Diagnosing Aortic Valve Stenosis by Parameter Extraction of Heart Sound Signals

The objective of this study was to develop an automatic signal analysis system for heart sound diagnosis. This should support the general practitioner in discovering aortic valve stenoses at an early stage to avoid or decrease the number of surgical interventions. The applied analysis method is based on classification of heart sound signals utilising parameter extraction. From the wavelet decomposition of a representative heart cycle as well as from the Short Time Fourier Transform (STFT) and the Wavelet Transform (WT) spectra new time series were derived. In several segments, parameters were extracted and analysed. In addition, features of the Fast Fourier Transform (FFT) of the raw signal were examined. In this study, 206 patients were enrolled, 159 with no heart valve disease or any other heart valve disease but aortic valve stenosis and 47 suffering from aortic valve stenosis in a mild, moderate or severe stage. To separate the groups, a linear discriminant function analysis was applied leading to a reduced parameter set. The introduced two classification stage (CS) system for automatic detection of aortic valve stenoses achieves a high sensitivity of 100% for moderate and severe aortic valve stenosis and a sensitivity of 75% for mild aortic valve stenosis. A specificity of 93.7% for patients without aortic valve stenosis is provided. The developed method is robust, cost effective and easy to use, and could, therefore, be a suitable method to diagnose aortic valve stenosis by general practitioners.     

Electrocardiographic prediction of the severity of aortic valvular stenosis

The ECG at rest and at 4 min after a symptom-limited exercise test was studied in 52 patients who were catheterized because a significant aortic valvular stenosis was suspected. The calculated valve area ranged from 0.2 to 1.1 cm2/m2 BSA. QRS amplitude criteria did not discriminate between slight and severe stenoses but a negative or biphasic T wave in lead V6 did, especially after exercise. Thirty-three of the 37 patients with an area of less than or equal to 0.5 cm2/m2 BSA showed negative/biphasic TV6 after exercise but only 4 of the 15 with an area of greater than or equal to 0.6 cm2/m2 BSA. Thus, this criterion had a sensitivity for stenoses less than or equal to 0.5 cm2/m2 BSA of 89%, a specificity of 73% and a predictive value of a positive test of 89% (the pre-test likelihood being 71%). The left ventricular pressures measured during supine exercise in 38 patients did not correlate to the TV6 patterns after exercise.     

Predictors of outcome in severe, asymptomatic aortic stenosis

BACKGROUND: Whether to perform valve replacement in patients with asymptomatic but severe aortic stenosis is controversial. Therefore, we studied the natural history of this condition to identify predictors of outcome. METHODS: During 1994, we identified 128 consecutive patients with asymptomatic, severe aortic stenosis (59 women and 69 men; mean [+/-SD] age, 60+/-18 years; aortic-jet velocity, 5.0+/-0.6 m per second). The patients were prospectively followed until 1998. RESULTS: Follow-up information was available for 126 patients (98 percent) for a mean of 22+/-18 months. Event-free survival, with the end point defined as death (8 patients) or valve replacement necessitated by the development of symptoms (59 patients), was 67+/-5 percent at one year, 56+/-5 percent at two years, and 33+/-5 percent at four years. Five of the six deaths from cardiac disease were preceded by symptoms. According to multivariate analysis, only the extent of aortic-valve calcification was an independent predictor of outcome, whereas age, sex, and the presence or absence of coronary artery disease, hypertension, diabetes, and hypercholesterolemia were not. Event-free survival for patients with no or mild valvular calcification was 92+/-5 percent at one year, 84+/-8 percent at two years, and 75+/-9 percent at four years, as compared with 60+/-6 percent, 47+/-6 percent, and 20+/-5 percent, respectively, for those with moderate or severe calcification. The rate of progression of stenosis, as reflected by the aortic-jet velocity, was significantly higher in patients who had cardiac events (0.45+/-0.38 m per second per year) than those who did not have cardiac events (0.14+/-0.18 m per second per year, P<0.001), and the rate of progression of stenosis provided useful prognostic information. Of the patients with moderately or severely calcified aortic valves whose aortic-jet velocity increased by 0.3 m per second or more within one year, 79 percent underwent surgery or died within two years of the observed increase. CONCLUSIONS: In asymptomatic patients with aortic stenosis, it appears to be relatively safe to delay surgery until symptoms develop. However, outcomes vary widely. The presence of moderate or severe valvular calcification, together with a rapid increase in aortic-jet velocity, identifies patients with a very poor prognosis. These patients should be considered for early valve replacement rather than have surgery delayed until symptoms develop.     

