Calcium Score Research Articles

Improved quantification of coronary stenosis in patients with high calcium scores using spectral reconstructions in coronary CT angiography

Abstract Background Coronary CT angiography has demonstrated reduced accuracy in patients with high calcium scores due to blooming artifacts, often resulting in overestimated stenosis. Purpose This study aimed to assess the impact of spectral reconstructions on coronary stenosis quantification in patients with high calcium scores (>500), utilizing invasive coronary angiography as the gold standard. Methods Twenty consecutive patients referred for coronary artery disease assessment underwent both coronary CT angiography and invasivecoronary angiography. Conventional 120 kV images, 100 keV virtual monoenergetic images, and iodine-no-water images were reconstructed. Two blinded operators independently reviewed the images. Lesions were qualitatively classified in both CCTA and invasive angiography as stenosis of 1-24%, 25-49%, 50-70%, and >70%. Results A total of 87 plaques were evaluated. Mean age was 72 years (SD=7.7) and 79% were male. Pre-test probability were low, medium and high in 15.8, 26.3% and 57.9% of patients respectively. Mean calcium score was 1662, with an average dose of 7.5 mSv (67.9% retrospective studies). Nitrates were administered in 89.5% of patients, and 47.4% received intravenous beta-blockers. Sensitivity, specificity, positive predictive value, and negative predictive value to detect lesions > 50% improved from 94%, 57%, 38%, 97% with conventional images to 94%, 82%, 59%, 98% with 100 keV virtual monoenergetic images. Conclusion Spectral reconstructions significantly enhance diagnostic accuracy in coronary CT angiography of severely calcified coronary arteries.

Comparison between coronary calcium score and segment involvement score when used in clinical routine

Abstract Data from a nationwide registry on coronary computer tomography angiography. Background The Coronary Artery Calcium Score (CACS) and segment involvement score (SIS) are crucial factors in assessing the severity of coronary artery disease (CAD) and determining the likelihood of future cardiovascular events. However, there are few large multicenter studies comparing the predictive value of CACS and SIS when used in the clinical routine. Objectives To compare CACS and SIS ability to predict cardiovascular outcomes when used in the clinical routine. Methods This retrospective cohort study included patients who underwent Coronary Computed Tomography Angiography (CCTA) for CAD evaluation between 2006-2022 in 29 different centers in Sweden. CACS was calculated using the Agatston method, and SIS was determined based on the number of coronary segments exhibiting plaque. For SIS, patients were categorized into SIS=0, SIS=1, SIS=2, SIS=3, SIS³4, for CACS patients were categorized into CACS=0, CACS=1-9, CACS=10-99, CACS=100-299, CACS³300. Patients were followed regarding the primary outcome of death or myocardial infarction. Multivariable Cox proportional hazards models were used for adjusting for potential confounders. Results A total of 23034 patients underwent CCTA and were followed for up to ten years. Median age (IQR) was 58 (49–67) years, 50% were women, 9% had diabetes mellitus, 42% had hypertension, 25% had hyperlipidemia, 5% had previously known CAD. There were 955 patients (4.1%) with myocardial infarction (MI) and 409 patients (2.2%) died during follow up. There was an increase in cardiovascular events with increasing SIS. When comparing SIS and presence of obstructive stenosis, SIS was a better predictor of outcome (Figure 1). There was also an increase cardiovascular events with increasing CACS (Figure 2). When adjusted for age, sex, risk factors, previous cardiovascular disease and intervention, both SIS and CACS were independently associated with outcome. When SIS and CACS were compared in a receiver operating characteristic curve, CACS had significantly larger AUC than SIS, (0.70[0.67-0.73] vs 0.62[0.60-0.63]). Conclusion Our findings show that both CACS and SIS are important and independent predictors of cardiovascular outcomes thereby offering a valuable tool for personalized risk stratification and management in clinical settings. When used in the clinical routine, CACS appears to be more strongly associated with outcome than SIS.Figure1 Survival SISFigure 2 Survival CACS

