XCR1+ conventional dendritic cell-induced CD4+ T helper 1 cell activation exacerbates cardiac remodeling after ischemic myocardial injury.

Cardiac remodeling has no established therapies targeting inflammation. CD4+ T-cell subsets have been reported to play significant roles in healing process after ischemic myocardial injury, but their detailed mechanisms of activation remain unknown. To explore immune reactions during cardiac remodeling, we applied a non-surgical model of coronary heart disease (CHD) induced by a high-fat diet (HFD-CHD) in SR-BI-/-/ApoeR61h/h mice. Flow cytometry analyses throughout the period of progressive cardiac dysfunction revealed that CD4+ T Helper 1 (Th1) cells were predominantly activated in T-cell subsets. Probucol was reported to attenuate cardiac dysfunction after coronary artery ligation model (ligation-MI) in rats. To determine whether probucol suppress cardiac remodeling after HFD-CHD, we treated SR-BI-/-/ApoeR61h/h mice with probucol. We found treatment with probucol in HFD-CHD mice reduced cardiac dysfunction, with attenuated activation of Th1 cells. RNA-seq analyses revealed that probucol suppressed the expression of CXCR3, a Th1-related chemokine receptor, in the heart. XCR1+ cDC1 cells, which highly expresses the CXCR3 ligands CXCL9 and CXCL10, were predominantly activated after HFD-CHD. XCR1+ cDC1 lineage skewing of pre-DC progenitors was observed in bone marrow, with subsequent systemic expansion of XCR1+ cDC1 cells after HFD-CHD. Activation of CXCR3+ Th1 cell and XCR1+ cDC1 cells was also observed in ligation-MI. Notably, post-MI depletion of XCR1+ cDC1 cells suppressed CXCR3+ Th1 cell activation and prevented cardiac dysfunction. In patient autopsy samples, CXCR3+ Th1 and XCR1+ cDC1 cells infiltrated the infarcted area. In this study, we identified a critical role of XCR1+ cDC1-activated CXCR3+ Th1 cells in ischemic cardiac remodeling.

Histological validation of cardiovascular magnetic resonance T1 mapping markers of myocardial fibrosis in paediatric heart transplant recipients.

BACKGROUND: Adverse fibrotic remodeling is detrimental to myocardial health and a reliable method for monitoring the development of fibrotic remodeling may be desirable during the follow-up of patients after heart transplantation (HTx). Quantification of diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) has been increasingly applied and validated histologically in adult patients with heart disease. However, comparisons of CMR findings with histological fibrosis burden in children are lacking. This study aimed to compare native T1 times and extracellular volume fraction (ECV) derived from CMR with the degree of collagen on endomyocardial biopsy (EmBx), and to investigate the association between myocardial fibrosis and clinical as well as functional markers in children after HTx. METHODS: EmBx and CMR were performed on the same day. All specimens were stained with picrosirius red. The collagen volume fraction (CVF) was calculated as ratio of stained collagen area to total myocardial area on EmBx. Native T1 values and ECV were measured by CMR on a mid-ventricular short axis slice, using a modified look-locker inversion recovery approach. RESULTS: Twenty patients (9.9 ± 6.2 years of age; 9 girls) after HTx were prospectively enrolled, at a median of 1.3 years (0.02-12.6 years) post HTx, and compared to 24 controls (13.9 ± 2.6 years of age; 12 girls). The mean histological CVF was 10.0 ± 3.4%. Septal native T1 times and ECV were higher in HTx patients compared to controls (1008 ± 32 ms vs 979 ± 24 ms, p < 0.005 and 0.30 ± 0.03 vs 0.22 ± 0.03, p < 0.0001, respectively). CVF showed a moderate correlation with native T1 (r = 0.53, p < 0.05) as well as ECV (r = 0.46, p < 0.05). Native T1 time, but not ECV and CVF, correlated with ischemia time (r = 0.46, p < 0.05). CONCLUSIONS: CMR-derived fibrosis markers correlate with histological degree of fibrosis on EmBx in children after HTx. Further, native T1 times are associated with longer ischemia times.

Stronger positive correlation of the left ventricular mass index and extracellular volume fraction with diastolic function in diabetic patients without myocardial infarction.

