A large di V erence in plasma concentrations of lipids between patients with aorticstenosis and the rest of the population would be very obvious and a small di V erence would be clini- cally irrelevant. A diVerence between the groups of two or three times the combined analytical and biological coe Y cient of variation for cholesterol in our population— approximately 0.7 to 1.05 mmol/l cholesterol— would be clinically relevant but not immedi- ately obvious. (The combined analytical and biological coe Y cient of variation for cholesterol is approximately 6% and the mean plasma cholesterol concentration in normal elderly people in our district is approximately 6 mmol/l.) We calculated that 20 patients with aorticstenosis and 20 case controls would be suYcient to detect at the 5% level a clinically relevant di V erence in fasting plasma concentra- tion of total cholesterol (0.7 to 1.05 mmol/l) between the groups, with a power of 90%. Pre- defined subgroup analyses were based on the presence of significant coronary artery disease and on aorticvalve morphology (that is, deter- mination of whether the valve was bicuspid or tricuspid by assessment at the time of valve replacement). Comparisons between the groups was with the paired t test (two tailed). A p value < 0.05 was considered significant.
We have frequently observed that patients with degen- erative AS have a characteristic mitral annular/lea ﬂ et calci- ﬁ cation (MALC) with a reduction in the effective annular area as well as a reduced lea ﬂ et opening ( ﬁ gure 1). However, the adverse impact of this ﬁ nding on mitral valve geometry and function has not been clari ﬁ ed. This ﬁ nding raises a signi ﬁ cant concern when operating on the aorticvalve in degenerative AS, because we have to deter- mine whether concomitant mitral valve surgery is required. We hypothesised that calci ﬁ c extension into the mitral valve causes a reduction in the effective annular area and lea ﬂ et mobility, leading to non-rheumatic MS in patients with degenerative AS. Three-dimensional transoe- sophageal echocardiography (3DTEE) enables a quantita- tive evaluation of the mitral pathology 9 10 and can potentially assess the extent and severity of MALC. Accordingly, the aims of this study were: (1) to determine
While, potential biomarkers found in plasma are less specific than those found in tissues, we have demon- strated the valvular origin of the increase in AACT in this biological fluid. This sample is easily accessible to clini- cians, as extraction requires non-invasive methods and it is routinely used in clinical analysis. Besides, current methods such as echocardiography are time-consuming and expensive when compared with plasma analysis. Moreover, high qualified staff are needed to interpret images due to their complexity and thus it would be easier to measure AACT in a clinical setting in order to diagnose CAS. It is now important to perform a study with a larger number of patients with different grades of injury in order to confirm that AACT levels increase with the severity of the disease as a physiological response to the processes that take place in the stenotic aorticvalve. This would allow us to establish ranges of protein concentrations in an attempt to predict which patients may develop a severe form of CAS, making it possible to apply more personal- ized treatment. In addition a prospective study would allow us to confirm the prognostic value of this protein.
No matter the cause, development of AS starts with the risk of leaflet changes and progresses over many years from early lesions to subsequent narrowing (stenosis) of the aor- tic valve orifice . During that time, the genetic predispos- ition or otherwise induced faulty valve repair system in concordance with continuous blood born mechanical forces and proatherogenic risk factors (i.e., hyperhomocys- teinemia, hyperlipidemia, abnormal calcium metabolism, smoking, metabolic syndrome, diabetes, hypertension, chronic renal failure, male gender, age) leads to endothelial dysfunctions followed by disruption of the subendothelial basement membrane, extracellular accumulation of plasma-derived atherogenic lipoproteins and infiltration/ac- tivation of monocyte-macrophage cells, mast cells, and T lymphocytes [3, 9–14]. That leads to intracellular lipid de- position, generation of oxidative stress with accumulation of oxidized lipids and apolipoproteins, foamy cells forma- tion, and upregulation of various pro-fibrotic and pro- inflammatory factors with concomitant inhibition of plasma derived or locally presents anti-calcific proteins. Acting to- gether, these factors promote extensive extracellular matrix remodeling, and activation of signaling pathways that promote neovascularization, inflammation and calcification [3, 9–14]. Concomitant transformation of normally quies- cent valvular interstitial cells (qVICs) to active myofibro- blastic (aVICs) phenotype in the valve interstitium and their subsequent differentiation to osteoblast-like cells (obVICs) with activation of pro-osteogenic signaling pathways is thought to be one of the central mechanisms contributing to the initiation and progression of AS . In addition, a subset of aortic valvular endothelial cells (VECs) undergo- ing endothelial- to-mesenchymal transition (EMT) and/or circulating osteoprogenitor cells (COPCs) may also contrib- ute to valvular calcification/ossification either by redifferen- tiating to an osteoblast-like phenotype or by promoting VICs activation through paracrine signaling [16–18].
