Muscular Subaortic Stenosis Research Articles

How should hypertrophic cardiomyopathy be classified?

Almost 50 years of study have underscored the considerable heterogeneity in clinical presentation, natural history, morphology, and the genetic substrates that characterize inherited hypertrophic cardiomyopathy.1–5 Similarly, the nomenclature applied to this complex cardiac disease has persistently created a measure of confusion for both patients and physicians with regard to the definition and perceptions of the disease. This ambiguity has had, in turn, substantial impact on accurate diagnosis, full understanding of disease expression, and ultimately, decisions regarding management. At this juncture, it would seem appropriate and timely to conceptually revisit and clarify this important issue of names, consistent with the evolving knowledge of the cardiomyopathies.6 Response by Elliott and McKenna see p 81 The historical confusion over the names used to describe the entity of hypertrophic cardiomyopathy has arisen over the years in 2 fundamental areas. The first of these concerns the nomenclature used in prior efforts to characterize the disease. For example, at last count there are more than 80 individual names that have been used over the last 5 decades (most by early investigators) to describe the disease entity, which is the subject of this commentary (ie, hypertrophic cardiomyopathy)7 (Figure 1). It is likely that the confusing array of designations used to describe hypertrophic cardiomyopathy has also undoubtedly contributed to its relatively low visibility among the general public despite a prevalence (ie, 1:500), which greatly exceeds that of many other better known but less common cardiac or noncardiac diseases8,9 (Figure 2). Figure 1. The multitude of names used to describe hypertrophic cardiomyopathy in the literature. Many of these traditional terms, such as idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, and muscular subaortic stenosis, emphasize obstruction to left ventricular outflow to the exclusion of the nonobstructive form of the disease. Figure 2. The prevalence of hypertrophic …

Apicoaortic Double-Valved Conduit in a 40-Year-Old Woman

A 40-year-old woman was admitted with pneumonia and septic shock. Chest x-ray showed bilateral pulmonary infiltrates, cardiomegaly, and a bioprosthetic valve in an unusual position near the left ventricular apex (Figure 1A). The patient had a history of muscular subaortic stenosis. At age 4, she underwent surgical resection, but severe subaortic stenosis recurred 5 years later when an apicoaortic conduit containing an Ionescu–Shiley bioprosthetic valve was placed between the left ventricular apex and the descending thoracic aorta. Six …

Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is a fascinating disease entity in which hypertrophy of the myocardium occurs, primarily as a result of mutations of genes encoding the cardiac sarcomere.1–3 Our knowledge of patients with this unique disease of the heart muscle has advanced significantly. Once thought to be a rare malignant disease with a high risk of sudden death, population studies have revealed hypertrophic cardiomyopathy to be a more common disease with a benign outlook in the majority of affected patients.4 Hypertrophic cardiomyopathy is now recognized to comprise a wide spectrum of disease processes, with varying genetics, anatomy, clinical presentation, and prognosis. The dynamic left ventricular outflow tract obstruction that was initially the hallmark of hypertrophic cardiomyopathy continues to be a source of controversy. Article p 2232 The pathophysiology of hypertrophic cardiomyopathy is complex and still not completely understood. The first description of hypertrophic cardiomyopathy came in 1957 when Sir Russell Brock5 found a functional subvalvular obstruction in patients undergoing aortic valvotomy for clinically suspected valvular aortic stenosis. In 1958, Teare6 described the cardiac anatomy of 8 young patients who died suddenly with severe asymmetric left ventricular hypertrophy with bizarre muscle bundle orientation. In the 1960s, Braunwald et al7 defined a specific disease process in which asymmetric septal hypertrophy, myofibril disarray, and dynamic outflow tract obstruction were found. Thus, the early focus of hypertrophic cardiomyopathy was on this dynamic obstruction; the response of the obstruction to changes in preload, afterload, and contractility formed the basis for diagnosis. With the advent of echocardiography, which allowed direct visualization of the hypertrophied myocardium, it became apparent that obstruction was not necessary for the diagnosis of hypertrophic cardiomyopathy. The entire relationship of obstruction to hypertrophic cardiomyopathy was subsequently questioned. Some thought that hypertrophic cardiomyopathy was primarily a disease of diastole, with obstruction …

Defective regional myocardial development and vascularization in one variant of tricuspid atresia—clinical and necropsy findings in three cases

SummaryFive previously reported cases have established the combination of a small right ventricle (sometimes with Uhl's anomaly), imperforate tricuspid valve with fibrotic tensor apparatus, congenital absence of the pulmonary valve, and an intact interventricular septum with muscular subaortic stenosis as a rare variant of tricuspid atresia. In this study of three new autopsy cases, we additionally identified Ebstein's malformation of the imperforate tricuspid valve, partial Uhl's anomaly, regional dysplasia of right ventricular myocardium and thinning of the interventricular septum by intramyocardial sinusoids from the right ventricle. All three new cases had epicardial anomalies of the right coronary artery—a fistula to right ventricle, ostial stenosis and proximal arterial hypoplasia. Sinusoidal connections from the right ventricle to the right coronary artery and to the sclerotic left anterior descending artery were identified in serial sections of the right ventricle and septum. Myofiber disarray, with thick walled intramyocardial arteries and sinusoids from left ventricle, involved the bulging subaortic interventricular septum. These studies are consistent with the hypothesis that defective development of the the right ventricle, along with its blood supply and associated atrioventricular and arterial valves, may underlie this unusual form of congenital heart disease.

