Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study.

BACKGROUND: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous. METHODS: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups. RESULTS: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses. CONCLUSIONS: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.

Different prognostic significance of coronary artery and aortic valve calcium in patients with chest pain.

OBJECTIVES: Coronary artery calcification (CorCa) identifies high cardiovascular risk in the general population. In this setting, aortic valve calcification (AoCa) showed contradictory results. Our goal has been to assess the prognostic power of CorCa and AoCa in patients with chest pain who underwent an ECG-gated cardiac multidetector CT (cardiac-MDCT). METHODS: A total of 528 patients without previous known coronary artery disease, with chest pain who underwent a cardiac-MDCT multidetector, were retrospectively recruited. The primary endpoint included death, acute coronary syndrome, stroke, and heart failure. RESULTS: A total of 61 patients (11.6%) had an event during a mean follow-up of almost 6 years (5.95 ± 2.98). The most frequent event was acute coronary syndrome (6.4%). Total mortality was 4.5%. Patients with CorCa > 0 had more events than those without CorCa (17.3% versus 4.3%; p < 0.001). Likewise, when only patients without AoCa were considered (n = 118), clinical events were more frequent in those with CorCa (12.7% versus 3.6%; p = 0.004). After excluding patients with coronary artery disease, events were more frequent in those with CorCa (12.6% versus 4.3%; p = 0.004). The higher the Agatston score, the more frequent the events. Patients with AoCa > 0 had more events than those without (16.5% versus 7.3%; p < 0.001), but in patients without CorCa, no difference in events was seen (6.2% versus 3.6%; p = 0.471). A Cox regression analysis showed age, smoking, prior stroke, and CorCa but not AoCa to be independently related to events. CONCLUSIONS: In summary, CorCa, but not AoCa, is related to cardiovascular events in patients with chest pain who undergo a cardiac-MDCT. CLINICAL RELEVANCE STATEMENT: We show that coronary artery calcification, but not aortic valve calcification, detected in a coronary CT scan is tightly related to cardiovascular events. Although this is a message already shown by other groups in the general population, we do believe that this work is unique because it is restricted to patients with chest pain sent to coronary CT. In other words, our work deals with what we face in our routine everyday practice. KEY POINTS: • The presence and the amount of coronary artery calcification are associated with cardiovascular events in patients with chest pain. • Aortic valve calcification is not associated with cardiovascular events in patients with chest pain.

Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification.

AIM: Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression. METHODS AND RESULTS: A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9-14.2] years. New-onset AVC was defined as an AVC score >0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2-37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15-1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02-1.65), but not with AVC progression (ß: -71 AU for each 50 mg/dL higher Lp(a); 95% CI -117; 35). Only baseline AVC score was significantly associated with AVC progression (P < 0.001). CONCLUSION: In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease.

Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Association of aortic valve calcium with dementia and stroke: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR). RESULTS: Overall, 6812 participants had AVC quantified with a mean age of 62.1 years old, 52.9 % were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5 %. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in a logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95 % CI 1.04-1.14) and persons with AVC ≥300 had nearly a two-fold higher risk (HR 1.77; 95 % CI 1.14-2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors. CONCLUSIONS: After multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors.

Prognostic and therapeutic implications of low aortic valve calcium score in patients with low gradient aortic stenosis.

INTRODUCTION: Low gradient (LG) aortic stenosis (AS) poses a diagnostic challenge. Aortic valve calcium score (AVCS) assessment has emerged as a complementary diagnostic method when echocardiography provides discordant results. However, the diagnostic and prognostic value of AVCS in LGAS has not been thoroughly studied. Our aims were to investigate the prognostic importance of AVCS in LGAS and to assess whether symptomatic patients with LGAS and low AVCS may benefit from aortic valve intervention (AVI). METHODS: 327 symptomatic patients (78.5±7.3 years, 51% women) with severe AS defined by the aortic valve area who underwent computed tomography for transcatheter aortic valve intervention (TAVI) planning were enrolled. AVCS was measured. AVCS<2000 AU in men and<1200 AU in women was considered low AVCS. RESULTS: 243 patients had high gradient (HG) and 84 had LGAS. Low AVCS was present in 25(10%) of the HG and 34(40%) of the LGAS cases. Over a median follow-up period of 4.9 years, 194 deaths occurred. In multivariate analysis, AVCS was a significant independent predictor of all-cause mortality among HGAS (aHR:2.317; CI:1.104-4.861; p= 0.026), but not among LGAS (aHR:0.848; CI:0.434-1.658; p=0.630) patients. After propensity score matching between patients who underwent AVI and those who were medically treated, AVI (94% TAVI) was a significant and independent predictor of survival among LG AS patients with low AVCS even after adjustment for clinical variables (aHR:0.102, CI:0.028-0.369; p<0.001). CONCLUSION: The prevalence of low AVCS is much higher in LGAS than in HGAS. In symptomatic severe LGAS low AVCS did not entail a better prognosis. AVI is equally beneficial in LGAS patients with high or low AVCS, similarly to HGAS.