CMRI in pure AS is limited, though it still provides useful information in the preprocedural evaluation of TAVR patients by excluding other types of cardiomyopathies, predominant aortic insufficiency, or lesser degree of stenosis. The calcific degenerative process of valvular AS limits CMRI due to signal absorption or susceptibility artifacts causing blackout regions around calcium. Several studies note similar sensitivity for detection of valvestenosis, with close correlation between CMRI, cardiac CT, and TEE measurements of planimetric valve area. CMRI is still able to quantify the severity of AS, the pres- ence of other types of outflow stenosis such as HOCM (hyper- trophic obstructive cardiomyopathy) and subaortic membranes or CABG (coronary artery bypass graft) graft patency when selecting TAVR patients. Accurate severity assessment of AS and the valve characteristics (bi- or tricuspid) are also within the scope of a CMRI examination. The location of outflow obstruc- tion and the measurement of peak aorticvalve velocity are per- formed using a phase-contrast imaging sequence, as shown in Figure 12. 37,45 Cine (steady-state free precession) CMRI can be
atherosclerotic plaque. Calcified valves including specimens with calcificaorticstenosis, calcified porcine xenograft valves, and a calcified aortic homograft valve were analyzed for Gla content, complete amino acid analysis, and tissue calcium and phosphorus levels. Normal porcine valves contained protein-bound Gla (2.0-10.6 Gla/10 4 amino acids): no Gla was present in normal valve leaflets. Furthermore, Gla levels paralleled tissue calcium content in the calcified valves. In addition, complete amino acid analysis indicated a decline in valvar collagen content plus increased acidic proteins in conjunction with valvar
We have utilized two pre-clinical models to examine the effects of an angiotensin II (AngII) type 1 receptor blocker (ARB), olmesartan medoxomil, on the three main classes of cardiovascular calcification: arterial calcification, intimal calcification, and calcificaorticvalve disease. Where appropriate or suggested by evidence, statins were examined in conjunction and in combination with ARBs. In vivo and ex vivo techniques were used to assess overall disease burden and the extent of calcification including magnetic resonance imaging, micro-computed tomography, histology, and immunohistochemistry. Interestingly, the ARB olmesartan medoxomil was able to robustly inhibit arterial calcification, but showed little effect in halting intimal or valvular calcification (Figure 5.1). Even when combined with statins, the ARB was unable to inhibit intimal or valvular calcification and, at least in the aorticvalve, may have promoted its progression. Taken together, our results suggest that distinct molecular mechanisms may give rise to arterial, intimal, and valvular calcification.
CAVD is a common cardiovascular disease in the elderly. Currently, there is no pharmacological intervention capable of halting CAVD progression. The pro-osteogenic effect of dsRNA may promote aorticvalve calcification and thus contributes to the mechanism underlying CAVD progression. Under- standing of the role of the innate immunoreceptor in regulating AVIC osteogenic responses may help in identification of therapeutic targets for pharmacolog- ically halting CAVD progression. It should be noted, however, that the low concentration of dsRNA used in this study is not an approximation of the dsRNA concentration in human aorticvalve tissue. As the concentration of dsRNA in valvular tissue is currently unknown, and it may vary in the different stages of calcificaorticvalve disease and among the mi- cro-environments surrounding aorticvalve interstitial cells, the results of this study should be interpreted in the context of the experimental conditions.
