coronary artery disease. Purpose To assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p=0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p=0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p=0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n=80) and 48.3% (n=73); p=0.42), or CMA values >1.56 (21.8% (n=33) and 21.8% (n=33); p=1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n=10) and 7.8% of men (n=66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p=0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p<0.001). Conclusions Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.Sex differences in CAD activityCase examples

A novel marker of cardiovascular risk stratification: the role of total cardiovascular calcium score using cardiac CT

Abstract Introduction It is widely accepted that coronary and valve calcification measured by cardiac CT, individually, are associated with cardiovascular events and mortality. However, the role of an encompassing marker of cardiovascular atherosclerosis could be more representative of the real cardiovascular risk. Objectives To determine the prognostic value of a combined coronary, valvular and aortic calcium score to predict long-term major adverse cardiac and cerebrovascular events (MACCE). Methods We conducted a single center study on 316 consecutive patients who underwent cardiac CT scan between January 2018 and December 2019. We excluded patients with poor imaging quality, constrictive pericarditis, prosthetic valves and/or devices. The calcium score of coronary arteries (CA), mitral valve (MV), aortic valve (AoV), ascending aorta (AAo) and aortic arch (AAc) were calculated from non-contrast ECG-gated CT using the Agatston method and were combined to derive a valvular (VA=MV+AoV), total cardiac (TC=CA+VA) and total cardiovascular (TCV=TC+AAo+AAc) calcium scores (Fig.1A). The primary endpoint was a composite of MACCE, defined as all-cause death, stroke, myocardial infarction and hospital admission for heart failure. Results A total of 275 CT scans were suitable for analysis. Mean age was 59.6±12.3 years, 48.4% were female. A total of 183 (66.7%) patients presented calcification in at least one location. Patients with calcification on any of the prespecified locations had higher prevalence of hypertension, dyslipidemia and type 2 diabetes mellitus (DM) than those without any calcium (p<0.05). After a median follow-up of 3.18 [IQR 2.84-3.69] years, 40 (14.5%) patients had met the primary endpoint. Regression analyses demonstrated that all CA, VA, TC and TCV scores were independent predictors of MACCE (p<0.05 for all). The best prediction models included calcium score (all combinations), age, sex, type 2 DM and smoking status (Fig.1B). The model with TCV score was the most powerful predictor of MACCE (χ2 47.8), followed by TC score (χ2 43.1). Of interest, the model with CA score had the poorest performance (χ2 35.4). Conclusion Coronary calcium score is a quick way to stratify risk in clinical practice, but its performance is too focused on coronary events. Total cardiovascular calcium score, however, is more encompassing, also quick to measure, and a more truthful depiction of the patient’s cardiac and cerebrovascular risk, potentially allowing a more tailored and timely approach to risk factors in clinical practice.

Rotational atherectomy versus orbital atherectomy for the treatment of calcified coronary lesions: a systematic review and meta-analysis of 81,873 patients

Abstract Background Previous studies have suggested that pre-treatment of coronary artery calcification with rotational atherectomy (RA) prior to stent deployment can enhance procedural success, but this does not necessarily translate into improved clinical outcomes. Recently, the Orbital Atherectomy (OA) system has been introduced into clinical practice to enhance lesion preparation. Purpose Our study aims to evaluate the safety and efficacy of both RA and OA as pre-treatment strategies before stent deployment in patients with coronary artery calcification. Methods We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. These were identified through systematic PubMed, Web of Science, Scopus, Embase, and Cochrane searches until January 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using Stata version 17. Results Our analysis included eleven studies encompassing 81,873 patients. No significant difference was observed between RA and OA in terms of major adverse cardiovascular events (MACE) (RR: 0.81 with 95% CI [0.64, 1.02], P= 0.07). However, OA was significantly associated with a decreased incidence of all-cause mortality (RR: 0.60 with 95% CI [0.52, 0.70], P< 0.01), target vessel revascularization (TVR) (RR: 0.43 with 95% CI [0.22, 0.82], P= 0.01), coronary artery bypass grafting (CABG) (RR: 0.78 with 95% CI [0.62, 0.97], P= 0.03), and fluoroscopy time (MD: -3.93 with 95% CI [-7.39, -0.48], P= 0.03). There was no significant difference between RA and OA in cardiac death (RR: 2.65 with 95% CI [0.94, 7.51], P= 0.07), target lesion revascularization (TLR) (RR: 0.57 with 95% CI [0.23, 1.41], P= 0.22), myocardial infarction (RR: 0.79 with 95% CI [0.62, 1.01], P= 0.06), stent thrombosis (RR: 0.33 with 95% CI [0.09, 1.23], P= 0.10), stroke (RR: 0.76 with 95% CI [0.57, 1.01], P= 0.06), re-admission (RR: 0.76 with 95% CI [0.48, 1.19], P= 0.23), vessel closure (RR: 0.78 with 95% CI [0.18, 3.33], P= 0.74), procedural duration (MD: -5.43 with 95% CI [-21.71, 10.84], P= 0.51), length of hospital stay (MD: 0.21 with 95% CI [-0.47, 0.90], P= 0.54), and contrast amount (MD: -3.68 with 95% CI [-9.37, 2.01], P= 0.21). Conclusion Both RA and OA as pre-treatment strategies before stent deployment demonstrate similar outcomes for numerous cardiovascular events. However, OA is associated with lower rates of all-cause mortality, TVR, CABG, and fluoroscopy time.

