Implications of third heart sounds in patients with valvular heart disease. The Veterans Affairs Cooperative Study on Valvular Heart Disease.

BACKGROUND. The presence of third heart sounds in patients with valvular heart disease is often regarded as a sign of heart failure, but it may also depend on the type of valvular disease. METHODS. We assessed the prevalence of third heart sounds and the relation between third heart sounds and cardiac function in 1281 patients with six types of valvular heart disease. RESULTS. The prevalence of third heart sounds was higher in patients with mitral regurgitation (46 percent) or aortic regurgitation (28 percent) than in those with aortic stenosis (11 percent) or mitral stenosis (8 percent). The left ventricular ejection fraction was significantly lower (P less than 0.001) when a third heart sound was detected in patients with aortic stenosis (0.38, vs. 0.56 in those without third heart sounds) or mixed aortic valve disease (0.40 vs. 0.55). However, the ejection fraction was only slightly lower in patients with mitral regurgitation and third heart sounds (0.51 vs. 0.57, P = 0.03). The pulmonary-capillary wedge pressure was higher (P less than 0.001) when a third heart sound was detected in patients with aortic stenosis (18.6 mm Hg, vs. 12.1 mm Hg in those without third heart sounds). There was no association between the wedge pressure and third heart sounds in patients with mitral regurgitation. The prevalence of third heart sounds increased with the severity of mitral regurgitation. CONCLUSIONS. In patients with mitral regurgitation, third heart sounds are common but do not necessarily reflect left ventricular systolic dysfunction or increased filling pressure. In patients with aortic stenosis, third heart sounds are uncommon but usually indicate the presence of systolic dysfunction and elevated filling pressure.     

The pathology of mitral papillary muscles in mitral regurgitation associated with discrete subaortic stenosis

Two patients needed mitral valve replacement for severe mitral regurgitation after surgical relief of subaortic stenosis. A third, much older patient (who died) also had mitral regurgitation after surgery to relieve subaortic stenosis and to close a ventricular septal defect. All the mitral valves showed both macroscopic and microscopic abnormalities, the latter being characterized by myocytolysis, vasculitis, and fibrosis. The severity of these abnormalities was inversely proportional to the age of the patient. The findings were compared with those (surgical and necropsy specimens) of five patients with congenital "left-sided" anomalies (group 1) and five with "right-sided" lesions (group 2). Coagulation necrosis and ischemic changes were observed in both of the control groups, but none demonstrated the combination of features observed in the patients with subaortic stenosis. The observation of myocytolysis, vasculitis, and fibrosis suggests that there may be a pathologic substrate for mitral valve malfunction in patients, especially very young ones, with subaortic stenosis.     

Double valve disease in systemic lupus erythematosus. Case report and literature review

A young, nonhypertensive female with advanced systemic lupus erythematosus (SLE) presented in congestive cardiac failure due to aortic and mitral regurgitation. The valvular lesions resulted from organization of valvular pocket Libman-Sacks vegetations. Her clinical course mimicked infective endocarditis. She is only the third recorded patient with SLE valvular disease warranting double valve replacement. This patient, who had her valvular disease at presentation (prior to initiation of steroid therapy), illustrates that untreated SLE per se may produce severe organic valvular disease.     

Mitral and aortic valve disease associated with ergotamine therapy for migraine. Report of two cases and review of literature

Ergotamine has been associated with numerous vascular complications but only rarely with fibrosing disorders or valvular heart disease. Two patients are described in whom severe valvular dysfunction developed during ergotamine therapy for migraine headache. The surgically excised mitral and aortic valves were involved by a proliferative process that was strikingly similar to lesions described in patients with carcinoid heart disease and methysergide-associated valvular disease.     

