Association of Right Ventricular Functional Parameters With Adverse Cardiopulmonary Outcomes: A Meta-analysis.

AIMS: We aimed to confirm that three-dimensional echocardiography-derived right ventricular ejection fraction (RVEF) is better associated with adverse cardiopulmonary outcomes than the conventional echocardiographic parameters. METHODS: We performed a meta-analysis of studies reporting the impact of unit change of RVEF, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) on clinical outcomes (all-cause mortality and/or adverse cardiopulmonary outcomes). Hazard ratios (HRs) were rescaled by the within-study SDs to represent standardized changes. Within each study, we calculated the ratio of HRs related to a 1 SD reduction in RVEF versus TAPSE, or FAC, or FWLS, to quantify the association of RVEF with adverse outcomes relative to the other metrics. These ratios of HRs were pooled using random-effects models. RESULTS: Ten independent studies were identified as suitable, including data on 1,928 patients with various cardiopulmonary conditions. Overall, a 1 SD reduction in RVEF was robustly associated with adverse outcomes (HR = 2.64 [95% CI, 2.18-3.20], P < .001; heterogeneity: I2 = 65%, P = .002). In studies reporting HRs for RVEF and TAPSE, or RVEF and FAC, or RVEF and FWLS in the same cohort, head-to-head comparison revealed that RVEF showed significantly stronger association with adverse outcomes per SD reduction versus the other 3 parameters (vs TAPSE, HR = 1.54 [95% CI, 1.04-2.28], P = .031; vs FAC, HR = 1.45 [95% CI, 1.15-1.81], P = .001; vs FWLS, HR = 1.44 [95% CI, 1.07-1.95], P = .018). CONCLUSION: Reduction in three-dimensional echocardiography-derived RVEF shows stronger association with adverse clinical outcomes than conventional right ventricular functional indices; therefore, it might further refine the risk stratification of patients with cardiopulmonary diseases.

Aortic calcification: A postmortem CT validation study in a middle-aged population.

BACKGROUND: Computed tomography (CT)-detected aortic calcification is strongly associated with aortic stiffness and is an accurate predictor of cardiovascular and all-cause mortality and cognitive decline. Some previous pathologic studies have shown calcium accumulation in the medial layer of the vessel wall, while others have suggested localisation in the atherosclerotic intimal layer. OBJECTIVES: The aim of this study was to histologically validate CT findings of aortic calcification for detectability and location in the aortic wall. METHODS: We acquired postmortem CT images and collected 170 aortic tissue samples from five different locations in the thoracic and abdominal aorta of 40 individuals who underwent autopsy. Microscopic slides were stained with haematoxylin and eosin and elastic van Gieson stain. Calcified lesions were characterised and calcifications were manually annotated in the intima and media. The presence and morphology of calcifications were scored on CT images. RESULTS: The mean age of the autopsied individuals was 63 years, and 28 % died of cardiovascular disease. Calcifications were present in 74/170 (44 %) samples. Calcification was more common in the abdominal aorta than in the thoracic aorta. In all samples with calcifications, 99 % were located in the intimal layer. Only 16/170 samples had a small amount of medial arterial calcification. The histological results showed an 85 % concordance for the presence or absence of CT calcifications. There was complete inter-method agreement for annularity of calcifications in 68 % of the samples (linear weighted kappa 0.68 (95 %CI 0.60-0.77). CONCLUSIONS: Aortic calcifications visible on CT are located in the intimal layer of the abdominal aorta wall, at least in aortas that are not aneurysmatic or dissected. The presence and annularity of these calcifications can be reliably determined by CT.

Central arterial pressure and patient-specific model parameter estimation based on radial pressure measurements.

