Mylène Shen

Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis : results from the PROGRESSA study

Aims Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS. Methods and results The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure ≥140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile–75th percentile]: +370 [126–824] vs. +157 [58–303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVCdensity: +96 [34–218] vs. +45 [14–82] AU/cm2, P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVCdensity (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3–199] vs. +41 [0–156] AU, P = 0.88). Conclusion This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS.

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 (ρ=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 (ρ=0.61, p<0.0001) but weak correlation in the BAV group (ρ=0.32, p=0.046). In the TAV group, the strength of the AVCd–MG correlation was similar in younger (<72 years old; ρ=0.59, p<0.0001) versus older (≥72 years old; ρ=0.61, p<0.0001) patients. In the BAV group, there was no correlation between AVCd and MG in younger patients (<51 years old; ρ=0.12, p=0.65), whereas there was a good correlation in older patients (≥51 years old; ρ=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. Trial registration number NCT01679431; Pre-results.

Impact of left ventricular remodelling patterns on outcomes in patients with aortic stenosis

Aims The objective of this study was to examine the association between the different patterns of left ventricular (LV) remodelling/hypertrophy on all-cause and cardiovascular mortality in patients with aortic stenosis (AS). Methods and results In total, 747 consecutive patients (69 ± 14 years, 57% men) with AS and preserved LV ejection fraction were included in this study. According to LV mass index and relative wall thickness, patients were classified into four LV patterns: normal, concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). One hundred and sixteen patients (15%) had normal pattern, 66 (9%) had EH, 169 (23%) had CR, and 396 (53%) had CH. During a median follow-up of 6.4 years, 339 patients died (242 from cardiovascular causes). CH was associated with higher risk of all-cause mortality compared with the three other LV patterns (all P < 0.05). After multivariable adjustment, CH remained associated with higher risk of mortality (HR = 1.27, 95% CI 1.01-1.61, P = 0.046). There was a significant interaction (P < 0.05) between sex and CH with regards to the impact on mortality: CH was associated with worse outcome in women (P = 0.0001) but not in men (P = 0.22). In multivariable analysis, CH remained associated with higher risk of worse outcome in women (HR = 1.56, 95% CI 1.08-2.24, P = 0.018). Conclusions This study shows that CH was independently associated with increased risk of mortality in AS patients with preserved ejection fraction. This association was observed in women but not in men. The pattern of LV remodelling/hypertrophy should be integrated in the risk stratification process in patients with AS.

Impact of Vascular Hemodynamics on Aortic Stenosis Evaluation: New Insights Into the Pathophysiology of Normal Flow—Small Aortic Valve Area—Low Gradient Pattern

Background About 50% of normal‐flow/low‐gradient patients (ie, low mean gradient [MG] or peak aortic jet velocity and small aortic valve area) have severe aortic valve calcification as measured by computed tomography. However, they are considered to have moderate aortic stenosis (AS) in current American College of Cardiology/American Heart Association guidelines. The objective was thus to evaluate the effect of hypertension and reduced arterial compliance (rAC) on MG and Vpeak measurements. Methods and Results Doppler‐echocardiography was performed in 4 sheep with experimentally induced severe and critical AS at: (1) normal aortic pressure, (2) during hypertension, and (3) with rAC. Hypertension and rAC induced a substantial decrease in MG/Vpeak compared with normal stage (both P≤0.03) despite a stable transvalvular flow (P>0.16). Hypertension and rAC resulted in a greater reduction of MG in critical (−42%) compared with severe (−35%) AS (P˂0.0001). Comprehensive Doppler‐echocardiography and computed tomography were performed in 220 AS patients (mean age: 69±13 years; MG 29±18 mm Hg) with normal flow. The population was divided in 3 groups according to the presence of hypertension and rAC. The slope of the linear association between MG/Vpeak and aortic valve calcification divided by the cross‐sectional area of the aortic annulus was significantly reduced in patients with hypertension and/or rAC compared with normotensive/normal AC patients (P<0.01). Accordingly, patients with normal‐flow/low‐gradient and severe aortic valve calcification density were more frequent in hypertension and rAC groups compared with the normotensive/normal‐AC group (16% and 12% compared with 2%; P=0.03). Conclusions Hypertension and rAC are associated with a substantial reduction in MG/Vpeak for similar aortic valve calcification (ie, similar AS anatomic severity), which may lead to underestimation of AS hemodynamic severity.