Problems in diagnosis and management of hypertrophic cardiomyopathy

In the first systemic characterization ofwhat is now known as hypertrophic cardiomyopathy, Teare reported gross asymmetric hypertrophy in 9 young adults who had died suddenly.' His report captured the essence of a disease in which cardiac hypertrophy, normally the heart's way of reducing wall tension during pressure overload, could occur inexplicably, within families as well as sporadically, and cause sudden death. In the 1960s, the diagnosis was based on a midsystolic murmur and the demonstration of a subaortic gradient at cardiac catheterization; giving rise to names such as idiopathic hypertrophic subaortic stenosis (IHSS), muscular subaortic stenosis (MSS) and hypertrophic obstructive cardiomyopathy (HOCM).2 With the advent of M-mode echocardiography in the 1970s came new diagnostic criteria. The most widely used of these was asymmetric hypertrophy of the interventricular septum, defined as a ratio of septal to posterior left ventricular wall thickness of at least 1.3. By the mid 1970s, asymmetric septal hypertrophy was considered by some to be the genetically determined, pathognomonic feature of the disease.3 M-mode echocardiography imaged the upper anterior septum usually the thickest part of the left ventricle, and the upper posterior wall usually the thinnest, and thus reemphasized the asymmetric nature of hypertrophy in the condition. The two other major echocardiographic diagnostic criteria for hypertrophic cardiomyopathy were the Mmode echocardiographic features of a left ventricular outflow tract (LVOT) gradient, systolic anterior motion of the mitral valve (SAM) and premature systolic closure of the aortic valve (Figure 1). When cross-sectional echocardiography became available in the 1980s, with its ability to image the whole heart, it became clear that apart from asymmetric septal hypertrophy, which was seen in 50 to 60% of the patients, hypertrophy could be concentric (20 to 30%),4 predominantly involve the distal left ventricle (10 to 15%), or affect single myocardial segments such as the middle or distal part of the posterior septum or lateral wall. Cross sectional echocardiography also showed that about a third of the patients with hypertrophic cardiomyopathy (HCM) had right ventricular hypertrophy (Figure 2), a feature which Teare had described in his original report. 5 The diagnostic criteria for hypertrophic cardiomyopathy have evolved over 3 decades as new techniques became available. The diagnosis now includes patients with unexplained left or right ventricular hypertrophy with or without intracavitary gradients.

Double inlet left ventricular main chamber, subaortic small left sided right ventricle and interrupted aortic arch type A. What operation is indicated when?

A case of a 23 year old female patient who suffered from the complex congenital heart lesion of a double inlet left ventricular main chamber, subaortic small left sided right ventricle and interrupted aortic arch type A is reported. With equally high blood pressures, the perfusion in the upper half of the body was maintained through the ascending aorta while the lower half and the lungs were supplied through the pulmonary artery and a patent ductus arteriosus (PDA). Angiographically, the bulbo-ventricular foramen appeared to be nonrestrictive. However, distinct signs of muscular subaortic stenosis were detected. The hemodynamic status principally allowed surgical correction when this became necessary because of increasing left heart failure. Treatment for this complex lesion undoubtedly required reduction of pulmonary perfusion, even when associated with the danger of increasing cyanosis. Various forms of surgical treatment (functional correction, palliative procedures) were discussed. The most elegant was performed without cardiopulmonary bypass: this consisted in connection of the pulmonary artery with the descending aorta using a 16 mm Dacron tube, reconstruction of the aortic arch by a prostheso-subclavian synthetic graft, suture ligation of the PDA, and banding of the pulmonary artery trunk distal to the origin of the prosthesis. One year after the operation, the patient's physical performance has improved. Moreover, despite the disappearance of cardiac failure she has not become more cyanotic during exertion.

Parental Genetic Contribution to Mode of Presentation in Pompe Disease

Echocardiograms were performed on parents of five infants with Pompe disease (glycogen storage disease, type II). Three of the infants had presented with congestive cardiomyopathy and two with dynamic muscular subaortic stenosis. No heart murmurs were audible in any of the parents of the five infants. The parents of the three infants without left ventricular outflow tract obstruction had normal echocardiographic results, whereas one parent of each of the infants with left ventricular outflow obstruction had asymmetric septal hypertrophy. The association between left ventricular outflow obstruction and parental asymmetric septal hypertrophy suggests that both septal hypertrophy and glycogen storage disease were inherited by these two infants.

