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

Impact of plasma Lp-PLA2 activity on the progression of aortic stenosis : the PROGRESSA study.

Objectives : The purpose of this prospective study was to examine the relationship between plasma lipoprotein–associated phospholipase A2 (Lp-PLA2) activity and the progression rate of aortic stenosis (AS). Background : We recently reported that Lp-PLA2 is highly expressed in stenotic aortic valves where it may contribute to the mineralization of valvular interstitial cells. Methods : Patients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. AS progression rate was assessed by annualized increase in peak aortic jet velocity (Vpeak), mean gradient (MG), and aortic valve area index (AVAi). Circulating Lp-PLA2 activity was measured and dichotomized based on the median value. Results : Of 183 patients included in this subanalysis of the PROGRESSA study, 70% were men and the mean age was 66 ± 13 years. Over the 2.5 ± 1.4 years of follow up, the AS progression rate tended to be higher in patients with high versus low Lp-PLA2 activity (annualized Vpeak = 0.17 ± 0.23 m/s vs. 0.12 ± 0.18 m/s; p = 0.14). There was a significant interaction (p < 0.05) between baseline AS severity and Lp-PLA2 activity with respect to impact on AS progression rate. In patients with mild AS (i.e., Vpeak <3 m/s; n = 123), increased Lp-PLA2 activity was associated with a significantly faster AS progression rate (Vpeak 0.16 ± 0.18 m/s vs. 0.09 ± 0.14 m/s; p = 0.01) but not in patients with moderate or severe AS (p = 0.99). After adjustment for other risk factors, increased Lp-PLA2 activity remained independently associated with faster AS progression rate (p = 0.005) in the former subset. Conclusions : There was no significant association between plasma Lp-PLA2 activity or mass and stenosis progression in the whole cohort. However, increased Lp-PLA2 activity was associated with a faster stenosis progression rate in the subset of patients with mild AS. These findings provide an impetus for the elaboration of a randomized trial targeting Lp-PLA2 activity in patients with early stages of calcific aortic valve disease

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

Visceral adiposity and left ventricular mass and function in patients with aortic stenosis : the PROGRESSA study

Background : Recent studies have reported that obesity, metabolic syndrome, and diabetes are associated with left ventricular (LV) hypertrophy (LVH) and dysfunction in patients with aortic stenosis (AS). The purpose of this study was to examine the association between amount and distribution of body fat and LVH and systolic dysfunction in AS patients. Methods : One hundred twenty-four patients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study and underwent Doppler echocardiography and computed tomography scan. Presence and severity of LVH was assessed according to LV mass indexed for height2.7 and LV dysfunction according to global longitudinal strain (GLS). Computed tomography was used to quantify abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, and total adipose tissue (TAT). Results : Body mass index (BMI) correlated strongly with TAT (r = 0.85), moderately with VAT (r = 0.70), and SAT (r = 0.69), and weakly with the proportion of VAT (VAT/TAT ratio: r = 0.19). In univariate analysis, greater BMI, TAT, VAT, SAT, and VAT/TAT were associated with increased LV mass index and greater VAT and VAT/TAT ratio were associated with reduced GLS. Multivariate analysis revealed that larger BMI (P < 0.0001) and greater VAT/TAT ratio (P = 0.01) were independently associated with higher prevalence of LVH, and only the VAT/TAT ratio (P = 0.03) was independently associated with reduced GLS. Conclusions : The results of this study suggest that total and visceral adiposity are independently associated with LVH in patients with AS. Furthermore, impairment of LV systolic function does not appear to be influenced by total obesity but is rather related to excess visceral adiposity. These findings provide impetus for elaboration of interventional studies aiming at visceral adiposity in the AS population.De récentes études ont rapporté que l’obésité, le syndrome métabolique et le diabète étaient associés à l’hypertrophie (HVG) et à la dysfonction ventriculaire gauche des patients souffrant d’une sténose aortique (SA). Le but de cette étude était d’examiner le lien entre la quantité et la répartition de la graisse corporelle, l’HVG et la dysfonction systolique chez les patients souffrant d’une SA. Méthodes : Cent vingt-quatre patients souffrant d’une SA ont été recrutés de manière prospective dans l’étude PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis), et ont subi une échocardiographie Doppler et une tomodensitométrie. La présence et la sévérité de l’HVG ont été évaluées au moyen de la masse VG indexée par la taille2.7 et la dysfonction systolique du VG par la déformation longitudinale globale du VG (DLG). La tomodensitométrie a été utilisée pour quantifier le tissu adipeux abdominal viscéral (TAV) et sous-cutané (TAS), et le tissu adipeux total (TAT). Résultats : L’indice de masse corporelle (IMC) corrélait fortement avec le TAT (r = 0,85), modérément avec le TAV (r = 0,70) et le TAS (r = 0,69), et faiblement avec la proportion de TAV (rapport TAV/TAT : r = 0,19). En analyse multivariée, des IMC, TAT, TAV, TAS et VAT/TAT plus élevés étaient associés à une augmentation de la masse VG indexée et un TAV et un rapport TAV/TAT plus élevés étaient associés à la réduction de la DLG. L’analyse multivariée a révélé qu’un IMC plus élevé (P < 0,0001) et un rapport TAV/TAT plus élevé (P = 0,01) étaient indépendamment associés à une HVG plus importante, et seul un rapport TAV/TAT était indépendamment associé à une réduction de la DLG. Conclusions : Les résultats de cette étude montrent que l’adiposité totale et l'adiposité viscérale sont indépendamment associées à une HVG chez les patients souffrant d’une SA. De plus, la détérioration de la fonction systolique VG ne semble pas être influencée par l’obésité totale, mais est plutôt liée à une adiposité viscérale excessive. Ces résultats incitent à l’élaboration d’études interventionnelles visant l’adiposité viscérale dans la population souffrant de SA

