Coronary Calcium Research Articles

#3001 MtDNA copy number correlates to coronary artery calcium score and biological age in kidney failure patients

Abstract Background and Aims Chronic kidney disease (CKD) and kidney failure are connected to increased oxidative stress and vascular calcification, which are indicators for development of comorbidities and mortality outcome. Mitochondrial (mt)DNA copy number has been reported as independent predictor for frailty and mortality outcome of various cardiovascular diseases (CVD) and cancer. We aimed that mtDNA copy number in whole blood of kidney failure patients can be correlated to coronary artery media calcification score and coronary artery calcium (CAC) score and be used as an independent predictor for comorbidities and mortality outcome. Method Quantitative PCR (qPCR) with TaqMan® probes for three mtDNA genes (mtND1, mtND4 and mtCOX1) and two single locus genes on nuclear DNA (hemoglobin subunit beta and 18S), for normalization, is performed on DNA samples isolated from collected blood of 196 kidney transplant donors and 211 recipients at basal timepoint and 32 at 1-year-follow-up timepoint, included in the KaroKidney biobank. Resulting mtDNA copy number is investigated for correlation to CAC score, patient mortality outcome, biological age determined by skin autofluorescence and other clinical parameters. Results In our Swedish kidney transplant cohort we can see statistically significant difference in mtDNA copy number between kidney failure patients (recipients) and healthy controls (donors). No obvious difference between females and males was observed. mtDNA copy number correlates to biological age determined by skin autofluorescence, CAC score and Framingham CVD risk score. In the 32 1-year-follow-up samples we could see significant increase/recovery of mtDNA copy number for male patients compared to their baseline before receiving a transplant. Conclusion In this study we show that mtDNA copy number in kidney failure patients correlates to biological age and CAC score, affirming mtDNA copy number as an independent predictor of frailty in this Swedish cohort of CKD patients. Additionally, we can see that a kidney transplant can lead to a significant increase of mtDNA copy number in blood one year later, suggesting a general increase in health quality.

Relationship Between Clinical Parameters and Histological Features of Epicardial Adipose Tissue and Aortic Valve Calcification Assessed on Computed Tomography.

The relationships of the clinical and biological attributes of epicardial adipose tissue (EAT) with aortic valve calcification (AVC) have not been characterized. We evaluated the relationships of the clinical and histological features of EAT with AVC assessed using computed tomography (CT).Methods and Results: We enrolled 43 patients undergoing cardiac CT examination prior to elective cardiac surgery in whom AVC was identified on CT. EAT volume and density, coronary calcium score (CCS), AVC score (AVCS), and coronary atherosclerosis on CT angiography were evaluated in each patient. During cardiac surgery, 2 EAT samples were obtained for immunohistochemistry. The number of CD68- and CD11c-positive macrophages and osteocalcin-positive cells was counted in 6 random high-power fields of EAT sections. EAT density, but not EAT volume normalized to body surface area, was positively correlated with the number of macrophages and osteocalcin-positive cells in EAT. There was a positive correlation between ln(AVCS), but not ln(CCS+1), and the number of macrophages and osteocalcin-positive cells in EAT. Multivariate analysis revealed significant positive correlations for ln(AVCS) with EAT density (β=0.42; P=0.0072) and the number of CD68-positive macrophages (β=0.57; P=0.0022), CD11c-positive macrophages (β=0.62; P=0.0003), and osteocalcin-positive cells (β=0.52; P=0.0021) in EAT. Inflammation and osteogenesis in EAT, reflected by high CT density, are associated with the severity of AVC representing aortic valve degeneration.

