Numerical investigation on the effect of bileaflet mechanical heart valve's implantation tilting angle and aortic root geometry on intermittent regurgitation and platelet activation.

Platelet activation induced by shear stresses and non-physiological flow field generated by bileaflet mechanical heart valves (BMHVs) leads to thromboembolism, which can cause fatal consequences. One of the causes of platelet activation could be intermittent regurgitation, which arises due to asynchronous movement and rebound of BMHV leaflets during the valve closing phase. In this numerical study, the effect of intermittent regurgitation on the platelet activation potential of BMHVs was quantified by modeling a BMHV in the straight and anatomic aorta at implantation tilt angles 0°, 5°, 10°, and 20°. A fully implicit Arbitrary Lagrangian-Eulerian-based Fluid-Structure Interaction formulation was adopted with blood modeled as a multiphase, non-Newtonian fluid. Results showed that the intermittent regurgitation and consequently the platelet activation level increases with the increasing implantation tilt of BMHV. For the straight aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 20° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 8.5°, 3°, and 0°, respectively. For the anatomic aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 24° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 14°, 10°, and 7°, respectively. For all the implantation orientations of BMHVs, intermittent regurgitation and platelet activation were always higher in the anatomic aorta than in the straight aorta. The study concludes that the pivot axis of BMHV must be implanted parallel to the aortic root's curvature to minimize intermittent regurgitation and platelet activation.

Abnormal cisatracurium pharmacodynamics and pharmacokinetics among patients with severe aortic regurgitation during anesthetic induction.

BACKGROUND: This study was designed to examine whether severe aortic regurgitation will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction. METHODS: A total of 32 patients were divided into two groups: the AR group (n = 16) and the control group (n = 16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 min after intravenous injection of 0.15 mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography. RESULTS: The onset time to maximal neuromuscular block was prolonged from 2.07 ± 0.08 min to 4.03 ± 0.14 min, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P < 0.05) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K12 = 0.19 ± 0.02 and K21 = 0.11 ± 0.01 in the AR group vs. K12=0.26 ± 0.01 and K21 = 0.19 ± 0.01 in the control group, P < 0.01) compared to the control group. CONCLUSION: Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings in this study underlie the importance of muscular blockade monitoring among patients with severe aortic regurgitation during anesthetic induction. REGISTRATION: Name of the registry: Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction. TRIAL REGISTRATION NUMBER: ChiCTR1800019654. Date of registration: November 20th 2018.

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS: We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS: After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS: The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).

High-sensitivity troponin T in asymptomatic severe aortic stenosis.

Background: In asymptomatic severe aortic stenosis (ASAS), treatment decisions are made on an individual basis, and case management presents a clinical conundrum. Methods: We prospectively phenotyped consecutive patients with ASAS using echocardiography, exercise echocardiography, cardiac MRI and biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT) and ST2) (n = 58). The primary endpoint was a composite of cardiovascular death, new-onset symptoms, cardiac hospitalization, guideline-driven indication for valve replacement and cardiovascular death at 12 months. Results: During the first year, 46.6% patients met primary endpoint. In multivariable analysis, aortic regurgitation ≥2 (p = 0.01) and hs-TnT (p = 0.007) were the only independent predictors of the primary endpoint. The best cutoff value was identified as hs-TnT >10ng/L, which was associated with a ∼10-fold greater risk of the primary endpoint (HR, 9.62; 95% CI, 2.27-40.8; p = 0.002). A baseline predictive model including age, sex and variables showing p < 0.10 in univariable analyses showed an area under the curve (AUC) of 0.79(0.66-0.91). Incorporation of hs-TnT into this model increased the AUC to 0.90(0.81-0.98) (p = 0.03). Patient reclassification with the model including hs-TnT yielded an NRI of 1.28(0.46-1.78), corresponding to 43% adequately reclassified patients. Conclusions: In patients with ASAS, hs-TnT >10ng/L was associated with high risk of events within 12 months. Including hs-TnT in routine ASAS management markedly improved prediction metrics.

Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions.

