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Structural and Histochemical Alterations in the Aortic Valves of Elderly Patients: A Comparative Study of Aortic Stenosis, Aortic Regurgitation, and Normal Valves.

ABSTRACT: The aim of this study was to reveal the pathogenesis of aortic stenosis (AS) and regurgitation (AR) by comparing differences in mechanical and biochemical alterations. We applied scanning acoustic microscopy (SAM) to measure the speed of sound (SOS) through valves to estimate the elasticity and monitor sensitivity to protease treatment, as the SOS is correlated with the stiffness of materials, which is reduced after digestion by proteases. The fibrosa of both the AS and AR groups were stiffer than the fibrosa of the normal group. The AR group displayed significantly stiffer fibrosa than the AS group, with the exception of calcified areas. The AS group showed significantly decreased SOS values following protease digestion, whereas the AR showed little reduction. The AS group presented type III collagen in the fibrosa and the ventricularis. In the AR group, both type I collagen and type III collagen coexisted in the fibrosa and the ventricularis. Upon immunostaining for advanced glycation end-products, the AS group showed sparse, weak staining, whereas the AR group presented a strong, band-like positive reaction in the fibrosa. In conclusion, tissue remodelling associated with damage and repair is associated with AS pathogenesis, whereas static chemical alterations with slow collagen turnover induce AR.

SUBMITTER: Miura K

PROVIDER: S-EPMC5056004 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Structural and Histochemical Alterations in the Aortic Valves of Elderly Patients: A Comparative Study of Aortic Stenosis, Aortic Regurgitation, and Normal Valves.

Miura Katsutoshi K Katoh Hideki H

BioMed research international 20160925

The aim of this study was to reveal the pathogenesis of aortic stenosis (AS) and regurgitation (AR) by comparing differences in mechanical and biochemical alterations. We applied scanning acoustic microscopy (SAM) to measure the speed of sound (SOS) through valves to estimate the elasticity and monitor sensitivity to protease treatment, as the SOS is correlated with the stiffness of materials, which is reduced after digestion by proteases. The fibrosa of both the AS and AR groups were stiffer th ...[more]

PMID: 27747234

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Project description:OBJECTIVES:To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). METHODS:MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57?±?0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. RESULTS:The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p?<?0.001), but there were no significant differences in AA distensibility (p?=?0.099), DA distensibility (p?=?0.498) or PWV (p?=?0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. CONCLUSIONS:In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. KEY POINTS:• Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I.

Project description:AimsConcurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR.Methods and resultsIn patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all-cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2 ), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00-4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13-9.47; P = 0.028). In the overall cohort, mitral annulus diameter < 3 cm (OR 1.74, 95% CI 1.02-2.97; P = 0.041) and QRS duration < 115 ms (OR 1.73, 95% CI 1.00-2.98; P = 0.049) were independently associated with improvement in MR. During median follow-up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90-3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40-8.05; P < 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44-3.47; P = 0.68).ConclusionsIn nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm2 in functional MR, and mitral annulus diameter < 3 cm and QRS duration < 115 ms in the overall population were associated with MR improvement. Post-operative improvement in organic MR was associated with better survival.

Project description:BackgroundThere is a lack of available data on specific prognostic comparisons between transcatheter aortic valve replacement (TAVR) using self-expandable valves (SEV) in patients with stenotic Type 0, Type 1 bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).ObjectivesTo evaluate the association between aortic valve morphology and outcomes following self-expandable TAVR.MethodsConsecutive patients with aortic stenosis(AS) undergoing self-expandable TAVR were enrolled and categorized into three groups (Type 0/Type 1 BAV or TAV) according to the Sievers classification. The primary endpoint was a composite of all-cause mortality and rehospitalization for heart failure (HF) within 2 years. Secondary outcomes included procedural complications and major cardiovascular events observed in clinical follow-ups. Clinical outcomes at 2 years following TAVR were compared among three groups using Kaplan-Meier curve and multivariable Cox proportional hazards regression models.ResultsA total of 344 AS patients (Type 0: 86; Type 1: 109; TAV: 149) were enrolled. The presence of moderate or severe paravalvular leak (PVL) was significantly higher in patients with Type 0 and Type 1 BAV versus TAV (10.47% vs. 16.51% vs. 6.71%, p = 0.043). All-cause 30-day mortality (2.33% vs. 0.92% vs. 2.68%, p = 0.626) and 2-year mortality (3.49% vs. 5.50% vs. 6.71%, p = 0.657) was comparable among the three groups. However, rehospitalization for HF within 2 years was significantly higher in Type 1 BAV (11.63% vs. 20.18% vs. 8.72%, p = 0.020). Multivariate Cox analysis showed that a higher STS score, Type 1 BAV morphology and excess leaflet calcification (≥ median calcium volume (CV) of the entire population) were independent predictors for HF rehospitalization. Additional intragroup Kaplan‒Meier analysis showed that excess leaflet calcification could predict higher long-term mortality and rehospitalization risk for HF(HR (95% CI): 3.430 (1.166-10.090), log rank p = 0.017) in Type 1 BAV patients.ConclusionOutcomes of self-expandable TAVR in BAV-AS patients might vary depending on valve subtypes. BAV patients with excess leaflet calcification and a raphe, especially calcified, had an increased risk of moderate PVL and HF readmission in mid-to-long term follow-ups.

Dataset Information

Structural and Histochemical Alterations in the Aortic Valves of Elderly Patients: A Comparative Study of Aortic Stenosis, Aortic Regurgitation, and Normal Valves.

Publications

Structural and Histochemical Alterations in the Aortic Valves of Elderly Patients: A Comparative Study of Aortic Stenosis, Aortic Regurgitation, and Normal Valves.

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