BACKGROUND: The structural and functional characteristics of the heart in patients with diabetes mellitus (DM) and without myocardial infarction (MI) are not fully understood. METHODS: We retrospectively analysed the data of patients with left ventricular ejection fraction (LVEF) ≥ 40% who underwent contrast-enhanced cardiac magnetic resonance imaging (CMR), which was also used to exclude MI, at two hospitals. Volumetric data and extracellular volume fraction (ECVf) of the myocardium evaluated using CMR were compared between patients with and without DM, and their association with diastolic function was evaluated. RESULTS: Among 322 analysed patients, 53 had DM. CMR revealed that the left ventricular mass index (LVMi) and ECVf were increased while LVEF was decreased in patients with DM after adjusting for patient characteristics (all P < 0.05). A stronger positive correlation was observed between LVMi and the early diastolic transmitral flow velocity to early diastolic mitral annular velocity ratio (E/e') in patients with DM than in those without DM (correlation coefficient [R] = 0.46, p = 0.001; R = 0.15, p = 0.021, respectively; p for interaction = 0.011). ECVf correlated with E/e' only in patients with DM (R = 0.61, p = 0.004). CONCLUSIONS: Patients with DM have increased LVMi and ECVf. Importantly, there was a difference between patients with and without DM in the relationship between these structural changes and E/e', with a stronger relationship in patients with DM. Furthermore, DM is associated with mildly reduced LVEF even in the absence of MI.

Living Arrangements Predict Frequent Alcohol Consumption Among University Students: A Retrospective Cohort Study.

PURPOSE: This study aimed to confirm the clinical impact of living arrangements on incidence of frequent alcohol consumption in university students. DESIGN: A retrospective cohort study. SETTING: A national university in Japan. SUBJECTS: 17,774 university students. MEASURES: The association between living arrangements on admission and the incidence of frequent alcohol consumption (≥4 days/week) was assessed using multivariable-adjusted Cox proportional-hazards models. RESULTS: Among 5,685, 692, and 5,151 male students living with family, living in the dormitory, and living alone, 5.0%, 6.2%, and 5.8% reported frequent alcohol consumption during the median observational period of 3.0 years, respectively. Living in the dormitory and living alone were identified as significant predictors of frequent alcohol consumption (multivariable-adjusted hazard ratios: 1.00 [reference], 1.39 [1.01-1.92], and 1.21 [1.03-1.42], respectively). On the contrary, living arrangements were not associated with the incidence of frequent alcohol consumption among of 6,091 female students, partly because of low incidence of frequent alcohol consumption (2.3%, 1.4%, and 2.6%, respectively). CONCLUSIONS: Living arrangements predicted frequent alcohol consumption among male university students, whereas not among female university students.

Application of Magnetic Resonance Strain Analysis Using Feature Tracking in a Myocardial Infarction Model.

This study validates the usefulness of myocardial strain analysis with cardiac cine magnetic resonance imaging (MRI) by evaluating the changes in the cardiac function and myocardial strain values longitudinally in a myocardial disease model. Six eight-week-old male Wistar rats were used as a model of myocardial infarction (MI). Cine images were taken in the short axis, two-chamber view longitudinal axis, and four-chamber view longitudinal axis directions in rats 3 and 9 days after MI and in control rats, with preclinical 7-T MRI. The control images and the images on days 3 and 9 were evaluated by measuring the ventricular ejection fraction (EF) and the strain values in the circumferential (CS), radial (RS), and longitudinal directions (LS). The CS decreased significantly 3 days after MI, but there was no difference between the images on days 3 and 9. The two-chamber view LS was -9.7 ± 2.1% at 3 days and -13.9 ± 1.4% at 9 days after MI. The four-chamber view LS was -9.9 ± 1.5% at 3 days and -11.9 ± 1.3% at 9 days after MI. Both the two- and four-chamber LS values were significantly decreased 3 days after MI. Myocardial strain analysis is, therefore, useful for assessing the pathophysiology of MI.

Association of secondhand smoke exposure and health-related lifestyle behaviors among male university employees in Japan.