One-dimensional arterial flow simulations are suitable to estimate the aortic pressure from peripheral measurements in a patient-specific arterial network. This study introduces a reduction of the system parameters, and a novel calculation method to estimate the patient-specific set and the aortic curve based on radial applanation tonometry. Peripheral and aortic pressure curves were measured in patients, optimization were carried out. The aortic pressure curves were reproduced well, with an overestimation of the measured Systolic and Mean Blood Pressures on average by 0.6 and 0.5 mmHg respectively, and the Root Mean Square Difference of the curves was 3 mmHg on average.

Radiography and Computed Tomography Detection of Intimal and Medial Calcifications in Leg Arteries in Comparison to Histology.

Calcifications are common in the tunica intima and tunica media of leg arteries. There is growing interest in medial arterial calcifications, as they may be modifiable with treatment. We aimed to investigate radiography and computed tomography (CT) for the detection and characterization of both types of arterial calcification in leg arteries in relation to histology. In a postmortem study we therefore investigated 24 popliteal and 24 tibial arteries. The reference standard was presence of arterial calcification and the dominance of intimal or medial calcification on histology. Radiographs and CT scans were scored for presence of calcification and for dominant intimal or medial pattern based on prespecified criteria (annularity, thickness, continuity). Both radiography and CT detected 87% of histologically proven calcifications but missed mild calcifications in 13%. When only the arteries with detected calcifications were included, a moderate agreement was observed on intimal/medial location of calcifications between histology and radiography (correct in 19/24 arteries (79%); Kappa 0.58) or CT (correct in 33/46 arterial segments (72%); Kappa 0.48). With both modalities there was a slight tendency to classify intimal calcifications as being located in the media and to miss media calcification. Our study demonstrates the potential and limitations of both radiography and CT to detect and classify arterial calcifications in leg arteries.

Coronary Artery Calcification as a Marker for Coronary Artery Stenosis: Comparing Kidney Failure to the General Population.

RATIONALE & OBJECTIVE: The presence of calcified plaques in the coronary arteries is associated with cardiovascular mortality and is a hallmark of chronic kidney failure, but it is unclear whether this is associated with the same degree of coronary artery stenosis as in patients without kidney disease. We compared the relationship of coronary artery calcification (CAC) and stenosis between dialysis patients and patients without chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 127 dialysis patients and 447 patients without CKD with cardiovascular risk factors underwent cardiac computed tomography (CT), consisting of non-contrast-enhanced CT and CT angiography. CAC score and degree of coronary artery stenosis were assessed by independent readers. PREDICTOR: Dialysis treatment. OUTCOME: Association between calcification and stenosis. ANALYTICAL APPROACH: Logistic regression to determine the association between CAC score and the presence of stenosis in a matched cohort and, in the full cohort, testing for the interaction of dialysis status with this relationship. RESULTS: 112 patients were matched from each cohort, totaling 224 patients, using propensity scores for dialysis, balancing numerous cardiovascular risk factors. Median CAC score was 210 (IQR, 19-859) in dialysis patients and 58 (IQR, 0-254) in patients without CKD; 35% of dialysis patients and 36% of patients without CKD had coronary artery stenosis ≥ 50%. Per each 100-unit higher CAC score, the matched dialysis cohort had significantly lower ORs for stenosis than the non-CKD cohort, 0.67 (95% CI, 0.52-0.83) for stenosis ≥ 50% and 0.75 (95% CI, 0.62-0.90) for stenosis ≥ 70%. LIMITATIONS: No comparison with the gold standard fractional flow reserve. CONCLUSIONS: Dialysis patients have higher risk for coronary artery stenosis with higher CAC scores, but this risk is comparatively lower than in patients without CKD with similar CAC scores. In dialysis patients, a high CAC score can easily be found without significant stenosis. Our data enable "translation" of degree of calcification to the probability of coronary stenosis in dialysis patients.

Sodium-glucose cotransporter 2 inhibitors reduce myocardial infarct size in preclinical animal models of myocardial ischaemia-reperfusion injury: a meta-analysis.

