Effect of age and aortic valve anatomy on calcification and haemodynamic severity of aortic stenosis

OBJECTIVE: To evaluate the effect of age and aortic valve anatomy (tricuspid (TAV) vs bicuspid (BAV) aortic valve) on the relationship between the aortic valve calcification (AVC) and the haemodynamic parameters of aortic stenosis (AS) severity. METHODS: Two hundred patients with AS and preserved left ventricular ejection fraction were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study and underwent a comprehensive Doppler echocardiography and multidetector CT (MDCT). Mean transvalvular gradient (MG) measured by Doppler echocardiography was used to assess AS haemodynamic severity and AVC was evaluated by MDCT using the Agatston method and indexed to the left ventricular outflow tract area to obtain AVC density (AVCd). All analyses were adjusted for sex. RESULTS: Thirty-nine patients had a BAV and 161 a TAV. Median age was 51 and 72 years for BAV and TAV patients, respectively. There was a modest correlation between MG and AVCd (p=0.51, p<0.0001) in the whole cohort. After dichotomisation for valve anatomy, there was a good correlation between AVCd and MG in the TAV group (p=0.61, p<0.0001) but weak correlation in the BAV group (p=0.32, p=0.046). In the TAV group, the strength of the AVCd-MG correlation was similar in younger (<72 years old; p=0.59, p<0.0001) versus older (=72 years old; p=0.61, p<0.0001) patients. In the BAV group, there was no correlation between AVCd and MG in younger patients (<51 years old; p=0.12, p=0.65), whereas there was a good correlation in older patients (=51 years old; p=0.55, p=0.009). AVCd (p=0.005) and age (p=0.02) were both independent determinants of MG in BAV patients while AVCd (p<0.0001) was the only independent determinant of MG in TAV patients. CONCLUSIONS: In patients with TAV as well as in older patients with BAV, AVCd appears to be the main factor significantly associated with the haemodynamic severity of AS and so it may be used to corroborate AS severity in case of uncertain or discordant findings at echocardiography. However, among younger patients with BAV, some may have a haemodynamically significant stenosis with minimal AVCd. The results of MDCT AVCd should thus be interpreted cautiously in this subset of patients

Effect of regional upper septal hypertrophy on echocardiographic assessment of left ventricular mass and remodeling in aortic stenosis

Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR). Methods: One hundred six patients (mean age, 63 6 15 years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness $ 13 mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis. Results: The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL, +60 6 31 g; BSB, +59 6 32 g; ML, +54 6 32 g; P = .02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias 10 6 20 mL, P < .001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P < .025 vs BL and BSB). Conclusions: Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH

Progression of AS in patients with BAV and TAV

Aims: To compare the progression of aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV). Methods and results: One hundred and forty-one patients with mild-to-moderate AS, recruited prospectively in the PROGRESSA study, were included in this sub-analysis. Baseline clinical, Doppler echocardiography and multidetector computed tomography characteristics were compared between BAV (n = 32) and TAV (n = 109) patients. The 2-year haemodynamic [i.e. peak aortic jet velocity (Vpeak) and mean transvalvular gradient (MG)] and anatomic [i.e. aortic valve calcification density (AVCd) and aortic valve calcification density ratio (AVCd ratio)] progression of AS were compared between the two valve phenotypes. The 2-year progression rate of Vpeak was: 16 (−0 to 40) vs. 17 (3–35) cm/s, P = 0.95; of MG was: 1.8 (−0.7 to 5.8) vs. 2.6 (0.4–4.8) mmHg, P = 0.56; of AVCd was 32 (2–109) vs. 52 (25–85) AU/cm2, P = 0.15; and of AVCd ratio was: 0.08 (0.01–0.23) vs. 0.12 (0.06–0.18), P = 0.16 in patients with BAV vs. TAV. In univariable analyses, BAV was not associated with AS progression (all, P ≥ 0.26). However, with further adjustment for age, AS baseline severity, and several risk factors (i.e. sex, history of hypertension, creatinine level, diabetes, metabolic syndrome), BAV was independently associated with faster haemodynamic (Vpeak: β = 0.31, P = 0.02) and anatomic (AVCd: β = 0.26, P = 0.03 and AVCd ratio: β = 0.26, P = 0.03) progression of AS. Conclusion: In patients with mild-to-moderate AS, patients with BAV have faster haemodynamic and anatomic progression of AS when compared to TAV patients with similar age and risk profile. This study highlights the importance and necessity to closely monitor patients with BAV and to adequately control and treat their risk factors