All patients with valvular AS presenting to the AUCH between 2009 and 2017 were subjected to balloon dilatation if they were fulfilling the inclusion criteria. They were 37 patients: 4 neonates,16 infant and 17child (>1-15 years). The male: female ratio was 3.6: 1. Any baby <4 kg with maximum Doppler gradient of 80-100 mmHg or with left ventricular (LV) systolic dysfunction or signs of cardiogenic shock and left ventricular hypertrophy (LVH) irrespective of the Doppler gradient, was included in the study. Any infant >4 kg or child with maximum Doppler gradient >70 mmHg and catheter peak to peak gradient >50 mmHg and with echocardiographic features of LVH (by 2 D- modality and M-mode), was included in the study. Cases associated with other congenital heart defects needing surgery, or associated with more than mild aortic regurgitation, or supravalvular aorticstenosis was excluded from the study. Written informed parental consent was obtained for every patient. All patients were examined by Doppler- echocardiography in the long-axis parasternal view, supra-sternal view, apical four chamber view and short axis parasternal view. They were assessed for the AoV morphology regarding the number of cusps and presence of raphae, aorticvalve annulus at long axis parasternal view, LVH and its degree, and whether there was initial aortic incompetence (Ai) and its grading (0-4). 11
All procedures were performed under local anesthesia at the puncture site, using either an antegrade or retrograde approach. The antegrade trans-septal ap- proach, using the INOUE balloon (TORAY, Japan), was performed as previously reported . Briefly, the balloon devices were delivered using a 14 Fr catheter via the femoral vein, with temporary pacing delivered using an 6 Fr catheter in the opposite femoral vein. A snare catheter, introduced via the radial artery, was secured to an extra-stiff, 0.032 in., guidewire, passing from the right femoral vein through the right atrium, left atrium, and left ventricle, and then across the aorticvalve, providing sufficient support to deliver and control the balloon device. Systemic arterial pres- sure was monitored using a 5 Fr pig tail catheter place in the ascending aorta via the other radial ar- tery. Though the INOUE balloon was our first choice for the antegrade approach, in case of difficulty cross- ing the INOUE balloon, the VACS II (Osypka AG, Germany) or TYSHAK (NumED CANADA INC., Canada) were selected as an alternate. In the conven- tional retrograde arterial approach, either a VACS II, TYSHAK, MAXI LD (Cardinal health Japan, Japan), or MUSTANG (Boston Scientific Limited, Ireland) balloon was used, based on the surgeon’s preference. The selected balloon was advanced from the femoral artery. The AcuNav (Siemens Medical Solutions, USA) was introduced using an 8 Fr catheter in the jugular vein and used to guide atrial septum punc- ture, to observe the aorticvalve during balloon infla- tion, and to monitor for complications, such as cardiac tamponade and aortic regurgitation. We per- formed contrast-enhanced multidetector computed tomography to measure the size and area of aortic annulus.
The aim of our study was to define, early in the post- operative phase, the Doppler-echocardiography hemody- namic performance of the bioprosthetic Carpentier- Edwards Perimount standard (CEPS) aortic valves com- pared to Carpentier-Edwards Perimount Magna (CEPM). The study was performed in a single, experi- enced echo-laboratory. The incidence of PPM, defined as an effective orifice area indexed (EOAi) <0,85 cm²/m² , was also evaluated. A clinical and Echo follow-up has been programmed in all patients with the aim to collect further data useful for the interpretation and clinical implications of echocardiography results.
as none/trivial ‘0’ , mild ‘1’ , moderate ‘2’ and severe ‘3’ . Parasternal short and long-axis views and five chamber views were used to assess the quantity and qualities of AR jets as well as the extent into the ventricle. Jet width was measured just below the ventricular side of the valve stent frame for PAR sufficient to avoid artifact and graded according to % width of the LVOT. The circum- ferential extent (%) of PAR was assessed in the paraster- nal short-axis view and graded according to the following definition: none/trivial (no or pinpoint jet), mild (jet <10%), moderate (10%– 29%) and severe (≥30%) . Aortic flow reversal was assessed from multiple windows including suprasternal notch and sub- costal views, and used for both PAR and pre-operative AR assessment. Pre-operative AR was assessed using standard imaging techniques . Where disagreement existed between echocardiographic parameters an additional blinded assessor was utilised and a consensus reached.