Muscular (hypertrophic) subaortic stenosis (hypertrophic obstructive cardiomyopathy): the evidence for true obstruction to left ventricular outflow.

The clinical and haemodynamic significance of the subaortic pressure gradient in patients with muscular (hypertrophic) subaortic stenosis (hypertrophic obstructive cardiomyopathy) has long been debated. In this report we summarize the evidence which indicates that true obstruction to left ventricular outflow exists in these patients. Rapid left ventricular ejection, through an outflow tract narrowed by ventricular septal hypertrophy, results in Venturi forces causing systolic anterior motion of the anterior (or posterior) mitral leaflets. Mitral leaflet-septal contact results in obstruction to outflow and the accompanying mitral regurgitation. The time of onset of mitral leaflet-septal contact determines the magnitude of the pressure gradient and the severity of the mitral regurgitation, as well as the degree of prolongation of left ventricular ejection time and the percentage of left ventricular stroke volume that is ejected in the presence of an obstructive pressure gradient. Early and prolonged mitral leaflet-septal contact results in a large pressure gradient, significant mitral regurgitation, as well as dramatic prolongation of the ejection time and a large percentage of left ventricular stroke volume being obstructed. Late and short mitral leaflet-septal contact results in little haemodynamic perturbation. Hypertrophic cardiomyopathy patients with obstructive pressure gradients are significantly more symptomatic than those without. Thus the obstructive pressure gradients in hypertrophic cardiomyopathy are of clinical as well as haemodynamic significance. To deny the existence of obstruction to outflow in patients with muscular subaortic stenosis is to deny these patients appropriate medical and surgical therapy.

Muscular subaortic stenosis: the quantitative relationship between systolic anterior motion and the pressure gradient.

We performed simultaneous echocardiographic and hemodynamic studies in 11 patients with muscular subaortic stenosis to determine whether systolic anterior motion (SAM) of the anterior mitral leaflet and the pressure gradient are related quantitatively. SAM without septal contact was associated with either no gradient or a small impulse gradient of less than 10 mm Hg. SAM with septal contact was always associated with a pressure gradient of more than 10 mm Hg. The size of the pressure gradient correlated inversely with the time periods: (1) onset of SAM-septal contact (r = .79, p less than .001) and (2) onset of aortic ejection to onset of SAM-septal contact (r = -.89, p less than .001). Size also correlated directly with the time period: (3) duration of SAM-septal contact (r = .80, p less than .001). Thus when the time from the onset of SAM to the onset of SAM-septal contact was long, SAM-septal contact developed late in systole, the duration of SAM-septal contact was brief and the pressure gradient was low. When SAM-septal contact developed in early systole, the duration of SAM-septal contact was long and the pressure gradient was high. With the index of time period (3) divided by time period (1), a regression equation was devised to predict the size of the pressure gradient (pressure gradient [mm Hg] = 25 [ratio] + 25; r = .90, p less than .001; SE +/- 15 mm Hg). The echocardiographic time period index was validated prospectively in nine other patients and the significant correlation with the hemodynamically determined gradient persisted (r = .89, p less than .01). We conclude that SAM and the pressure gradient are related quantitatively in muscular subaortic stenosis. These observations have implications regarding the mechanism and significance of the pressure gradient in muscular subaortic stenosis.

Muscular subaortic stenosis: the temporal relationship between systolic anterior motion of the anterior mitral leaflet and the pressure gradient.

Muscular subaortic stenosis: the temporal relationship between systolic anterior motion of the anterior mitral leaflet and the pressure gradient.

Muscular subaortic stenosis: hemodynamic and clinical improvement after disopyramide.

A quarter of a century has passed since Brock's original report1 of the condition characterized by asymmetric septal hypertrophy and a subaortic pressure gradient (muscular subaortic stenosis).2 The pressure gradient may be affected by changes in myocardial contractility, systemic vascular resistance, and ventricular volume.3 Propranolol has little effect on the pressure gradient at rest, but it may diminish the increment that occurs with exercise.4 Verapamil has a greater effect than propranolol in reducing the gradient at rest, although substantial gradients (>50 mm Hg) have persisted even after high doses of intravenous verapamil, and in one patient the gradient markedly increased. . . .

Effect of negative intrathoracic pressure on left ventricular outflow tract obstruction in muscular subaortic stenosis.