Bone density and progression of aortic valve stenosis

Background Recent data suggest that there may be an association between low bone mineral density (BMD) and/or altered bone metabolism and calcific aortic stenosis (AS). We examined the association between BMD and faster hemodynamic and anatomic progression rate of AS. Methods and Results One hundred ninety-four patients (65±13 years, 71% men) with AS prospectively recruited in the PROGRESSA study were included in this sub-analysis. Patients underwent Doppler-echocardiography and within 3 months, a multidetector computed tomography (MDCT) exam and a dual X-ray absorptiometry exam. Among all patients included, 162 patients had a follow-up of Doppler-echocardiography exam and 103 patients a follow-up of MDCT exam to determine the annualized hemodynamic (i.e. annualized increase in peak aortic jet velocity [Vpeak]) and anatomic (i.e. annualized increase in aortic valve calcification [AVC]) progression rates of AS, respectively. According to the tertiles of femoral neck BMD, defined by sex-specific thresholds, there were no significant differences in baseline hemodynamic (lower tertile: 2.7 [2.3-3.0] vs. mid-tertile: 2.6 [2.4-3.0] vs. upper tertile: 2.7 [2.5-3.1] m/s, p=0.79) or anatomic (lower tertile: 690 [350-1280] vs. mid-tertile: 577 [253-926] vs. upper tertile: 636 [244-1103] AU, p=0.33) severity of AS (Figure Panel A and B). During a mean follow-up of 2.6±1.3 years, there were no significant differences in hemodynamic (lower tertile: +0.09 [0.02‒0.19] vs. mid-tertile: +0.05 [0.01‒0.18] vs. upper tertile: +0.07 [-0.01‒0.18] m/s/year, p=0.54) and anatomic (lower tertile: +95 [51-166] vs. mid-tertile: +72 [34-122] vs. upper tertile: +87 [29-203] AU, p=0.72) progression rate of AS (Figure Panel C and D). However, patients with osteoporosis (i.e. T-score ≤-2.5; n=8) presented a trend toward or significantly more severe AS at baseline (Vpeak: 2.9 [2.6-3.4] vs. 2.6 [2.4-3.0] m/s, p=0.13 / AVC: 1499 [682-1758] vs. 618 [275-1051] AU, p=0.03), and a trend for faster AS progression rate (Vpeak: +0.20 [0.07‒0.21] vs. +0.07 [0.01‒0.18] m/s/year, p=0.12 / AVC: +163 [68-258] vs. +87 [37-173] AU/year, p=0.58). In multivariable analyses, BMD was not associated with faster AS progression rate (all, p≥0.21), while osteoporosis was significantly associated with hemodynamic progression (p=0.01) but not with anatomic progression of AS (p=0.73), the latter likely related to the lower number of patients. Conclusion In this study, the absence of association between lower BMD and AS progression, may be at least related to the fact that there were very few patients with abnormally low BMD, likely reflecting the fact that the study population was optimally treated for osteoporosis

ApoB/ApoA-I ratio is associated with faster hemodynamic progression of aortic stenosis : results from the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study

Background : Previous studies reported that middle‐aged patients with atherogenic lipoprotein‐lipid profile exhibit faster progression of aortic valve stenosis (AS). The ratio of apolipoprotein B/apolipoprotein A‐I (apoB/apoA‐I) reflects the balance between atherogenic and anti‐atherogenic lipoproteins. The aim of this study was to examine the association between apoB/apoA‐I ratio and AS hemodynamic progression and to determine whether this association varies according to age. Methods and Results : A total of 159 patients (66±13 years, 73% men) with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. Hemodynamic progression of AS was determined by the change in peak aortic jet velocity (Vpeak) measured by Doppler‐echocardiography between baseline and 2‐year follow‐up. Patients in the top tertile of apoB/apoA‐I ratio (≥0.62) had a faster progression rate of AS compared with those in the bottom/mid tertiles (Vpeak progression: 0.30 [0.09˗0.49] versus 0.16 [0.01˗0.36] m/s, P=0.02). There was a significant interaction (P=0.007) between apoB/apoA‐I ratio and age. Among younger patients (ie, aged <70 years; median value of the cohort), those in the top tertile of apoB/apoA‐I ratio had a 3.4‐fold faster AS progression compared with those in the bottom/mid tertiles (Vpeak progression: 0.34 [0.13˗0.69] versus 0.10 [−0.03˗0.31] m/s, P=0.002), whereas there was no significant difference between tertiles in the subgroup of older patients (P=0.83). After comprehensive adjustment, higher apoB/apoA‐I ratio was significantly associated with faster AS progression in the subset of younger patients (all, standardized β≥0.36; P≤0.01). Conclusions : Higher apoB/apoA‐I ratio is significantly associated with faster hemodynamic progression of AS in the younger patients. These findings suggest that atherogenic lipid factors may play a crucial role in the pathogenesis of AS in younger patients, but may be are less important in older patients