Fate and management of tricuspid regurgitation following transcatheter pulmonary valve replacement

Tricuspid regurgitation (TR) is a common anomaly complicating left and right heart disease. In patients with congenital right heart anomalies, TR is highly prevalent, and when severe, it is associated with adverse clinical events. Multiple mechanisms can contribute to TR in these patients including: concomitant congenital anomaly of tricuspid leaflets, presence of pacemaker lead crossing the valve, and anomalies of the right ventricle and tricuspid annulus leading to functional TR. It is important to emphasize the heterogeneity of these mechanisms in individual patients. Functional TR, as an example, can result from the variable combination of annulus dilation, right ventricular (RV) dilation, deformation, and/or systolic dysfunction, which can be attenuated by compensatory leaflet growth to prevent valve regurgitation. These factors are important as they can influence the likelihood of valve repair, thus helping to guide an eventual decision to repair, replace, or leave the valve untouched. There is an increasing role for newer imaging modalities (3-dimensional echocardiography and cardiac magnetic resonance) to assess those variables and guide therapeutic management. Management of TR is controversial in patients with right heart congenital anomalies who are undergoing pulmonary valve (PV) surgery. One important question is the relevance of correcting functional TR when an important proportion of patients will improve their TR spontaneously after pulmonary valve replacement (PVR), suggesting that a conservative approach for TR is acceptable for a large subset of patients. The other dilemma in therapeutic decisionmaking arises from the risk of recurrence of TR after tricuspid annuloplasty, which may be related to continued RV remodeling and tricuspid annulus dilation in the late post-operative phase