Secondhand smoke (SHS) exposure causes various health problems associated with an unhealthy lifestyle. However, the lifestyles of individuals exposed to SHS have not been characterized extensively. Therefore, this cross-sectional study aimed to investigate the association between SHS exposure and lifestyle behaviors. The participants were 2379 healthy male employees at Osaka University who underwent health examinations. Physical and biochemical parameters and lifestyle behavior data were obtained from all the participants. Participants with SHS exposure had significantly higher body mass index, waist circumference, and serum levels of triglycerides and uric acid than that of those without SHS exposure. SHS exposure was significantly correlated with several lifestyle behaviors, including TV time, frequency of breakfast consumption and fried food consumption, vegetable and fruit intake, alcohol consumption frequency and daily alcohol intake, and smoking status. Thus, SHS exposure may be associated with an unhealthy lifestyle. The lifestyle behaviors of the smoke-excluded population were assessed further; however, SHS exposure was still associated with dietary and drinking habits. Since participants with SHS exposure are likely to have an unhealthy life and combined unhealthy lifestyle behaviors, the confounding effect of these factors should be considered when assessing the impact of SHS exposure on health.

Soluble angiotensin-converting enzyme 2 association with lipid metabolism.

Increased expression of angiotensin-converting enzyme 2 (ACE2) is one of the likely explanations for disease severity in patients with coronavirus disease 2019 (COVID-19). In this study, we aimed to test whether soluble ACE2 (sACE2) levels are correlated to known risk factors of severe COVID-19 including biochemical parameters, body mass index and smoking habits. We cross-sectionally evaluated serum sACE2 levels in obese or tobacco-smoking populations and compared them to those in non-obese and non-smoking healthy participants. Additionally, fibroblast growth factor-21 (FGF21) was investigated as a candidate regulator of sACE2. A total of 220 male participants aged 30-59 years undergoing an annual health checkup were enrolled in this study: 59 obese, 80 smokers, and 81 healthy. Serum sACE2 levels were significantly higher in obese participants but not in tobacco-smoking participants when compared to healthy participants. sACE2 levels were significantly correlated with total cholesterol and triglycerides but not with body mass index. Furthermore, no regulatory relationship was found between FGF21 and sACE2. Lipid metabolism disorders accompanied by upregulation of serum sACE2 may be underlying mechanisms of COVID-19 aggravation and might be a novel breakthrough treatment target.

Pathophysiological evaluations of initial plaque development after heart transplantation via serial multimodality imaging and cytokine assessments.

BACKGROUND: Detailed morphological characteristics of de novo and donor-transmitted plaques and the association of serum T-lymphocyte cytokine levels with plaque progression of coronary allograft vasculopathy within 1 year after heart transplantation are unknown. METHODS: In this retrospective analysis of data in a prospectively maintained database, 40 heart transplant recipients were included. We performed serial 3 vessel optical coherence tomography and intravascular ultrasound analyses, at the 8 week (baseline) and 12 month post-transplantation follow-ups, and serum cytokine measurements (n = 23). The correlation between serum cytokines and Δplaque burden (between baseline and follow-up) was evaluated depending on plaque morphology. RESULTS: Thirteen de novo plaques (maximum intimal thickness ≥0.5 mm at the 12 month follow-up without plaques at baseline) were identified in 8 recipients, and 31 donor-transmitted plaques (maximum intimal thickness ≥0.5 mm at baseline) were detected in 17 recipients. Compared with donor-transmitted plaques, the Δplaque burden in the de novo plaques, with mainly fibrous morphology, was high (38.8% [29.6%-41.2%] vs 8.7% [1.33%-13.6%], p < 0.001). Stratification of the morphology of donor-transmitted plaques revealed that the Δplaque burden in fibrous plaques (10.6% [7.0%-18.0%]) was similar to that in fibroatheroma (10.3% [8.7%-23.8%]). Serum interleukin-31 levels at baseline correlated with fibrous plaque proliferation (r = 0.73, p = 0.007) even under immunosuppressive conditions, whereas other cytokines (interleukin-1ß, interleukin-17, and interferon-gamma) were mostly undetectable. CONCLUSIONS: Intimal fibrous proliferation contributed to the progression of donor-transmitted and de novo plaques. Serum interleukin-31 levels at baseline may contribute to intimal fibrous proliferation within 1 year after heart transplantation.

Skipping Breakfast and Incidence of Frequent Alcohol Drinking in University Students in Japan: A Retrospective Cohort Study.