Ascending aortic aneurysms in unicommissural aortic valve disease

BackgroundAneurysms of the ascending aorta occur as result of intrinsic changes in the aortic wall and have been well documented in patients with bicuspid aortic valve (BAV). In few reported clinical studies, documenting aneurysmal dilatation in unicommissural aortic valves (UAV); there have been no comments on the aortic wall pathology. This study presents the pathological findings of the ascending aorta in patients with UAV.Materials and MethodsThe clinical data from 39 patients with concomitant excision of the UAV and aneurysmal aortic tissue were reviewed. In all cases, the gross features of the valve and aortic segments were noted and submitted for histology. The sections of the aorta were semi-quantitatively graded for the extent of medionecrosis, cystic medial change, fibrosis, and elastic tissue changes (fragmentation/ loss) in the media. The medial alterations were correlated with patient age, gender, and valvular dysfunction, and compared to aneurysmal disease in BAV and three-cuspid aortic valves (TAV) excised over a 3-year period.ResultsAmong 39 patients studied, a majority were males (92.3%), with a mean age at surgery of 39.92 years. Only three patients (7.69%) were above the age of 50 years. Eighteen patients (46.1%) had aortic stenosis with regurgitation. Ascending aorta diameters ranged from 4 to 5.5 cm. The overall pattern of medial changes was nearly the same in all cases of UAV, irrespective of age and nature of valvular dysfunction. Most cases showed mild histological changes, with medionecrosis and fibrosis being the more common and consistent features. However, varying grades of change affected different portions of the media and/or the aortic wall in the same patient. The changes in UAV aortae were comparable to the changes seen in the TAV and BAV, but these differed with the age of onset.ConclusionsThis study demonstrates the presence of medial changes in the ascending aortic tissue in all patients of UAV with aneurysms. These changes, while mild to moderate in degree, likely have a similar pathogenetic mechanism as those seen in BAV disease. The significant difference in age, at the time of surgery, suggests a more rapid progression of the aortic changes.     

Cartilaginous metaplasia in calcific aortic valve disease

In a 49-year-old man, symptoms of aortic valve stenosis developed that required surgical intervention with valve replacement. Pathologic examination of the valve showed severe calcific aortic sclerosis and foci of hyaline cartilage. The authors believe that these foci are secondary to cartilaginous transformation of mesenchymal valvular tissue. This represents abnormal repair of valvular tissue damaged, in this case, by the nodular calcific process of calcific aortic stenosis.     

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     

主动脉内球囊反搏治疗心脏瓣膜置换术后低心排综合征的疗效比较

目的 比较主动脉内球囊反搏(IABP)治疗单纯主动脉瓣狭窄及其他心脏瓣膜病换瓣术后低心排综合征疗效的差异,探讨提高心脏瓣膜病IABP治疗效果的可行途径.方法 回顾性分析2004年6月至2009年1月本科室心脏瓣膜置换术后出现低心排综合征21例患者的临床资料,均采用经皮股动脉穿刺法行IABP治疗.其中单纯主动脉瓣狭窄患者10例,其他瓣膜病患者11例,比较2组IABP治疗的成功率.因低心排综合征致无法脱离体外循环术中紧急置入IABP 10例,其余11例均为术后在重症监护病房(ICU)紧急置入,比较2组IABP治疗的成功率.结果 21例换瓣术后低心排综合征患者IABP治疗成功11例.IABP对单纯主动脉瓣狭窄患者及其他心脏瓣膜病患者换瓣术后低心排综合征的治疗成功率分别为90.0%(9/10)和18.2%(2/11),前者明显高于后者(P＜0.05).术中和术后IABP置入的成功率分别为80.0%(8/10)和27.3%(3/11),术中IABP置入的成功率明显高于术后(P＜0.05).结论 针对性地尽早应用IABP有望提高其对心脏瓣膜置换术后低心排综合征的疗效.     

Valvulopathy in primary antiphospholipid syndrome. Prospective echocardiography study

Echocardiographic studies have demonstrated a high prevalence of valvular disease in patients with primary antiphospholipid syndrome (PAPS). However, there are no studies assessing changes over time in valvular abnormalities. We conducted a study to determine whether there are changes over time in valvular lesions as detected by serial transesophageal echocardiography (TEE). Twelve patients with a first TEE had a second evaluation after a mean period of 13.5 months. There were 10 women and two men with a mean age of 38 years. Two patients had normal TEE on both initial and follow-up studies. Ten patients (83%) had valvular abnormalities, predominantly of the mitral and aortic valves in both studies. Abnormalities consisted of thickening, nodules, regurgitation, regurgitation and stenosis, and calcification. The type and frequency of lesions changed over time. As an example, one mitral valve nodule disappeared on follow up but three new aortic nodules developed even though all patients were receiving anticoagulant therapy. Two patients with mitral and aortic nodules presented cerebral ischemia. Mitral valvuloplasty was performed in one case. These results show that valvular abnormalities in patients with PAPS resolve, appear, or persist irrespective of anticoagulant therapy. Regurgitation is often mild or moderate, but stenosis may appear.     