Full-Moon Coronary Calcification as Detected With Computed Tomography Angiography in Chronic Total Occlusion Percutaneous Coronary Intervention

"Full moon" is a central calcification that occludes the entire vessel on coronary computed tomography angiography (CCTA). We examined the association of “full moon” calcification as identified by CCTA, on clinical and procedural outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We studied patients who underwent elective CTO PCI in two European centers and had pre-procedural CCTA. The primary endpoint was the inability to cross the lesion and/or the need for extensive debulking techniques. Secondary endpoints were procedural success, in-hospital cardiac mortality, the need for extensive debulking techniques, myocardial infarction (MI), major adverse cardiac events (MACE, defined as in hospital death, MI and clinically driven target vessel revascularization) and stent thrombosis. Secondary procedural endpoints included procedural time, fluoroscopy time, number of guidewires and balloons, stent length, number and diameter and contrast volume. Multivariable logistic regression analysis was performed identifying potential covariates related to the primary outcome according to knowledge and prior studies. Subsequently, a stepwise selection approach was performed to select factors with the greatest predictive value. Among 140 patients included, 28 (20%) had a “full moon” calcified CTO-plaque. Patients in the full moon group were older and had more cardiovascular risk factors. There was not significant difference in the need for retrograde approach and antegrade dissection and re-entry (ADR) techniques in the “full moon” group vs the other groups (32.1% vs 37.5%, p=0.59 and 0% vs 1.7%, p=0.47 respectively). Compared with patients who did not have full moon morphology, full moon patients had higher incidence of the primary outcome (53.5% vs 12.5%;p<0.001). On multivariable analysis that included chronic kidney failure and prior coronary artery bypass surgery, full moon calcification was associated with higher incidence of the primary endpoint; OR 6.5;95% CI 2.1-20.5;p=0.001). Moreover, lower procedural success (71.4% vs 87.5%;p=0.03), higher incidence of coronary perforations (14.2% vs 3.5%;p<0.02) and higher procedural [172.5 (118.0-237.5) vs 144.0 (108.50-174.75); p=0.02] and fluoroscopic time [62.6 (38.1-83.0) vs 42.8 (29.5-65.7); p=0.03] were observed in the “full moon” group. Overall MACE did not differ between the two groups (1 patient in the “full moon” group vs 1 patient in the no “full moon” group; 3.5% vs 0.8%, p=0.29). In conclusion, “full moon” calcification on CCTA was independently associated with procedural complexity and adverse outcomes in CTO-PCI.

CORONARY INFLAMMATION ON CHEST COMPUTED TOMOGRAPHY AND COVID–19 MORTALITY

Abstract Aims The main factors associated with coronavirus disease–19 (COVID–19) mortality are age, comorbidities, pattern of inflammatory response and SARS–CoV–2 lineage involved in infection. However, the clinical course of the disease is extremely heterogeneous, and reliable biomarkers predicting adverse prognosis are lacking. Our aim was to elucidate the prognostic role of a novel marker of coronary artery disease inflammation, peri–coronary adipose tissue attenuation (PCAT), available from high–resolution chest computed tomography (HRCT), in COVID–19 patients with severe disease requiring hospitalization. Methods and Results Two distinct groups of patients, admitted to Parma University Hospital in Italy with COVID–19 in March 2020 and March 2021 (first and third wave peaks of COVID–19 pandemic in Italy, with prevalence of wild–type and B.1.1.7 SARS–CoV–2 lineage, respectively) were retrospectively enrolled. The primary endpoint was in–hospital mortality. Demographic, clinical, laboratory, HRCT data and coronary artery HRCT features (coronary calcium score and PCAT attenuation) were collected to establish which variables were associated with mortality. Among the 769 patients enrolled, 555 (72%) were discharged alive and 214 (28%) died. In multivariable logistic regression analysis age (p&amp;lt;0.001), number of chronic illnesses (p&amp;lt;0.001), smoking habit (p=0.006), P/F ratio (p=0.001), platelet count (p=0.002), blood creatinine (p&amp;lt;0.001), non–invasive mechanical ventilation (p&amp;lt;0.001), HRCT visual score (p&amp;lt;0.001) and PCAT (p&amp;lt;0.001), but not the calcium score, were independently associated with in–hospital mortality. Conclusion Coronary inflammation, measured with PCAT on HRCT, was independently associated with higher mortality in patients with severe COVID–19, while the pre–existent coronary atherosclerotic burden was not associated with adverse outcomes after adjustment for covariates.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics

Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P < 0.001). The calcium-omics model identified 73.5% of MACE cases in the high-risk group, a 13.2% improvement as compared to Agatston, suggesting that calcium-omics could be used to better identity candidates for intensive follow-up and therapies. The categorical net-reclassification index was NRI = 0.153. Our findings from this exploratory study suggest the utility of calcium-omics in improved risk prediction. These promising results will pave the way for more extensive, multi-institutional studies of calcium-omics.