AIMS/HYPOTHESIS: Large cardiovascular outcome trials demonstrated that the cardioprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors might reach beyond glucose-lowering action. In this meta-analysis, we sought to evaluate the potential infarct size-modulating effect of SGLT2 inhibitors in preclinical studies. METHODS: In this preregistered meta-analysis (PROSPERO: CRD42020189124), we included placebo-controlled, interventional studies of small and large animal models of myocardial ischaemia-reperfusion injury, testing the effect of SGLT2 inhibitor treatment on myocardial infarct size (percentage of area at risk or total area). Standardised mean differences (SMDs) were calculated and pooled using random-effects method. We evaluated heterogeneity by computing Τ2 and I2 values. Meta-regression was performed to explore prespecified subgroup differences according to experimental protocols and their contribution to heterogeneity was assessed (pseudo-R2 values). RESULTS: We identified ten eligible publications, reporting 16 independent controlled comparisons on a total of 224 animals. Treatment with SGLT2 inhibitor significantly reduced myocardial infarct size compared with placebo (SMD = -1.30 [95% CI -1.79, -0.81], p < 0.00001), referring to a 33% [95% CI 20%, 47%] difference. Heterogeneity was moderate (Τ2 = 0.58, I2 = 60%). SGLT2 inhibitors were only effective when administered to the intact organ system, but not to isolated hearts (p interaction <0.001, adjusted pseudo-R2 = 47%). While acute administration significantly reduced infarct size, chronic treatment was superior (p interaction <0.001, adjusted pseudo-R2 = 85%). The medications significantly reduced infarct size in both diabetic and non-diabetic animals, favouring the former (p interaction = 0.030, adjusted pseudo-R2 = 12%). Treatment was equally effective in rats and mice, as well as in a porcine model. Individual study quality scores were not related to effect estimates (p = 0.33). The overall effect estimate remained large even after adjusting for severe forms of publication bias. CONCLUSIONS/INTERPRETATION: The glucose-lowering SGLT2 inhibitors reduce myocardial infarct size in animal models independent of diabetes. Future in vivo studies should focus on clinical translation by exploring whether SGLT2 inhibitors limit infarct size in animals with relevant comorbidities, on top of loading doses of antiplatelet agents. Mechanistic studies should elucidate the potential relationship between the infarct size-lowering effect of SGLT2 inhibitors and the intact organ system.

Determinants of 18F-NaF uptake in femoral arteries in patients with type 2 diabetes mellitus.

BACKGROUND: The goal of this study was to investigate the potential determinants of 18F-NaF uptake in femoral arteries as a marker of arterial calcification in patients with type 2 diabetes and a history of arterial disease. METHODS AND RESULTS: The study consisted of participants of a randomized controlled trial to investigate the effect of vitamin K2 (NCT02839044). In this prespecified analysis, subjects with type 2 diabetes and known arterial disease underwent full body 18F-NaF PET/CT. Target-to-background ratio (TBR) was calculated by dividing the mean SUVmax from both superficial femoral arteries by the SUVmean in the superior vena cava (SVC) and calcium mass was measured on CT. The association between 18F-NaF TBR and cardiovascular risk factors was investigated using uni- and multivariate linear regression corrected for age and sex. In total, 68 patients (mean age: 69 ± 8 years; male: 52) underwent 18F-NaF PET/CT. Higher CT calcium mass, total cholesterol, and HbA1c were associated with higher 18F-NaF TBR after adjusting. CONCLUSION: This study shows that several modifiable cardiovascular risk factors (total cholesterol, triglycerides, HbA1c) are associated with femoral 18F-NaF tracer uptake in patients with type 2 diabetes.

The Association Between Marital Status, Coronary Computed Tomography Imaging Biomarkers, and Mortality in a Lung Cancer Screening Population.