Disproportionately high aortic valve calcium scores in atrial fibrillation: implications for transcatheter aortic valve replacement.

AIMS: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity in patients with atrial fibrillation (AF) compared with patients with sinus rhythm (SR), potentially delaying intervention in AF. This study compared outcomes in patients with AF and SR following transcatheter aortic valve replacement (TAVR) and investigated delay in TAVR based on computed tomography aortic valve calcium score (AVCS). METHODS AND RESULTS: Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. Baseline characteristics and overall survival were compared between those with SR and AF. There were 820 patients (mean age 81 years; 41.6% females) included in this study. AF was present in 356 patients. Patients with AF were older (82.2 vs. 80.5, P = 0.003) and had a lower MG compared with patients with SR (42.0 vs. 44.9, P = 0.002) with similar indexed aortic valve area (0.4 vs. 0.4, P = 0.17). Median AVCS was higher in AF (males: AF 2850.0 vs. SR 2561.0, P = 0.044; females: AF 1942.0 vs. SR 1610.5, P = 0.025). Projected AVCS, assuming the same age of diagnosis, was similar between AF and SR. Median survival post-TAVR was worse in AF compared with SR (3.2 vs. 5.4 years, log rank P < 0.001). AF, lower MG, higher right ventricular systolic pressure, dialysis, diabetes, and significant tricuspid regurgitation were associated with higher mortality (P < 0.05 for all). CONCLUSION: Older age and higher AVCS in patients with AF compared with those with SR suggest that AS was both underestimated and more advanced at TAVR referral.

Regional assessment of aortic valve calcification using topographic maps in contrast-enhanced CT: in-vivo sex and severity-based differences in calcific presentation.

Background: Procedural planning for transcatheter aortic valve replacement (TAVR) is routinely performed using contrast computed tomography (CT) in patients with severe aortic stenosis (AS). Despite its potential, little investigation has been done into the possibility of aortic valve calcification (AVC) scoring in contrast-enhanced CT. Contrast CT has superior spatial and contrast resolution compared to the non-contrast Agatston score protocol, which would allow for development of better pattern and distribution descriptors of calcific lesions in the aortic valve (AV). Methods: We developed a new false positive rate (FPR) based method that can quantify leaflet calcification based on shape overlap metrics. We also introduce a novel regional scheme for quantifying the shape and structure of calcification using topographic maps. The study was designed to: (I) determine the feasibility of using a novel method based on FPR to detect AVC using contrast-enhanced CT images by assessing the volume scores measured using FPR versus non-contrast methods and alternative contrast methods for volume scoring based on fixed or dynamic HU thresholds. (II) Develop a new scheme for assessing calcific geometry and structure and evaluate patterns of calcification in the varied presentation of AS. Results: Our results show a very strong correlation with non-contrast volume (r=0.919, P<0.001; n=178) and Agatston scores (r=0.913, P<0.001; n=178) that were evaluated using a standard calcium scoring technique. Finally, we analyzed the differences and similarities in the patterns of calcific deposition with respect to sex and degree of severity. Conclusions: The FPR method demonstrates the best overall agreement with non-contrast scores across both low and high ends of calcific density compared to luminal attenuation methods. In addition, we showed that leaflet calcific deposition follows distinctive patterns across the belly of the leaflet, with the rate of calcific progression peaking at the non-coronary cusp (NCC) leaflet and lowest for the right-coronary cusp. Females experience significantly lower calcific deposition compared to males despite showing similar patterns and symptoms. Our findings suggest that precise regional assessment of calcific progression could be an important tool for monitoring AS development as well as predicting peri-procedural complications in TAVR.