Depressed Systemic Arterial Compliance is Associated with the Severity of Heart Failure Symptoms in Moderate-to-Severe Aortic Stenosis: a Cross-Sectional Retrospective Study

Background: Patients with aortic stenosis (AS) may develop heart failure even in the absence of severe valve stenosis. Our aim was to assess the contribution of systemic arterial properties and the global left ventricular afterload to graded heart failure symptoms in AS.Methods: We retrospectively reviewed medical records of 157 consecutive subjects (mean age, 71±10 years; 79 women and 78 men) hospitalized owing to moderate-to-severe degenerative AS. Exclusion criteria included more than mild aortic insufficiency or disease of another valve, atrial fibrillation, coronary artery disease, severe respiratory disease or anemia. Heart failure symptoms were graded by NYHA class at admission. Systemic arterial compliance (SAC) and valvulo-arterial impedance (Zva) were derived from routine echocardiography and blood pressure.Results: Sixty-one patients were asymptomatic, 49 presented mild (NYHA II) and 47 moderate-to-severe (NYHA III-IV) heart failure symptoms. Mild symptoms were associated with lower SAC and transvalvular gradients, while more severe exercise intolerance coincided with older age, lower systolic blood pressure, smaller aortic valve area and depressed ejection fraction. By multiple ordinal logistic regression, the severity of heart failure symptoms was related to older age, depressed ejection fraction and lower SAC. Each decrease in SAC by 0.1 ml/m² per mmHg was associated with an increased adjusted odds ratio (OR) of a patient being in one higher category of heart failure symptoms graded as no symptoms, mild exercise intolerance and advanced exercise intolerance (OR: 1.16 [95% CI, 1.01-1.35], P=0.045).Conclusions: Depressed SAC may enhance exercise intolerance irrespective of stenosis severity or left ventricular systolic function in moderate-to-severe AS. This finding supports the importance of non-valvular factors for symptomatic status in AS.     

The impact of the aortic valve impairment on the distant coronary arteries hemodynamics: a fluid–structure interaction study

Atherosclerosis is still the leading cause of death in the developed world. Although its initiation and progression is a complex multifactorial process, it is well known that blood flow-induced wall shear stress (WSS) is an important factor involved in early atherosclerotic plaque initiation. In recent clinical studies, it was established that the regional pathologies of the aortic valve can be involved in the formation of atherosclerotic plaques. However, the impact of hemodynamic effects is not yet fully elucidated for disease initiation and progression. In this study, our developed 3D global fluid–structure interaction model of the aortic root incorporating coronary arteries is used to investigate the possible interaction between coronary arteries and aortic valve pathologies. The coronary hemodynamics was examined and quantified for different degrees of aortic stenosis varying from nonexistent to severe. For the simulated healthy model, the calculated WSS varied between 0.41 and 1.34 Pa which is in the atheroprotective range. However, for moderate and severe aortic stenoses, wide regions of the coronary structures, especially the proximal sections around the first bifurcation, were exposed to lower values of WSS and therefore they were prone to atherosclerosis even in the case of healthy coronary arteries.     

Biopsy of the heart valves. 872 cases

In this study, 872 heart valves surgically excised from 810 patients during a period of 5 years (1994 through 1998) were examined pathologically. There was a predominance of aortic (506 patients) versus mitral valves (246 pts.). While aortic valves came more often from men (364) than from women (142), in mitral valves the M:F ratio is 82/164. Isolated calcific aortic stenosis appeared as the most frequent valvular disease (418 pts.), with predominance of its sclerotic-senile type (238 pts.). Mitral stenosis (185 pts.) remains the classical post-rheumatic disease. The relative frequency of a subvalvular stenosing mitral lesion is stressed. The "pure" incompetence of both aortic (70 pts.) and mitral (56 pts.) valve was usually based on valvular myxoid degeneration. An aorto-mitral disease requiring replacement of both valves (51 pts.) presented typically as a post-rheumatic lesion, however, a combination of a post-rheumatic mitral with a degenerative-sclerotic aortic valve disease may be possible. In 30 patients, the valvular replacement was performed for infective endocarditis or a post-IE lesion, mostly of the aortic valve. With the almost non-existence of acute rheumatic fever and with the increasing average age of population in this country, we may expect a long-term decline in mitral valve disease and an increase in aortic valve disease, particularly in the sclerotic type of aortic stenosis.     