Left ventricular asymmetric remodeling and subclinical left ventricular dysfunction in patients with calcific aortic valve stenosis : results from a subanalysis of the PROGRESSA study

Background: LV asymmetric remodeling (LVAR) is a feature commonly found in AS patients and it is presumed to be mainly related to the severity of valve stenosis. The aim of this study was to determine the associated factors and impact on left ventricular (LV) systolic function of LVAR in patients with mild and moderate aortic valve stenosis (AS). Methods: Clinical, Doppler-echocardiographic and computed-tomographic data of 155 AS patients with preserved LV ejection fraction (≥50%) prospectively recruited in the PROGRESSA study (NCT01679431) were analyzed. LVAR was defined as a septal wall thickness ≥ 13 mm and a ratio of septal/posterior wall thickness > 1.5. LV global longitudinal strain (LV-GLS) was available in 129 patients. Plasma levels of N-terminal natriuretic B-type peptides (Nt-proBNP) were also measured. Results: Mean age was 63 ± 15 years (70% men). LVAR was present in 21% (n = 33) of patients. A series of nested multivariate analysis revealed that age was the only factor associated with LVAR (all p ≤ 0.03). Additionally, these patients had higher baseline Nt-proBNP ratio (median [25–75 percentiles]: 1.04 [0.66–2.41] vs. 0.65 [0.33–1.19], p = 0.02), and significantly reduced LV-GLS (17.9[16.6–19.5] vs. 19.3[17.4–20.7] |%|, p = 0.04). A 1:1 matched analysis showed a significant association of LVAR with reduced LV-GLS (17.9[16.6–19.5] vs. 19.8[18.1–20.7] |%|, p = 0.02) and elevated Nt-proBNP (134[86–348] vs. 83[50–179]pg/ml, p = 0.03). Multivariable analysis also revealed that LVAR remains significantly associated with reduced LV-GLS (p = 0.03) and elevated Nt-proBNP (p = 0.001). LVAR was significantly associated with increased risk of major adverse cardiac events and death (Hazard ratio [95% confidence interval]: 2.32[1.28–4.22], p = 0.006). Conclusions: LVAR was found in ~20% of patients with mild or moderate AS and was not related to the degree of AS severity or concomitant comorbidities, but rather to older age. LVAR was significantly associated with reduced LV longitudinal systolic function, increased Nt-proBNP levels, and higher risk of major adverse events and death. These findings provide support for closer clinical and echocardiographic surveillance of patients harboring this adverse LV remodeling feature

Left ventricle non-compaction in bicuspid aortic valve patients

Objective The aim of this study was to compare the prevalence of left ventricle non-compaction (LVNC) criteria (or hypertrabeculation) in a cohort of patients with bicuspid aortic valve (BAV) and healthy control subjects (CTL) without cardiovascular disease using cardiovascular MR (CMR). Methods 79 patients with BAV and 85 CTL with tricuspid aortic valve and free of known cardiovascular disease underwent CMR to evaluate the presence of LVNC criteria. The left ventricle was assessed at end-systole and end-diastole, in the short-axis, two-chamber and four-chamber views and divided into the 16 standardised myocardial segments. LVNC was assessed using the non-compacted/compacted (NC/C) myocardium ratio and was considered to be present if at least one of the myocardial segments had a NC/C ratio superior to the cut-off values defined in previous studies: Jenni et al (>2.0 end-systole); Petersen et al (>2.3 end-diastole); or Fazio et al (>2.5 end-diastole). Results 15 CTL (17.6%) vs 8 BAV (10.1%) fulfilled Jenni et al’s criterion; 69 CTL (81.2%) vs 49 BAV (62.0%) fulfilled Petersen et al’s criterion; and 66 CTL (77.6%) vs 43 BAV (54.4%) fulfilled Fazio et al’s criterion. Petersen et al and Fazio et al’s LVNC criteria were met more often by CTL (p=0.006 and p=0.002, respectively) than patients with BAV, whereas this difference was not statistically significant according to Jenni et al’s criterion (p=0.17). In multivariable analyses, after adjusting for age, sex, the presence of significant valve dysfunction (>mild stenosis or >mild regurgitation), indexed LV mass, indexed LV end-diastolic volume and LV ejection fraction, BAV was not associated with any of the three LVNC criteria. Conclusion Patients with BAV do not harbour more LVNC than the general population and there is no evidence that they are at higher risk for the development of LVNC cardiomyopathy