How to decide appropriate percutaneous coronary intervention (PCI) technique for managing heavy calcified coronary lesions: serial case-report

Background: Coronary artery calcification (CAC) is still challenging for interventional cardiologists. Their contribution to major adverse cardiac events occurs from the high risk of stent thrombosis or in-stent restenosis and target lesion revascularization. Optimal preparation, such as coronary plaque modification before stenting, is required to reduce the risk of periprocedural adverse events. This case presentation aimed to describe the appropriate management of heavy calcified coronary lesions. Case Presentation: Two cases of heavy calcified coronary lesions with different baselines as Acute Coronary Syndromes (ACS) and elective PCI were presented. In our ACS patients, the Primary PCI was done by coronary angioplasty without stenting because of the complexity of the heavily calcified lesion. A referral to tertiary health care was made for further PCI procedures using a combination of calcium-ablation and balloon-based techniques. A treatable complication occurred after the orbital atherectomy was performed with good results. The second case was an elective PCI patient with heavy calcified lesions findings from coronary angiography. The balloon-based technique was performed using non-compliant and scoring balloons without complication and showed good results. Conclusion: The challenging points in managing heavy calcified coronary lesions are procedure complexity and the higher stent failure rate. Many modifying coronary calcification algorithms using advanced modalities have been proposed, which could be used to select the appropriate technique as experienced and increase the success rate. Keyword: balloon-based technique, calcium-ablation technique, heavy calcified coronary lesion, orbital atherectomy

Can the presence of aortic or coronary artery calcifications in the standard of care baseline CT or PET-CT scan of patients with Hodgkin or non-Hodgkin lymphoma be used as a predictor of MACE?

Abstract Background Major adverse cardiovascular events (MACE), commonly defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and heart failure, represent a significant cause of mortality among patients with cancer. With increased rates of both cancer and cancer survivorship, the identification of new predictive markers for the development of MACE in this population is crucial for implementing effective preventive and risk-mitigation strategies. Purpose To determine whether the presence of calcifications in the coronary arteries (CAC) or aorta (CA) of lymphoma patients, as reported in standard-of-care PET-CT (Positron Emission Tomography-Computed Tomography) or chest CT (Computed Tomography) scan, can predict the occurrence of MACE. Methods A Retrospective analysis was conducted on a cohort of patients diagnosed with Hodgkin or non-Hodgkin lymphoma and treated with anthracycline-based chemotherapy. Patients were diagnosed from January 1, 2013, and followed through to June 30, 2023. The reference point for the study was the radiologist’s report of the PET-CT or chest CT conducted before the initiation of anthracycline therapy. Patients who did not undergo a PET-CT or CT before the start of treatment, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CA and CAC was associated with the development of MACE. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression. Results 326 patients were included with a mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was reported in 75 patients (23%) and CA in 18 (6%). In the univariate regression model, a statistically significant association was found between the presence of both CA and CAC with the risk of MACE. CAC showed a stronger association with the development of MACE than CA (HR: 3.7 [1-7.9], p=0.0005 vs HR: 2.9 [1- 8.5], p=0.050). In multivariable analysis CAC emerged as the strongest predictor of MACE (HR: 2.9 [1.3 – 6.4], p=0.01), after accounting for hypertension, diabetes, dyslipidemia, and GFR <60 (Table 1), while the association with CA attenuated (HR: 2.01 [0.7-6.5], p=0.2010) and was no longer significant (Table 2). Conclusion CAC in the standard-of-care PET/-CT scans was a predictor of MACE in lymphoma patients treated with anthracyclines, while the association with CA weakened in multivariable analyses and was likely underpowered given the small number of patients with CA. If replicated, this finding warrants closer surveillance of this group of patients and can be considered as a non-invasive cardiovascular risk marker.