Virtual non-contrast series of photon-counting detector computed tomography angiography for aortic valve calcium scoring.

The aim of our study was to evaluate two different virtual non-contrast (VNC) algorithms applied to photon counting detector (PCD)-CT data in terms of noise, effectiveness of contrast media subtraction and aortic valve calcium (AVC) scoring compared to reference true non-contrast (TNC)-based results. Consecutive patients underwent TAVR planning examination comprising a TNC scan, followed by a CTA of the heart. VNC series were reconstructed using a conventional (VNCconv) and a calcium-preserving (VNCpc) algorithm. Noise was analyzed by means of the standard deviation of CT-values within the left ventricle. To assess the effectiveness of contrast media removal, heart volumes were segmented and the proportion of their histograms > 130HU was taken. AVC was measured by Agatston and volume score. 41 patients were included. Comparable noise levels to TNC were achieved with all VNC reconstructions. Contrast media was effectively virtually removed (proportions > 130HU from 81% to < 1%). Median calcium scores derived from VNCconv underestimated TNC-based scores (up to 74%). Results with smallest absolute difference to TNC were obtained with VNCpc reconstructions (0.4 mm, Br36, QIR 4), but with persistent significant underestimation (median 29%). Both VNC algorithms showed near-perfect (r²>0.9) correlation with TNC. Thin-slice VNC reconstructions provide equivalent noise levels to standard thick-slice TNC series and effective virtual removal of iodinated contrast. AVC scoring was feasible on both VNC series, showing near-perfect correlation, but with significant underestimation. VNCpc with 0.4 mm slices and Br36 kernel at QIR 4 gave the most comparable results and, with further advances, could be a promising replacement for additional TNC.

Aortic Valve Calcium Score by Computed Tomography as an Adjunct to Echocardiographic Assessment-A Review of Clinical Utility and Applications.

Aortic valve stenosis (AS) is increasing in prevalence due to the aging population, and severe AS is associated with significant morbidity and mortality. Echocardiography remains the mainstay for the initial detection and diagnosis of AS, as well as for grading of severity. However, there are important subgroups of patients, for example, patients with low-flow low-gradient or paradoxical low-gradient AS, where quantification of severity of AS is challenging by echocardiography and underestimation of severity may delay appropriate management and impart a worse prognosis. Aortic valve calcium score by computed tomography has emerged as a useful clinical diagnostic test that is complimentary to echocardiography, particularly in cases where there may be conflicting data or clinical uncertainty about the degree of AS. In these situations, aortic valve calcium scoring may help re-stratify grading of severity and, therefore, further direct clinical management. This review presents the evolution of aortic valve calcium score by computed tomography, its diagnostic and prognostic value, as well as its utility in clinical care.

Aortic Valve Calcium in Relation to Subclinical Cardiac Dysfunction and Risk of Heart Failure.

BACKGROUND: The link between (mild) aortic valve calcium (AVC) with subclinical cardiac dysfunction and with risk of heart failure (HF) remains unclear. This research aims to determine the association of computed tomography-assessed AVC with echocardiographic measurements of cardiac dysfunction, and with HF in the general population. METHODS: We included 2348 participants of the Rotterdam Study cohort (mean age 68.5 years, 52% women), who had AVC measurement between 2003 and 2006, and without history of HF at baseline. Linear regression models were used to explore relationship between AVC and echocardiographic measures at baseline. Participants were followed until December 2016. Fine and Gray subdistribution hazard models were used to assess the association of AVC with incident HF, accounting for death as a competing risk. RESULTS: The presence of AVC or greater AVC were associated with larger mean left ventricular mass and larger mean left atrial size. In particular, AVC ≥800 showed a strong association (body surface area indexed left ventricular mass, ß coefficient: 22.01; left atrium diameter, ß coefficient: 0.17). During a median of 9.8 years follow-up, 182 incident HF cases were identified. After accounting for death events and adjusting for cardiovascular risk factors, one-unit larger log (AVC+1) was associated with a 10% increase in the subdistribution hazard of HF (subdistribution hazard ratio, 1.10 [95% CI, 1.03-1.18]), but the presence of AVC was not significantly associated with HF risk in fully adjusted models. Compared with the AVC=0, AVC between 300 and 799 (subdistribution hazard ratio, 2.36 [95% CI, 1.32-4.19]) and AVC ≥800 (subdistribution hazard ratio, 2.54 [95% CI, 1.31-4.90]) were associated with a high risk of HF. CONCLUSIONS: Presence and high levels of AVC were associated with markers of left ventricular structure, independent of traditional cardiovascular risk factors. Larger computed tomography-assessed AVC is an indicative of increased risk for the development of HF.