RATIONALE: Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures. OBJECTIVE: To investigate the time course of HMW multimers changes in models and patients with instantaneous induction/reversal of pathological high shear and its related bedside assessment. METHODS AND RESULTS: We investigated the time course of the induction/recovery of HMW multimers defects under instantaneous changes in shear stress in an aortic stenosis rabbit model and in patients undergoing implantation of a continuous flow left ventricular assist device. We further investigated the recovery of HMW multimers and monitored these changes with PFA-CADP in aortic stenosis patients undergoing transcatheter aortic valve implantation or balloon valvuloplasty. Experiments in the aortic stenosis rabbit model and in left ventricular assist device patients demonstrated that induction/recovery of HMW multimers occurs within 5 minutes. Transcatheter aortic valve implantation patients experienced an acute decrease in shear stress and a recovery of HMW multimers within minutes of implantation which was sustained overtime. In patients with residual high shear or with residual aortic regurgitation, no recovery of HMW multimers was observed. PFA-CADP profiles mimicked HMW multimers recovery both in transcatheter aortic valve implantation patients without aortic regurgitation (correction) and transcatheter aortic valve implantation patients with aortic regurgitation or balloon valvuloplasty patients (no correction). CONCLUSIONS: These results demonstrate that variations in von Willebrand factor multimeric pattern are highly dynamic, occurring within minutes after changes in blood flow. It also demonstrates that PFA-CADP can evaluate in real time the results of transcatheter aortic valve procedures.

Troponin I and echocardiography in patients with systemic sclerosis and matched population controls.

OBJECTIVES: Cardiac manifestations in systemic sclerosis (SSc) are associated with poor prognosis. Few studies have investigated cardiac troponins in SSc. We studied the relationships between echocardiographic abnormalities, cardiac biomarkers, and disease manifestations in a population-based cohort of patients with SSc and controls. METHOD: The study comprised 110 patients with SSc and 105 age- and sex-matched population-based controls. We examined ventricular function, heart valves, and estimated pulmonary arterial pressure (ePAP) by echocardiography in all participants. Disease characteristics, manifest ischaemic heart disease (IHD), and measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were tabulated. RESULTS: NT-proBNP and hs-cTnI levels were higher in SSc patients than controls. Both NT-proBNP and hs-cTnI were associated with the presence of echocardiographic abnormalities. Forty-four SSc patients and 23 control subjects had abnormal echocardiograms (p = 0.002). As a group, SSc patients had lower (but normal) left ventricular ejection fraction (LVEF, p = 0.02), more regional hypokinesia (p = 0.02), and more valve regurgitations (p = 0.01) than controls. Thirteen patients and four controls had manifest IHD. Decreased right ventricular (RV) function (n = 7) and elevated ePAP (n = 15) were exclusively detected among SSc patients. CONCLUSIONS: Both NTproBNP and hs-cTnI were associated with echocardiographic abnormalities, which were more prevalent in SSc patients than in controls. Our results thus suggest that hs-cTnI could be a potential cardiac biomarker in SSc. Low RV function and signs of pulmonary hypertension (PH) were uniquely found in the SSc group. SSc patients had more valve regurgitation than controls, an observation that warrants more clinical attention.

Perioperative anticoagulation management during aortic valve replacement complicated by antiphospholipid syndrome.

Patients with antiphospholipid syndrome (APS) are at high-risk for thrombotic and bleeding complications during cardiopulmonary bypass. We report an APS patient who successfully underwent aortic valve replacement while heparin concentrations were monitored using a patient-specific titration curve using viscoelastic coagulation testing.

Clinical impact of paravalvular leaks on biomarkers and survival after transcatheter aortic valve implantation.

BACKGROUND: There is accumulating evidence that up to 20% of the implanted devices after TAVI are associated with a significant degree of paravalvular leaks, which appear to be associated with a negative clinical outcome. METHODS: A total of 355 patients with severe aortic valvular stenosis (AVS) were treated by TAVI (Corevalve n = 222, Edwards Sapien n = 133). Survival, NT-proBNP and the grade of PVL were quantified up to 12 months after implantation. RESULTS: Technical success rate was 97.8%. Thirty-day mortality was 9.6%. Post-procedural transvalvular aortic regurgitation was seen only in a minority of cases (5%), whereas PVL were frequently observed (grade: <1+ in 58.2%, ≥1-<2 in 33.9%, and ≥2 in 7.9%). There was a clear relation-ship between PVL and adverse outcome (P < 0.001). After a transient increase, NT-proBNP showed a significant decline. Interestingly, a PVL ≥2+ was associated with a much higher rise in NT-proBNP compared to the other groups (P < 0.01), and a post-procedural increase in NT-proBNP by more than 1640 ng L(-1) within 5 days was associated with a significant increase in rate of death (P < 0.01). CONCLUSIONS: TAVI is an efficient treatment option for high-risk patients with severe AVS. The incidence of PVL is an inacceptable clinical problem. Serial measurement of NT-proBNP can be used for risk-stratification in patients with a significant PVL. In general, PVL graded ≥2+ is associated with a dramatically increased 6-month mortality. Therefore, any action to reduce paraprosthetical regurgitation is highly recommended.