Measures of insulin resistance and aortic valve calcification in the general population

Abstract Background Insulin resistance (IR) is a key component in several cardiovascular risk factors. The triglyceride-glucose index (TyG index), triglyceride to high density lipoprotein-cholesterol ratio (TG/HDL-C) and visceral adiposity index (VAI) are easily accessible surrogate measures of IR and have been associated with coronary artery calcification and other cardiovascular diseases. Less is known about IR and aortic valve calcification (AVC). Purpose To investigate the association between different measures of IR (TyG index, TG/HDL-C, VAI) and AVC. Method The Swedish Cardiopulmonary Bioimage Study (SCAPIS) recruited 30 154 randomly selected individuals aged 50 to 64 years from the general population in Sweden between 2013 to 2018. AVC was assessed visually on cardiac computed tomography and categorized as present or absent. TyG index was calculated based on triglyceride and glucose levels, TG/HDL-C ratio using triglyceride and HDL-C levels and VAI using waist circumference, triglyceride and HDL-C levels. The association between IR indexes (as continuous variables by 1 unit increment and categorical variables by quartiles) and AVC was assessed using multivariable logistic regression models. Results In total, measures of IR were available in 29 268 participants of whom 2118 (7%) had AVC. Mean IR index levels were higher in participants with compared to without AVC (TyG index: 8.65 vs. 8.49; p<0.01; TG/HDL-C: 1.11 vs. 0.91; p<0.01 and VAI: 1.73 vs. 1.48; p<0.01). All three indices of IR were associated with AVC in continuous analyses. Subsequently, in multivariable logistic regressions adjusted for age, sex, study site and smoking, there was a stepwise increase in the risk of AVC with increasing quartiles of TyG index, TG/HDL-C and VAI (Figure 1). Conclusion Three different surrogate measures of IR (TyG index, TG/HDL-C and VAI) were all associated with AVC in a middle-aged general population suggesting that they could all be used as risk markers in clinical practice.

Coronary atherosclerotic burden in master athletes: relationship with cardiovascular risk and volume of exercise

Abstract Background Although prior studies suggesting an association between coronary artery calcification (CAC) and lifelong exercise, the clinical relevance and mechanisms for this interaction remains unknown. Recent evidence suggests that a significant amount of exercise might not be linked to a more favourable composition of coronary plaques. We aimed to analyse the prevalence of high coronary atherosclerotic (CAS) burden assessed by coronary CT scan (CCTA) in master athletes, according to cardiovascular (CV) risk and volume of exercise. Methods A total of 105 master male athletes (48±5.6 years old), asymptomatic and without known CV disease, were prospectively studied. A high CAS burden was defined as the presence of at least one of the following characteristics in CCTA: CAC score >100; CAC score >75th percentile; obstructive plaques; plaques in the left main, three vessels or two vessels including the proximal anterior descending artery; segment Involvement Score (SIS) >5; CT-adapted Leaman score (CT-LeSc) ≥5T. his variable was evaluated according to the CV risk, stratified by SCORE2, and volume of exercise, determined by metabolic equivalent task score (MET/hour/week). Results Most athletes (n=88) were engaged in endurance sports, during 17.1±9.8 years, with a median exercise volume of 66 [IQR 44-103] METs/hour/week. The mean SCORE2 was 2.8±1.5%, with 76.9% of athletes classified as having a low to moderate CV risk, and none having very high-risk. A high CAS burden was present in 25.7% of the athletes, without significant differences according to the SCORE2 risk categories [Low- Moderate Vs. High Risk: 25.5% Vs. 37.5%, respectively ; p=0.142] nor volume of exercise [below Vs. above median: 30.6% Vs. 21.4%, respectively; p=0.283)] (Figure 1 A). Combining these variables, athletes with high CV risk and a high volume of exercise showed significantly higher occurrence of a high CAS burden compared to those with low-moderate risk and high volume of exercise (50% Vs. 15.6%; p=0.017). Among athletes with low-moderate risk, high volume of exercise trended to be protective (15.6% Vs. 31.4%; p=0,092), while there was a similar rate of high CAS burden in athletes with low volume of exercise, independently of risk class (Figure 1B). Conclusions In our cohort of master athletes, one fourth demonstrated a high burden of CAS burden evaluated by CCTA. While a higher volume of exercise combined with high cardiovascular risk showed an association with worse coronary composition it trended to be protective in athletes with lower risk. Integrating clinical and exercise-related data is crucial for evaluating athletes amidst the complex associations between exercise, cardiovascular risk, and CAS burden, necessitating longitudinal studies for comprehensive understanding.Figure 1Figure 2

Prevalence of high-risk plaque features on cardiac computed tomography scans in patients with a coronary artery calcium score of zero