Artificial intelligence-enhanced electrocardiography analysis as a promising tool for predicting obstructive coronary artery disease in patients with stable angina.

The clinical feasibility of artificial intelligence (AI)-based electrocardiography (ECG) analysis for predicting obstructive coronary artery disease (CAD) has not been sufficiently validated in patients with stable angina, especially in large sample sizes. A deep learning framework for the quantitative ECG (QCG) analysis was trained and internally tested to derive the risk scores (0-100) for obstructive CAD (QCGObstCAD) and extensive CAD (QCGExtCAD) using 50 756 ECG images from 21 866 patients who underwent coronary artery evaluation for chest pain (invasive coronary or computed tomography angiography). External validation was performed in 4517 patients with stable angina who underwent coronary imaging to identify obstructive CAD. The QCGObstCAD and QCGExtCAD scores were significantly increased in the presence of obstructive and extensive CAD (all P < 0.001) and with increasing degrees of stenosis and disease burden, respectively (all P trend < 0.001). In the internal and external tests, QCGObstCAD exhibited a good predictive ability for obstructive CAD [area under the curve (AUC), 0.781 and 0.731, respectively] and severe obstructive CAD (AUC, 0.780 and 0.786, respectively), and QCGExtCAD exhibited a good predictive ability for extensive CAD (AUC, 0.689 and 0.784). In the external test, the QCGObstCAD and QCGExtCAD scores demonstrated independent and incremental predictive values for obstructive and extensive CAD, respectively, over that with conventional clinical risk factors. The QCG scores demonstrated significant associations with lesion characteristics, such as the fractional flow reserve, coronary calcification score, and total plaque volume. The AI-based QCG analysis for predicting obstructive CAD in patients with stable angina, including those with severe stenosis and multivessel disease, is feasible.

Sex-based differences and risk of recurrence in patients with atrial fibrillation undergoing pulmonary vein isolation

IntroductionStudies suggest increased likelihood of atrial fibrillation (AF) recurrence after catheter ablation (CA) in women than in men, indicating that sex may be an independent risk factor for recurrence. Nevertheless, the influence of sex on AF recurrence and underlying mechanisms remains unclear. MethodsRetrospective, single-centre study including patients undergoing AF CA between 2017 and 2021. Late recurrence (LR) was defined as AF recurrence ≥90 days after ablation, whereas early recurrence (ER) occurred within 90 days. Results656 patients (32% women) were included, with a median follow-up period of 26 months. Compared to men, women undergoing CA were older, had higher body mass indexes, and had higher rates of hypertension, thyroid dysfunction, and valvular disease. Women also had increased LR risk after CA (HR 1.76, 95% CI [1.19, 2.59]). A time-split multivariable analysis at one year of follow-up showed no difference in LR risk during the first 12 months after CA (HR 1.19, 95% CI [0.73, 1.94]); however, LR risk increased in women (HR 2.90, 95% CI [1.68, 5.01]) after 12 months. In a sex-stratified analysis, coronary calcium score (CCS) >100 was associated with increased LR risk in men (HR 1.81, 95% CI [1.06, 3.08]), but not in women. Cardiac adipose tissue volume was not associated with increased LR risk. ConclusionsFewer women underwent CA than men and LR was more frequent in women, particularly one year after the procedure. CCS was associated with increased LR risk in men.

Noninvasive Atherosclerotic Phenotyping: The Next Frontier into Understanding the Pathobiology of Coronary Artery Disease.