Impact of Aortic Valve Calcification and Sex on Hemodynamic Progression and Clinical Outcomes in AS

Aortic valve calcification (AVC) is the main culprit lesion of calcific aortic valve stenosis (AS) and is a strong determinant of AS severity and powerful risk factor for mortality [(1,2)][1]. Multidetector computed tomography (MDCT) provides accurate, reproducible quantitation of AVC. Recent

Prevalence of left ventricle non-compaction criteria in adult patients with bicuspid aortic valve versus healthy control subjects

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.

IMPACT OF METABOLIC SYNDROME AND/OR DIABETES ON LEFT VENTRICULAR MASS IN PATIENTS WITH SEVERE AORTIC STENOSIS BEFORE AND AFTER AORTIC VALVE REPLACEMENT

In aortic stenosis (AS), metabolic syndrome (MetS) and diabetes mellitus (DM) are associated with more left ventricular (LV) hypertrophy. We aimed to examine the impact of MetS/DM on LV mass in patients with severe AS referred to aortic valve replacement (AVR) and on the LV mass regression after AVR

Relationship Between Proximal Aorta Morphology and Progression Rate of Aortic Stenosis

Background The aim of this study was to examine the association between abnormal morphology of the proximal aorta and aortic stenosis (AS) progression rate. The main hypothesis was that morphologic changes of the proximal aorta, such as effacement of the sinotubular junction (STJ), result in increased biomechanical stresses and contribute to calcification and progression of AS. Methods Between 2010 and 2012, 426 patients with mild to moderate AS were included in this study. Proximal aortic dimensions were measured at three different levels (i.e., sinus of Valsalva, STJ, and ascending aorta), and sinuses of Valsalva/STJ and ascending aorta/STJ ratios were used to determine degree of aortic deformity. AS progression rate was assessed by annualized increase in mean gradient (median follow‐up time, 3.1 years; interquartile range, 2.6–3.9 years). The degree of aortic flow turbulence was examined in 18 matched patients with and without STJ effacement using cardiac magnetic resonance phase‐contrast imaging. Results Patients’ mean age was 71 ± 13 years, and 64% were men. Patients with low ratios had greater AS progression (P < .05). After comprehensive adjustment, sinuses of Valsalva/STJ (P = .025) and ascending aorta/STJ (P = .027) ratios were independently associated with greater AS progression rate. Compared with patients without STJ effacement, those with effacement of the STJ had higher degrees of aortic flow turbulence (24.4% vs 17.2%, P = .038). Conclusions Effacement of the STJ is independently associated with greater AS progression, regardless of arterial hemodynamics, aortic valve phenotype, or baseline AS severity. Patients with abnormal proximal aortic geometry had disturbed aortic flow patterns. These findings suggest an interrelation between proximal aorta morphology and stenosis progression. HighlightsEffacement of the sinotubular junction is associated with greater aortic stenosis progression.Effacement of the STJ is associated with a higher degree of flow turbulence in the proximal aorta.Proximal aortic root morphology should be factored into the surgical evaluation

Association of Left Ventricular Global Longitudinal Strain With Asymptomatic Severe Aortic Stenosis: Natural Course and Prognostic Value