Abstract Introduction Coronary artery calcium (CAC) score of zero (so-called "power of zero") is associated with a very low rate of major adverse cardiac events (MACE), especially during short and midterm follow-up. However, a CAC score of zero does not definitively exclude the presence of atherosclerotic plaques or obstructive coronary artery disease (CAD). The composition of atherosclerotic plaques and the frequency of high-risk plaque features in this population are not well described. Purpose We sought to characterize the composition of atherosclerotic plaques and assess the frequency of high-risk plaque features on contrast-enhanced computed tomography (CT) images in patients with a zero CAC score. Methods The study enrolled patients with stable chest pain suspected of CAD referred for coronary CT imaging and having a CAC score of zero. Coronary CT angiography images were assessed by an expert reader to identify atherosclerotic plaques and high-risk plaque features in all coronary arteries with a diameter ≥1.5mm. The coronary artery lumen and plaques were manually segmented, and the degree of stenosis was evaluated following the Coronary Artery Disease Reporting and Data System (CAD-RADS) criteria. The presence of four high-risk plaque features was identified: positive remodeling, spotty calcification, low-attenuation plaque, and napkin ring sign. Total plaque volume, percent atheroma volume, and plaque composition were quantified using dedicated software (Figure 1). Results A total of 145 patients (mean age 54.2±12.1 years, 35.9% males) were included in the analysis. At least one coronary artery plaque was identified in 30 individuals (20.7%). 22 (15.2%), 7 (4.8%), and 1 (0.7%) patients were categorized into CAD-RADS 1, CAD-RADS 2, and CAD-RADS 3 categories, respectively. Among 30 patients with any coronary artery plaque, at least one high-risk feature was found in 10 individuals (33.3%), while 3 individuals (10.0%) had two features. Positive remodeling was found in 7 (23.3%), spotty calcification in 3 (10.0%), low-attenuation plaque in 3 (10.0%), and napkin ring sign in 0 patients, respectively (Figure 1). The mean total plaque volume was 48.2±54.3mm³, and the mean percent atheroma volume was 1.2±0.8%. Total plaque volume comprised low-attenuation (0.4%), fibro-fatty (58.9%), fibrous (39.4%), and calcified (1.3%) plaque volumes. Notably, in 3 (10.0%) individuals, the presence of calcified plaque was identified, which on non-contrast CT images did not meet the Agatston criteria for the CAC score. Conclusions Our study demonstrates a significant prevalence of atherosclerotic plaques and high-risk plaque features in patients with a CAC score of zero. Specifically, one in every five study participants had identifiable atherosclerotic plaque, with one in every three of those exhibiting one or more high-risk plaque features. The prognostic significance of these findings warrants further evaluation in studies with longitudinal follow-up.

Progress in understanding the genetic underpinning of coronary artery disease: from genotype to phenotype

Abstract Background The functional dissection of genetic risk opens the door to strategies for pharmacological manipulation of molecular and cellular processes implicated in human diseases, including coronary artery disease (CAD). Aim To assess the relationship between a set of single nucleotide polymorphisms previously associated with CAD and coronary artery calcium (CAC) score in an asymptomatic population from Portugal. Methods Prospective study in a cohort of 1,284 subjects aged 59.3±8.9 years, 73.6% males without apparent CAD. The CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff nomogram. Anthropometric, conventional, and biochemical risk factors were evaluated. Thirty-three single nucleotide polymorphisms were genotyped by TaqMan real-time PCR. Bivariate and multivariate logistic regression analysis estimated variables associated with the CAC score. Results After bivariate analysis, PHACTR1 rs1332844 C>T, a downstream regulator of the endothelin-1 gene, showed a significant association with CAC score (p=0.015), together with CDKN2B-AS1 variants rs4977574 A>G in the locus 9p21.3 (p=0.002) and rs1333049 G>C (p=0.010). MTHFD1L gene encodes a mitochondrial enzyme responsible for homocysteine remethylating in methionine, and rs6922269 G>A showed protection against artery calcification (p=0.013). After multivariate logistic regression, PHACTR1 rs1332844 (CT+TT) (p=0.009) and CDKN2B-AS1 rs4977574 A>G (GG) (p=0.002) remained in the equation as independently associated with arterial calcification, together with male sex (p=0.039), age (p<0.0001), hypertension (p=0.001), diabetes (p<0.0001), smoking status (p<0.0001) and obesity (p=0.020). MTHFD1L rs6922269 AA also remained as significant protection from arterial calcification (p=0.027). Conclusion The present work showed two genetic variants, PHACTR1 and CDKN2B-AS1, linked to arterial wall calcification, herewith clinical and environmental risk factors. MTHFD1L showed protection. Understanding the genetic basis of vessel calcification can enable lifestyle changes or pharmacologic therapy to attenuate risk before the disease becomes clinic. More research in this field is critical to understanding the genetic basis of CAD through an intermediate phenotype, coronary arterial wall calcification.