Prevalence and outcomes of patients with discordant high gradient aortic stenosis

Abstract Background Conflicting prognostic results have been reported in patients with discordant high gradient aortic stenosis (DHG-AS, the combination of a mean pressure gradient ≥40 mmHg and an aortic valve area (AVA) >1cm² ). Moreover, existing studies only included selected patients without concomitant aortic regurgitation. Purpose We assessed the prevalence and survival of patients presenting with DHG-AS in an unselected group of consecutive patients presenting to the echocardiography laboratory of a tertiary referral center. Methods 3,547 adult patients with AVA ≤1.5cm² and peak aortic jet velocity ≥2.5m/s or mean gradient ≥25mmHg who presented between 2005 and 2015 were included. Baseline clinical and echocardiographic data, and, when available, aortic valve calcium score (AVC) were collected in an institutional database, with subsequent retrospective analysis. The primary endpoint was all cause mortality during follow-up. Results DHG-AS was observed in 163 patients (11.6% of all patients with a gradient ≥ 40mmHg). After adjustment for potential confounders, overall mortality rate of patients with DHG-AS was similar to that of concordant severe AS (AVA ≤1cm², mean gradient ≥40mmHg; CSev-AS) patients (N=1,243; HR: 0.98[0.68;-1.44]; p=0.91), and discordant low gradient-AS (AVA ≤1cm²; gradient <40 mmHg; HGDLG-AS) patients (N=1,131, HR: 0.85[0.58-1.26]; p=0.42), and was worse than that of concordant moderate AS (AVA >1.0cm², gradient <40mmHg; CMod-AS) patients (N=1,010; HR: 0.54[0.36-0.81]; p=0.003, Fig 1). After adjustment for aortic velocities, aortic regurgitation had no significant impact on survival. Calcium scoring was performed in 716 patients, including 40 patients with DHG-AS. AVC in DHG-AS was higher than in patients with CMod-AS and DLG-AS, and not significantly different from that of CSev-AS. The AVC ratio (AVC divided by the sex-specific thresholds) was higher in patients with DHG-AS as compared to both CMod-AS and DLG-AS patients (Fig 2). Conclusions DHG-AS is not uncommon. Although an AVA ≥1.0 cm² is often seen as reassuring and mistaken as moderate AS, a high-pressure gradient conveys a poor prognosis, whatever the AVA and independently of the presence of concomitant aortic regurgitation.

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.

Which is better for predicting and discriminating cardiovascular events: a traditional risk score, a calcium score or a genetic risk score?

Abstract Background The most effective approach to prevent coronary artery disease (CAD) in the general population remains to quantify the individual risk of CAD followed by controlling risk factors. There has been a lot of curiosity to investigate several scores individually for improving risk prediction. However, whether one would be better than the other in the same population is still unclear. Aim To evaluate the performance of the three individual scores, European SCORE2, Coronary artery calcium score (CACS) and a Genetic risk score (GRS), in predicting and discriminating cardiovascular (CV) events in an asymptomatic Portuguese population. Methods Prospective, observational population-based study, including 1002 asymptomatic subjects (mean age 53.1±6.8 years, 73.8% male) selected from a normal Portuguese population, without apparent CAD and diabetes at baseline. Data were recorded at the end of an extended follow-up (average 6.5±4.9 years). The European SCORE2, a computed tomography CACS, and a GRS were created to evaluate CV events’ predictive and discriminative ability through Receiver Operating Characteristics (ROC) analysis and Harrell’s C-statistics. Results ROC curve analysis showed 0.723 for SCORE2, 0.815 for CACS and 0.649 for GRS. Harrell’s C-statistics were 0.731 in the SCORE2, 0.785 for CACS and 0.684 for GRS. Conclusion The CAC score was the best individual score to predict and discriminate CV events in our asymptomatic population. Its capacity to identify high-risk individuals and those asymptomatic with subclinical atherosclerosis may improve CV risk management strategies to prevent future cardiovascular events. This result can be explained because CAC score, more than a risk marker, represents the existence of disease in the vessel wall.