High prevalence of amyloid in 150 surgically removed heart valves—a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions

IntroductionThe prevalence, pathophysiology, and clinical indicators of valvular amyloid deposition have not been clarified yet.MethodsOne hundred fifty surgically resected heart valve specimens [67.4±1.0 years; aortic stenosis (AS), n=100; aortic regurgitation, n=19; mitral stenosis, n=7; mitral regurgitation, n=24] were qualitatively, semiquantitatively, and immunohistochemically analyzed and correlated with clinical data.ResultsAmyloid was found in 83/150 specimens with highest prevalence in AS (74/100), intermediate prevalence in mitral stenosis (2/7) and regurgitation (7/24), and lowest prevalence in aortic regurgitation (2/19). Severe and polymorphic amyloid deposits were almost exclusively found in AS (35/100). Filamentous cloudy amyloid patterns occurred with the same frequency in AS (29/100). A combination of both was found only in AS (n=7/100). By immunohistochemistry, none of the most common amyloid proteins was identified except for a weak staining by the apolipoprotein AI antibody, but more intense adjacent to amyloid deposits. Amyloid correlated with valvular thickening (P<.05), hyperlipidemia (P=.07), coronary artery disease (P=.084), and obesity (P=.082).ConclusionsLocalized valvular amyloid is predominantly found in stenotic aortic valves. It appears to depend on atheroinflammatory conditions and high shear-stress hemodynamics. Further studies are needed to identify the underlying protein.     

二尖瓣双病变和联合瓣膜病变二尖瓣口面积的测定

目的∶探讨二尖瓣双病变和联合瓣膜病变二尖瓣口面积（ＭＶＡ）的准确测定方法。材料与方法∶分别用二维超声（２ＤＥ）、压差减半时间（ＰＨＴ）、彩色多普勒二尖瓣口血流截面积（ＣＤＦ）和椭圆形面积法（ＣＤＪ）测定４３ 例风湿性心脏病二尖瓣狭窄（ＭＳ）拟行人工瓣置换术患者的ＭＶＡ,其中合并主动脉瓣反流（ＭＳ＋ ＡＲ） １０ 例,合并二尖瓣反流（ＭＳ＋ ＭＲ） １２ 例,（ＭＳ＋ ＭＲ＋ ＡＲ） ２１ 例,并与手术标本的实测面积（ＯＰ）相比较。结果∶ＣＤＦ法三组均为高度相关;２ＤＥ法ＭＳ＋ ＡＲ组为良好相关,其余两组亦为高度相关;ＰＨＴ法三组虽为高度相关,但在ＭＳ＋ ＭＲ和ＭＳ＋ ＭＲ＋ ＡＲ组显著低估了ＯＰ;ＣＤＪ法三组均显著低估了ＯＰ。结论∶二尖瓣狭窄合并二尖瓣反流或同时并主动脉瓣反流但以二尖瓣反流显著时,ＰＨＴ法明显低估了二尖瓣口面积,而此时应用ＣＤＦＩ测量二尖瓣口血流截面积却不失为一种新的简便而较为准确的定量二尖瓣狭窄的方法,临床上值得推广。     

Time—frequency analysis of heart murmurs. Part I: Parametric modelling and numerical simulations

The object of this study is to compare the performance of two new bilinear time—frequency representation techniques with the spectrogram to characterise the behaviour of heart murmurs produced by bioprosthetic heart valves implanted in the mitral or aortic position. The murmurs are those of mitral stenosis, mitral regurgitation, aortic stenosis, aortic regurgitation, a diastolic musical murmur and a systolic musical murmur. In the first part of the study, the general characteristics of the amplitude and the spectral content of these murmurs are determined by visual observation of the spectrogram of phonocardiograms obtained from several patients with known valvular pathology complemented with a literature review. A parametric model is then generated for each murmur signal. Stenotic and regurgitant murmurs are modelled as the sequential output of a bank of low-pass filters excited by a white noise input signal. The basic parameters of each filter are selected to simulate, as a function of time, the basic characteristics of random heart murmurs. Musical murmurs are modelled as a frequency-modulated deterministic sinusoid of constant amplitude. Numerical simulations of these random and musical heart murmurs are then generated and will be used in Part II to determine the best of three time-frequency representation techniques for analysing heart murmur signals.     

Truffle's revenge: a pig-eating fungus.

A 77-year-old female initially presented with symptomatic mitral valve stenosis involving a bioprosthesis that had been implanted 8 months earlier for myxomatous mitral valve disease and severe valvular regurgitation. The patient was taken for a second mitral valve replacement due to stenosis. Intraoperatively, the bioprosthetic mitral valve was noted to have an unusual clot-like mass on the atrial side. Initial fungal smears were positive for yeast stains, and pathology revealed extensive colonization by thick filamentous fungus with apparent true hyphae, pseudohyphae, and yeast forms. The fungus was identified as Hormographiella aspergillata, the asexual form of Coprinus cinereus, a common inky cap mushroom that grows in the lawn. She was treated with 6 weeks of liposomal amphotericin B and then switched to voriconazole for long-term (lifelong) suppressive therapy in the setting of a new mechanical mitral valve. The only other reported case of infective endocarditis caused by a Coprinus species occurred in a 53-year-old man who had developed native aortic valve fungal endocarditis and died [J Med Microbiol (1971);4(3):370-4]. The valve isolate was identified as probable C. cinereus.     