SAM (systolic anterior motion) is defined as the dynamic motion of the anterior mitral valve leaflet to the left ventricular outflow tract (LVOT) during systole and was first described about 40 years ago by Termini et al. . Systolic anterior motion (SAM) related to left ventricular outflow tract obstruction (LVOTO) can vary from causing clinically silent disease to severe LVOTO in a diversity . Although the mitral valve’s SAM usually is seen in asymmetric septal type of hypertrophic cardiomyopathy, but also can be seen in hypertensive heart disease, after the aortic and mitral valve surgery in diabetic people, in acute myocardial infarction, and even in asymptomatic patients during dobutamine pharmaco- logical stress test and is a condition that causes the dynamic LVOTO . A va- riety of surgical procedures have been reported in adult patients for the removal of SAM, but no experience in infants exists in the literature on these techniques. In this study, we wanted to present a patient which we encountered with signifi- cant left ventricular outflow tract obstruction (LVOTO) related to SAM after Ross-Konno operation and how we overcame this period with no problems and the strategy we used.
validation will include 120 patients undergoing trans- femoral-TAVI (TF-TAVI) (Edwards Lifesciences, Irvine, California, USA), 120 patients undergoing (minimally invasive or full sternotomy) SAVR with any commercially available valve and up to 50 patients being treated medi- cally. To avoid geographical or cultural variability, special attention will be payed on an even distribution of the patients enrolled within the centres. The TASQ has been produced in English and was validated in five languages— English, French, German, Italian and Spanish—to ensure that patients can receive the questionnaire in their native language. Translation was conducted by members of all target countries including two forward and one back- ward translation steps followed by cognitive interviews on five patients with a heart condition and final proof- reading. For each language, 58 patients will be recruited. For comparative purposes, patients will be required to complete the TASQ, as well as the KCCQ and SF-12, at baseline, predischarge, as well as at 30 days and 3 months follow-up. The three questionnaires will be given to the patient sequentially, but in a random order.
Anesthetic management should include TEE. A transvenous pacemaker or an epimyocardial pacing wire should be placed for rapid ventricular pacing if required or to permit ventricular pacing in case of post-procedural heart block. During the procedure, heparin should be administered to maintain an activated clotting time of 250–300 seconds, which can be reversed by protamine at the end of the procedure. Attention should be paid to volume depletion in those elderly patients with typically severely hypertrophied ventricles. Both prolonged hypotension – for example, due to repeated episodes of rapid ventricular pacing – and tachycardia should be avoided. If rapid ventricular pacing is required during valve deployment, it is advisable to test the patient’s response to rapid pacing before the procedure, especially in patients with reduced ventricular ejection fraction. 7,44,48
PVE occurred at 0.11% per patient-year and was respon- sible for one early death in this series. This was of the culture-negative variety detected pre-operatively in a six year-old boy. Mechanical prostheses predispose to device-related infections especially those caused by coa- gulase-negative staphylococci, which are able to adhere to a variety of surfaces and produce an antibiotic-resis- tant biofilm [23,24]. The risk for early PVE is higher in patients undergoing valve replacement surgery during active infective endocarditis, especially if the causal organism is unknown. Once established, PVE carries a mortality rate that may be as high as 70% . The established treatment for PVE is rigorous intravenous antimicrobial therapy, although this has extremely lim- ited success. The majority of cases require surgical removal and replacement of the infected prosthesis.