The role of coronary artery calcium score and european score2 in primary prevention of cardiovascular disease

Abstract Background There is limited evidence about the role of using coronary artery calcium (CAC) score in conjunction with the European SCORE2 (systematic coronary risk evaluation) for the identification of individuals at higher risk of cardiovascular disease. Purpose To evaluate the relationship between CAC score and the European SCORE2 for cardiovascular risk stratification in an asymptomatic population in primary prevention. Methods This is a preliminary analysis from a single-centre, prospective, randomised 1:1, controlled trial assessing the use of CAC score vs standard preventive strategies in asymptomatic individuals undergoing primary cardiovascular prevention. The 10-year risk of cardiovascular events was assessed with either SCORE2 (ages 45-69) or SCORE2-OP (ages 70-89). Subjects were classified as 1) low to moderate risk, 2) high risk, and 3) very high risk according to SCORE2/SCORE2-OP. CAC score was assessed by ECG gated low-dose computed tomography with no contrast administration. A CAC score of zero was considered to reclassify risk one level downward in high or very-high risk patients. CAC score ≥ 100 was used to reclassify risk one level upward in patients with low to moderate risk and a CAC score > 1000 to reclassify risk upward in subjects with high risk. Results A total of 1,252 participants: 627 in the CAC group and 625 in the control group, median age 55 yrs, 25th-75th 50-61 yrs, with availability of SCORE2 and SCORE2-OP were included in this analysis. SCORE2/SCORE 2-OP was similar in the CAC and control groups. Among the subjects in the CAC group, there was a highly significant difference in SCORE2/SCORE 2-OP between participants with CAC score = zero and those with CAC > zero (median 5.6, 25th-75th 3.6-8.55 vs 2.9, 1.8-4.6, p< 0.001) as well as between those with CAC ≥ 100 and those with CAC score < 100 [median 6.8, 25th-75th (10.3-4.5) vs 3.3 (2.0-5.3), p<0.001]. The prevalence of CAC score = zero was 75% in the low to moderate risk group, 47% in the high risk, and 20% in the very high risk, p<0.001. By contrast the prevalence of CAC score ≥ 100 was 7% in the low to moderate risk group, 24% in the high risk, and 45% in the very high risk, p< 0.001. The proportion of patients classified as low to moderate risk group was 72% with CAC score vs 59% without CAC score, high risk 23% with CAC score vs 35% without CAC score, very high risk 5% vs 6% respectively, p<0.001. Using CAC score risk reclassification occurred in 48% downward and 2% upward in originally classified high risk subjects, 7% upward in originally classified low to moderate risk, and 20% downward in originally classified very high risk subjects. Conclusions CAC score may lead to risk reclassification in a substantial proportion of individuals, in particular among those originally classified as high risk by the SCORE2/SCORE2-OP. The cardiovascular risk prediction accuracy of adding CAC score to SCORE2/SCORE2-OP awaits validation at long-term follow-up.

Prediction of atrial fibrillation recurrence after ablation: the impact of machine learning and recurrence during the blanking period