Left ventricular cellular hypertrophy in pressure- and volume-overload valvular heart disease

To determine the dependence of myocyte hypertrophy in chronic valvular heart disease on the site and type of lesion, the myocardium was studied from 11 patients with either pressure-overload hypertrophy (PO; four patients with aortic stenosis and two with mixed aortic stenosis/insufficiency) or pure volume-overload hypertrophy (VO; two patients with mitral regurgitation and three with aortic insufficiency). These patients, all without coronary artery disease, died zero to 34 days after valve replacement surgery. Diameters of 25 longitudinally oriented myocytes in the circular midwall myocardium were measured with a calibrated light microscope eyepiece reticle on each of five transmural, transverse, histologic sections from the apical, anterolateral, posterolateral, anteroseptal, and posteroseptal left ventricle. Statistical analysis by modified two-way analysis of variance (ANOVA) demonstrated that mean myocyte size (based on 125 measurements) varied widely among cases but was not statistically different among sites. The myocyte diameter for PO lesions (25.9 +/- 1.1 micron, mean +/- SEM) was significantly greater (P less than 0.05) than that for pure VO lesions (20.4 +/- 0.7 micron), despite equal relative heart weights (measured/predicted from body weight: 2.5 +/- 0.2 [mean +/- SD] versus 2.5 +/- 0.5). This study suggests that 1) cellular hypertrophy in valvular heart disease occurs uniformly throughout the left ventricular myocardium; and 2) mean myocyte diameters are greater in PO than in VO hypertrophy for equivalent cardiac enlargement.     

Valvular regurgitation impact on left ventricular 2-dimensional and Doppler echocardiographic indices in patients with essential hypertension

BackgroundBlacks have both a higher hypertension prevalence and accelerated cardiac end organ damage. Because blacks also have a higher prevalence of valvular heart disease, which occurs at a younger age than for whites, we further examined the contribution of valvular regurgitation to the severity of hypertensive heart disease in Nigerians.MethodsWe evaluated and compared echocardiograph-ic indexes in 75 essential hypertensive Nigerians with (n = 48) and without (n = 27) valvular regurgitations. Demographic and echocardiographic indices, as well as the types and severity of valvular lesions were compared between the groups using bivariate logistic regression and analysis of variance.ResultsThe 2 groups were of similar demographics, but those with regurgitations had larger cardiac size (p < .05), greater mass (147 ± 31 vs 122 ± 32 g/m², p = .01) higher volume (p < .01), and left atrial size (35.6 ± 4.6 vs 33.3 ± 4.6 mm, p < .05). Atrial size, cardiac volume, and dimension were independent correlates/predictors of regurgitation occurrence. Relative wall thickness of at least 0.6 was more common in regurgitation patients. Cardiac mass was correlated to increasing age (r = 0.23, p = .043). The valvular lesions frequencies were aortic regurgitation, 8; mitral regurgita-tion, 22; and mixed, 18. The aortic orifice dimension was significantly different among the regurgitant cases, highest in aortic regurgitation (p = .001). Aortic orifice dimension increased with hypertension duration (p = .028).ConclusionsRegurgitant lesions are common and occur early in hypertensive Africans. Apparently mild valvular regurgitation may accentuate preclinical concentric hypertrophy in hypertensive blacks.     

Etiology of acquired valvular heart disease in adults. A survey of 18,132 autopsies and 100 consecutive valve-replacement operations

The cardiac valve pathology in 18,132 autopsies was analyzed. A total of 1,136 patients (6.3%) had acquired valvular disease. The most commonly diseased cardiac valve was the mitral valve (49%), followed by the aortic valve (42%) and the tricuspid (9%) and pulmonary valves (0.3%). Rheumatic fever accounted for 99.7% of cases of mitral stenosis and 68.4% of mitral incompetence. The autopsy incidence of mitral stenosis remained constant over 30 years (1950 to 1979). Only 44.4% of the cases of acquired aortic stenosis were due to rheumatic fever. Review of 100 consecutive, surgically excised native valves revealed that if the pathologist is given adequate information regarding the macroscopic appearance of the intact valve prior to excision, an accurate etiopathologic diagnosis can be made in 81% of cases compared with only 35% of cases without such information.     