Despite recent advances, coronary artery disease remains one of the leading causes of mortality worldwide. Noninvasive imaging allows atherosclerotic phenotyping by measurement of plaque burden, morphology, activity and inflammation, which has the potential to refine patient risk stratification and guide personalized therapy. This review describes the current and emerging roles of advanced noninvasive cardiovascular imaging methods for the assessment of coronary artery disease. Cardiac computed tomography enables comprehensive, noninvasive imaging of the coronary vasculature, and is used to assess luminal stenoses, coronary calcifications, and distinct adverse plaque characteristics, helping to identify patients prone to future events. Novel software tools, implementing artificial intelligence solutions, can automatically quantify and characterize atherosclerotic plaque from standard computed tomography datasets. These quantitative imaging biomarkers have been shown to improve patient risk stratification beyond clinical risk scores and current clinical interpretation of cardiac computed tomography. In addition, noninvasive molecular imaging in higher risk patients can be used to assess plaque activity and plaque thrombosis. Noninvasive imaging allows unique insight into the burden, morphology and activity of atherosclerotic coronary plaques. Such phenotyping of atherosclerosis can potentially improve individual patient risk prediction, and in the near future has the potential for clinical implementation.

Angiographic Characteristics and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention: Insights From the cVAD PROTECT III Study.

Prior studies have found that patients with chronic kidney disease (CKD) have worse outcomes following percutaneous coronary intervention (PCI). There are no data about patients with advanced CKD undergoing Impella-supported high-risk PCI. We, therefore, aimed to evaluate angiographic characteristics and clinical outcomes in patients with CKD who received Impella-supported high-risk PCI as part of the catheter-based ventricular assist device PROTECT III study (A Prospective, Multi-Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump [IABP] in Patients Undergoing Non Emergent High Risk PCI). Patients enrolled in the PROTECT III study were analyzed according to their baseline estimated glomerular filtration rate (eGFR). The primary outcome was 90-day major adverse cardiovascular and cerebrovascular events (the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization). Of 1237 enrolled patients, 1052 patients with complete eGFR baseline assessment were evaluated: 586 with eGFR ≥60 mL/min per 1.73 m2, 190 with eGFR ≥45 to <60, 105 with eGFR ≥30 to <45, and 171 with eGFR <30 or on dialysis. Patients with lower eGFR (all groups with eGFR <60) were more frequently females and had a higher prevalence of hypertension, diabetes, anemia, and peripheral artery disease. The baseline Synergy Between PCI With Taxus and Cardiac Surgery score was similar between groups (28.2±12.6 for all groups). Patients with lower eGFR were more likely to have severe coronary calcifications and higher usage of atherectomy. There were no differences in individual PCI-related coronary complications between groups, but the rates of overall PCI complications were less frequent among patients with lower eGFR. Major adverse cardiovascular and cerebrovascular events at 90 days and 1-year mortality were significantly higher among patients with eGFR <30 mL/min per 1.73 m2 or on dialysis. Patients with advanced CKD undergoing Impella-assisted high-risk PCI tend to have higher baseline comorbidities, severe coronary calcification, and higher atherectomy usage, yet CKD was not associated with a higher rate of immediate PCI-related complications. However, 90-day major adverse cardiovascular and cerebrovascular events and 1-year mortality were significantly higher among patients with eGFR<30 mL/min per 1.73 m2 or on dialysis. Future studies of strategies to improve intermediate and long-term outcomes of these high-risk patients are warranted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136392.

Assessment of cardiovascular risk and coronary calcium deposits in women with hypopituitarism

Assessment of cardiovascular risk and coronary calcium deposits in women with hypopituitarism

Extension of interval between adjacent pulse delivery cycles to deal with myocardial ischemia by intravascular lithotripsy: case report

BackgroundIntravascular lithotripsy (IVL) represents a novel approach in the management of coronary calcification. This technique employs acoustic pressure waves, generated by a shockwave balloon, to effectively fracture both superficial and deep calcification in situ. The efficacy and safety of IVL have been convincingly demonstrated through the Disrupt CAD I-IV studies. While IVL is associated with the occurrence of atrial and ventricular arrhythmias, there is no evidence to indicate it causes myocardial ischemia.Case DescriptionA 71-year-old man was admitted presenting with chest pain. His previous coronary angiography revealed stenosis and calcification in the left anterior descending branch. An attempt to predilate the lesion using two Lacrosse non-slip element balloons was unsuccessful. Ventricular premature beats and transient ST-segment depression were captured during the utilization of IVL. The operator gradually extended the pulse emission interval across two consecutive cycles to mitigate myocardial ischemia. Notably, when the interval reached 30s, the patient had no chest pain or ST-segment changes. Subsequent images of intravascular ultrasound confirmed calcification ruptures. Therapeutic intervention included the placement of a stent and the application of a drug-coated balloon in the left anterior descending branch. A telephonic follow-up six months later indicated the patient had no discomfort.ConclusionsThis case underscores the effectiveness of gradually extending the pulse emission interval as a strategic complement to the clinical application of IVL. In certain clinical scenarios, it may become imperative to suspend the pulse delivery to improve myocardial blood supply.