Serial optical coherence tomography assessment of coronary atherosclerosis and long-term clinical outcomes

Abstract Background The impact of high-risk coronary artery plaques identified using optical coherence tomography (OCT) on late luminal narrowing and clinical events remains poorly understood. Methods This multicenter prospective study included 176 patients who underwent percutaneous coronary intervention (PCI) and serial OCT at baseline and 1-year follow-up to investigate non-target regions with angiographically intermediate stenosis. The primary outcome measure was luminal narrowing within the matched regions of interest in the non-target regions over a 1-year period. The secondary outcome measures included all-cause death, cardiac death, nonfatal myocardial infarction, and ischemia-driven coronary artery revascularization within 3 years. Results At 1 year after PCI, the coronary artery lumen area in non-target regions significantly decreased from 6.06 (95% confidence interval [CI], 5.60–6.53) to 5.88 (95% CI, 5.41–6.35) mm2, with a difference of -0.18 (95% CI, -0.22 to -0.14 mm2; P<0.001). This decrease was pronounced in thin-cap fibroatheromas (TCFAs), thick-cap fibroatheromas, mixed plaques, and fibrous plaques. The prevalence of TCFAs decreased from 3.4% to 3.3% (P<0.001), whereas that of thick-cap fibroatheromas also decreased from 35% to 33% (P<0.001). Patients with TCFA had a significantly higher risk of ischemia-driven non-target vessel revascularization (hazard ratio [HR], 2.42; 95% CI, 1.03–5.71; P=0.04), primarily due to revascularization in the imaged region. The higher prevalence of fibroatheroma was associated with a numerically increased risk of imaged region revascularization (HR per 10%, 1.38; 95% CI, 0.97–1.97; P=0.07). The prevalence of coronary artery calcium significantly increased from 31% at baseline to 34% at 1-year follow-up (P<0.001), accompanied by a significant increase in calcium thickness and angle. Diabetes and current smoking habits were independently associated with increasing calcium prevalence. No significant association was observed between the prevalence of coronary artery calcium and clinical outcomes within 3 years. Conclusions Coronary artery lumen area significantly decreased over a 1-year interval, particularly in TCFAs, thick-cap fibroatheromas, mixed plaques, and fibrous plaques. Although no significant association was noted between coronary artery calcium prevalence and clinical outcomes within 3 years, the interaction between calcium progression and long-term clinical events necessitates further investigation.

Relationship between coronary artery calcium score and plaque vulnerability in patients with established coronary artery disease

Abstract Introduction Coronary artery calcium (CAC) score is widely used for risk stratification. However, in patients with established coronary artery disease (CAD), its clinical implication and relationship with plaque vulnerability have not been fully investigated. Purpose We sought to investigate the relationship between CAC score and plaque vulnerability assessed by optical coherence tomography (OCT). Methods Patients with CAD who had both CAC score and OCT prior to percutaneous coronary intervention were included. The patients with a prior history of coronary revascularization were excluded. Patients were divided into five groups based on CAC score; CAC score of 0, 1-99, 100-399, 400-999, and over 1000. Vulnerable features in culprit plaque assessed by OCT were compared among these five groups. Results In 460 patients, the prevalence of lipid-rich plaque, macrophage, and cholesterol crystal significantly differed among the five groups: lowest in the patients with a CAC score of zero. The prevalence of thin-cap fibroatheroma (TCFA) tended to be lower in those with a CAC score of zero (Figure). In the two-group comparison between the group with a CAC score of zero and the other four groups, the prevalence of lipid-rich plaque (60.5 vs. 85.9%, p < 0.001), macrophage (48.8 vs. 74.1%, p < 0.001), TCFA (16.3 vs. 35.0%, p = 0.013), and cholesterol crystal (11.6 vs. 32.9%, p = 0.004) was significantly lower in the patients with CAC score of zero. No significant difference in vulnerable features was observed among the four groups with CAC scores > 0. CAC score of zero was independently negatively associated with the lipid-rich plaque (odds ratio [OR] 0.246, p < 0.001), macrophage (OR 0.348, p = 0.003), TCFA (OR 0.285, p = 0.006), and cholesterol crystal (OR 0.273, p = 0.010) after adjustment with patient characteristics. Conclusion This is the first study that investigated the relationship between CAC score and plaque vulnerability assessed by OCT in patients with known CAD. Patients with CAC score of zero have a significantly lower prevalence of vulnerable plaque features compared to those with CAC score > 0.

