Rate of progression of severity of valvular aortic stenosis

Twenty-six patients with valvular aortic stenosis were followed up for an average period of 9 years after the initial evaluation when the valvular disease had been considered too mild for surgical treatment. The valve area was 0.7-1.9 (mean 1.2) cm2 at the first study and 0.3-2.0 (mean 0.9) cm2 at the second. The mean annual decrease was about 0.1 cm2 in ten and less in the remaining patients. Advanced age and low physical working capacity at the first investigation were associated with rapid progression of the severity of the stenosis, but rapid progression was not predictable. At follow-up the combination of 1) calcifications of the valve on chest X-ray, 2) low physical working capacity and 3) negative/biphasic T wave in V6 after exercise was present in 100% of the severe stenoses (much less than 0.6 cm2) and in 10% of the mild (much greater than 1.0 cm2). The rate of progression of valvular aortic stenosis in adults is usually slow, but moderate stenoses may become severe within a few years.     

Program for estimation of severity in valvular stenosis

This paper presents a program written for a Texas Instruments TI-59 programmable calculator equipped with “Texas Instruments Thermal Printer PC-100C”, for estimation of severity in valvular stenosis. The major constraint imposed on the program was that it should be operable by a physician, nurse, or technician with previous computer experience. The program uses the hydraulic Gorlin and Gorlin formula for the valve areas calculation and a typical run is presented.     

Identifying severe aortic valvular stenosis by bedside examination

Sixty-seven consecutive symptomatic patients with aortic valvular stenosis (AS) and no or slight aortic incompetence were prospectively examined bedside by a senior cardiologist before an invasive pre-operative investigation. A history of effort syncope had the highest predictive value (pos), 100%, for a significant degree of AS (defined as a calculated valve area less than or equal to 0.9 cm2 or a peak systolic pressure difference across the valve of greater than or equal to 40 mmHg). The absence of effort syncope had a predictive value (neg) of 40%. The corresponding figures for peak intensity of the murmur in mid-systole were 93 and 82%, respectively. For the combination of effort syncope and/or mid-systolic peak intensity of the murmur (borderline findings included) the predictive values were 90% (pos) and 94% (neg), respectively. No other combination of symptoms and physical finding was more discriminating. This combination of criteria for prediction of a significant stenosis was prospectively applied to the next 39 AS patients. The criteria were fulfilled by 29 patients and all were found to have a significant AS as were four of the 10 patients not fulfilling the criteria. These four falsely negative patients had a valve area/peak pressure difference of 0.5, 0.8, 0.8 cm2 and 43 mmHg. The inter-observer variation was studied in a third series by two senior cardiologists independently examining 22 AS patients. They were concordant in all with regard to a history of effort syncope and in all but one (0.6 cm2) with regard to the timing of the peak murmur. Bedside examination of an AS patient by an experienced cardiologist has a good predictivity for severity, and the inter-observer variation is low. Non-invasive laboratory investigations have only a supplementary role. However, as many patients have effort angina, a pre-operative invasive procedure including coronary arteriography is often unavoidable.     

Consequences of intramyocardial arterial lesions in aortic valvular stenosis.

Proliferative lesions, which included collagen deposition, developed with age in intramyocardial arteries of 27 patients with aortic stenosis and matched controls. Those with the most extensive intramyocardial artery lesions developed massive subendocardial infarcts during surgery. Using histologic quantitation, the percent of intramyocardial arteries with lesions in a patient was correlated with decreases in the amount of muscle in arterioles between the subepicardial and subendocardial zones of the left ventricle. The mean decrease in arteriolar muscle was 43% in patients with aortic stenosis and 19% in controls. Blood pressures correlate with the amount of muscle in arterioles, so subendocardial perfusing pressures were presumably low in those with aortic stenosis. Patients with the greatest decrease in arteriolar muscle across the myocardium had the most impaired left ventricular function, i.e., highest end diastolic pressures, lowest ejection fractions, and lowest mean fiber shortening rates.     

Regression of valvular aortic stenosis due to homozygous familial hypercholesterolemia following plasmapheresis

Summary A 39-year-old male with homozygous familial hypercholesterolemia confirmed by tissue culture suffered from mild aortic insufficiency and valvular stenosis with a gradient of 20 mm Hg across the aortic valve. Plasmapheresis carried out every 2 weeks for 4 years resulted in a marked reduction in the serum cholesterol level and in a regression of the valvular stenosis, as shown by echocardiography and by left heart catheter.Abbreviations ECG electrocardiogram - LVH left ventricular hypertrophy - USP US pharmacopoea These studies were partly supported by a grant from the Deutsche Forschungsgemeinschaft     

Can cardiac catheterization accurately assess the severity of aortic stenosis? AnIn Vitro pulsatile flow study

An accurate hemodynamic assessment of aortic stenosis has important clinical implications. In clinical practice, cardiac catheterization is often used to assess the severity of aortic stenosis. However, in conducting catheterization, the precise position of the catheter tip is often not known or controlled. From the standpoint of hydrodynamics, the position of the catheter tip may affect pressure measurement due to the complicated flow fields distal to the valve. This fact is particularly true when the diagnosed valve is stenotic. The study was aimed to investigate how the position of the catheter tip in catheterizing aortic stenosis affects pressure measurement. The experiments were conducted in anin vitro pulse duplicator system. Laser flow visualization was used to examine the flow fields in the vicinity of varying degrees of aortic stenosis, and a pressure transducer with a side-hole catheter was used to measure pressures. Minimal variation in transvalvular pressure drop measured along the radial direction was observed for varying degrees of valvular aortic stenosis. This implies that, in catheterization, the placement of the catheter tip along the radial direction does not seem to affect pressure measurement. However, along the axial direction, pressure recovery was observed for all the cases studied. Therefore, within the region of pressure recovery, the position of the catheter tip may affect the pressure drop measurement. This may cause inaccuracy in assessing the severity of aortic stenosis. However, this concern may be overcome by pulling the catheter slightly further downstream, so that the position of the catheter tip is outside of the pressure recovery region.     