Aortic insufficiency in patients with sustained left ventricular systolic dysfunction after axial flow assist device implantation.

BACKGROUND: Predicting the occurrence of aortic insufficiency (AI) during left ventricular assist device (LVAD) support has remained unsolved. METHODS AND RESULTS: We enrolled 52 patients who had received continuous flow LVAD (14 axial and 38 centrifugal pumps) and who been followed for ≥6 months between Jun 2006 and Dec 2013. Native aortic valve (AV) opening was observed in 18 patients (35%) with improved LV systolic function, and none of them had AI. On multivariate logistic regression analysis preoperative shorter heart failure duration was the only independent predictor of postoperative native AV opening (P=0.042; odds ratio [OR], 0.999). Of the remaining 34 patients (65%) with closed AV, 11 had AI with enlargement of the aortic root and narrow pulse pressure. Among those with closed AV, axial pump use (n=13) was the only significant predictor of the development of AI (P=0.042; OR, 4.950). Patients with AI had lower exercise capacity and a higher readmission rate than those without AI during 2-year LVAD support (55% vs. 8%; P<0.001). CONCLUSIONS: Native AV opening during LVAD support is profoundly associated with reversal of LV systolic function, especially in patients with preoperative shorter heart failure duration. Among those in whom the native AV remains closed, low pulsatility of axial flow pump may facilitate aortic root remodeling and post-LVAD AI development that results in worse clinical outcome.

Timing of Dynamic NT-proBNP and hs-cTnT Response to Exercise Challenge in Asymptomatic Children with Moderate Aortic Valve Regurgitation or Moderate Aortic Valve Stenosis.

Patients with congenital aortic valve stenosis (AVS) can remain asymptomatic but may develop progressive and often underestimated exercise intolerance. The risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated patients warrants earlier intervention. The timing for curative therapy for severe AVS is clear, but optimal timing for moderate stenosis (modAS) is unknown. AVS often coexists with aortic regurgitation, which adds a volume overload to an already pressure-overloaded LV, adding an additional challenge to the estimation of disease severity. We investigated the possible value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) upon treadmill exercise challenge in children with asymptomatic modAS versus moderate regurgitation (modAR). The aim was to determine optimal timing of peak biochemical response. Blood samples were obtained at rest, and then at 20, 40 and 60 min after peak exercise comparing modAS and modAR to healthy controls. Exercise performance was equivalent in all groups, with no difference for biomarker levels at rest. The increase in NT-proBNP was significant in modAR at 40 min (99.2 ± 48.6 ng/L; p = 0.04) and 60 min into recovery (100.0 ± 53.7 ng/L; p = 0.01), but not in modAS. The increase in hs-cTnT was significant only at 60 min into recovery for modAS and modAR. NT-proBNP and hs-cTnT following exercise challenge are possible discriminant biomarkers of modAR from modAS and controls at 60 min into recovery despite comparable exercise performance. This offers a promising avenue for future stratification of aortic valve disease and optimal timing of intervention.

Autoantibodies to oxidized low-density lipoprotein in patients with aortic regurgitation: association with aortic diameter size.

BACKGROUND: Aortic regurgitation (AR) is a condition associated with volume overload, causing left-ventricular (LV) remodeling, eccentric LV hypertrophy and eventually heart failure. LV remodeling associated with AR is regulated by mechanical stress, neurohormonal activation, inflammation and oxidative stress. Since anti-oxidized low-density lipoprotein (LDL) antibodies (Abs) are a measurable marker of oxidative stress, we hypothesized that an increased level of circulating oxidized LDL (oxLDL) Abs may be related to remodeling of the left ventricle in patients with significant AR. METHODS: We assessed IgG anti-oxLDL Abs in 31 patients with significant AR and compared them to 30 patients with similar risk factors and no valvular disease. Abs to oxLDL were determined by ELISA. RESULTS: The 2 groups had similar clinical characteristics. There was no difference between patients with AR and patients with no AR in the level of anti-oxLDL Abs. However, in all patients and controls, anti-oxLDL Abs correlated positively with the diameter of the ascending aorta (AA; r = 0.32, p = 0.016) and the level of oxLDL Abs was significantly higher in patients with an AA diameter ≥39 mm. On multivariate analysis, only white blood cell count and AA diameter were related to anti-oxLDL Abs in all patients. CONCLUSIONS: We did not find a difference in the level of anti-oxLDL Abs between patients with AR and controls; however, there was a strong correlation between anti-oxLDL Abs and AA diameter.