The paradox of CAC score and plaque vulnerability

Abstract Introduction The effect of coronary artery calcification on plaque vulnerability remains unclear. The coronary artery calcium (CAC) score, quantified using coronary computed tomography, has a strong correlation with total atherosclerotic burden and risk of adverse cardiac events. Nevertheless, different patterns in the distribution of coronary artery calcium have been reported to convey different effects on plaque stability. Some biomechanical models suggest that microcalcifications can intensify stress in the fibrous cap, promoting plaque rupture. On the other hand, large calcium deposits are hypothesized to promote plaque stability, as statin therapy has been shown to promote the calcification of atherosclerotic lesions. The purpose of this study is to investigate the relationship between CAC score and vulnerable plaque using coronary computed tomographic angiography (CCTA) in patients with an acute coronary syndrome (ACS). Methods CCTA was performed in 444 patients; these patients were divided into two groups (those with vulnerable plaque and those without). CAC score of each patient was obtained. We calculated median value of CAC score of both groups and compared them using Two Sample Mann-Whitney U Test. All tests were 2-sided, p values below a threshold of 0.05 were considered to be significant. All statistical analyses were performed using IBM SPSS Statistics 29.0 (SPSS Inc, Chicago, IL). Results Out of 444 patients with an ACS and evaluated with CCTA, vulnerable plaques were found in 57 patients (13%). The median value of CAC score in patients with vulnerable plaques was significantly higher compared with patients without vulnerable plaques (mean CAC score 1065,07 AU (95% Confidence Intervals 526,26-2656,40 AU) vs 444,03 AU (95% CI 120,18-766,88 AU, p < 0.001). Using Mann–Whitney U test, we found a statistically significant difference between CAC score of patients with vulnerable plaques and those that did not have such plaques. Conclusion Although CAC score is a reliable marker of atherosclerosis it is still uncertain whether CAC score is an indicator of plaque vulnerability. In our study, CAC score was higher in patients with vulnerable plaque compared to those without such plaques. A highly statistically significant difference was found between the median value of CAC score between these two groups of patients.Boxplot

Deep learning detection of subclinical cardiovascular dysfunction in type 2 diabetes through retinal photography

Abstract Background Type 2 diabetes (T2D) is associated with excess atherosclerotic coronary disease and heart failure risk, with several cardiac abnormalities described in asymptomatic patients. Routine digital retinal photography performed for screening of diabetic retinopathy (DR) has the potential to identify patients with underlying cardiovascular disease (CVD). We aimed to determine whether features extracted from digital retinal photographs could detect subclinical cardiovascular dysfunction in asymptomatic people with T2D. Methods We prospectively enrolled adults with T2D and no history or symptoms of CVD to undergo extensive phenotyping with multiparametric stress perfusion cardiac MRI and CT coronary artery calcium scoring. Digital retinal photographs acquired for routine diabetic eye screening and performed within one year of cardiac evaluation were interrogated for retinopathy grading and using four deep learning (DL) models (Xception, Inception, EfficientNet, and MobileNet) to capture complex patterns within the retinal vasculature. Each subject had four retinal photographs (two of each eye) for DL analysis. Cardiac image analysis was performed blinded to participant details and independent of retinal images. Subjects with and without DR were compared. Participants were divided into training (80%) and validation datasets (20%) prior to DL analysis. DL models employed to predict from retinal images: presence or absence of coronary artery calcium on non-contrast CT, myocardial perfusion reserve <2.5, left ventricular (LV) global longitudinal strain <16%, absolute stress and rest myocardial blood flood (mL/g/min) used as continuous variables. AUC was used to assess the ability of DL models to discriminate between those without and without subclinical CVD. Results An initial 254 subjects (comprising 1,016 retinal photographs) were included in the analysis: 212 (83%) with no DR, 42 (17%) with grade 1 (mild background) DR. Key cardiac imaging parameters in subjects with and without DR are displayed in Table 1. The groups were well matched for age, sex, body mass index and blood pressure. Overall, those with grade 1 DR had higher atheroma burden, evidence of increased LV filling pressures (E/e’) and poorer systolic function, but no differences in stress and rest myocardial blood flow or myocardial perfusion reserve. However, all four DL models failed to achieve sufficient discrimination of any of the evaluated cardiac imaging parameters, with the majority achieving AUC scores below 50% for all cardiac parameters. Conclusion Asymptomatic adults with grade 1 DR exhibit more subclinical atherosclerosis and cardiovascular dysfunction than those without DR. However, DL transfer models could not discriminate between subjects with and without cardiovascular disease. Further work is needed to better define whether retinal screening may be used to identify those people with T2D most at risk of underlying cardiovascular disease.Subjects demographics

Detection of biventricular volume increase in overweight and obese by using a novel index of the ideal human - a single center non-contrast-enhanced cardiac CT study

