Sex Differences in Factors Associated With Progression of Aortic Valve Calcification in the General Population

Background: Guidelines recommend measurement of the aortic valve calcification (AVC) score to help differentiate between severe and nonsevere aortic stenosis, but a paucity exists in data about AVC in the general population. The aim of this study was to describe the natural history of AVC progression in the general population and to identify potential sex differences in factors associated with this progression rate. Methods: Noncontrast cardiac computed tomography was performed in 1298 randomly selected women and men aged 65 to 74 years who participated in the DANCAVAS trial (Danish Cardiovascular Screening). Participants were invited to attend a reexamination after 4 years. The AVC score was measured at the computed tomography, and AVC progression (ΔAVC) was defined as the difference between AVC scores at baseline and follow-up. Multivariable regression analyses were performed to identify factors associated with ΔAVC. Results: Among the 1298 invited citizens, 823 accepted to participate in the follow-up examination. The mean age at follow-up was 73 years. Men had significantly higher AVC scores at baseline (median AVC score 13 Agatston Units [AU; interquartile range, 0–94 AU] versus 1 AU [interquartile range, 0–22 AU], P <0.001) and a higher ΔAVC (median 26 AU [interquartile range, 0–101 AU] versus 4 AU [interquartile range, 0–37 AU], P <0.001) than women. In the fully adjusted model, the most important factor associated with ΔAVC was the baseline AVC score. However, hypertension was associated with ΔAVC in women (incidence rate ratios, 1.58 [95% CI, 1.06–2.34], P =0.024) but not in men, whereas dyslipidemia was associated with ΔAVC in men (incidence rate ratio: 1.66 [95% CI, 1.18–2.34], P =0.004) but not in women. Conclusions: The magnitude of the AVC score was the most important marker of AVC progression. However, sex differences were significant; hence, dyslipidemia was associated with AVC progression only among men; hypertension with AVC progression only among women. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: ISRCTN12157806.

Multicenter Prospective Cohort on Aortic Valve Stenosis in Japanese Patients With End Stage Kidney Disease in Tokai Region (ASKIT)

Background:The prevalence of aortic valve stenosis (AS) in patients on maintenance dialysis is high and the prognosis is poor. Because only few large cohort studies have analyzed patients with AS on dialysis, the factors that cause AS in such patients remain unclear.Methods:This multicenter, prospective cohort study included 2,786 patients on dialysis who underwent transthoracic echocardiography between July 1, 2017 and June 30, 2018. Patients with a maximum aortic jet velocity (Vmax) ≥2.0 m/s, pressure gradient (PG) between the left ventricle and ascending aorta (mean PG) ≥20 mmHg, or aortic valve area (AVA) ≤1.0 cm2 were categorized into the AS group. Of these, patients with Vmax ≥3.0 m/s, mean PG ≥20 mmHg, or AVA ≤1.0 cm2 were categorized into the severe AS group. The AS and severe AS groups were then compared with the non-AS group to identify the risk factors for AS using multivariate logistic analysis. We also compared the risk factors for AS with and without aortic valve calcification, which is the stage prior to age-related AS.Results:Of the 2,786 patients analyzed, 555 (20.0%) and 139 (6.9%) were categorized into the AS and severe AS groups, respectively. Multivariate logistic analysis revealed that aging, long-term dialysis, and elevated serum phosphorus levels were associated with AS in the AS and severe AS groups (p <0.05). Additional investigation using stratified multivariate analysis revealed that groups with serum phosphorus levels of 5.0–5.9 mg/dL and >6.0 mg/dL had a higher risk of AS than those with serum phosphorus levels of <4.0 mg/dL (odds ratio: 2.24; p = 0.01 and odds ratio: 2.66, p = 0.005, respectively). Aortic valve calcification was associated with aging, long-term dialysis, diabetes mellitus, administration of vitamin D receptor activators, elevated serum calcium levels, and anemia (p <0.05 for all).Conclusions:Dialysis patients had a high prevalence of AS, and AS was associated with aging, long dialysis duration, and elevated serum phosphorus levels.Trial registration: UMIN000026756, Registered on March 29, 2017.