Relationship between Cardiovascular Calcium and Atrial Fibrillation.

Coronary artery calcium score (CACS) is associated with increased risk of atrial fibrillation (AF). However, the relationship between the burden of CACS and extra-coronary calcium and the AF is unclear. This cross-sectional study retrospectively analyzed the data of 143,529 participants (74.9% men; mean age, 41.7 ± 8.6 years) who underwent health examination including non-contrast cardiac CT and electrocardiography, from 2010 to 2018 to evaluate the association between cardiac calcium and AF. AF was diagnosed in 679 participants. The prevalence of AF was significantly increased as the CACS increased (p < 0.01). Multivariable analysis adjusted for age, sex, body mass index, hypertension, diabetes, hyperlipidemia, smoking, alcohol, and history of coronary artery disease showed a significant association between a high CACS ≥1000 and AF (OR 2.26, 95% CI 1.07-4.77, p = 0.032). In a subgroup analysis of participants with a CACS ≥100, aortic valve and thoracic aorta calcium were significantly associated with AF (OR 3.49, 95% CI 1.57-7.77, p = 0.002 and OR 2.19, 95% CI 1.14-4.21, p = 0.01, respectively). High CACS was associated with AF, and extra-coronary atherosclerosis was associated with AF in participants with a moderate to very high CACS.

Lipoprotein(a) and Subclinical Vascular and Valvular Calcification on Cardiac Computed Tomography: The Atherosclerosis Risk in Communities Study.

Background Lipoprotein(a) (Lp(a)) is a potent causal risk factor for cardiovascular events and mortality. However, its relationship with subclinical atherosclerosis, as defined by arterial calcification, remains unclear. This study uses the ARIC (Atherosclerosis Risk in Communities Study) to evaluate the relationship between Lp(a) in middle age and measures of vascular and valvular calcification in older age. Methods and Results Lp(a) was measured at ARIC visit 4 (1996-1998), and coronary artery calcium (CAC), together with extracoronary calcification (including aortic valve calcium, aortic valve ring calcium, mitral valve calcification, and thoracic aortic calcification), was measured at visit 7 (2018-2019). Lp(a) was defined as elevated if >50 mg/dL and CAC/extracoronary calcification were defined as elevated if >100. Logistic and linear regression models were used to evaluate the association between Lp(a) and CAC/extracoronary calcification, with further stratification by race. The mean age of participants at visit 4 was 59.2 (SD 4.3) years, with 62.2% women. In multivariable adjusted analyses, elevated Lp(a) was associated with higher odds of elevated aortic valve calcium (adjusted odds ratio [aOR], 1.82; 95% CI, 1.34-2.47), CAC (aOR, 1.40; 95% CI, 1.08-1.81), aortic valve ring calcium (aOR, 1.36; 95% CI, 1.07-1.73), mitral valve calcification (aOR, 1.37; 95% CI, 1.06-1.78), and thoracic aortic calcification (aOR, 1.36; 95% CI, 1.05-1.77). Similar results were obtained when Lp(a) and CAC/extracoronary calcification were examined on continuous logarithmic scales. There was no significant difference in the association between Lp(a) and each measure of calcification by race or sex. Conclusions Elevated Lp(a) at middle age is significantly associated with vascular and valvular calcification in older age, represented by elevated CAC, aortic valve calcium, aortic valve ring calcium, mitral valve calcification, thoracic aortic calcification. Our findings encourage assessing Lp(a) levels in individuals with increased cardiovascular disease risk, with subsequent comprehensive vascular and valvular assessment where elevated.