Abstract The bi-ventricular volume (BVV) can be measured from non-contrast-enhanced CT images in patients referred for coronary artery calcium (CAC) scoring. Such determined BVV has been found to correlate with left ventricular mass and to predict increased risk of all-cause and CV mortality in patients with type 2 diabetes mellitus. Currently, no data are available that quantifying the effect of body size on BVV using NCE-CT. We used a new indexing parameter that consisted of two parts: height and the difference between numerical values of height and body surface area (BSA). In the "ideal human", the difference is zero. Any deviation from this value determines the share of body mass regardless of height. Aim We hypothesize that a novel indexation way allows for better discrimination of the increased bi-ventricular volume in overweight and obese patients. Method We retrospectively analyzed the CT data from 2466 patients with CAC scoring over the last 15 years. Among them 1606 women and 860 men with an average age of 64 ± 11 years (range 21-93). The fatless bi-ventricular volume was measured manually using commercial software on a dedicated workstation (Vitrea2). Values of the raw (measured, ml) BVV and BVV normalized for height, BSA, and the novel parameter i.e. [h+ (h-BSA)], were compared in patients taking into account body mass index (BMI) categories of normal weight (25% of patients), overweight (40%) and obese (35%). Results Overall, the measured BVV [ml] was significantly greater in males (414±97) than in females (297±66) (p<0.001). BVV decreased non-linearly from before 40ties to mid-60ties, and then remained nearly stable. In normal-weight males, the measured BVV (370±80ml) was greater than in normal-weight females (279±61ml) (p<0.001). In overweight males, the BVV was 411±89ml; in overweight females, the BVV reached 290±59ml (p<0.001). These differences were non-significantly different from the sample of patients with normal BMI. In obese patients, mean values significantly differed between males and females (442±106 vs 321±71 ml, p<0.001). As the absolute value of the BVV should be interpreted in the context of body habitus, normalization for height, BSA, and the novel index were used. The results of these examinations are given in the figure. Conclusions Commonly used methods of indexing the volumetric parameters of the ventricles, as well as the novel indexing approach showed similar results in patients with normal body weight. The proposed indexation allowed for discriminating the increase in BVV that is easy to overlook in overweight. The use of body surface area for volumetric normalization is misleading as it provides similar values in normal, overweight, and obese patients, and should therefore be avoided. We should consider whether ventricular size standards based on a study population under 50 years of age create reliable conditions for detecting ventricular enlargement at an older age.

Reduced inflammation assessed by pericoronary adipose tissue is associated with coronary plaque calcification

Abstract Introduction Pericoronary adipose tissue attenuation (PCAT) quantified from coronary computed tomography angiography (CCTA) is increasingly recognized as an inflammation marker in coronary artery disease (CAD). Inflamed PCAT has been linked to non-calcified plaque (NCP) and cardiovascular morbidity and mortality. Nevertheless, gaps remain in understanding how PCAT behaves during plaque stabilization. Purpose We investigated associations between coronary artery inflammation assessed by PCAT and the presence and type of coronary plaques, plaque burden, and coronary calcification. Methods An observational study involving 506 patients with suspected chronic coronary syndrome who underwent CCTA. PCAT was averaged across the proximal 40 mm segments of all three coronary vessels to represent the patient level. Plaque presence and types (calcified, mixed, and soft) were assessed. Total, NCP, and calcified plaque (CP) burdens were measured as normalized atheroma volumes. Coronary calcification was quantified using Agatson coronary artery calcification (CAC) score and categorized based on cut-offs of 0, 100, 400. Results The mean PCAT was -81.1 ±6.3 Hounsfield Unit (HU) without plaque and -79.7 ±6.0 HU with plaque (p= 0.01). PCAT differed between calcified (-81.8 HU), mixed (-79.8 HU), and soft (-77.0 HU) plaques (p<0.0001). Multivariate linear analysis (adjusted for clinical risk factors, cardiovascular medication, and tube voltage) showed PCAT positively associated with total plaque burden (estimate= 1.1 [95% CI: 0.3-1.8], p=0.004) and NCP burden (estimate= 2.4 [95% CI: 1.4-3.4]; p<0.0001), while the association with CP burden was negative, but not statistically significant (estimate= -1.7 [95%CI : -4.1-0.7], p=0.2). Multivariate linear analysis, which accounted for both calcified and non-calcified plaque, reaffirmed the positive association to NCP burden (estimate= 2.7 [95% CI: 1.7-3.7]; p<0.0001) and a significant negative association between CP burden (estimate= - 3.3 [95% CI: -5.8- -1.0]; p=0.007) and PCAT. No significant differences in PCAT levels were found among patients with a CAC score of 0 and those with CAC scores exceeding 400, or across different stages of CAC score categories (p>0.8). Conclusion PCAT increased with plaque presence, rising from calcified to mixed to soft plaques. Increased NCP burden associated with higher PCAT, while higher CP burden seemed to reduce PCAT, though not statistical significant. Interestingly, when NCP was absent, higher levels of CP burden were associated with reduced inflammation. This supports the hypothesis of plaque stabilization, proposing that calcification might stabilize the vessel and indirectly contribute to reducing inflammation.Figure 1 PCAT by plaque typesTable 1 PCAT & plaque burden