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.     

Congenital intracardiac band: a rare cause of nonrheumatic combined aortic and mitral regurgitation.

A patient had a congenital intracardiac band lying across the aortic valve that caused combined aortic and mitral valvular regurgitation. The band was excised, and the damaged aortic valve was replaced with a prosthesis. The case illustrates that not all congenital intracardiac bands are completely asymptomatic and not all bivalvular incompetence is rheumatic in origin.     

A comparison of different feature extraction methods for diagnosis of valvular heart diseases using PCG signals

This article presents a novel method for diagnosis of valvular heart disease (VHD) based on phonocardiography (PCG) signals. Application of the pattern classification and feature selection and reduction methods in analysing normal and pathological heart sound was investigated. After signal preprocessing using independent component analysis (ICA), 32 features are extracted. Those include carefully selected linear and nonlinear time domain, wavelet and entropy features. By examining different feature selection and feature reduction methods such as principal component analysis (PCA), genetic algorithms (GA), genetic programming (GP) and generalized discriminant analysis (GDA), the four most informative features are extracted. Furthermore, support vector machines (SVM) and neural network classifiers are compared for diagnosis of pathological heart sounds. Three valvular heart diseases are considered: aortic stenosis (AS), mitral stenosis (MS) and mitral regurgitation (MR). An overall accuracy of 99.47% was achieved by proposed algorithm.     

Cardiovascular magnetic resonance in the evaluation of heart valve disease

Background

Over the last 25 years, cardiovascular magnetic resonance imaging (CMR) has emerged as an alternative to echocardiography for assessment of valvular heart disease (VHD). Although echo remains the first-line imaging modality for the assessment of patients with VHD, CMR can now provide a comprehensive assessment in many instances. Using a combination of techniques, CMR provides information on valve anatomy and enables quantitative analysis of the severity of the valve lesion.

Main text

In this review, the fundamentals of CMR in assessment of VHD are described, together with its strengths and weaknesses. We detail the utility of CMR for studying all aspects of VHD, including valve anatomy, flow quantification as well as ventricular volumes and function. The optimisation of CMR for evaluating the commonest valve lesions (aortic stenosis, aortic regurgitation, mitral regurgitation, mitral stenosis) as well as in right-sided VHD and prosthetic valves is summarised. The focus of this review is to enable the reader to optimise the use of CMR in his or her own evaluation of heart valve lesions in clinical practice.

Conclusions

CMR can be used for the comprehensive evaluation of VHD. This exciting, non-invasive imaging modality is likely to have increasing utility in the clinical evaluation of patients with VHD.

     

Computational analysis of the effect of mitral and aortic regurgitation on the function of ventricular assist devices using 3D cardiac electromechanical model

Valvular insufficiency affects cardiac responses and the pumping efficacy of left ventricular assist devices (LVADs) when patients undergo LVAD therapy. Knowledge of the effect of valvular regurgitation on the function of LVADs is important when treating heart failure patients. The goal of this study was to examine the effect of valvular regurgitation on the ventricular mechanics of a heart under LVAD treatment and the pumping efficacy of an LVAD using a computational model of the cardiovascular system. For this purpose, a 3D electromechanical model of failing ventricles in a human heart was coupled with a lumped-parameter model of valvular regurgitation and an LVAD-implanted vascular system. We used the computational model to predict cardiac responses with respect to the severity of valvular regurgitation in the presence of LVAD treatment. An LVAD could reduce left ventricle (LV) pressure (up to 34%) and end-diastolic ventricular volume (up to 80%) and maintain cardiac output at the estimated flow rate from the LVAD under the condition of mitral regurgitation (MR); however, the opposite would occur under the condition of aortic regurgitation (AR). Considering these physiological responses, we conclude that AR, and not MR, diminishes the pumping function of LVADs.     