PURPOSE: The purpose of this study was to elucidate the impact of being unmarried on coronary computed tomography (CT) imaging biomarkers and mortality in a lung cancer screening population. MATERIALS AND METHODS: In this retrospective case-control study, 5707 subjects (3777 married; mean age: 61.9±5.1 y and 1930 unmarried; mean age: 61.9±5.3 y) underwent low-dose CT as part of the National Lung Screening Trial (NLST). The median follow-up time was 6.5 (Q1-Q3: 5.6 to 6.9) years. Being unmarried was defined as never married, widowed, separated, or divorced. Being married was defined as married or living as married. Our primary endpoint was cardiovascular disease (CVD)-related death; our secondary endpoint was all-cause mortality. Coronary CT imaging biomarkers (calcium score, density, and volume) on low-dose chest CT scan were calculated using dedicated automatic software. Weighted Cox proportional-hazards regression was performed to examine the association between marital status and death. Kaplan-Meier curves were generated to visualize subject survival. RESULTS: Being unmarried was significantly associated with an increased risk for CVD-related death (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.31-1.91) and all-cause mortality (HR: 1.39; 95% CI: 1.26-1.53), which remained significant even after adjusting for traditional cardiovascular risk factors (HR CVD death: 1.75; 1.44-2.12 and HR all-cause mortality: 1.58; 95% CI: 1.43-1.74) and coronary calcium score (HR CVD death: 1.58; 95% CI: 1.31-1.91 and HR all-cause mortality: 1.40; 95% CI: 1.27-1.54). CONCLUSIONS: Being unmarried is associated with an increased CVD-related death and all-cause mortality mainly due to cardiovascular etiology. On the basis of this, marital status might be taken into consideration when assessing individuals' health status.

Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers.

OBJECTIVES: The aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening. BACKGROUND: CAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry. METHODS: We performed a nested case-control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality. RESULTS: CAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease. CONCLUSIONS: CAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.

Anatomical and Functional Computed Tomography for Diagnosing Hemodynamically Significant Coronary Artery Disease: A Meta-Analysis.

OBJECTIVES: This meta-analysis determined the diagnostic performance of coronary computed tomography (CT) angiography (CTA), CT myocardial perfusion (CTP), fractional flow reserve CT (FFRCT), the transluminal attenuation gradient (TAG), and their combined use with CTA versus FFR as a reference standard for detection of hemodynamically significant coronary artery disease (CAD). BACKGROUND: CTA provides excellent anatomic, albeit limited functional information for the evaluation of CAD. Recently, various functional CT techniques emerged to assess the hemodynamic consequences of CAD. METHODS: This meta-analysis was performed in adherence to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, EMBASE, and Web of Science were searched from inception until September 7, 2017. Bayesian random effects analysis was used to compute pooled sensitivity, specificity, and the summary receiver-operating characteristic curve of the index tests and compare them with the FFR as a reference standard. Analyses were performed on vessel and patient levels. Because CTA has excellent sensitivity, specificity was considered most relevant. Individual FFRCT values were collected. RESULTS: Overall, 54 articles and 5,330 patients were included. At vessel level, pooled specificity of CTP (0.86; 95% confidence interval [CI]: 0.76 to 0.93), FFRCT (0.78; 95% CI: 0.72 to 0.83) and TAG (0.77; 95% CI: 0.61 to 0.89) were substantially higher than that of CTA (0.61; 95% CI: 0.54 to 0.68). The addition of FFRCT, CTP, and TAG to CTA resulted in high to excellent specificities (0.80 to 0.92). The summary receiver-operating characteristic curve at vessel level yielded superior diagnostic accuracy for CTP, FFRCT, and combined CTA and CTP, compared with CTA. A subanalysis of on-site versus off-site FFRCT revealed no substantial differences between the sensitivity (0.84 vs. 0.85) and specificity (0.80 vs. 0.73) of the 2 techniques. In a second subanalysis, dynamic CTP showed higher sensitivity (0.85 vs. 0.72), but had a lower specificity (0.81 vs. 0.90) than static CTP. CONCLUSIONS: CTP and FFRCT demonstrated a substantial improvement in the identification of hemodynamically significant CAD compared with CTA; therefore, their integration to clinical workflow before revascularization is recommended.