Abstract Introduction Pulmonary vein isolation is superior to antiarrhythmic drugs for rhythm control in patients with atrial fibrillation (AF). Nevertheless, recurrences within the first year are still significant. Several clinical risk scores were developed to predict AF recurrence; however, despite good results in development cohorts, the results in external validation are usually poor, limiting the general applicability of these scores. Purpose We aimed to develop machine learning (ML) models to predict AF recurrences within the first year after catheter ablation and compare their performance with conventional risk scores. Methods We used a retrospective dataset of a tertiary hospital center, including all consecutive patients submitted to the first AF ablation between 2017 and 2021. The dataset included 76 features: patient characteristics, medical history, baseline echocardiography, calcium score, procedure variables, and early recurrence (ER) during the 90-day blanking period. The outcome was defined as the occurrence of an electrocardiographically documented late recurrence (LR) of atrial tachycardia/AF > 30s between 3-12 months. Three different supervised ML models (penalized logistic regression, random forests, and XGBoost) were developed on the training cohort, and hyperparameters were tuned using 10-fold cross-validation. A testing dataset was held out to estimate the final performance (25%). The following risk scores were calculated: APPLE, CAAP-AF, and BASE-AF2 (the last includes ER). Areas under the curve (AUC) of receiver operating characteristic curves were compared using DeLong’s test. Results 679 patients were included: 62.7% males, median age of 59±16 years, and 78.2% with paroxysmal AF. The median time from diagnosis to ablation was 2±4 years. 74.2% underwent radiofrequency ablation and the remaining cryoablation. ER occurred in 12.5%, and most of these patients also experienced LR (68.7 vs 19.6% in those without ER, p<0.001). LR was observed in 25.6%. The XGBoost model showed the best performance with an AUC 0.774, 95% confidence interval (CI) 0.688–0.844) outperforming existing scores (picture 1): APPLE score AUC 0.607, 95% CI 0.562–0.653, p-value<0.001; CAAP-AF score AUC 0.622, 95% CI 0.576–0.668, p-value=0.002; BASE-AF2 AUC 0.628, 95% CI 0.581–0.675, p-value= 0.003. Variable importance analysis showed a significant drop in the performance of the models when ER was not considered, indicating its high importance in predicting LR (picture 2). Conclusions Recurrence during the blanking period was the most important predictor of LR in our population. The ML model was superior to conventional risk scores. ML models might be an essential tool to improve the prediction of outcomes and clinical decision-making for optimal follow-up.ROC curvesFeature Importance

Cusp-overlap technique to reduce permanent pacemaker implantation rate after transcatheter aortic valve implantation

Abstract Background Persistent conduction disturbances requiring permanent pacemaker (PPM) implantation are one of the most common complications after Transcatheter Aortic Valve Implantation (TAVI). Cusp-Overlap Technique (COT) is a novel approach for self-expandable valve implantation to minimize the rate of procedural complications, mainly PPM implantation. Purpose To determine if the COT during TAVI with self-expandable valves leads to a reduction of PPM implantation rate in the real-world setting. Methods A retrospective analysis of consecutive patients undergoing TAVI between January 2020 and November 2023 in one high-volume tertiary care center in Portugal was conducted. Two groups were defined, the COT group and the control group based on the fluoroscopic approach. A baseline comparison between the 2 groups was made using independent-samples t-test and chi-square analysis to determine if there was a difference between the prevalence of known risk factors for PPM implantation after TAVI. Afterwards, chi-square analysis was used to determine if COT led to a reduction in the PPM implantation rate. Results Of the 539 completed procedures in this timeframe, 289 were excluded due to previous pacemaker implantation, use of a valve not amenable to COT or valve-in-valve implantation. COT was used in 57.6% of eligible cases. Baseline comparison did not show a significant difference in the prevalence of several known risk factors for PPM implantation, including complete right bundle branch block, atrio-ventricular block, calcium score, aortic ring dimensions and pre/post-dilation. PPM implantation after TAVI was required in 31.6% of cases. In the COT group the PPM implantation rate was 22.9% and in the control group 43.4%. Chi-square analysis showed a very statistically significant difference between the 2 analyzed groups (p-value = 0.001). Conclusion PPM implantation remains a frequent complication of TAVI. However, this study showed that the utilization of COT leads to a reduction of the PPM implantation rate.