Frequency of alcohol drinking is a potential predictor of binge drinking of alcohol, a serious social problem for university students. Although previous studies have identified skipping breakfast as a predictor of various health-compromising behaviors and cardiometabolic diseases, few studies have assessed the association between skipping breakfast and the incidence of frequent alcohol drinking. This retrospective cohort study included 17,380 male and 8799 female university students aged 18-22 years admitted to Osaka universities between 2004 and 2015. The association between breakfast frequency (eating every day, skipping occasionally, and skipping often/usually) and the incidence of frequent alcohol drinking, defined as drinking ≥4 days/week, was assessed using multivariable-adjusted Cox proportional hazards models. During the median observational period of 3.0 years, 878 (5.1%) men and 190 (2.2%) women engaged in frequent alcohol drinking. Skipping breakfast was significantly associated with the incidence of frequent alcohol drinking (adjusted hazard ratios [95% confidence interval] of eating every day, skipping occasionally, and skipping often/usually: 1.00 [reference], 1.02 [0.84-1.25], and 1.48 [1.17-1.88] in men; 1.00 [reference], 1.60 [1.03-2.49], and 3.14 [1.88-5.24] in women, respectively). University students who skipped breakfast were at a higher risk of frequent alcohol drinking than those who ate breakfast every day.

Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy.

Although patients with nonalcoholic fatty liver disease have been reported to have cardiac dysfunction, and appropriate model has not been reported. We established a novel mouse model of diet-induced steatohepatitis-related cardiomyopathy and evaluated the effect of pemafibrate. C57Bl/6 male mice were fed a (1) chow diet (C), (2) high-fat, high-cholesterol, high-sucrose, bile acid diet (NASH diet; N), or (3) N with pemafibrate 0.1 mg/kg (NP) for 8 weeks. In the liver, macrophage infiltration and fibrosis in the liver was observed in the N group compared to the C group, suggesting steatohepatitis. Free cholesterol accumulated, and cholesterol crystals were observed. In the heart, free cholesterol similarly accumulated and concentric hypertrophy was observed. Ultrahigh magnetic field magnetic resonance imaging revealed that the left ventricular (LV) ejection fraction (EF) was attenuated and LV strain was focally impaired. RNA sequencing demonstrated that the NOD-like receptor and PI3 kinase-Akt pathways were enhanced. mRNA and protein expression of inflammasome-related genes, such as Caspase-1, NLRP3, and IL-1ß, were upregulated in both the liver and heart. In the NP compared to the N group, steatohepatitis, hepatic steatosis, and cardiac dysfunction were suppressed. Sequential administration of pemafibrate after the development of steatohepatitis-related cardiomyopathy recovered hepatic fibrosis and cardiac dysfunction.

Unusual Case of Giant Nonthrombosed Right Coronary Artery Pseudoaneurysm With Coronary Artery Fistula.

Coronary artery aneurysm and pseudoaneurysm are rare and mainly result from atherosclerosis. We present a successfully treated case of a giant right coronary artery aneurysm and pseudoaneurysm with a coronary artery fistula, which might have developed after cardiac surgery for a right ventricular tumor 35 years earlier. (Level of Difficulty: Advanced.).

Serum FGF21 levels are altered by various factors including lifestyle behaviors in male subjects.

Fibroblast growth factor (FGF) 21 has various functions, including glucose and lipid metabolism. This cross-sectional study aimed to investigate specific conditions that might influence the functions of FGF21. 398 men who underwent a health examination were enrolled in this study. Physical and biochemical parameters and information on several lifestyle behaviors were obtained from all subjects. FGF21 levels correlated with age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and HbA1c. Moreover, FGF21 levels were significantly associated with lifestyle behaviors, including smoking status and breakfast and alcohol consumption frequency. Multivariable regression analysis showed that age, ALT, γ-GTP, smoking status, and breakfast and alcohol consumption frequency were independent variables for FGF21 levels. Assessment among the non-obese and obese groups showed that FGF21 levels correlated with WC, SBP, and TC only in the non-obese group. Thus, serum FGF21 levels were affected by several factors, including lifestyle behaviors, age, and liver function. To assess the functions of FGF21 in individuals, considering these factors would be essential.

Differences in routes of guiding catheters for left coronary artery according to access sites assessed by the combined angiography-computed tomography system.