Rapid calcification of the bovine pericardial valve in adolescence. Critical aortic stenosis, hemolytic anemia, and quantitative renal hemosiderosis

A 16-year-old boy developed marked calcific stenosis of an Ionescu-Shiley valve that was implanted in the aortic position 42 months before his sudden death. Renal hemosiderosis caused by intravascular hemolysis was quantitated by atomic absorption spectrophotometry. The accelerated calcification of the bovine pericardial valve in our patient supports the view that, in general, xenografts should not be used in adolescents. Frequent follow-up evaluations are imperative in young patients who receive these valves to avoid the irrevocable progression of valvular stenosis and hemolytic anemia.     

Cronic non-rheumatic valvular heart disease. An autopsy study.

The frequency of chronic non-rheumatic valvular heart disease in Iceland was investigated via autoposies performed from November 1965 through December 1974. During this period, about 12.400 Icelanders died at the age of 16 years and older and 28.8 per cent of these were included in the study. At autopsy, males outnumbered females by 2:1. The frequency of calcific aortic stenosis was found to be 3.63 per cent and the prevalence was calculated to be 3.17 per cent among males and 4.50 per cent among females. Calcific aortic stenosis in tricuspid valves was more frequent in females and calcific aortic stenosis in bicuspid valves was more frequent in males. Among the hearts with calcific aortic stenosis, 70.8 per cent were found to have normally tricuspid valves, 25.4 per cent bicuspid valves and 3.8 per cent tricuspid valves with an unicommissural fusion. In 0.59 per cent of the hearts the aortic valve was either bicuspid or had an uncommissural fusion without the features of calcific stenosis. However, a functional stenosis was suggested by the increased weight of most of these hearts. The frequency of bicuspid aortic valves was 1.2 per cent with a prevalence in males of 1.54 per cent and in females 0.50 per cent. A calcified mitral annulus was found in 1.98 per cent of the hearts and in most, it was either associated with calcific aortic stenosis in a tricuspid valve, or it was a single valvular disease. Rheumatic valvular disease was found in 1.08 per cent of the heart examined.     

Indication for percutaneous aortic valve implantation

The incidence of valvular aortic stenosis has increased over the past decades due to improved life expectancy. Surgical aortic valve replacement is currently the only treatment option for severe symptomatic aortic stenosis that has been shown to improve survival. However, up to one third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to high comorbidities resulting in a higher operative mortality rate. In the past such patients could only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement with the goal of offering a therapeutic solution for patients who are unfit for surgical therapy. Currently there are two catheter-based treatment systems in clinical application (the Edwards SAPIEN aortic valve and the CoreValve ReValving System), utilizing either a balloon-expandable or a self-expanding stent platform, respectively.     

Aortic valve endocarditis in a dog due to Bartonella clarridgeiae

We report the first documented case of endocarditis associated with Bartonella clarridgeiae in any species. B. clarridgeiae was identified as a possible etiological agent of human cat scratch disease. Infective vegetative valvular aortic endocarditis was diagnosed in a 2.5-year-old male neutered boxer. Historically, the dog had been diagnosed with a systolic murmur at 16 months of age and underwent balloon valvuloplasty for severe valvular aortic stenosis. Six months later, the dog was brought to a veterinary hospital with an acute third-degree atrioventricular block and was diagnosed with infective endocarditis. The dog died of cardiopulmonary arrest prior to pacemaker implantation. Necropsy confirmed severe aortic vegetative endocarditis. Blood culture grew a fastidious, gram-negative organism 8 days after being plated. Phenotypic and genotypic characterization of the isolate, including partial sequencing of the citrate synthase (gltA) and 16S rRNA genes indicated that this organism was B. clarridgeiae. DNA extraction from the deformed aortic valve and the healthy pulmonic valve revealed the presence of B. clarridgeiae DNA only from the diseased valve. No Borrelia burgdorferi or Ehrlichia sp. DNA could be identified. Using indirect immunofluorescence tests, the dog was seropositive for B. clarridgeiae and had antibodies against Ehrlichia phagocytophila but not against Ehrlichia canis, Ehrlichia ewingii, B. burgdorferi, or Coxiella burnetii.     