The validation of four published algorithms to predict the need for pacemaker implantation after TAVR

Background The identification of patients with high risk for PPMI after TAVR might change our decision as regard the type of the prosthesis and allow more patients' acceptance for this complication. Objective: we investigated the predictors of PPMI after TF-TAVR and validated the accuracy of four published algorithms in this group of patients. Methods and results We retrospectively examined all patients who were in need for pacemaker implantation during the index hospitalisation after TAVR between 2016 and 2019. We searched for the predictors of the new PPMI after TAVR in this group of patient and compared it with a matched group of patients. Moreover, we tested the accuracy of four published algorithms. The first tested algorithm from Kaneko et al had positive predictive value (PPV), negative predictive value (NPV) and accuracy from 50%, 65% and 60% consecutively. The second tested algorithm from Jilaihawi et al had PPV, NPV and accuracy from 13.6%, 100% and 26.9% consecutively. The third tested algorithm from Maeno et al had PPV, NPV and accuracy from 37%, 56% and 45% consecutively. The forth tested algorithm from Fujiti et al had PPV, NPV and accuracy from 42%, 65% and 50% consecutively. In this study, 3 ECG-predictors (RBBB, the presence of AF and LAHB) and 3 CT-predictors (Aortic valve calcification Volume &gt;500mm3, eccentricity index &gt;0.25, deep valve implantation in relation to the length of membranous septum) were independent predictors of PPMI. Moreover, the rate of preimplantation ballon valivuloplasty was higher in the group with new PPMI. Using these independent predictors, the new 7 points score was developed by assigning 1 point for each one. AUC of the new score in the derivation cohort was 0.809 (95% CI 0.758–0.86), with an optimal cut-off threshold of 4 points. All other scores had AUC from 0.6 or lower. In a validation cohort of 100 patients, the predictive value of the score was confirmed (AUC, 0.72; 95% CI, 0.70–0.87; P&lt;0.001). Conclusion The four studied score systems had low accuracy to predict new PPMI after TAVR in our cohort of patients. The new score is more complex but might be more accurate. FUNDunding Acknowledgement Type of funding sources: None.

Correlation between Peri-Coronary Epicardial Adipose Tissue Volume, Cardiac Calcification and the Severity of Coronary Artery Disease by Multi Slice Computed Tomography