Plasmin induces apoptosis of aortic valvular myofibroblasts

Previous studies have described remodelling of the extracellular substratum by matrix metalloproteinases (MMPs) in aortic valves. However, involvement of the fibrinolytic system has not yet been analysed. We hypothesized that plasminogen and plasminogen activator(s) are present in aortic valves and that plasminogen activation could induce the degradation of adhesive proteins and apoptosis of the valvular myofibroblasts. We employed ELISA, western blotting, fibrin‐agar zymography, and immunochemistry to detect components of the plasminogen activation system, in samples of aortic valves and valvular myofibroblasts in primary culture. Using myofibroblast cultures, real‐time measurement of plasminogen activation was performed in the absence and presence of inhibitors (amiloride, ε‐aminocaproic acid, and an MMP inhibitor); the degradation of fibronectin was visualized on western blots; and the apoptotic process was assessed by detection of phosphatidylserine exposure (binding of FITC‐annexin V) and DNA fragmentation (TUNEL and ELISA). We demonstrate that a time‐ and plasminogen concentration‐dependent generation of plasmin occurs on the surface of cultured valvular myofibroblasts expressing both u‐PA and t‐PA. Only u‐PA appears to activate plasminogen as t‐PA is essentially found in complex with PAI‐1. Plasmin‐dependent degradation of pericellular proteins, such as fibronectin, leads to cell detachment and apoptosis. In conclusion, various proteins of the fibrinolytic system are synthesized in vitro by cultured myofibroblasts from aortic valves, leading to plasmin‐dependent cell detachment‐induced apoptosis, a biological process named anoikis. The presence of plasminogen in aortic valves suggests that this process may be operating in vivo and may participate in valvular tissue remodelling, as also suggested by the finding of apoptotic cells in valvular tissue. This is the first demonstration of the presence and potential role of enzymes of the fibrinolytic system in aortic valves. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Isolated stenosis of the aortic orifice

Five known to-day causes of the isolated aortal valve stenosis are reviewed: 1) atherosclerosis, 2) premature calcinosis of congenital bicuspidalis aortal valve; 3) rheumatism; 4) infectious endocarditis; 5) mesenchymal dysplasia. The authors consider that aortal valve calcinosis developing against the background of valve atherosclerosis complicates the above diseases and differential diagnosis of aortal stenosis causes.     

射血分数-压差比值评价伴左心功能不全的主动脉瓣狭窄程度

目的初步探讨射血分数-压差比值评价伴左心功能不全的主动脉瓣狭窄程度可行性。方法80例左心室收缩功能不全的主动脉瓣狭窄患者，其中男32例，女性48例，年龄38～85岁，平均年龄42岁。用彩色多普勒超声测量主动脉瓣口面积（AVA）、左心室射血分数（EF），Bernoulli方程计算主动脉瓣口跨瓣压差（△P），Simpson容积描记法计算射血分数压差比值即EFPR（EFPR=EF／△P），分析AVA与△P、EFPR之间的相关性；用ROC曲线比较△P、EFPR两参数评价主动脉瓣狭窄程度的敏感度和特异度。结果对主动脉瓣狭窄伴左心室收缩功能不全患者，用Simpson容积描记法计算ERPR估测AVA较Bemoulli方程计算的△P法更准确（r=0.9172对r=-0.6796，P〈0.001）；将EFPR小于1.0、△P大于10.7kda（80mmHg）来估测重度主动脉瓣狭窄伴左心功能不全时，EFPR和△uP的敏感度和特异度分别为87.5％、68.6％（P〈0.05）和98.3％、37.2％（P〈0.01），表明EFPR估测重度主动脉瓣狭窄伴左心功能不全患者的特异度及敏感度较高。结论EFPR能准确估测主动脉瓣狭窄患者主动脉瓣狭窄程度，特别对伴左心功能不全的重度主动脉瓣狭窄患者瓣膜狭窄程度的评价。EFPR较传统参数有更高敏感性和特异性。     

Discrete subvalvular aortic stenosis

Discrete Subaortic Stenosis is one of the many lesions responsible for left ventricular outflow tract (LVOT) obstruction. It may present as in an isolated from as membranous or fibromuscular ring below the aortic valve or in association with other congenital anamolies such as VSD, PDA, coarctation of aorta, hypoplastic aortic annulus, double chamber right ventricle among others. The condition is rarely diagnosed antenataly or in infancy but often manifests in the first decade of life with features of progressive LVOT obstruction, LV hypertrophy and dysfunction aortic regurgitation due to damage to the aortic cusps because of the jet from the subaortic narrowing which may also render the aortic valve prone to infective endocarditis. Interaction of genetic predisposition and morphologically deformed long and narrow LVOT cause rheological abnormalities and increased shear stress in the region of subaortic stenosis and seem to be the main etiological factor alongwith poorly defined role of more extensive but subtle changes in the LV endocardium. Condition can be easily diagnosed by cross-sectional and Doppler echocardiography and confirmed by demonstrating a pressure gradient below aortic valve on cardiac catheterisation and LV angiography. Surgical membranectomy alongwith myotomy or myomectomy remain the mainstay of treatment but long term results are not satisfactory as there is a high rate of recurrences requiring reoperations. A close follow up with serial echocardiographic examinations is very helpful in early detection of subaortic obstruction in patients who have so called functional murmurs in the childhood.