Doppler Mean Gradient Is Discordant to Aortic Valve Calcium Scores in Patients with Atrial Fibrillation Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Doppler mean gradient (MG) may underestimate aortic stenosis (AS) severity when obtained during atrial fibrillation (AF) because of lower forward flow compared with sinus rhythm (SR). Whether AS is more advanced at the time of referral for aortic valve intervention in AF compared with SR is unknown. The aim of this study was to examine flow-independent computed tomographic aortic valve calcium scores (AVCS) and their concordance to MG in AF versus SR in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Patients who underwent TAVR from 2016 to 2020 for native valve severe AS with left ventricular ejection fraction ≥ 50% were identified from an institutional TAVR database. MGs during AF and SR in high-gradient AS (HGAS) and low-gradient AS (LGAS) were compared with AVCS (AVCS/MG ratio). AVCS were obtained within 90 days of pre-TAVR echocardiography. RESULTS: Six hundred thirty-three patients were included; median age was 82 years (interquartile range [IQR], 76-86 years), and 46% were women. AF was present in 109 (17%) and SR in 524 (83%) patients during echocardiography. Aortic valve area index was slightly smaller in AF versus SR (0.43 cm2/m2 [IQR, 0.39-0.47 cm2/m2] vs 0.46 cm2/m2 [IQR, 0.41-0.51 cm2/m2], P = .0003). Stroke volume index, transaortic flow rate, and MG were lower in AF (P < .0001 for all). AVCS were higher in men with AF compared with SR (3,510 Agatston units [AU] [IQR, 2,803-4,030 AU] vs 2,722 AU [IQR, 2,180-3,467 AU], P < .0001) in HGAS but not in LGAS. AVCS were not different in women with AF versus SR. Overall AVCS/MG ratios were higher in AF versus SR in HGAS and LGAS (P < .03 for all), except in women with LGAS. CONCLUSIONS: AVCS were higher than expected by MG in AF compared with SR. The very high AVCS in men with AF and HGAS at the time of TAVR suggests late diagnosis of severe AS because of underestimated AS severity during progressive AS and/or late referral to TAVR. Additional studies are needed to examine the extent to which echocardiography may be underestimating AS severity in AF.

Aortic Valve Calcium Score Is Associated With Acute Stroke in Transcatheter Aortic Valve Replacement Patients.

Background: Transcatheter aortic valve replacement (TAVR) is the treatment of choice for patients with severe aortic stenosis who are at a moderate or higher surgical risk. Stroke is a recognised and serious complication of TAVR, and it is important to identify patients at higher stroke risk. This study aims to discover if aortic valve calcium score calculated from pre-TAVR computed tomography is associated with acute stroke in TAVR patients. Methods: We conducted a retrospective, observational cohort study of 433 consecutive patients undergoing TAVR between January 2017 and December 2019 at the Hammersmith Hospital. Results: This cohort had a median age of 83 years (interquartile range, 78-87), and 52.7% were male. Fifty-two patients (12.0%) had a history of previous stroke or transient ischemic attack. Median aortic valve calcium score was 2145 (interquartile range, 1427-3247) Agatston units. Twenty-two patients had a stroke up to the time of discharge (5.1%). In a logistic regression model, aortic valve calcium score was significantly associated with acute stroke (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.01-1.53; P = .02). Acute stroke was also significantly associated with peripheral arterial disease (OR, 4.32; 95% CI, 1.65-10.65; P = .0018) and a longer procedure time (OR, 1.01; 95% CI, 1.00-1.02; P = .0006). Conclusions: Aortic valve calcium score from pre-TAVR computed tomography is an independent risk factor for acute stroke in the TAVR population. This is an additional clinical value of the pre-TAVR aortic valve calcium score and should be considered when discussing periprocedural stroke risk.

Estimation of Aortic Valve Calcium Score Based on Angiographic Phase Versus Reduction of Ionizing Radiation Dose in Computed Tomography.