Left atrial volume in obesity and hypertension: an innovative "ideal human" index allows for weighing their impact - a non-contrast cardiac CT study

Abstract Left atrial (LA) enlargement is a common and early feature of cardiac involvement in the natural history of obesity and arterial hypertension (AH). Mechanisms involved in this process are cumulative, and partly shared, thus separating and balancing their contributions is challenging. In a proportion of patients referred for coronary artery calcium (CAC) scoring, these clinical entities are present. The LA volume (LAV) is relatively easy to quantify from a CT scan. Measured LAV values can be misleading unless constitutional parameters (height (h) or body size area (BSA), are considered. We introduced a new indexing parameter, consisting of height and the difference between numerical values of height and BSA. In the "ideal human", the difference is zero. Any deviation from this value determines the share of body mass regardless of height. Aim We hypothesize that a novel indexation approach allows for earlier detection of the increased LAV in normotensive and AH patients considering the body mass index. Method We retrospectively analyzed CT data from 2535 patients, 1658 w (64±10 ys), and 876 m (aged 6±11ys), with CAC scoring over the last 15 years The LAV was determined by using commercially available software. The raw and indexed (for h, BSA, and the novel parameter [h+ (h-BSA)]) LAV volumes were compared in patients with normal BMI (<25kg/msg), overweight (25-29.9), and obesity (≥30) who with normal blood pressure or with AH. Results The LAV was larger in high BMI categories than in normal BMI. In non-AH subjects, the LAV increased from an average of 71 ml (normal) to 80 ml (overweight) and 90 ml (obese). In AH, the LAV increase showed a similar trend of averages (77, 88, 94 ml, F=2.59,p<0.01). Indexing LAVs were non-concordant, as shown in Figure. Thus, one can recognize that LAV normalization for the new index has brought the differences most evident and persuasive. In normal BMI, indexation ways did not significantly affect the LAV estimation. Whilst the body weight increased, no difference could be recognized for values indexing for BSA (red). The LAV indexation for height (blue) cannot help diagnose its increase in obesity. The distinguishing strength can be seen while using the [h-(h-BSA)] denominator (green). It indicates that in any scenario, body mass gain plays a greater role in the LAV increase than AH does. Conclusions Body mass is a more important factor that is associated with LAV than AH.. Common methods of LAV indexing, especially referred to as BSA, introduce errors leading to values mimicking normality in non-healthy people and should be forbidden. The proposed indexation way can help overcome the observed discrepancies and support early recognition of the consequences of obesity and hypertension.

Significant impact of a novel whole heart motion correction algorithm on cardiac computed tomography and aortic valve calcium scores

Abstract Introduction A new whole-heart motion-correction algorithm has been available in cardiac computed tomography (CT), and it has already revealed the higher diagnostic accuracy of significant coronary artery stenosis in cases with higher heart rate at the CT scan. Recently, aortic valve calcium scores (AVCS) are often measured for the decision-making of surgical treatment of aortic valve stenosis. However, the measurement of AVCS of the aortic valve has potential risks of motion artifact of the aortic valve. Therefore, we would like to know the clinical impact of a new whole-heart motion correction algorithm for accurately measuring aortic valve AVCS without motion artifacts. Purpose The purpose of this study is to evaluate the impact of a new whole-heart motion-correction algorithm on non-contrast cardiac CT images and the AVCS in trans-catheter aortic valve regurgitation (TAVR) candidates with severe aortic valve stenosis. Materials and methods Forty-two consecutive TAVR candidates (83 ± 7 years old, 21 males) who underwent ECG-gated CT using 256-row detector CT from November 2023 to February 2024 at our hospital were analyzed. The best phase non-contrast cardiac images were automatically selected, and they were reconstructed with both the standard (STD) algorithm and the new whole-heart motion-correction algorithm. AVCS was calculated using semi-automatic commercially available software. The aortic valve's image noise was also measured. Results Non-contrast best cardiac phase images were successfully reconstructed using the new motion correction algorithm in 36 patients (86%). The best cardiac phase was mainly the diastolic phase in 29 patients (81%). The overall Agatston score and calcified volume of the aortic valve in SSF2 were 1779 ± 896, and 1403 ± 689, respectively, and they were lower than 2195 ± 1132 and 1656 ± 851 of STD (all P < 0.01). Conclusion The new whole-heart motion-correction algorithm worked in almost all TAVR candidates, and revealed lower AVCS and shows a potential for increasing AVCS accuracy.