Cardiovascular ochronosis

A 64-year-old man with alkaptonuric ochronosis required aortic valve replacement for severe aortic stenosis and single-vessel aortocoronary artery bypass grafting for a subtotally occluded obtuse marginal branch of the circumflex coronary artery. Operative findings included ochronosis of a partly calcified aortic valve and the aortic intima. The aortic valve and a punch biopsy specimen of the ascending aorta were removed at surgery and were studied with transmission electron microscopy and light microscopy. The ultrastructural studies of the aortic valve revealed intracellular and extracellular deposits of ochronotic pigment. A portion of the extracellular ochronotic pigment represented degenerated cells. Large deposits of extracellular ochronotic pigment were associated with areas of valvular calcification. Electron microscopic study of the aorta disclosed ochronotic pigment in macrophages and smooth-muscle cells. Aggregates of extracellular ochronotic pigment in the intima and media appeared to be in locations of necrotic cells. Light microscopy also showed intracellular and extracellular deposits of ochronotic pigment. Our study suggests that extensive extracellular deposits of ochronotic pigment in the aortic valve may serve as a stimulus for dystrophic calcification. This may play a role in the development of aortic valve calcification and aortic stenosis associated with alkaptonuric ochronosis. To our knowledge, this is the first ultrastructural study of the aortic valve and aorta in alkaptonuric ochronosis.     

Influence of receptor activator of nuclear factor kappa B on human aortic valve myofibroblasts

Calcific aortic valve stenosis, the main heart valve disease in the elderly, is based on progressive calcification and fibrous thickening of the valve. Several reports addressed the pathogenesis of tissue calcification in this disorder, but few data exist on the molecular mechanisms of the fibrosis and remodeling of the extracellular matrix. The cytokine "receptor activator of nuclear factor kappa B ligand" (RANKL), is expressed in stenotic aortic valves and involved in valvular calcification during calcific aortic valve stenosis. The present study aimed to assess the influence of RANKL on the molecular mechanisms of connective tissue remodeling. In an established cell culture model of primary human aortic valve myofibroblasts, stimulation with RANKL increased cell proliferation as compared to medium alone. Matrix metalloproteinase (MMP)-1 was detectable time-dependently in conditioned media from RANKL-stimulated cells, but absent in media from control cells. MMP-1 activity was increased by RANKL, as measured by collagenase activity assay. Zymography showed an increase in active MMP-2 in RANKL-stimulated cells. These results support the concept that MMPs are involved in the connective tissue remodeling during calcific aortic valve stenosis. RANKL might regulate this process by promoting cell proliferation and MMP expression and activation.     

Loss of pressure,energy and performance at simulated stenoses in pulsatile quasiphysiological flow

Losses of pressure, energy and performance at simulated aortic valvular stenoses have been measured with a circulation simulator, which reproduces quasiphysiological flow conditions in a heart model. In hydrodynamics, the Strouhal number is generally used in the analysis of unsteady flow. In this paper, the Strouhal number is applied to an analogue of the physiological circulation. The parameters stroke volume, pulse frequency, systolic time and cross-sectional areas of stenosis and aorta are included in the dimensionless Strouhal number. The results are presented as potential functions of the Strouhal number. Assuming that these functions are applicable to the human circulation, the cross-sectional area of a stenosis, as well as the energy and performance losses at the stenosis, can be calculated from measurements of pressure difference, stroke volume, systolic and diastolic duration and aortic diameter. A further result was that stenoses having a cross-sectional area greater than 25% of the aortic area cause small losses. However, when this area is less than 25% of the aortic area, the losses grow exponentially.     

A metric for the stiffness of calcified aortic valves using a combined computational and experimental approach

Calcific aortic valve disease is the most common heart valve disease. It is associated with a significant increase in cardiovascular morbidity and mortality and independently increases the cardiovascular risk. It is then important to develop parameters that can estimate the stiffness of the valve. Such parameters may contribute to early detection of the disease or track its progression and optimize the timing for therapy. In this study, we introduce a metric representing the stiffness of the native aortic calcified valve over a wide range of stenosis severities. Our approach is based on three-dimensional structural finite-element simulations and in vitro measurements. The proposed method is developed first in a pulse duplicator; its clinical applicability is then evaluated in three patients with severe aortic stenosis. Our results indicate that the value of the proposed metric varies considerably between healthy valves and valves with very severe aortic stenosis, from 0.001 to 7.38 MPa, respectively. The method introduced in this study could give useful information regarding the stiffness of the valve leaflets with potential application to the evaluation of aortic sclerosis and aortic stenosis.