P905Association of ionized serum magnesium with progression of aortic valve calcification

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Mary ◽  
H Issa ◽  
A Boullier ◽  
L Henaut ◽  
C Avondo ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Prospective Cohort ◽  
Serum Magnesium ◽  
Left Ventricular ◽  
Valve Disease ◽  
Aortic Valve Area ◽  
Aortic Valve Calcification ◽  
Normal Range ◽  
Valve Calcification

Abstract Background Calcific aortic valve disease (CAVD) is the most common heart valve disease among adults. It is a progressive disease whose final step leads to severe aortic stenosis (AS). Pharmacotherapeutic strategies aimed to limit the progression of valve leaflet calcification could be beneficial to slow-down the CAVD progression and to preserve left ventricular function. Several recent clinical studies demonstrated that lower serum magnesium (Mg) level is associated with vascular calcification. Whether serum magnesium is a determinant of aortic calcific stenosis progression remains unkwown. Methods In an ongoing prospective cohort of AS patients (COFRASA/GENERAC) we studied the association between serum Mg with the aortic valve calcification prevalence and progression. Serum Mg was measured at baseline in both its ionized (iMg) and total (tMg) forms. AS stenosis severity was evaluated at baseline and yearly thereafter using mean pressure gradient (MPG), the aortic valve area indexed to body surface (AVAi) assessed by echocardiography and the degree of aortic valve calcification (AVC) assessed by computed tomography. Annual progression was calculated as: (final measurement − baseline measurement)/follow-up duration. Results We enrolled 356 patients (73.1±10 years, 73% men), the mean follow-up duration was 2.5±2 years. There was a highly significant correlation between iMg and t Mg concentrations values (r=0.85, p<0.0001). Approximately 37% and 25% of patients have respectively iMg values ≤0.45 mmol/L (normal range 0.45–0.60 mmol/L) and t Mg ≤0.80 mmol/L (normal range 0.80–0.95 mmol/L). At baseline, lower i Mg and t Mg were significantly associated with sex, diabètes, lower heamoglobin and hypertension but not with AVC neither with MPG or AVAi. After mean follow-up of 2.5±2 years, the annual mean Log AVC progression was significantly greater (p=0.01) in patients with values of iMg ≤0.45 mmol/L (2,04±0.73) as compared to patients with iMg >0,45 mmol/L (1.78±0.94). Annual Mean MGP and AVAi also progressed greater in patients with low iMg but without reaching a significant level. Similar association was not found with tMg. In multivariate analysis, iMg remained significantly associated with the progression of AVC (odds ratio per 0.1 mmol/L increment [95% confidence interval] = 0.36 [0.15–0.83]; p=0.015) independently of age, tMg, glucose, type 2 diabetes, Tobacco use, baseline AVC, MPG and AVAi. Conclusion In a prospective cohort of asymptomatic patients with a wide range of AS severity, low serum ionized Mg but not low total Mg was independently associated with AVC progression. Acknowledgement/Funding ANR -RHU-STOPAS

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

2021 ◽  
Author(s):  
Lida Khurrami ◽  
Jacob Eifer Møller ◽  
Jes Sanddal Lindholt ◽  
Jordi Sancez Dahl ◽  
Maise Hoeigaard Fredgart ◽  
...  
Keyword(s):  
Aortic Valve ◽  
General Population ◽  
Peak Velocity ◽  
Left Ventricular ◽  
Steady Increase ◽  
Aortic Valve Area ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Background Population ◽  
Echocardiographic Findings

Abstract 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.

Abstract P098: Inhibitory Role of Notch1 in Calcific Aortic Valve Disease Is Mediated by Sox9

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Chetan P Hans ◽  
Asha Acharya ◽  
Sara N Koenig ◽  
Haley A Nichols ◽  
Cristi L Galindo ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Aortic Valve Disease ◽  
Notch Signaling Pathway ◽  
Valve Disease ◽  
Calcium Deposition ◽  
Aortic Valve Calcification ◽  
Calcific Aortic Valve Disease ◽  
Valve Calcification