PET Molecular Targets and Near-Infrared Fluorescence Imaging of Atherosclerosis.

PURPOSE OF REVIEW: With this review, we aim to summarize the role of positron emission tomography (PET) and near-infrared fluorescence imaging (NIRF) in the detection of atherosclerosis. RECENT FINDINGS: 18F-FDG is an established measure of increased macrophage activity. However, due to its low specificity, new radiotracers have emerged for more specific detection of vascular inflammation and other high-risk plaque features such as microcalcification and neovascularization. Novel NIRF probes are engineered to sense endothelial damage as an early sign of plaque erosion as well as oxidized low-density lipoprotein (oxLDL) as a prime target for atherosclerosis. Integrated NIRF/OCT (optical coherence tomography) catheters enable to detect stent-associated microthrombi. Novel radiotracers can improve specificity of PET for imaging atherosclerosis. Advanced NIRF probes show promise for future application in human. Intravascular NIRF might play a prominent role in the detection of stent-induced vascular injury.

CT myocardial perfusion imaging: ready for prime time?

The detection of functional coronary artery stenosis with coronary CT angiography (CCTA) is suboptimal. Additional CT myocardial perfusion imaging (CT-MPI) may be helpful to identify patients with myocardial ischaemia in whom coronary revascularization therapy would be beneficial. CT-MPI adds incremental diagnostic and prognostic value over obstructive disease on CCTA. It allows for the quantitation of myocardial blood flow and calculation of coronary flow reserve and shows good correlation with 15O-H2O positron emission tomography and invasive fractional flow reserve. In addition, patients prefer CCTA/CT-MPI over SPECT, MRI and invasive coronary angiography. CT-MPI is ready for clinical use for detecting myocardial ischaemia caused by obstructive disease. Nevertheless, the clinical utility of CT-MPI to identify ischaemia in patients with non-obstructive/microvascular disease still has to be established. KEY POINTS: • CT-MPI can improve the positive predictive value of CCTA for lesion-specific ischaemia. • CT-MPI adds incremental prognostic value over CCTA for major adverse cardiac events. • CT-MPI correlates with 15 O-H 2 O PET. • CT-MPI/CCTA shows high overall patient satisfaction.

Experience With an On-Site Coronary Computed Tomography-Derived Fractional Flow Reserve Algorithm for the Assessment of Intermediate Coronary Stenoses.

Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) is a new technique for the diagnosis of ischemic coronary artery stenoses. The aim of this prospective study was to evaluate the diagnostic performance of a novel on-site computed tomography-based fractional flow reserve algorithm (CT-FFR) compared with invasive FFR as the gold standard, and to determine whether its diagnostic performance is affected by interobserver variations in lumen segmentation. We enrolled 44 consecutive patients (64.6 ± 8.9 years, 34% female) with 60 coronary atherosclerotic lesions who underwent coronary CTA and invasive coronary angiography in 2 centers. An FFR value ≤0.8 was considered significant. Coronary CTA scans were evaluated by 2 expert readers, who manually adjusted the semiautomated coronary lumen segmentations for effective diameter stenosis (EDS) assessment and on-site CT-FFR simulation. The mean CT-FFR value was 0.77 ± 0.15, whereas the mean EDS was 43.6 ± 16.9%. The sensitivity, specificity, positive predictive value, and negative predictive value of CT-FFR versus EDS with a cutoff of 50% were the following: 91%, 72%, 63%, and 93% versus 52%, 87%, 69%, and 77%, respectively. The on-site CT-FFR demonstrated significantly better diagnostic performance compared with EDS (area under the curve 0.89 vs 0.74, respectively, p <0.001). The CT-FFR areas under the curve of the 2 readers did not show any significant difference (0.89 vs 0.88, p = 0.74). In conclusion, on-site CT-FFR simulation is feasible and has better diagnostic performance than anatomic stenosis assessment. Furthermore, the diagnostic performance of the on-site CT-FFR simulation algorithm does not depend on the readers' semiautomated lumen segmentation adjustments.