Coronary calcifications as assessed on routine non-gated chest CT; a gatekeeper to tailor downstream additional imaging in patients with stable chest pain

Background and aimsCurrently applied methods for risk-assessment in coronary artery disease (CAD) often overestimate patients’ risk for obstructive CAD. To enhance risk estimation, assessment of coronary artery calcium (CAC) can be applied. In 10 % of patients presenting with stable chest pain a previous non-gated computed tomography (CT) has been performed, suitable for CAC-assessment. This study is the first to investigate the clinical utility of CAC-assessment on non-gated CT for risk-assessment of obstructive CAD in symptomatic patients. MethodsFor this analysis, all patients referred for coronary computed tomography angiography (CCTA), in whom a previous non-gated chest CT was performed were included. The extent of CAC was assessed on chest CT and ordinally scored. CAD was assessed on CCTA and obstructive CAD defined as stenosis of ≥70 %. Patients were stratified according to CAC-severity and percentages of patients with obstructive CAD were compared between the CAC groups. ResultsIn total, 170 patients of 32–88 years were included and 35 % were male. The percentage of obstructive CAD between the CAC groups differed significantly (p < 0.01). A calcium score of 0 ruled out obstructive CAD irrespective of sex, pre-test probability, type of complaints and number of risk factors with a 100 % certainty. Furthermore, a mild CAC score ruled out obstructive CAD in patients with low – intermediate PTP or non-anginal complaints with 100 % certainty. ConclusionWhen available, CAC on non-gated chest CT can accurately rule out obstructive CAD and can therefore function as a radiation-free and cost-free gatekeeper for additional imaging in patients presenting with stable chest pain.

Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study

IntroductionThe use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational...

Impact of coronary calcium morphology on intravascular lithotripsy.

Coronary calcification negatively impacts optimal stenting. Intravascular lithotripsy (IVL) is a new calcium modification technique. We aimed to assess the impact of different calcium morphologies on IVL efficacy. This was a prospective, multicentre study (13 tertiary referral centres). Optical coherence tomography (OCT) was performed before and after IVL, and after stenting. OCT-defined calcium morphologies were concentric (mean calcium arc >180°) and eccentric (mean calcium arc ≤180°). The primary outcomes were angiographic success (residual stenosis <20%) and the presence of fracture by OCT in concentric versus eccentric lesions. Ninety patients were included with a total of 95 lesions: 47 concentric and 48 eccentric. The median number of pulses was 60 (p=1.00). Following IVL, the presence of fracture was not statistically different between groups (79.0% vs 66.0% for concentric vs eccentric; p=0.165). The number of fractures/lesion (4.2±4.4 vs 2.3±2.8; p=0.018) and ≥3 fractures/lesion (57.1% vs 34.0%; p=0.029) were more common in concentric lesions. Angiographic success was numerically but not statistically higher in the concentric group (87.0% vs 76.6%; p=0.196). By OCT, no differences were noted in final minimum lumen area (5.9±2.2 mm2 vs 6.2±2.1 mm2; p=0.570), minimum stent area (5.9±2.2 mm² vs 6.25±2.4 mm2; p=0.483), minimum stent expansion (80.9±16.7% vs 78.2±19.8%), or stent expansion at the maximum calcium site (100.6±24.2% vs 95.8±27.3%) (p>0.05 for all comparisons of concentric vs eccentric, respectively). Calcified nodules were found in 29.5% of lesions; these were predominantly non-eruptive (57%). At the nodule site, dissection was more common than fracture with stent expansion of 103.6±27.2%. In this prospective, multicentre study, the effectiveness of IVL followed by stenting was not significantly affected by coronary calcium morphology.