Importance The optimal timing to operate in patients with asymptomatic severe aortic stenosis (AS) remains controversial. Left ventricular global longitudinal strain (LV GLS) may help to identify patients who might benefit from undergoing earlier aortic valve replacement. Objective To investigate the prevalence of impaired LV GLS, the natural course of LV GLS, and its prognostic implications in patients with asymptomatic severe AS with preserved left ventricular ejection fraction (LVEF). Design, Setting, and Participants This registry-based study included the institutional registries of 3 large tertiary referral centers and 220 patients with asymptomatic severe AS and preserved LVEF (>50%) who were matched for age and sex with 220 controls without structural heart disease. The echocardiograms of patients and controls were performed between 1998 and 2017. Exposures Both clinical and echocardiographic data were assessed retrospectively. Severe AS was defined by an indexed aortic valve area less than 0.6 cm2/m2. Left ventricular global longitudinal strain was evaluated on transthoracic echocardiography using speckle tracking imaging. Main Outcomes and Measures The prevalence of impaired LV GLS, the natural course of LV GLS, and the association of impaired LV GLS with symptom onset and the need for aortic valve intervention. Results Two hundred twenty patients (mean [SD] age, 68 [13] years; 126 men [57%]) were included. Despite comparable LVEF, LV GLS was significantly impaired in patients with asymptomatic severe AS compared with age- and sex-matched controls without AS (mean [SD] LV GLS, −17.9% [2.5%] vs −19.6% [2.1%]; P < .001). After a median follow-up of 12 (interquartile range, 7-23) months, mean (SD) LV GLS significantly deteriorated (−18.0% [2.6%] to −16.3% [2.8%]; P < .001) while LVEF remained unchanged. Patients with impaired LV GLS at baseline (>−18.2%) showed a higher risk for developing symptoms (P = .02) and needing aortic valve intervention (P = .03) at follow-up compared with patients with more preserved LV GLS (⩽−18.2%). Conclusions and Relevance Subclinical myocardial dysfunction that is characterized by impaired LV GLS is often present in patients with asymptomatic severe AS with preserved LVEF. Left ventricular global longitudinal strain further deteriorates over time and impaired LV GLS at baseline is associated with an increased risk for progression to the symptomatic stage and the need for aortic valve intervention.

Impact of Metabolic Syndrome and/or Diabetes Mellitus on Left Ventricular Mass and Remodeling in Patients with Aortic Stenosis before and after Aortic Valve Replacement

In aortic stenosis (AS), metabolic syndrome (MetS), and diabetes mellitus (DM) are associated with more pronounced left ventricular (LV) hypertrophy and more concentric remodeling. We aimed to assess the impact of MetS and DM on LV mass, remodeling, and LV mass regression after aortic valve replacement (AVR) in patients with severe AS. We included 177 patients with severe AS and preserved LV ejection fraction (>50%). All patients underwent a complete echocardiogram before and 1 year after AVR. Forty-seven (27%) patients had MetS, 37 (21%) DM, and 93 (52%) neither MetS nor DM (No MetS-DM). Before AVR, indexed LV mass was higher in MetS and DM groups compared with No MetS-DM group (56.1 ± 14.2, 56.2 ± 18.2 vs 49.2 ± 14.1 g/m2.7, respectively; p <0.01). Prevalence of LV hypertrophy was higher in MetS and DM than in No MetS-DM patients (66%, 65% vs 44%, p <0.01) as well as LV mass to end-diastolic volume ratio (2.10 ± 0.44 and 2.21 ± 0.63 vs 1.96 ± 0.41 g/ml, respectively, p = 0.03). After multivariate analysis, DM and MetS were independently associated with higher baseline LV mass (p <0.05). One year after AVR, decrease in LV mass was significant (p <0.001) in all 3 groups. MetS was independently associated with less LV mass regression and higher LV mass 1 year after AVR. Therefore, MetS and DM patients showed more residual LV hypertrophy than those with No MetS-DM (57%, 38%, and 17%, p <0.01). In conclusion, MetS and DM were associated with higher preoperative LV mass, more LV hypertrophy, and more concentric remodeling. One year after AVR, MetS showed less significant LV mass regression and both DM and MetS persisted with more residual LV hypertrophy.