The effect of four-phasic versus three-phasic contrast media injection protocols on extravasation rate in coronary CT angiography: a randomized controlled trial.

OBJECTIVES: Contrast media (CM) extravasation is a well-known complication of CT angiography (CTA). Our prospective randomized control study aimed to assess whether a four-phasic CM administration protocol reduces the risk of extravasation compared to the routinely used three-phasic protocol in coronary CTA. METHODS: Patients referred to coronary CTA due to suspected coronary artery disease were included in the study. All patients received 400 mg/ml iomeprol CM injected with dual-syringe automated injector. Patients were randomized into a three-phasic injection-protocol group, with a CM bolus of 85 ml followed by 40 ml of 75%:25% saline/CM mixture and 30 ml saline chaser bolus; and a four-phasic injection-protocol group, with a saline pacer bolus of 10 ml injected at a lower flow rate before the three-phasic protocol. RESULTS: 2,445 consecutive patients were enrolled (mean age 60.6 ± 12.1 years; females 43.6%). Overall rate of extravasation was 0.9% (23/2,445): 1.4% (17/1,229) in the three-phasic group and 0.5% (6/1,216) in the four-phasic group (p = 0.034). CONCLUSIONS: Four-phasic CM administration protocol is easy to implement in the clinical routine at no extra cost. The extravasation rate is reduced by 65% with the application of the four-phasic protocol compared to the three-phasic protocol in coronary CTA. KEY POINTS: • Four-phasic CM injection-protocol reduces extravasation rate by 65% compared to three-phasic. • The saline pacer bolus substantially reduces the risk of CM extravasation. • The implementation of four-phasic injection-protocol is at no cost.

Iterative model reconstruction reduces calcified plaque volume in coronary CT angiography.

OBJECTIVE: To assess the impact of iterative model reconstruction (IMR) on calcified plaque quantification as compared to filtered back projection reconstruction (FBP) and hybrid iterative reconstruction (HIR) in coronary computed tomography angiography (CTA). METHODS: Raw image data of 52 patients who underwent 256-slice CTA were reconstructed with IMR, HIR and FBP. We evaluated qualitative, quantitative image quality parameters and quantified calcified and partially calcified plaque volumes using automated software. RESULTS: Overall qualitative image quality significantly improved with HIR as compared to FBP, and further improved with IMR (p<0.01 all). Contrast-to-noise ratios were improved with IMR, compared to HIR and FBP (51.0 [43.5-59.9], 20.3 [16.2-25.9] and 14.0 [11.2-17.7], respectively, all p<0.01) Overall plaque volumes were lowest with IMR and highest with FBP (121.7 [79.3-168.4], 138.7 [90.6-191.7], 147.0 [100.7-183.6]). Similarly, calcified volumes (>130 HU) were decreased with IMR as compared to HIR and FBP (105.9 [62.1-144.6], 110.2 [63.8-166.6], 115.9 [81.7-164.2], respectively, p<0.05 all). High-attenuation non-calcified volumes (90-129 HU) yielded similar values with FBP and HIR (p=0.81), however it was lower with IMR (p < 0.05 both). Intermediate- (30-89 HU) and low-attenuation (<30 HU) non-calcified volumes showed no significant difference (p=0.22 and p=0.67, respectively). CONCLUSIONS: IMR improves image quality of coronary CTA and decreases calcified plaque volumes.

Aortic root dimensions are predominantly determined by genetic factors: a classical twin study.

OBJECTIVES: Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. METHODS: In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). RESULTS: Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CONCLUSION: CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. KEY POINTS: • Aortic root dimensions are determined by genetic and environmental effects. • Transthoracic echocardiography (TTE) demonstrated moderate to no genetic effects on aortic root dimensions. • Computed tomography angiography might provide more accurate heritability estimates compared to TTE. • Three-dimensional imaging techniques are needed to reliably quantify aortic root dimensions.