ALCOHOL DRINKING MAY MODIFY THE ASSOCIATION BETWEEN HDL-CHOLESTEROL AND CORONARY CALCIUM SCORE IN AN OLDER POPULATION

Objective: The associations between lipids and Coronary Calcium Score (CAC score) remain controversial. We aimed to investigate if high-density lipoprotein cholesterol (HDL-C) is correlated with Coronary Calcium Score among older adults. Design and method: A total of 819 older aged more than 55 years old (Men: 378 and Women: 441) without coronary sent from the Healthy Aging Longitudinal Study in Taiwan were evaluated the Coronary Calcium Score by Low-Dose CT Scan in 2023. The metabolic features were measured at baseline (2nd wave 2014∼2019). CAC score was calculated by the Agatston score formula by an FDA-approved automated AI program (AView, Coreline) and modified by an experienced cardiac CT technologist if necessary. Linear and logistic regression were used to investigate the association between HDL-cholesterol and CAC score. Results: The median [Q1 and Q3] of CAC score was 122.6 [23.2 and 392.7]. The proportion of all older adults was 20.15% (n=165) for CAC Score less than ten, 55.31% (n=453) for CAC score between 11 and 400, and 24.5% for CAC score more than 400. HDL-Cholesterol (age-sex adjusted R [adj-R]=-0.208, p&lt;.0001) and triglycerides (adj-R=0.122, p&lt;.0001) were significantly associated with log-CAC, but LDL-cholesterol (adj-R=-0.005, p=0.8915) and total cholesterol(adj-R=-0.054, p=0.1237) did not. All blood pressure measures, body mass index, and waist circumference were significantly positively associated with log-CAC. Older age, male gender, elevated systolic blood pressure, higher HBA1C, and lower HDL-C were independently associated with CAC. Furthermore, HDL-C was significantly associated with log-CAC Score in those with alcohol drinking habits (standardized beta [STB] = -0.207, p=0.003), but not in those without alcohol drinking habits (STB=-0.05, p=0.2717) (p-value for interaction=0.016). The odds ratios of low HDL-cholesterol (&lt;40 for men and &lt;50 mg/dL for women) at baseline for higher CAC (&lt;10, 11∼400, 400+) were 1.91 (95% confidence intervals: 1.10∼3.31) and 1.26 (0.85∼1.85) for those with and without alcohol drinking habits, respectively. Conclusions: Lower HDL-cholesterol was associated with higher future CAC scores among older adults in this retrospective design. Furthermore, this association could be altered by alcohol consumption.

Abstract 3118: An Unusual Case Of Severe Multivessel Atherosclerotic Coronary Artery Disease In A Very Young Patient

Introduction: Premature coronary artery disease (CAD) is defined as CAD prior to the age of 55 for men and 65 for women, while CAD in young is defined as age &lt;45 years. In the last decade, incidence of global premature CAD has increased by 25 %. Case presentation: A 20-year-old female with medical history of dyslipidemia, hypertension, type 1 diabetes mellitus and family history of premature coronary artery disease presented to the emergency room with chief complaint of chest pain and shortness of breath. EKG revealed sinus tachycardia and poor R-wave progression on anterior precordial leads. Serum troponin trend was unremarkable. Echocardiogram revealed severely reduced left ventricular (LV) ejection fraction of 20-25% with global LV hypokinesis, trace mitral and tricuspid regurgitation. Given new onset cardiomyopathy and family history of premature CAD, CT heart with coronary calcium scoring was performed which was concerning for severe LAD disease. Surprisingly, coronary angiogram revealed severe atherosclerotic disease in LAD, left circumflex and right coronary artery territories. Patient was started on guideline directed medical therapy for cardiomyopathy and has been referred to tertiary center for surgical revascularization. Discussion: To our best knowledge only one case has been reported before in the literature when a 21-year-old male patient had multivessel CAD requiring surgical revascularization. However, we report a case, which will be the youngest ever to have severe multivessel CAD needing surgical revascularization in the future. Cole et al, in a study of 800 young patients with CAD at long term follow up of 15 years, showed an overall mortality rate of 30 %, with 83% mortality rate in patients with EF&lt; 30%, thus carrying a poor long-term prognosis.(2) Hence, an early initiation of treatment, including both medical therapy and revascularization should strongly be considered in these young patient population. Conclusion: With the increasing prevalence of premature CAD and associated risk factors, age alone should not be taken as a reliable indicator for risk stratifying patients. Emphasizing awareness among young adults with high risk of CAD that primary prevention and early lifestyle modification are of paramount importance.