Évaluation de la conformité d’une pharmacie satellite d’hémato-oncologie

Résumé Objectif : Évaluer la conformité d’une pharmacie satellite d’hémato-oncologie. Mise en contexte : Le nombre de traitements préparés à la pharmacie satellite d’hémato-oncologie de l’Hôpital de l’Enfant-Jésus du Centre hospitalier affilié universitaire de Québec a considérablement augmenté au fil des années. La parution de l’alerte du National Institute for Occupational Safety and Health concernant la prévention des expositions occupationnelles aux antinéoplasiques et autres médicaments dangereux a mené à une réévaluation du travail à la pharmacie satellite en fonction des normes et recommandations existantes. L’analyse de cinq références pertinentes au travail en salle stérile servant à la préparation de médicaments cytotoxiques a permis d’identifier les situations problématiques et des correctifs pouvant être apportés. Conclusion : Les principales recommandations concernent l’ajout d’un assistant technique et un plan de réaménagement physique de la pharmacie satellite pour y inclure une antichambre et augmenter l’espace de travail disponible. Abstract Objective: To evaluate the conformity of a hematology- oncology satellite pharmacy. Context: The number of treatments prepared at the hematology-oncology satellite pharmacy of the Hôpital de l’Enfant-Jésus (affiliated with the Centre Hospitalier Universitaire du Québec) has increased considerably over the last few years. A notice issued by the National Institute for Occupational Safety and Health regarding prevention of occupational exposure to antineoplastics and to other dangerous medications lead to the re-evaluation of the work being done in the pharmacy satellite as a function of current norms and recommendations. Five references concerning the preparation of cytotoxic medications in an aseptic preparation area were analyzed in order to identify and find solutions to problematic situations. Conclusion: The main recommendations include the addition of a pharmacy technician and a plan to physically reorganize and renovate the satellite pharmacy to include an antechamber and more available work space. Key words: satellite pharmacy, hematology, oncology, evaluation, norm, reorganization, cytotoxic

Enquête québécoise sur la démarche du bilan comparatif des médicaments

RésuméObjectifs : Dresser un état des lieux des pratiques du bilan comparatif des médicaments dans les hôpitaux du Québec en 2016 et obtenir au moyen d’un sondage l’avis des pharmaciens sur l’état actuel et son évolution. Mise en contexte : Les pratiques hétérogènes entourant la conciliation médicamenteuse contribuent à réduire la conformité des pratiques par rapport à celles attendues. Malgré les nombreuses études publiées, il n’existe pas de portrait réel des pratiques actuelles au Québec. Résultats : Vingt-huit chefs de département ont répondu à l’enquête (taux de participation de 82 %). La plupart du temps, le pharmacien participe à la réalisation du meilleur schéma thérapeutique possible, en revanche, les médecins semblent moins s’y investir. Les infirmières et les assistants techniques en pharmacie ont des réponses mitigées sur leur rôle. Au congé des usagers, 59 % des répondants affirment que le pharmacien participe au bilan comparatif des médicaments en préparant ou en validant les ordonnances. Cela représente un pourcentage d’ordonnances de départ validées variant entre 2 et 100 %.Conclusion : Cette étude descriptive fait le point sur les pratiques entourant le bilan comparatif des médicaments dans les établissements de santé du Québec. Un tel bilan implique plusieurs intervenants, en particulier les pharmaciens, les infirmières, les assistants techniques et les médecins. L’utilisation d’outils très divers entraîne un manque d’uniformité de cette démarche dans le réseau. L’information découlant du processus de prescription médicamenteuse semble essentielle pour assurer l’optimisation du processus de conciliation.AbstractObjectives: To provide an overview of medication reconciliation practices in Quebec hospitals in 2016 and to obtain, by means of a survey, pharmacists’ opinions regarding the current state and the evolution of medication reconciliation. Background: The heterogeneity of practices surrounding medication reconciliation contribute to reducing their compliance with the expected practices. Despite the numerous published studies, there is no actual description of the current practices in Quebec. Results: Twenty-eight department heads responded to the survey (participation rate: 82 %). Most often, pharmacists participate in providing the best possible therapeutic regimen, but physicians seem to get less involved. Nurses and pharmacy technical assistants gave mitigated responses regarding their role. Fifty-nine percent of the respondents indicated that the pharmacist participates in medication reconciliation at patient discharge by preparing or verifying the prescriptions, the proportion of discharge prescriptions verified ranging from 2 to 100 %. Conclusion: This descriptive study explores the practices surrounding medication reconciliation in Quebec’s health-care facilities. Medication reconciliation involves several health professionals, notably, pharmacists, nurses, pharmacy technical assistants and physicians. The use of a wide array of tools leads to a lack of uniformity in medication reconciliation in the health-care system. The information from the medication prescribing process seems essential for ensuring the optimization of the reconciliation process

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