The aim of the study was to evaluate the estimation efficacy of aortic valve calcium score (AVCS) based on the multislice computed tomography (MSCT) angiographic phase. The evaluation of the reduced amount of ionizing radiation dose was performed because of this estimation. The study included 51 consecutive patients who qualified for transcatheter aortic valve implantation (TAVI) (78.59 ± 5.72 years). All subjects underwent MSCT: in the native phase dedicated to AVCS as well as angiographic phases aimed to morphologically assess the aortic ostium and arterial accesses for TAVI. Based on the native phase, an AVCS assessment was performed for axial reconstructions at 3.0 mm and 2.0 mm slice thickness (AVCSnative3.0 and AVCSnative2.0). Based on the angiographic phase AVCS was estimated for axial reconstruction at 0.6 mm slice thickness with increased values of lesion density in aortic valve cusps/aortic valve annulus, which is considered a calcification, from a typical value of 130 HU to 500 HU and 600 HU (AVCSCTA0.6 500 HU and AVCSCTA0.6 600 HU). Mathematical formulations were developed, allowing for AVCS native calculation based on AVCS values estimated based on the angiographic phase: AVCSnative3.0 = 813.920 + 1.510 AVCSCTA0.6 500 HU; AVCSnative3.0 = 1235.863 + 1.817 AVCSCTA0.6 600 HU; AVCSnative2.0 = 797.471 + 1.393 AVCSCTA0.6 500 HU; AVCSnative2.0 = 1228.310 + 1.650 AVCSCTA0.6 600 HU. The amount of a potential reduction in dose length product (DLP) in the case of AVCS estimation was 4.45 ± 1.54%. In summary, relying solely on the angiographic phase of MSCT examination before TAVI, it is possible to conclusively estimate AVCS. This estimation results in a marked reduction in radiation dose in MSCT.

Cholesterol efflux promoting function of high-density lipoproteins in calcific aortic valve stenosis.

Background and aims: Cholesterol efflux capacity is a functional property of high-density lipoproteins (HDL) reflecting the efficiency of the atheroprotective reverse cholesterol transport process in humans. Its relationship with calcific aortic valve stenosis (CAVS) has not been fully assessed yet. Methods: We evaluated HDL-CEC in a patient population with varying degrees of aortic valvular calcific disease, assessed using echocardiography and cardiac computed tomography. Measurement of biomarkers that reflect osteogenic and tissue remodeling, along with dietary and gut microbiota-derived metabolites were performed. Results: Patients with moderate-severe CAVS had significantly lower HDL-CEC compared to both control and aortic sclerosis subjects (mean: 6.09%, 7.32% and 7.26%, respectively). HDL-CEC displayed negative correlations with peak aortic jet velocity and aortic valve calcium score, indexes of CAVS severity (ρ = -0.298, p = 0.002 and ρ = -0.358, p = 0.005, respectively). In multivariable regression model, HDL-CEC had independent association with aortic valve calcium score (B: -0.053, SE: 0.014, p < 0.001), GFR (B: -0.034, SE: 0.012, p = 0.007), as well as with levels of total cholesterol (B: 0.018, SE: 0.005, p = 0.002). Conclusion: These results indicate an impairment of HDL-CEC in moderate-severe CAVS and may contribute to identify potential novel targets for CAVS management.

Diagnostic and Prognostic Accuracy of Aortic Valve Calcium Scoring in Patients With Moderate-to-Severe Aortic Stenosis.

Background: Assessing the true severity of aortic stenosis (AS) remains a challenge, particularly when echocardiography yields discordant results. Recent European and American guidelines recommend measuring aortic valve calcium (AVC) by multidetector row computed tomography (MDCT) to improve this assessment. Aim: To define, using a standardized MDCT scanning protocol, the optimal AVC load criteria for truly severe AS in patients with concordant echocardiographic findings, to establish the ability of these criteria to predict clinical outcomes, and to investigate their ability to delineate truly severe AS in patients with discordant echocardiographic AS grading. Methods and Results: Two hundred and sixty-six patients with moderate-to-severe AS and normal LVEF prospectively underwent MDCT and Doppler-echocardiography to assess AS severity. In patients with concordant AS grading, ROC analysis identified optimal cut-off values for diagnosing severe AS using different AVC load criteria. In these patients, 4-year event-free survival was better with low AVC load (60-63%) by these criteria than with high AVC load (23-26%, log rank p < 0.001). Patients with discordant AS grading had higher AVC load than those with moderate AS but lower AVC load than those with severe high-gradient AS. Between 36 and 55% of patients with severe LG-AS met AVC load criteria for severe AS. Although AVC load predicted outcome in these patients as well, its prognostic impact was less than in patients with concordant AS grading. Conclusions: Assessment of AVC load accurately identifies truly severe AS and provides powerful prognostic information. Our data further indicate that patients with discordant AS grading consist in a heterogenous group, as evidenced by their large range of AVC load. MDCT allows to differentiate between truly severe and pseudo-severe AS in this population as well, although the prognostic implications thereof are less pronounced than in patients with concordant AS grading.