Valuable Predictors for Non-measurability of Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography.

Background The fractional flow reserve (FFR) derived from coronary computed tomography (CT) angiography (FFRCT) is a variable tool for coronary disease diagnosis that non-invasively provides the value of FFR. It can add physiological information tocoronary CT angiography (CCTA) and reduce unnecessary invasive coronary angiography (CAG). However, it cannot be analyzed in some cases, which is also called "non-measurability." While FFRCT has become globally widespread, the current data on non-measurability are lacking. This study aimed to determine the rate of non-measurability and identify predictors thereof in routine clinical settings to explore potential approaches to reduce the non-measurability rate. Methods and results This retrospective observational single-center studyincluded consecutive patients who underwent FFRCTanalysis in Japan. The mean age of the overall population was 71.3 ± 10.6, and an FFRCTof ≤0.8 was seen in 47.6% of patients with a measurable FFRCT. Of the 307 enrolled patients, FFRCT analysis was not feasible in 21 cases (6.8%). Heart rate (HR) at a CT scan and coronary calcium scores (CCS) were significantly higher in patients with non-measurability than those in patients whose FFRCT was appropriately analyzed (HR: 69.6±8.9 bpm vs. 61.0±11.1 bpm; p < 0.01; CCS; 931.2 (290.8, 1451.3) vs. 322.9 (100.7, 850.0); p < 0.01). Multiplelogisticregression showed that HR was an independent predictor for non-measurability (odds ratio: 1.05; 95% confidential interval: 1.02, 1.09; p < 0.01)). Based on the receiver operating characteristic curve analysis, the optimal cut-off value of HR and CCS was 63 bpm (specificity: 67.1%; sensitivity: 76.2%) and 729.2 (specificity: 71.3%; sensitivity: 66.7%). In addition, the combination of two features (HR > 63 bpm and CCS > 729.2) showed a high negative predictive value (99.3%) for FFRCT non-measurability. Conclusions In this study, the rate of FFRCTnon-measurability was 6.8%. Higher HR at a CT scan and CCS were significantly associated with non-measurability, and in cases with both HR and CCS below a specified threshold, the likelihood of ruling out non-measurability could be significantly high. Our findings suggest that reducing the HR to ideally under 63 bpm at the time of the CT scan significantly ensures feasibility. Further study on large-scale cohorts is warranted.

Coronary Calcium Is Elevated in Patients with Myocardial Infarction without Standard Modifiable Risk Factors.

Objectives: Recent reports have highlighted myocardial infarction (MI) patients without standard modifiable risk factors (SMRF), noting them to be surprisingly common and to have a substantial risk of adverse outcomes. The objective of this study was to address the challenge of identifying at-risk patients without SMRF and providing preventive therapy. Methods: Patients presenting between 2001 and 2021 to Intermountain Health catheterization laboratories with a diagnosis of MI were included if they also had a coronary artery calcium (CAC) scan by computed tomography within 2 years. SMRF were defined as a clinical diagnosis or treatment of hypertension, hyperlipidemia, diabetes, or smoking. The co-primary endpoints in SMRF-less patients were: (1) proportion of patients with an elevated (>50%ile) CAC score, and (2) an indication for statin therapy (i.e., CAC ≥ 100 AU or ≥75%ile). The 60-day and long-term major adverse cardiovascular events were determined. A comparison set included MI patients with SMRF. Results: We identified 429 MI patients with a concurrent CAC scan, of which 60 had no SMRF. SMRF status did not distinguish most risk factors or interventions. No-SMRF patients had a high CAC prevalence and percentile (82% ≥ 50%ile; median, 80%ile), and 77% met criteria for preventive therapy. As expected, patients with SMRF had high CAC scores and percentiles. Outcomes were more favorable for No-SMRF status and for lower CAC scores. Conclusions: Patients without SMRF presenting with an MI have a high prevalence and percentile of CAC. Wider application of CAC scans, including in those without SMRF, is promising as a method to identify an additional at-risk population for MI and to provide primary preventive therapy.