Circulating progenitor and apoptotic progenitor cells in patients with aortic regurgitation.

BACKGROUND: Endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury. Reduced numbers of EPCs are related to endothelial dysfunction and adverse clinical events, suggesting that endothelial injury in the absence of sufficient repair by circulating EPCs promotes the progression of vascular disease or valvular disorder. The aim of the present study was to assess the number and role of EPCs in patients with aortic valve regurgitation (AR). METHODS AND RESULTS: We assessed the number of EPCs and apoptotic EPCs in 31 patients with significant AR and compared them with 30 patients who had similar risk factors and no valvular disease. The numbers of EPCs and apoptotic EPCs were assessed by flow cytometry. The 2 groups had similar clinical characteristics. Patients with AR had fewer circulating EPCs and late apoptotic EPCs as compared with the control group (0.054 ± 0.03% vs. 0.079 ± 0.06%, P=0.039 and 0% (0-3.4%) vs. 5% (0-14%), P=0.03, respectively). In patients with AR, circulating EPCs correlated negatively with septal thickness (r=-0.47, P=0.01), whereas late apoptotic EPCs had a negative correlation with left ventricular end-systolic diameter (r=-0.57, P=0.01). CONCLUSIONS: Patients with AR have fewer EPCs and late apoptotic EPCs. These data suggest an impaired valvular endothelial cell regenerative process in patients with AR.

Decreased paraoxonase 1, arylesterase enzyme activity, and enhanced oxidative stress in patients with mitral and aortic valve insufficiency.

BACKGROUND: Oxidative stress is reportedly associated with several cardiovascular diseases. The antioxidant ability of high density lipoprotein (HDL) is, at least in part, attributable to the pleiotropic serum paraoxonase (PON1). The aim of the study was to investigate the body oxidant/antioxidant balance in patients with mitral regurgitation (MR) and aortic regurgitation (AR) to get new points of view for the underlying oxidative mechanisms. METHODS: Oxidative stress index (OSI), total oxidant status (TOS), and total antioxidant status (TAS) were examined in addition to the PON1 and arylesterase (ARE) enzyme activities in fifty-six patients and thirty-seven healthy control subjects. RESULTS: Serum PON1 and ARE enzyme activities were statistically significantly reduced in heart valve disease (HVD) patients (p = 0.0005 and p < 0.0001, respectively), whereas TOS and OSI levels were found to be significantly higher (p = 0.0021 and p < 0.0001, respectively). CONCLUSIONS: Serum PON1 activity is reduced in patients with HVD, caused by elevated oxidative stress and disturbances of heart valve metabolism. The findings from this novel detailed approach, implicate an inflammatory/oxidative stress process in the pathogenesis of the valve's presentation associated with the HVD. The strength of the significance in differences encourage us to propose that the role of oxidative stress in HVD pathogenesis is very prominent, and oxidative stress markers are potential ancillary tests to evaluate the state of the disease.

Elevated proportion of small, dense low-density lipoprotein particles and lower adiponectin blood levels predict early structural valve degeneration of bioprostheses.

OBJECTIVES: Long-term durability of bioprosthetic heart valves (BPs) are limited by structural valve degeneration (SVD) leading to stenosis and/or regurgitation. In this study, we sought to determine the metabolic markers associated with SVD. METHODS: In a cohort of 220 patients with an aortic BP (mean follow-up of 2.5 ± 1.2 years), we compared the metabolic and blood lipid profile including the levels of adiponectin and the proportion of small, dense low-density lipoprotein (LDL) particles (%LDL(<)(255Å)) in individuals developing echocardiographic evidence of early BP hemodynamic dysfunction with subjects having no features of BP dysfunction. RESULTS: Patients developing BP dysfunction (n = 69; 31.3%) had a tendency of higher triglyceride levels. Moreover, patients with BP dysfunction had an increased proportion of %LDL(<)(255Å). In multivariate linear regression analysis, after adjustment for age, gender, BP size and hypertension, the %LDL(<)(255Å) (p = 0.04) was significantly associated with BP dysfunction. In addition, patients with an elevated level of %LDL(<)(255Å) along with a decreased plasma adiponectin level were at a very high risk of developing early BP hemodynamic dysfunction (OR = 2.54, p = 0.04). CONCLUSION: BP dysfunction is significantly associated with an increased proportion of small, dense LDL.

Cardiac surgery in patients with Gilbert's syndrome.

We report the case of a 58-year-old patient with Gilbert's syndrome and multiple cardiovascular pathologies, including aortic regurgitation with a dilated aortic root, severe mitral regurgitation, and chronic atrial fibrillation. A Bentall procedure, mitral valve repair, and modified radiofrequency MAZE procedure were performed. The management of Gilbert's syndrome in patients undergoing cardiac surgery is reviewed.