Introduction: Aortic valve calcification is the most common form of valvular heart disease; however the mechanism(s) underlying calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. Objective: To investigate the molecular changes associated with the calcification of aortic valve that occurs with inhibition of Notch signaling. Methods and Results: The expression of Notch signaling pathway members was validated in the aortic valve cusps from adult mice, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1 signaling, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of many cartilage-specific genes that constitute the valve extracellular matrix (ECM). Analysis of these cartilage-specific genes demonstrated that several were transcriptional targets of Sox9, a master regulator of chondrogenesis, which has been previously shown to be essential for proper valve development and maintenance. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, utilizing transfection studies, addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. Conclusions: Loss of Notch signaling contributes to aortic valve calcification by a Sox9-dependent mechanism. Further elucidation of the Notch1-Sox9 molecular pathway and its role in the maintenance of the ECM will lead to an improved mechanistic understanding of aortic valve calcification and development of novel therapeutic strategies for CAVD.

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

2022 ◽  
Author(s):  
Axel Diederichsen ◽  
Jes Sanddal Lindholt ◽  
Jacob Eifer Møller ◽  
Oke Gerke ◽  
Lars Melholt Rasmussen ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Sex Differences ◽  
Aortic Valve ◽  
General Population ◽  
Incidence Rate ◽  
Interquartile Range ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Factors Associated

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.

Abstract 15775: The Impact of B-type Natriuretic Peptide Activation on the Association of Left Ventricular Longitudinal Strain With All-cause Mortality

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zi Ye ◽  
Maurice Enriquez-Sarano ◽  
Joseph Malouf ◽  
Hector I Michelena ◽  
Allan S Jaffe ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Natriuretic Peptide ◽  
Longitudinal Strain ◽  
Left Ventricular ◽  
Aortic Valve Area ◽  
Increased Risk ◽  
Highly Correlated ◽  
The Impact ◽  
Normal Lvef

Introduction: Left ventricular longitudinal strain (LV-LS) 1) predicts mortality in patients with aortic stenosis (AS) and 2) is highly correlated to type-B natriuretic peptide (BNP) values. The BNP ratio (measured BNP/maximal expected BNP value specific for age and sex) is a powerful independent predictor of death in patients with AS. Hypothesis: we hypothesize that BNP activation (i.e. BNP ratio >1) affects the association between LV-LS and mortality in patients with asymptomatic AS and preserved LV ejection fraction (EF ≥50%). Methods: 315 patients (age 74±12 years, 56% men and mean aortic valve area = 1.02±0.15cm2) underwent simultaneous Doppler echocardiographic and BNP measurements. LV-LS was calculated as the average of 12 LV segments from apical 2- and 4-chamber views using Velocity Vector Imaging. Results: Mean LV-LS was -16.8±3.2%, LV EF 66±7%, median BNP level 121 (interquartile 48-320) pg/ml. 58% of patients had BNP activation. Better LV-LS was associated with lower log BNPratio (regression coefficient 0.10, p<0.001). After a median follow-up of 6.5 yrs (interquartile: 3.6-8.2), 119 deaths occurred. After adjustment for age, sex, Charlson score index, hemoglobin level, aortic valve replacement (as a time dependent variable), LV-LS and log BNPratio were separately associated with increased risk for death (all p<0.01). Further adjustment for predictors of mortality, LV-LS and log-BNP ratio remained associated with increased risk for death (hazard ratio HR [95%CI]: 1.09 [1.03-1.15]; p=0.003 and 1.82 [1.52-2.19]; p<0.0001 respectively). In patients without BNP activation (i.e. normal BNP), LV-LS was associated with mortality (HR: 1.22 [1.04-1.43]; p=0.01) while it was not in patients with BNP activation (p=0.22). Conclusions: In patients with asymptomatic AS, without clinically obvious myocardial impairment (i.e. normal LVEF), a notable proportion of patients present with myocardial alterations detected by an elevated BNPratio or reduced LV-LS. These signs of myocardial alterations were predictive of mortality after diagnosis. Thus both BNP and LV-LS should be assessed in the clinical setting to provide complementary information on prognosis in patients with asymptomatic AS and preserved LV EF.