Computed tomography for prediction of stent underexpansion after percutaneous recanalization of calcified coronary chronic total occlusions

Abstract Background Coronary calcifications are the leading cause of stent underexpansion after percutaneous coronary intervention (PCI) and are commonly encountered in chronic total occlusions (CTO). Coronary computed tomography angiography (CCTA) is uniquely suited for pre-procedural assessment of coronary calcifications. Recently quantitative CCTA, providing exact volumes of each plaque component, has shown additional value in future risk assessment compared with conventional qualitative CCTA. Purpose The aim of this study was to evaluate whether CCTA predicts intravascular ultrasound (IVUS)-defined suboptimal stent expansion following percutaneous recanalization of calcified CTO lesions. Methods We retrospectively identified consecutive patients with a CCTA performed within 6-months prior to successful PCI of a calcified CTO (defined as calcification within the target lesion on CCTA). All patients had final IVUS of implanted stents (Figure 1). Patients requiring atherectomy were excluded. The primary outcome was IVUS-derived stent expansion index (SEI), defined as stent area divided by vessel area (both measured at the site of maximum calcium). SEI<0.4 indicated suboptimal stent expansion. The site of maximum calcium was a cross-section with greatest calcium arc on pre-stent IVUS within the target lesion. CCTA calcium analysis was performed by a researcher blinded to the IVUS and angiography results. Measurements included total-, vessel-, and lesion-specific calcium score (CAC), total calcium length, maximum calcium thickness and maximum CT calcium attenuation at the target lesion defined as occlusion site and adjacent severely diseased segments. Calcium quantification was performed using a semi-automated software to obtain volumes and burdens of calcified and non-calcified plaque components within the target lesion. Results The cohort included 43 patients (age 64.9±10.0 years, 88% males) with 43 CTO lesions. Mean final stent area at maximum calcium by IVUS was 8.2±2.1mm². Mean SEI was 0.47±0.1, and suboptimal SEI of <0.4 was found in 10 (23.3%) lesions. Lesions with suboptimal stent expansion (SEI<0.4) were characterized by numerically higher total-, vessel- and lesion-specific CAC, higher maximum calcium attenuation, greater calcium length and remodeling index compared with patients with optimal stent expansion (Table 1). However, only calcified plaque volume (105 [IQR 27-271] vs. 29 [4-96]mm³, P=0.02) and calcified plaque burden (16 [7-24] vs. 6 [1-10]%, P=0.03) were significantly greater in lesions with suboptimal stent expansion compared with lesions with optimal stent expansion, respectively. Calcified plaque volume ≥51 mm³ within the target lesion predicted suboptimal stent expansion with 70% sensitivity and 62.5% specificity (AUC 0.74). Conclusion CCTA-derived calcium volume identifies CTO lesions at greater risk of stent underexpansion. Such lesions require more aggressive plaque modification prior to stent implantation.

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

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.

AI-enabled cardiac chambers volumetry in non-contrast coronary artery calcium CT scans vs. contrast-enhanced coronary CT angiography scans in the same patients

Abstract Introduction We have developed an AI-enabled automated volumetry of cardiac chambers (AutoChamber) that works both on non-contrast ECG-gated cardiac CT scans used for coronary artery calcium (CAC) score, and non-contrast non-gated lung cancer screening CT scans. We have recently reported the agreement between AutoChamber measurements vs cardiac MRI measurements. Here we report AutoChamber results on non-contrast CAC scans and contrast enhanced coronary CT angiography (CTA). Methods We have obtained CT images from a previously published study in which 131 cases underwent non-contrast CAC and contrast enhanced CCTA at research institute. The cases consisted of 52.4% women with ages 55.0 ± 10.1 years. The cardiac chambers volume in 131 cases of contrast enhanced CCTA were measured using automated chamber volumetry by Philips Brilliance Volume v 4.5; Philips Healthcare. Results The correlations between Philips’ automated chamber volumetry in contrast enhanced CCTA scans versus AutoChamber automated volumetry in non-contrast CAC scans for left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV), and left ventricular wall (LVW) volume were 0.73, 0.65, 0.85, 0.93, 0.90, respectively (P for all <0.01). Conclusion AI-enabled AutoChamber volumetry based on non-contrast cardiac scans is feasible, and correlates reasonably well with contrast-enhanced cardiac CT scans. Further studies are warranted to reproduce these results and explore the add-on value of AutoChamber to CAC scans.

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.