Strain value in the assessment of left ventricular function and prediction of heart failure markers in aortic regurgitation.

BACKGROUND: This study aimed to examine the relationship between biochemical heart failure markers and conventional left ventricular (LV) measurements and strain assessed by speckle-tracking echocardiography in chronic aortic regurgitation (AR) patients. METHODS AND RESULTS: LV strain, rotation assessed by speckle-tracking echocardiography, LV measurements, mitral annular plane excursion measured by M-mode, and systolic annular plane velocity measured by tissue Doppler echocardiography were analyzed in 64 controls and 65 chronic AR patients. Reduced LV longitudinal strain with increased apical rotation was seen in normal plasma NT-proBNP patients. Increased NT-proBNP (>400 pg/mL) was associated with reduced longitudinal and circumferential strain, diminished mitral annular plane excursions and systolic annular plane velocity. Global systolic longitudinal strain was an indepentent predictor of NT-proBNP level. Longitudinal strain less than 16.0% was the cutoff value for NT-proBNP>400 pg/mL (P<0.05). CONCLUSIONS: LV strain analysis in conjunction with NT-proBNP evaluation is a useful tool in assessing LV function in AR patients.

Endothelin-1 and brain natriuretic peptide plasma levels decrease after aortic surgery.

BACKGROUND AND AIM OF THE STUDY: Endothelin-1 (ET-1) and B-type natriuretic peptide (BNP) have been reported to be involved in numerous cardiovascular diseases. The study aim was to monitor the circulating plasma levels of these peptides in patients affected by aortic disease, and to identify any changes in such levels after surgical treatment. METHODS: A total of 81 patients (52 males, 29 females; mean age 64 +/- 11 years) with aortic disease underwent surgery. The conditions included aortic valve stenosis (n=36), aortic valve regurgitation (n=11), ascending aortic aneurysm (n=6), and combined ascending aortic aneurysm and valvulopathy (n=28). Circulating plasma levels of ET-1 and BNP were measured in all patients before and at 12 months after surgery. RESULTS: Compared to the preoperative situation, significant decreases were found postoperatively in plasma levels of ET-1 (4.2 +/- 0.1 versus 3.1 +/- 0.1 pM; p < 0.001) and BNP (0.071 versus 0.017 ng/ml; p < 0.001), combined with an increased cardiac function and decreased ventricular dimensions. The preoperative levels of both peptides were similar in all patient groups, and were decreased to a similar extent regardless of the diagnosis. Basal levels of ET-1 were higher in the trileaflet aortic valve compared to the bicuspid valve (4.0 +/- 0.1 versus 3.6 +/- 0.1 pM; p = 0.04). CONCLUSION: Circulating plasma levels of ET-1 and BNP were decreased after surgery for aortic valve disease. The decrease was unrelated to the presence of ascending aortic aneurysm, and most likely represents a response to cardiac remodeling and the improved functional status of the patients.

Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender.

BACKGROUND: Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO) mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice. METHODS: The grade (0 to 4) of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57) mice. RESULTS: Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive) remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68) using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice. CONCLUSION: The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.

Molecular recognition of aortic valve stenosis and regurgitation.

OBJECTIVE: Aortic valve stenosis (AS) presents a disease during which there are changes of the aortic valve structure that modify the blood structure of patients. The aim of this study was to improve the effectiveness of differential diagnostics of aortic stenosis and aortic regurgitation using molecular techniques on both mRNA (RT-PCR) and protein (biochip protein). PATIENTS AND METHODS: An experimental group (n = 58) consisting of patients with aortic valve stenosis (n = 26) and aortic regurgitation (AR, n = 32) was compared with a control group (n = 35). Both blood serum and valve tissue samples were used for the determination of gene expression specific genes related to inflammatory response (CRP, IL6, IL2R, IL6R, TNFR1, and 2) as well as genes and proteins involved in remodeling of the extracellular matrix (MMP9, TIMP, Emilin-1). RESULTS: We found that hsCRP and IL6 plasma levels of patients with AS were higher than both controls and patients with AR (mean 5.6 ng/ml). The differences between AS and AR were detected only in mRNA levels of MMP9 and TIMP where increased levels characteristic for AS were found (about 74%, p < 0.01 and 87%, p < 0.001 higher than AR). CONCLUSIONS: The achieved results could contribute to the improvement of early diagnosis of selected cardiovascular disease in the future and improve the quality of patient's life.