ABSTRACT The authors in that article addressed a very important and relevant issue. Background Epicardial adipose tissue (EAT) is a complex endocrine organ that plays an important role in the development of unfavorable metabolic and cardiovascular risk profile. EAT may express a variety of inflammatory mediators which may contribute to the pathogenesis of coronary artery disease (CAD). Aortic and mitral valve calcification may reflect generalized atherosclerosis in the elderly and may be a marker of high prevalence and severity of CAD. There is a direct correlation (extent, severity and the future CV events) between the coronary artery calcium and the CAD. Aim and Objectives To correlate peri-coronary epicardial adipose tissue and coronary artery calcification and valvular (aortic and mitral) calcification with the severity of the coronary artery disease. Patients and Methods The study recruited 200 patients with suspected coronary artery disease. The amount of EAT surrounding the left main and the three main coronary arteries was quantified in axial cuts with the most distinct layer of EAT. The amount of calcium in the aortic and mitral valve and the coronaries were quantified with multi-detector computed tomography MDCT using dedicated software for measuring calcium score that is based on Agatson score. Coronary artery disease severity was assessed in terms of number of vessels affected and the severity of coronary stenosis by multi-planner reformation technique. Results Based on the finding of the MDCT and according to the presence of calcification in the aortic or the mitral valves, and the significance of the coronary artery disease, patients were classified into two groups, group (I): 115 patients with normal coronaries or with non significant lesions in their coronaries, and group (II): 85 patients with significant coronary artery disease. The Mean ± SD (in millimeters) of EAT for the entire study cohort in various coronary artery locations were as follows: LM EAT 9.82 ± 2.67, proximal LAD EAT 10.06 ± 2.80, mid LAD EAT 9.15 ± 2.41, distal LAD EAT 6.46 ± 1.87, proximal LCX EAT 8.10 ± 1.90, distal LCX EAT 6.83 ± 1.79, proximal RCA EAT 10.23 ± 2.42, mid RCA EAT 9.26 ± 2.72, distal RCA EAT 7.25 ± 2.58. Statistically highly significant difference was observed between the two groups with regards to LM EAT, proximal, mid and distal LAD EAT, proximal and distal LCX EAT, proximal, mid and distal RCA EAT (8.38 ± 2.18 Vs 11.77 ± 1.94 P: 0.000, 8.49 ± 2.21 Vs 12.18 ± 2.00, 7.93 ± 1.77 Vs 10.81 ± 2.16, 5.45 ± 1.26 Vs 7.82 ± 1.68 P: 0.000, 7.08 ± 1.34 Vs 9.46 ± 1.67, 6.05 ± 1.50 Vs 7.89 ± 1.61 P: 0.000, 9.01 ± 1.94 Vs 11.88 ± 1.99, 8.07 ± 2.32 Vs 10.86 ± 2.39, 6.31 ± 2.26 Vs 8.51 ± 2.45 P: 0.000; respectively). Statistically highly significant difference was observed between the two groups with regards calcium score and the severity of CAD in the three major vessels (LAD, LCX and RCA) and the total calcium score in all vessels (35 (16 – 85.5) Vs 179.5 (59.5 – 243) P: 0.000, 20.5 (7 – 50.5) Vs 56 (33 – 95) P: 0.000, 31 (9 – 54) Vs 97 (54 – 199) P: 0.000, 12 (0 – 84) Vs 286 (106 – 511) P:0.000; respectively) while calcium score in the LM was not statistically significant with the severity of CAD (4 (3 – 26) Vs 12 (9 – 16) P: 0.360). As regards aortic valve calcification there was statistically highly significant difference between the two groups; P value 0.000, while mitral valve calcification was found to be not statistically significant between the two groups P: 0.272. Conclusion The present study demonstrated a significant correlation between the peri-coronary epicardial adipose tissue, coronary calcification and aortic valve calcification and the severity of the coronary artery disease.

Aortic valve calcification among elderly males from the general population, associated echocardiographic findings, and clinical implications

Aims Aortic valve calcification (AVC) detected by non-contrast computed tomography (NCCT) associates with morbidity and mortality in patients with aortic valve stenosis. However, the importance of AVC in the general population is sparsely evaluated. We intend to describe the associations between AVC score on NCCT and echocardiographic findings as left atrial (LA) dilatation, left ventricular (LV) hypertrophy, aortic valve area (AVA), peak velocity, mean gradient, and aortic valve replacement (AVR) in a population with AVC scores ≥300 AU. Methods and results Of 10 471 males aged 65–74 years from the Danish Cardiovascular Screening trial (DANCAVAS), participants with AVC score ≥300 AU were invited for transthoracic echocardiography and 828 (77%) of 1075 accepted the invitation. AVC scores were categorized (300–599, 600–799, 800–1199, and ≥1200 AU). AVR was obtained from registries. AVC was significantly associated with a steady increase in LA dilation (10.5%, 16.3%, 15.8%, 19.6%, P = 0.031), LV hypertrophy (3.9%, 6.6%, 8.9%, 10.1%, P = 0.021), peak velocity (1.7, 1.9, 2.1, 2.8 m/s, P = 0001), mean gradient (6, 8, 11, 19 mmHg, P = 0.0001), and a decrease in AVA (2.0, 1.9, 1.7, 1.3 cm2, P = 0.0001). The area under the curve was 0.79, 0.93, and 0.92 for AVA ≤1.5 cm2, peak velocity ≥3.0 m/s, and mean gradient ≥20 mmHg, respectively, and the associated optimal AVC score thresholds were 734, 1081, and 1019 AU. AVC &gt; 1200 AU was associated with AVR (P &lt; 0.0001). Conclusion Among males from the background population, increasing AVC scores were associated with LA dilatation, LV hypertrophy, AVA, peak aortic velocity, mean aortic gradient, and AVR.