Performance of Prediction Models for Diagnosing Severe Aortic Stenosis Based on Aortic Valve Calcium on Cardiac Computed Tomography: Incorporation of Radiomics and Machine Learning.

OBJECTIVE: We aimed to develop a prediction model for diagnosing severe aortic stenosis (AS) using computed tomography (CT) radiomics features of aortic valve calcium (AVC) and machine learning (ML) algorithms. MATERIALS AND METHODS: We retrospectively enrolled 408 patients who underwent cardiac CT between March 2010 and August 2017 and had echocardiographic examinations (240 patients with severe AS on echocardiography [the severe AS group] and 168 patients without severe AS [the non-severe AS group]). Data were divided into a training set (312 patients) and a validation set (96 patients). Using non-contrast-enhanced cardiac CT scans, AVC was segmented, and 128 radiomics features for AVC were extracted. After feature selection was performed with three ML algorithms (least absolute shrinkage and selection operator [LASSO], random forests [RFs], and eXtreme Gradient Boosting [XGBoost]), model classifiers for diagnosing severe AS on echocardiography were developed in combination with three different model classifier methods (logistic regression, RF, and XGBoost). The performance (c-index) of each radiomics prediction model was compared with predictions based on AVC volume and score. RESULTS: The radiomics scores derived from LASSO were significantly different between the severe AS and non-severe AS groups in the validation set (median, 1.563 vs. 0.197, respectively, p < 0.001). A radiomics prediction model based on feature selection by LASSO + model classifier by XGBoost showed the highest c-index of 0.921 (95% confidence interval [CI], 0.869-0.973) in the validation set. Compared to prediction models based on AVC volume and score (c-indexes of 0.894 [95% CI, 0.815-0.948] and 0.899 [95% CI, 0.820-0.951], respectively), eight and three of the nine radiomics prediction models showed higher discrimination abilities for severe AS. However, the differences were not statistically significant (p > 0.05 for all). CONCLUSION: Models based on the radiomics features of AVC and ML algorithms may perform well for diagnosing severe AS, but the added value compared to AVC volume and score should be investigated further.

Development of a deep learning-based algorithm for the automatic detection and quantification of aortic valve calcium.

PURPOSE: We aimed to develop a deep learning (DL)-based algorithm for automated quantification of aortic valve calcium (AVC) from non-enhanced electrocardiogram-gated cardiac CT scans and compare performance of DL-measured AVC volume and Agatston score with those of visual gradings by radiologist readers for classification of AVC severity. METHOD: A total of 589 CT examinations performed at a single center between March 2010 and August 2017 were retrospectively included. The DL algorithm was designed to segment AVC and to quantify AVC volume, and Agatston score was calculated using attenuation values. Manually measured AVC volume and Agatston score were used as ground truth. To validate AVC segmentation performance, the Dice coefficient was calculated. For observer performance testing, four radiologists determined AVC grade in two reading rounds. The diagnostic performance of DL-measured AVC volume and Agaston score for classifying severe AVC was compared with that of each reader's assessment. RESULTS: After applying the DL algorithm, the Dice coefficient score was 0.807. In patients with AVC, accuracy of DL-measured AVC volume for AVC grading was 97.0 % with area under the curve (AUC) of 0.964 (95 % confidence interval [CI] 0.923-1) in the test set, which was better than the radiologist readers (accuracy 69.7 %-91.9 %, AUC 0.762-0.923) with manually measured AVC volume as ground truth. When manually measured AVC Agatston score was used as ground truth, accuracy of DL-measured AVC Agatston score for AVC grading was 92.9 % with AUC of 0.933 (95 % CI 0.885-0.981) in the test set, which was also better than the radiologist readers (accuracy 77.8-89.9 %, AUC 0.791-0.903). CONCLUSIONS: DL-based automated AVC quantification may be comparable with manual measurements. The diagnostic performance of the DL-measured AVC volume and Agatston score for classification of severe AVC outperforms radiologist readers.