Abstract 6145: Low Fetuin-A Concentrations Predict the Progression of Aortic Valve Calcification in Non-Dialyzed Patients

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ralf Koos ◽  
Vincent Brandenburg ◽  
Andreas Horst Mahnken ◽  
Georg Mühlenbruch ◽  
Sven Stanzel ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Smoking Status ◽  
Serum Levels ◽  
Valve Disease ◽  
Analysis Of Covariance ◽  
Human Antibody ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Fetuin A

Human fetuin-A (alpha 2 -Heremans Schmid glycoprotein) has been identified as the most potent circulating inhibitor of vascular and soft-tissue calcification. We aimed to investigate the relationship between the serum fetuin-A level and the progression of aortic valve calcification (AVC) assessed by retrospectively ECG-gated Multislice Spiral Computed Tomography (MSCT) in patients with calcific aortic valve disease. A prospective study in 77 non-dialyzed patients (mean age 70 ± 8 years) with echocardiographically proven aortic valve disease was performed. In all patients serum fetuin-A levels were measured by nephelometry (BNII, Dade Behring Holding, Liederbach, Germany) using a polyclonal rabbit anti-human antibody against fetuin-A. For quantification of AVC all patients underwent 16-slice MSCT (Sensation 16, Siemens, Forchheim, Germany with scan parameters as follows: 420ms tube rotation time, 12× 0.75mm collimation, tube voltage 120KV). After a mean follow-up of 12.6 ± 1.4 months a second non-enhanced MSCT examination for quantification of AVC was performed. Images were reconstructed at 60% of the RR interval. AVC was assessed using Agatston AVC score. In multifactorial analysis of covariance including fetuin-A levels, baseline AVC score, the covariables sex, age, body mass index, C-reactive protein, glomerular filtration rate, serum lipids, diabetes, smoking status and hypertension, only fetuin-A levels revealed a significant effect on the progression of AVC (p<0.001). Post-hoc analysis demonstrated that patients with baseline fetuin-A levels lower than the median of the cohort (0.72g/l) showed a significantly higher increase of AVC scores (34.6 ± 31.4%, n=39) than patients with fetuin-A levels larger than the median (10.0 ± 11.2%, p<0.001) despite comparable baseline AVC scores. Vice versa, patients with progressive AVC > 10% (n=48, 62%) had lower fetuin-A serum levels at baseline than non-progressors (n=29, 38%; 0.66±0.13g/L versus 0.82±0.11 g/L, p<0.001). The present study suggests that low fetuin-A serum levels indicating systemic calcification inhibitor deficiency were associated with increased progression of AVC independently of the renal function.

Abstract 15609: Risk of Aortic Valve Disease and Aortopathy in Patients With Bicuspid Aortic Valve Referred to a Central County Hospital in Denmark

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kristina Procida ◽  
Riina Oksjoki ◽  
Sandra Wulffeld ◽  
Dorthe Guldbrand Nielsen ◽  
Soren Schmiegelow ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Valve Disease ◽  
Left Ventricular ◽  
Valve Disease ◽  
Left Ventricular Ejection ◽  
Aortic Valve Area ◽  
Ventricular Ejection Fraction