Coronary artery calcium scans powered by artificial intelligence (AI-CAC) predicts atrial fibrillation and stroke comparably to cardiac magnetic resonance imaging: MESA

Abstract Background AI-CAC provides more actionable information than the Agatston coronary artery calcium (CAC) score. We have recently shown in the Multi-Ethnic Study of Atherosclerosis (MESA) that AI-CAC automated left atrial (LA) volumetry enabled prediction of atrial fibrillation (AF) as early as one year. In this study we evaluated the performance of AI-CAC LA volumetry versus LA measured by human experts using cardiac magnetic resonance imaging (CMRI) for predicting AF and stroke, and compared them with CHARGE-AF risk score, Agatston score, and NT-proBNP. Methods We used 15-year outcomes data from 3552 asymptomatic individuals (52.2% women, age 61.7±10.2 years) who underwent both CAC scans and CMRI in the MESA baseline examination. CMRI LA volume was previously measured by human experts. Data on BNP, CHARGE-AF risk score and the Agatston score were obtained from MESA. Discrimination was assessed using the time-dependent area under the curve (AUC). Results Over 15 years follow-up, 562 cases of AF and 140 cases of stroke accrued. The AUC for AI-CAC versus CMRI for AF and stroke were not significantly different (0.802 vs. 0.798 and 0.762 vs. 0.751 respectively, p=0.60). AI-CAC significantly improved the continuous Net Reclassification Index (NRI) for prediction of AF and stroke when added to CHARGE-AF risk score (0.28, 0.21), NT-proBNP (0.43, 0.37), and Agatston score (0.69, 0.41) respectively (p for all<0.0001). Conclusion AI-CAC automated LA volumetry and CMRI LA volume measured by human experts similarly predicted incident AF and stroke over 15 years. Further studies to investigate the clinical utility of AI-CAC for AF and stroke prediction are warranted.

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.

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

Incidental detection and quantification of coronary artery calcification in ungated thoracic computed tomography for prognostic assessment. Preliminary results from the ICARUS registry

Abstract Background Coronary artery calcium (CAC) score improves cardiovascular risk stratification in asymptomatic individuals. However, whether CAC can be quantified in ungated thoracic computed tomography (uTCT) performed for other indications, and if this CAC score associates with cardiovascular outcomes, hasn’t been confirmed yet. Purpose We aim to analyse the extension of CAC and its prognostic value in terms of major adverse cardiovascular events (MACE) in patients who underwent uTCT for other indications. Methods We analysed a preliminary sample of 115 uTCT performed in 2015 in our hospital. We studied the presence and extension of CAC and quantified the global CAC score by Agatston method using validated software. Patients were categorized according to Coronary Artery Calcium Data and Reporting System (CAC-DRS) categories. Cardiovascular risk factors, lipidic control and pharmacological therapy of the cohort were registered. We analysed the time to first 3P-MACE, defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, whichever occurred first. A p-value <0.05 was considered statistically significant. Results Mean age of the cohort was 60.8±16.1 years (53% male, 53% smokers). Mean LDL-cholesterol was 121.67±34.91 mg/dL, and 35.1% received lipid-lowering therapy. In more than half (n=59, 51.3%) of the population CAC was detected. Mean CAC score was 312.99±774.48 Agatston units, and patients were categorized in CAC-DRS category 1 (n=19, 16.5%), category 2 (n=15, 13%) and category 3 (n=25, 21.7%). Patients with CAC were older (71±10.1 vs. 50.1±14.2 years, p<0.001), had higher burden of cardiovascular risk factors and prevalence of chronic kidney disease (CKD; n=8, 13.6% vs. n=1, 1.8%, p=0.03) and higher levels of triglycerides (143.2±80.5 vs. 106.8±36.2 mg/dL, p=0.004), but not LDL-cholesterol. Eleven (9.6%) patients presented 3P-MACE during a mean follow-up of 6.55±2.82 years. CAC score independently predicted 3P-MACE (HR 1.06 [1.01-1.11] per 100 Agatston units, p=0.02) along with CKD (HR 6.94 [1.58-30.46], p=0.01) and basal glucose levels (HR 1.03 [1.02-1.04] per mg/dL, p<0.001). Conclusions CAC can be incidentally detected in more than half of our unselected cohort of patients undergoing uTCT for other indications. CAC score quantification by Agatston method is feasible in uTCT and associates with a higher risk of MACE during follow-up.Incidental CAC detection in uTCT

Lipoprotein(a) as a predictive marker of coronary artery calcification (CAC). The results from the STAR-Lp(a) cohort study.