A large proportion of our study consisted of TAVI car- ried out using the apical approach, with 77 of the pa- tients (51.3 %) treated using the femoral route and 72 (48 %) using the apical route. The usual distribution is more in favor of the femoral approach: 74 % of the pa- tients in FRANCE 2  and 69.5 % in PARTNER A  received the implant via the femoral route, compared with 19 % and 29.6 %, respectively, for the apical route. This significantly higher percentage for the apical route is due in part to the delay in marketing the Edwards 29 valve for the femoral route. Mortality at 6 months essen- tially results from extracardiac causes and is linked to comorbidities in elderly patients. This difference in mor- tality rates is probably explained by the increased use of the apical approach among our population, with a trend of increased mortality in this cohort. It has, in fact, been demonstrated that mortality rates are more significant in the apical approach than in the femoral one [12–15].
6. Lindman BR, Pibarot P, Arnold SV, Suri R, McAndrew TC, Maniar HS, Zajarias A, Kodali S, Kirtane AJ, Thourani VH, Tuzcu EM, Svensson LG, Waksman R, Smith CR, Leon MB. Transcatheter versus surgical aorticvalve replacement in patients with diabetes and severe aorticstenosis at high risk for surgery: an analysis of the PARTNER trial. J Am Coll Cardiol. 2013;63:1090–9. 7. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu
There is a propensity for premature fibrosis, stiffening, and calcium deposition resulting in significant stenosis and cusp prolapse (due to redundancy of conjoined leaflet ), fibrotic retraction, or dilatation of the Sinotu- bular Junction resulting in Regurgitation in abnormally functioning congenital bicuspid aortic valves as “valvu- lopathy”. In addition, patients with poor lipid profile and those who smoke also act as an elevated rik of devel- oping hemodynamically significant bicuspid aorticvalvestenosis . Aortopathy refers to dilated aortic root, usually associated with BAV and may lead to aortic aneurysm, dissection (the most feared complication—4%) and rupture due to accelerated degeneration of the aortic media, indicating that BAV disease is an ongoing pa- thological process and not a discrete developmental event. Certain Gene mutations (NOTCH 1) have been im- plicated in fibrillin—1 deficiency in tissues. MMPs (matrix metalloproteinases) become activated, degrading the structural support of the aorta and medial weakness, resulting aortopathy in BAV. Recently, it is stated that identification of hemodynamics for leaflet fusion patterns enables detection of specific aortic regions susceptible to dysfunction. Variance in WSS (wall shear stress) and flow displacement are important in aortic leaflet mor- phology . In BAV, helical and high velocity outflow patterns are consistent with aortic dilatation hemody- namics and RL fusion causes dilation of mid-ascending aorta, while RN fusion is associated with dilation in aor- tic root  as shown in Figure 11, distal ascending aorta and transverse arch are not dilated in this patient. Atherosclerotic aorticvalvestenosis occur more frequently in patients with severe hypercholesterolemia and is observed in children with homozygous type II hyperlipoproteinemia  (total serum cholesterol >800 mg/dl from birth). Immunohistochemical evidence of chlamydia Pneumoniae has been found in early lesions of age related degenerative aorticstenosis .
The subpopulation of subjects showing progressive aorticvalve disease (n=9) was explored. Five patients progressed to symptomatic AVS after their 6-month visit. Another four remained asymptomatic, but showed progressive disease during echocardiographic examination after 1 year of follow-up. Since biomarker results from these progressive patients cannot be used to determine biolog- ical variation, we explored whether the investigated biomarkers have potential value to discriminate stable from progressive AVS. The annual variation (defined as the difference between initial measurement and meas- urement after 1 year) was calculated for each biomarker in all progressive subjects. These values were compared with the (log-normal) RCVs found in the stable popu- lation (figure 3). Hs-TnT and NT-proBNP variation was higher in one of nine subjects with progressive disease, whereas the RCV of ST2 was surpassed in one of nine subjects. None of the progressive subjects showed varia- tion higher than the RCV for BNP and hs-TnI.