Differences in guiding catheters (GCs) manipulations and selections among different access sites are currently unclear. We examined the differences in the routes of GCs for the left coronary artery (LCA) among the right radial, left radial, and femoral approaches. We used a combined angiography-computed tomography (CT) system that enabled to perform CT scans during percutaneous coronary intervention (PCI). We enrolled 88 patients who underwent CT scans during LCA PCI or percutaneous transluminal septal myocardial ablation. To evaluate the route of GCs, we analyzed the positions of the catheter's contact point on the contralateral aortic wall to the LCA ostium, which were expressed by the angle formed by the vertical line and the diagonal line from the GC shaft to the center of the aorta. The procedures were performed via the right radial in 47 cases, left radial in 20, and femoral approach in 21. The positions of the catheter's contact point were significantly different depending on the approaches (interquartile range - 3.7 [- 14.3 to 7.8], - 46.5 [- 76.9 to - 9.3], and - 30.7 [- 39.4 to - 22.4] degrees, respectively; p < 0.001). Multivariate analysis demonstrated that access sites and LCA ostium locations had significant impacts on the positions of the catheter's contact point. The routes of LCA GCs were different among the right radial, left radial, and femoral approaches.

Associations of Skipping Breakfast, Lunch, and Dinner with Weight Gain and Overweight/Obesity in University Students: A Retrospective Cohort Study.

Although multiple studies have identified skipping breakfast as a risk factor for weight gain, there is limited evidence on the clinical impact of skipping lunch and dinner on weight gain. This retrospective cohort study including 17,573 male and 8860 female university students at a national university in Japan, assessed the association of the frequency of breakfast, lunch, and dinner with the incidence of weight gain (≥10%) and overweight/obesity (body mass index ≥ 25 kg/m2), using annual participant health checkup data. Within the observation period of 3.0 ± 0.9 years, the incidence of ≥10% weight gain was observed in 1896 (10.8%) men and 1518 (17.1%) women, respectively. Skipping dinner was identified as a significant predictor of weight gain in multivariable-adjusted Poisson regression models for both men and women (skipping ≥ occasionally vs. eating every day, adjusted incidence rate ratios, 1.45 (95% confidence interval: 1.04-2.01) and 1.67 (1.33-2.09) in male and female students, respectively), whereas skipping breakfast and lunch were not. Similarly, skipping dinner, not breakfast or lunch, was associated with overweight/obesity (1.74 (1.07-2.84) and 1.68 (1.02-2.78) in men and women, respectively). In conclusion, skipping dinner predicted the incidence of weight gain and overweight/obesity in university students.

Multiple percutaneous coronary interventions worsen outcomes for subsequent surgical correction of chronic ischemic mitral regurgitation.

Objective: We investigated whether or not a history of multiple percutaneous coronary interventions (PCIs) is associated with clinical outcomes after surgery for ischemic mitral regurgitation. Methods: A total of 309 patients with chronic ischemic mitral regurgitation and left ventricular ejection fraction ≤40% who underwent restrictive mitral annuloplasty were classified as follows: patients with no or 1 previous PCI (nonmultiple PCI group [n = 211]) and patients with 2 or more previous PCIs (multiple PCIs group [n = 98]). Mean follow-up duration was 53 ± 40 months. Results: Before surgery, there were no intergroup differences in patient demographic characteristics except for lower estimated glomerular filtration rate in patients with multiple PCIs. These patients underwent concomitant coronary artery bypass grafting less frequently with a lower number of distal anastomoses (P < .05 for both). The 30-day mortality was 3.3% and 2.0% in the nonmultiple and multiple PCIs group, respectively (P = .72). During follow-up, there were 157 deaths. Patients with multiple PCIs showed lower 5-year survival rate (44% vs 64%; P = .002). After adjustments with inverse-probability-of-treatment weighting, multiple PCIs history was an independent risk factor for mortality (adjusted hazard ratio, 1.4; 95% confidential interval, 1.1-1.7; P = .002). Patients with multiple PCIs showed less improvement in left ventricular ejection fraction (interaction effect P < .001). Conclusions: In patients with ischemic mitral regurgitation, a history of previous multiple PCIs was associated with increased risk of long-term postoperative mortality, with less improvement in left ventricular ejection fraction.

Cardiac computed tomography-derived myocardial mass at risk using the Voronoi-based segmentation algorithm: A histological validation study.