Introduction: Patients with bicuspid aortic valve (BAV) are at increased risk of developing severe aortic valve disease and aortopathy at an early age. We therefore performed a retrospective study to describe all patients diagnosed with BAV in an entire region of Denmark. Methods: We included patients≥18 years old with BAV, who had a transthoracic echocardiography (TTE) at our hospital before May 2020, and through electronic health records and our echocardiography database, we achieved baseline data. Results: A total of 545 patients with BAV (74.1% men) were identified. At the time of BAV diagnosis the median age was 54 years (IQR 42-62), and the causes for referral to TTE were primarily chest discomfort (21.1%), dyspnea (17.6%), or a newly discovered murmur (40.0%). Upon diagnosis 19.3% of the patients had an aortic valve area (AVA)<1,0 cm 2 , 2.4% had severe aortic regurgitation and the majority (84.0%) had normal left ventricular ejection fraction. The ascending aorta was dilated in 51.9% of the patients while aortic coarctation was found in 5.1% of all patients. According to Sievers BAV classification 24.4% (N=133) had Type 0, 58.7% (N=320) had Type 1 left/right(L/R) fusion, 10.6% (N=58) had Type 1 right/noncoronary (R/N) fusion, 2.6% (N=14) had Type 1 left/noncoronary (L/N) fusion and 2.2% (N=12) had Type 2. Coexisting diabetes mellitus (10.1%), ischemic heart disease (13.2%) and chronic obstructive pulmonary disease (10.1%) was low, whereas hypertension was frequent (47.9%). The majority had sinus rhythm (75.6%) and normal eGFR (84.4%). Surgery was performed in 37.3% (N=203) of all patients and primarily due to aortic valve stenosis (N=172, 84.7%). Surgery was performed in a higher frequency of patients with Sievers Type 1 L/N fusion (N=9, 4.4%; 64.3% of all Type 1 L/N) and Type 2 (N=10, 4.9%, 83.3% of all Type 2) and lowest in patients with Sievers Type 0 (N=35, 17.2%; 26.3% of all Type 0). However, likelihood of surgery was only significantly different between patients with BAV Type 2 and Type 1 L/R (OR 14.21 (2.83-71.35). Conclusion: In this cohort of patients with BAV a higher fraction of patients with BAV type 1 L/N and BAV type 2 required valve replacement compared with particularly BAV type 0 suggesting important differences according to BAV subtype.

Impact of pericoronary inflammation assessed by coronary computed tomography angiography on the progression of aortic valve calcification

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Misawa ◽  
T Sugiyama ◽  
Y Kanaji ◽  
M Hoshino ◽  
M Yamaguchi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Aortic Valve ◽  
Computed Tomography Angiography ◽  
Coronary Computed Tomography Angiography ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Coronary Computed Tomography ◽  
The Mean ◽  
The Impact

Abstract Background Aortic valve calcification (AVC) has been known as an independent predictor for adverse cardiovascular events and all-cause mortality. Previous studies demonstrated that AVC was associated with aortic valve inflammation and atherosclerosis. However, the relationship between the progression of AVC and pericoronary inflammation remains undetermined. Purpose The purpose of this study was to evaluate the impact of the pericoronary inflammation on the progression of AVC. Methods A total of 107 patients with suspected or known chronic coronary syndromes who underwent clinically indicated serial 320-slice coronary computed tomography angiography (CTA) at Tsuchiura Kyodo General Hospital from January 2011 to June 2019 were retrospectively studied. Pericoronary inflammation was assessed by pericoronary adipose tissue attenuation (PCATA) defined as the mean CT attenuation value of PCATA (−190 to −30 Hounsfield units [HU]) on proximal 40 mm segments of coronary arteries. AVC was quantified by Agatston score on CTA. The mean aortic attenuation (HU Aorta) and the standard deviation (SD) in the region of interest at the level of the sinotubular junction was measured. AVC was defined as the threshold for calcium detection (mean HU Aorta + 2SD). AVC index was calculated as follows: (follow-up/baseline) AVC divided by follow-up period. AVC progression was defined as newly-developed AVC at follow-up or an increased AVC index during follow-up. All patients were divided into two groups according to the presence or absence of AVC progression, and clinical characteristics and CT findings were compared between these two groups. Results AVC progression was observed in 26 patients (24.3%) between 2 serial CT examinations (median, 34 months). There was no significant difference in age, gender and the prevalence of other cardiovascular risk factors between the 2 groups. Patients in AVC progression group were associated with higher prevalence of elevated PCATA-LAD, higher LV mass index at baseline and the initial AVC presence. Receiver-operating characteristic curve analysis revealed that the optimal cut off value of PCATA-LAD for predicting AVC progression was −68.26 HU (area under the curve 0.605; 95% confidence interval [CI], 0.465–0.745). Multivariable logistic regression analysis revealed that baseline PCATA-LAD ≥−68.26 HU (odds ratio [OR], 3.12; 95% CI, 1.04–9.35, p=0.042) and the presence of baseline positive AVC (OR, 6.84; 95% CI, 2.34–20.0, p=0.0004) were independent predictors of AVC progression. Conclusions The increased pericoronary inflammation and the presence of AVC may help identify patients with high risk for future AVC progression. Funding Acknowledgement Type of funding source: None

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