Abstract Background Lipoprotein(a) [Lp(a)] concentration is an independent risk factor for cardiovascular disease, including atherosclerosis. Purpose The aim of the study was to assess the relationship between the elevated Lp(a) levels, and the risk of developing atherosclerosis assessed using coronary artery calcium (CAC) score. Methods The analysis was conducted among 553 primary prevention patients (65.7% women, the average age was 65.8±10.1 years) from the outpatient specialist care who underwent coronary computed tomographic angiography (CTA). This group accounted for 22.3% of all patients (n=2475) included in the registry. Lp(a) levels were assessed in three groups: <30 mg/dL (<75 nmol/l) (normal level), 30-50 mg/dL (75-125 nmol/l) (moderate cardiovascular risk) and >50 (>125 nmol/l) (high cardiovascular risk). Patients were divided into groups: with normal CAC score (CAC=0), with CAC 1-100 (presence of atherosclerotic), and those with CAC>100 (advanced atherosclerosis). Statistical analysis was performed using STATISTICA 13.1. Quantitative variables were known by providing descriptive statistics (mean and standard deviation [SD]). The chi-square test was used to assess the relationship between quantitative variables and Mann-Whitney and Kruskal Wallis in the case of qualitative variables. Pearson's correlation coefficient was used to measure correlation. To determine the effect of factors on the probability of occurrence CAC=0 a multivariate logistic regression model was built. P<0.05 was judged as significant. Results Positive significant correlation between CAC score and age was revealed (r=0.266, p<0.001). An analogous relationship was observed regarding to glucose level (r=-0.123, p=0.012). This was not observed for Lp(a). However, we showed a significant relationship between the level of Lp(a) and CAC score (r=0.113, p=0.009) (Fig. 1). Lp(a) levels increased with the CAC score increase. For every 10 mg/dL (25 nmol/l) of Lp(a), CAC score increases by 15.7±0.57 (p=0.006). The mean CAC among patients with normal Lp(a) level was 203.1 (±412.6) and respectively 206.6 (±460.1) in those with moderate cardiovascular risk and 335.6 (±784.9) for people with high risk (p=0.183). In the regression model the factors determining the absence of atherosclerosis (CAC=0; "power of zero") included female gender (OR = 4.05; 95CI: 2.48-6.59), age under 65 (OR = 0.31; 95CI: 0.07-1.34 for aged 40-65), and Lp(A)≤50 mg/dl (≤125 nmol/l) (OR=2.26; 95CI: 1.12-4.61). People with hypertension had a significantly lower odds of CAC=0 (OR=0.58; 95CI: 0.38-0.89). Conclusions The study showed a significant linear relationship between increased Lp(a) levels, and the progression of atherosclerosis expressed by the CAC score. Results confirm some existing recommendations that if an elevated Lp(a) level is found in a patient for primary prevention, a CT scan of the coronary arteries with assessment of the CAC score should be considered for more appropriate risk stratification.