BACKGROUND: Myocardial mass at risk (MMAR) is an important predictor of adverse cardiac events in patients with ischemic heart disease. This study aims to validate the accuracy of MMAR calculated from cardiac computed tomography (CCT) data using the Voronoi-based segmentation algorithm in comparison with actual MMAR measured on ex-vivo swine hearts prepared by injecting a dye into the coronary arteries. METHODS: Fifteen extracted swine hearts had India ink injected into one of the major coronary arteries. Subsequently, all coronary arteries manually injected with methylcellulose-based iohexiol-370 were imaged by 16-row CT. The ventricles were cross-sectioned perpendicularly to the long axis of the left ventricle (LV). The stained area and the total LV area of individual slices were measured, and actual MMAR was calculated as the ratio of the LV volume with the disc-summation method. CT-based MMAR of each coronary artery was calculated automatically with the Voronoi-based segmentation algorithm. The results were compared using Pearson's correlation coefficient. RESULTS: The median value of CT-based MMAR was 50.8% for the left anterior descending artery (LAD), 36.6% for the left circumflex artery (LCX), and 23.0% for the right coronary artery (RCA). Actual MMAR was 49.8% for LAD, 32.2% for LCX, and 25.9% for RCA. CT-based MMAR was significantly related to actual MMAR (r = 0.92, p = 0.02 for LAD; r = 0.96, p = 0.009 for LCX; r = 0.96, p = 0.009 for RCA). CONCLUSION: CT-based MMAR obtained by Voronoi-based segmentation algorithm reliably estimates actual MMAR measured on ex-vivo swine hearts.

Preliminary report on a cost-utility analysis of revascularization by percutaneous coronary intervention for ischemic heart disease.

Few socioeconomic studies have so far reported on revascularization for stable ischemic heart disease in Japan. This study aimed to validate the sensitivity of the health-related quality of life (HRQOL) scale for determining the pathology and medical technology to be used and to validate the application of a cost-utility analysis model. We studied 32 patients who had undergone percutaneous coronary intervention (PCI) (mean age 67.9 ± 7.3 years). For HRQOL, utility and quality of life (QOL) were examined using the EuroQol 5 Dimension (EQ-5D) and EuroQol Visual Analogue Scale (EQ-VAS), respectively. The changes in the utility index before and after PCI were compared between the PCI and coronary angiography (CAG) groups to determine the sensitivity of the EQ-5D that was used to calculate quality-adjusted life years (QALY). Additionally, to estimate the cost-utility of PCI 120 months after the procedure, we analyzed our study results and the results of previous reports using the Markov chain model. The utility index was found to improve in the PCI group (0.08 ± 0.15), whereas it decreased in the CAG group (-0.02 ± 0.11) (p = 0.049). The estimated result of the cost-utility analysis as the increase in utility above baseline level was the expected value, that is, 70,000 US$/QALY. Our findings suggest that QALY may be valid as a utility index in the clinical and economic evaluation of PCI in Japan.

Reproducibility and clinical potential of myocardial mass at risk calculated by a novel software utilizing cardiac computed tomography information.

To select the best revascularization strategy a correct understanding of the ischemic territory and the coronary anatomy is crucial. Stress myocardial perfusion single photon emission computed tomography (SPECT) is the gold standard to assess ischemia, however, SPECT has important limitations such as lack of coronary anatomical information or false negative results due to balanced ischemia in multi-vessel disease. Angiographic scores are based on anatomical characteristics of coronary arteries but they lack information on the extent of jeopardized myocardium. Cardiac computed tomography (CCT) has the ability to evaluate the coronary anatomy and myocardium in one sequence, which is theoretically the ideal method to assess the myocardial mass at risk (MMAR) for any target lesion located at any point in the coronary tree. In this study we analyzed MMAR of the three main coronary arteries and three major side branches; diagonal (Dx), obtuse marginal (OM), and posterior descending artery (PDA) in 42 patients with normal coronary arteries using an algorithm based on the Voronoi method. The distribution of MMAR among the three main coronary arteries was 44.3 ± 5.6 % for the left anterior descending artery, 28.2 ± 7.3 % for the left circumflex artery, and 26.8 ± 8.6 % for the right coronary artery. MMAR of the three major side branches was 11.3 ± 3.9 % for the Dx, 12.6 ± 5.2 % for the OM and 10.2 ± 3.4 % for the PDA. Intra- and inter-observer analysis showed excellent correlation (r = 0.97; p < 0.0001 and r = 0.95; p < 0.0001, respectively). In conclusion, CCT-based MMAR assessment is reliable and may offer important information for selection of the optimal revascularization procedure.