Red blood cell abnormalities in cardiac valvular disease

Nineteen patients with morphological abnormalities of the red blood cells are described, and these formed approximately 3% of the total cases of cardiac valvular disease. In two patients the abnormal blood film developed after the insertion of an aortic and mitral valve prosthesis respectively, but in another two patients the abnormal blood film was corrected by aortic valve surgery. Anisopoikilocytosis may have been associated with microangiopathic haemolytic anaemia in one patient, but in the others the cardiac valvular disease was severe and other mechanical factors were not present. The mitral valve was involved in 16 patients and the aortic valve in eight.Elliptocytosis was the only abnormality in 11 blood films, schistocytes and burr cells were present in seven, and in three there were a few microspherocytes. Family studies in seven patients produced evidence of hereditary elliptocytosis in three.Anaemia was present in only two patients. One of these had infective endocarditis, and the other developed overt haemolytic anaemia following the replacement of a diseased mitral valve by a Starr-Edwards prosthesis. In this latter case there was a transiently positive direct antiglobulin test, and the anaemia and abnormal blood picture were corrected without further surgical treatment. Haemolytic anaemia did not develop in 23 patients after the insertion of an aortic valve prosthesis or homograft.Indirect evidence of haemolysis was obtained in some patients who were not anaemic. There was a reticulocytosis in one third and serum haptoglobins were decreased or absent in over half of the patients tested.     

A case of aortic and mitral valve involvement in granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA) (Wegener’s) is a necrotizing systemic vasculitis of the small-sized blood vessels, affecting kidneys, lungs, upper respiratory tract and skin. Cardiac valvular involvement is an uncommon manifestation of GPA. We report the case of a 60-year-old woman with arthritis and lung nodules due to GPA without antineutrophil cytoplasmic antibodies (ANCA) at time of diagnosis. Remission was obtained with cyclophosphamide and corticosteroid. Azathioprine was then prescribed for 2 years. Four years later, she developed severe inflammatory aortic and mitral valvular involvement characterized by GPA typical histopathological valvular lesions. Search for ANCA was positive at this time (anti-myeloperoxidase). Cardiac valvular involvement is a rare and potentially fatal complication of GPA and may misleadingly suggest infectious endocarditis. A review of literature revealed few cases of histologically well-documented cardiac valvular involvement in GPA. Pathologists should be aware of valvular heart diseases in GPA, which usually comprise valvular necrotic lesions without any microbial agents.     

Usefulness of echocardiography in detection of subclinical carditis in acute rheumatic polyarthritis and rheumatic chorea

Detailed echocardiographic analysis was performed in 10 children with first episode of acute rheumatic fever who presented with acute rheumatic polyarthritis or rheumatic chorea and had no clinically detectable evidence of active carditis. Significant changes were observed in the form of mitral valve prolapse with regurgitation in 3, aortic valve prolapse with regurgitation in 1 and mitral valve billowing without regurgitation in 1 patient each. A significant (p < 0.001) anterior mitral chordal elongation was observed in both the groups--rheumatic polyarthritis and chorea when compared with age and sex matched control subjects. Mitral annular diameter was found to be increased (p < 0.001) in patients presenting with polyarthritis alone. These observations of clinically silent but echocardiographically detectable element of carditis forms the basis of how patients of acute rheumatic fever develop permanent valvular deformities in their latter lives without revealing any cardiac affection earlier.     

Left ventricular response to isometric exercise in aortic valve diseases and its value in the optimal timing of aortic valve replacement

In order to evaluate the left ventricular response to isometric exercise in different types of aortic valve disease, isometric exercise tests were performed during cardiac catheterization in 14 patients with pure aortic stenosis, 20 with combined aortic stenosis and regurgitation, and 18 with pure aortic regurgitation. Patients with angina pectoris in whom coronary angiography had not been performed were excluded. Thirty-seven patients were recatheterized 12 months after aortic valve replacement, and the ventricular response to exercise was re-evaluated. Preoperatively, the ejection fraction did not change significantly during exercise in patients with aortic stenosis, tended to decrease in patients with combined valve lesion, and decreased significantly in patients with aortic regurgitation (p less than 0.001). In the three patients whose ejection fraction during preoperative exercise decreased to below 0.40, it remained below 0.50 after successful aortic valve replacement. It appears possible to reveal left ventricular dysfunction in many patients with aortic regurgitation and in some with combined aortic valve disease by means of isometric exercise. The severely depressed ventricular dysfunction during exercise does not appear to correct totally after surgery.