Impact of calcification on Murray law-based quantitative flow ratio for physiological assessment of intermediate coronary stenoses.

To investigate the influence of coronary calcification on the diagnostic performance of Murray law-based quantitative flow ratio (μQFR) in identifying hemodynamically significant coronary lesions referenced to fractional flow reserve (FFR). A total of 571 intermediate lesions from 534 consecutive patients (66.1 ± 10.0 years, 67.2% males) who underwent coronary angiography and simultaneous FFR measurement were included. Calcific deposits were graded by angiography as none or mild (spots), moderate (involving ≤ 50% of the reference vessel diameter), and severe (> 50%). Performance of μQFR to detect functional ischemia (FFR ≤ 0.80) was evaluated, including diagnostic parameters and areas under the receiver-operating curves (AUCs). The discrimination of ischemia by μQFR was comparable between none/mild and moderate/severe calcification (AUC: 0.91 [95% confidence interval: 0.88-0.93] vs. 0.87 [95% confidence interval: 0.78-0.94]; p = 0.442). No statistically significant difference was observed for μQFR between the two categories in sensitivity (0.70 vs. 0.69, p = 0.861) and specificity (0.94 vs. 0.90, p = 0.192). Moreover, μQFR showed significantly higher AUCs than quantitative coronary angiographic diameter stenosis in both vessels with none/mild (0.91 vs. 0.78, p < 0.001) and moderate/severe calcification (0.87 vs. 0.69, p < 0.001). By multivariable analysis, there was no association between calcification and μQFR-FFR discordance (adjusted odds ratio: 1.529, 95% confidence interval: 0.788-2.968, p = 0.210) after adjustment for other confounding factors. μQFR demonstrated robust and superior diagnostic performance for lesion-specific ischemia compared with angiography alone regardless of coronary calcification.

Ultra-high-resolution CT vs. invasive angiography for detecting hemodynamically significant coronary artery disease: Rationale and methods of the CORE-PRECISION multicenter study

BackgroundDirect coronary arterial evaluation via computed tomography (CT) angiography is the most accurate noninvasive test for the diagnosis of coronary artery disease (CAD). However, diagnostic accuracy is limited in the setting of severe coronary calcification or stents. Ultra-high-resolution CT (UHR-CT) may overcome this limitation, but no rigorous study has tested this hypothesis. MethodsThe CORE-PRECISION is an international, multicenter, prospective diagnostic accuracy study testing the non-inferiority of UHR-CT compared to invasive coronary angiography (ICA) for identifying patients with hemodynamically significant CAD. The study will enroll 150 patients with history of CAD, defined as prior documentation of lumen obstruction, stenting, or a calcium score ≥400, who will undergo UHR-CT before clinically prompted ICA. Assessment of hemodynamically significant CAD by UHR-CT and ICA will follow clinical standards. The reference standard will be the quantitative flow ratio (QFR) with <0.8 defined as abnormal. All data will be analyzed in independent core laboratories. ResultsThe primary outcome will be the comparative diagnostic accuracy of UHR-CT vs. ICA for detecting hemodynamically significant CAD on a patient level. Secondary analyses will focus on vessel level diagnostic accuracy, quantitative stenosis analysis, automated contour detection, in-depth plaque analysis, and others. ConclusionCORE-PRECISION aims to investigate if UHR-CT is non-inferior to ICA for detecting hemodynamically significant CAD in high-risk patients, including those with severe coronary calcification or stents. We anticipate this study to provide valuable insights into the utility of UHR-CT in this challenging population and for its potential to establish a new standard for CAD assessment.