Head-to-Head Comparison of Different Software Solutions for AVC Quantification Using Contrast-Enhanced MDCT

Aortic valve calcification (AVC) in aortic stenosis patients has diagnostic and prognostic implications. Little is known about the interchangeability of AVC obtained from different multidetector computed tomography (MDCT) software solutions. Contrast-enhanced MDCT data sets of 50 randomly selected aortic stenosis patients were analysed using three different software vendors (3Mensio, CVI42, Syngo.Via). A subset of 10 patients were analysed twice for the estimation of intra-observer variability. Intra- and inter-observer variability were determined using the ICC reliability method, Bland-Altman analysis and coefficients of variation. No differences were revealed between the software solutions in the AVC calculations (3Mensio 941 ± 623, Syngo.Via 948 mm3 ± 655, CVI42 941 ± 637; p = 0.455). The best inter-vendor agreement was found between the CVI42 and the Syngo.Via (ICC 0.997 (CI 0.995–0.998)), followed by the 3Mensio and the CVI42 (ICC 0.996 (CI 0.922–0.998)), and the 3Mensio and the Syngo.Via (ICC 0.992 (CI 0.986–0.995)). There was excellent intra- (3Mensio: ICC 0.999 (0.995–1.000); CVI42: ICC 1.000 (0.999–1.000); Syngo.Via: ICC 0.998 (0.993–1.000)) and inter-observer variability (3Mensio: ICC 1.000 (0.999–1.000); CVI42: ICC 1.000 (1.000–1.000); Syngo.Via: ICC 0.996 (0.985–0.999)) for all software types. Contrast-enhanced MDCT-derived AVC scores are interchangeable between and reproducible within different commercially available software solutions. This is important since sufficient reproducibility, interchangeability and valid results represent prerequisites for accurate TAVR planning and its widespread clinical use.

Cross-sectional study of aortic valve calcification and cardiovascular risk factors in older Danish men

ObjectiveAortic valve calcification (AVC) and coronary artery calcification (CAC) are predictors of cardiovascular disease (CVD), presumably sharing risk factors. Our objectives were to determine the prevalence and extent of AVC in a large population of men aged 60–74 years and to assess the association between AVC and cardiovascular risk factors including CAC and biomarkers.MethodsParticipants from the DANish CArdioVAscular Screening and intervention trial (DANCAVAS) with AVC and CAC scores and without previous valve replacement were included in the study. Calcification scores were calculated on non-contrast CT scans. Cardiovascular risk factors were self-reported, measured or both, and further explored using descriptive and regression analysis for AVC association.Results14 073 men aged 60–74 years were included. The AVC scores ranged from 0 to 9067 AU, with a median AVC of 6 AU (IQR 0–82). In 8156 individuals (58.0%), the AVC score was >0 and 215 (1.5%) had an AVC score ≥1200. In the regression analysis, all cardiovascular risk factors were associated with AVC; however, after inclusion of CAC ≥400, only age (ratio of expected counts (REC) 1.07 (95% CI 1.06 to 1.09)), hypertension (REC 1.24 (95% CI 1.09 to 1.41)), obesity (REC 1.34 (95% CI 1.20 to 1.50)), known CVD (REC 1.16 (95% CI 1.03 to 1.31)) and serum phosphate (REC 2.25 (95% CI 1.66 to 3.10) remained significantly associated, while smoking, diabetes, hyperlipidaemia, estimated glomerular filtration rate and serum calcium were not.ConclusionsAVC was prevalent in the general population of men aged 60–74 years and was significantly associated with all modifiable cardiovascular risk factors, but only selectively after adjustment for CAC ≥400 AU.Trial registration numberNCT03946410 and ISRCTN12157806.