Establishment and validation of a prediction model for the outcome of rheumatic mitral valve repair surgery based on transthoracic echocardiography

Abstract Background The outcome of mitral valve repair over replacement in degenerative diseases has been recognized, but the patient selection of mitral valve repair in rheumatic diseases are still controversial. At present, there is a lack of comprehensive evaluation methods for rheumatic mitral valve disease, which cannot guide the selection of patients before surgery. Purpose The aim of this study was to establish a comprehensive evaluation method and innovative indicators for rheumatic mitral valve disease using transthoracic echocardiography, and to establish a model for predicting the outcome of rheumatic mitral valve repair. Methods This prospective, multicenter, observational cohort study included 167 patients who underwent rheumatic mitral valve surgery in 4 centers from 2022 to 2023. Each enrolled patient underwent a comprehensive transthoracic echocardiography evaluation and measured 94 ultrasound indicators, mainly covering leaflets, annulus, subvalvular apparatus, and atrial and ventricular function. The main endpoint event was the failure of mitral valve repair (including switching to replacement after repair, and moderate to severe stenosis or regurgitation during follow-up after repair). Patients were randomly assigned to the modeling and validation groups at a ratio of 7:3. In the modeling group, LASSO regression was used for variable selection, and logistic regression was used for modeling. A nomogram was drawn and a webpage rating calculator was created. In the validation group, model comparisons were conducted using the C-statistic and Net Reclassification Index (NRI). Results 112 patients (67.1%) underwent mitral valve repair with satisfactory results, 47 patients (28.1%) ultimately underwent mitral valve replacement, and 8 patients (4.8%) found moderate to severe mitral stenosis or regurgitation during follow-up after repair. Three indicators, including mitral valve orifice area, leaflet calcification score, and anterior leaflet-annulus angle, were selected through LASSO regression. No collinearity was found between the three indicators, and they were ultimately included in the logistic regression model. The C statistics in the modeling group and validation group were 0.846 and 0.958, respectively, indicating that the constructed model has satisfactory predictive ability. Compared to the Wilkins score, the proportion of correctly classified items increased by 19.8%, significantly better than the Wilkins score. Finally, a nomogram was drawn based on the model, and a web rating calculator was created to guide clinical decision-making. Conclusion This study explored a comprehensive evaluation method and innovative indicators for rheumatic mitral valve disease by transthoracic echocardiography, established and validated a model for predicting the outcome of repair surgery, and had certain guiding significance for doctors to choose suitable patients for rheumatic mitral valve repair.Validation of the predictive modelNomogram

Prognosis of Zero Coronary Artery Calcium Score in Symptomatic Patients of South Asian Descent - an Experience from a Tertiary Care Center in Pakistan.

The absence of CAC in asymptomatic individuals is associated with a very low incidence of cardiovascular events. Of symptomatic patients, 1-2% with zero CAC score have non-calcified coronary artery atherosclerosis, and at least one third of cardiovascular events occur in individuals with zero CAC. South Asians (SA) have proportionally higher case fatality rates for CVD, relatively younger age of presentation, and accelerated rate of atherosclerosis when compared with other ethnic groups. All consecutive patients who underwent a CTCA to evaluate angina or angina-equivalent symptoms during the study duration were enrolled retrospectively. Patients with prior myocardial infarction, history of revascularization, and congenital heart disease were excluded. MACE was defined as the total of cardiac death, non-fatal myocardial infarction, and/or non-elective revascularization. A total of 534 patients were enrolled after final exclusion. The mean age was 53 years ± 11. Males constituted 68.4% of the study population. Dyslipidemia was the most common co-morbid condition identified (50%), followed by diabetes (18.4%) and hypertension (3.6%). At least 28.8% of patients with zero CAC scores had the presence of coronary artery disease (soft plaque) of any degree. Obstructive CAD (>50%) was present in 5.8% of patients. Follow-up was available for 61.4% of patients. On a mean follow-up of 96.6 months ± 49.8 (range 21-194 months), all-cause MACE was observed in 8.8% of patients. The most common MACE was angina (3.96%) and all-cause mortality (3%). The baseline characteristics and MACE did not differ in patients with and without obstructive CAD. The baseline characteristics did not differ significantly between patients with and without MACE. The incidence of soft plaque in this SA cohort is higher than that reported in international studies. However, in symptomatic SA, a CAC score of zero carries a good long-term prognosis, irrespective of the degree of CAD.