To study the effect of respiration and negative intrathoracic pressure on the left ventricular outflow tract gradient in patients with muscular subaortic stenosis, we studied nine patients using various respiratory maneuvers at the time of cardiac catheterization. Deep inspiration decreased the left ventricular outflow tract gradient from 60 +/- 11 to 34 +/- 6 mm Hg (p less than 0.01) and decreased the left ventricular ejection time (corrected for heart rate) from 0.42 +/- 0.01 to 0.38 +/- 0.01 second (p less than 0.001). The Müller maneuver decreased the left ventricular outflow tract gradient from 69 +/- 13 to 7 +/- 3 mm Hg (p less than 0.001) and decreased the corrected left ventricular ejection time from 0.42 +/- 0.02 to 0.24 +/- 0.01 second (p less than 0.01). In keeping with this amelioration of left ventricular outflow tract obstruction, echocardiography showed a reduction or abolition of the systolic anterior motion of the anterior mitral leaflet, and auscultatory and phonocardiographic studies revealed a decrease or abolition of the apical systolic murmur. These findings indicate that negative intrathoracic pressure reduced the left ventricular outflow tract gradient in muscular subaortic stenosis. We believe that negative intrathoracic pressure produced these changes by increasing left ventricular afterload through an increase in left ventricular transmural pressure, resulting in a decrease in the left ventricular outflow tract obstruction. These observations provide an explanation for the decrease in pressure gradient that occurs on inspiration in patients with muscular subaortic stenosis.

Electrophoretic profiles of nonhistone nuclear proteins of human hearts with muscular subaortic stenosis.

Muscular subaortic stenosis (MSS) is a genetically determined cardiomyopathy, whereas right ventricular infundibular hypertrophy (IH) apparently is an acquired condition. Since genetic expression in eukaryotic cells may be regulated primarily by DNA-associated proteins, we isolated and characterized the proteins of heart nuclei from nine patients with MSS, eight with IH, and two with normal (N) hearts. More than 150 proteins could be identified by two-dimensional polyacrylamide gel electrophoresis. Proteins in the entire region from pH 7.0 to 9.0 with molecular weights (Mr) ranging from 35,000 to 41,000 and a protein focusing from pH 5.2 to 5.3 with Mr of 55,000 were strikingly reduced in MSS. Again the electrophoretic patterns of N and IH were similar. The electrophoretic patterns of nonhistone nuclear protein (NHNP) in MSS relative to N showed a striking resemblance to those demonstrated previously for the early stage (myolytic phase) of hamster cardiomyopathy relative to the matched control. Since NHNP interacting with DNA appears to play a major role in genetic expression, it is possible that some of the manifestations of MSS could be due to different components of NHNP in the affected hearts.

Surgical treatment of idiopathic hypertrophic subaortic stenosis in children.

Five children with idiopathic hypertrophic subaortic stenosis (IHSS) were operated upon during the past 7 years and all survived. Their ages ranged from 4 years and 5 months to 14 years (mean 8 years and 5 months). The operations performed were 1 right ventricular myectomy and 4 transaortic left ventricular myotomies. Whether surgery performed in childhood would change the natural history or not is still unknown, however, according to our results and many available reports, we have so far reached the following conclusions; 1. Transaortic left ventrlcular myotomy or myectomy is a safe and effective operation for localized muscular subaortic stenosis in children. 2. Because the disease is progressive, operation in childhood may be worth to be considered, when the resting or provocative pressure gradient is excessive. 3. For those who have a marked increase in left ventricular outflow pressure gradient by the provocation, operation would be considered even though the gradient at rest is less than 50 mmHg.

New concepts in hypertrophic obstructive cardiomyopathy I

HYPERTROPHIC obstructive cardiomyopathy is a form of primary myocardial disease with a characteristic clinical and pathological expression. The disorder is referred to by several names. Braunwald and associates¹introduced and popularized the term "idiopathic hypertrophic subaortic stenosis" in the United States, Wigle and associates²coined the term "muscular subaortic stenosis" in Canada, while in Europe it is generally referred to as hypertrophic obstructive cardiomyopathy (HOCM), following the lead of Goodwin and associates³at the Royal Postgraduate School of Medicine in London. A term that includes subaortic stenosis is unfortunate, since the disorder may be expressed without left ventricular outflow obstruction and since patients have been described as having isolated infundibular subpulmonic stenosis. It is more accurate and potentially less confusing to refer to the disorder as hypertrophic cardiomyopathy and add the word "obstructive" if either left or right ventricular outflow obstruction can be demonstrated.⁴The historical aspects of

Newer Concepts in Hypertrophic Obstructive Cardiomyopathy I

HYPERTROPHIC obstructive cardiomyopathy is a form of primary myocardial disease with a characteristic clinical and pathological expression. The disorder is referred to by several names. Braunwald and associates¹introduced and popularized the term "idiopathic hypertrophic subaortic stenosis" in the United States, Wigle and associates²coined the term "muscular subaortic stenosis" in Canada, while in Europe it is generally referred to as hypertrophic obstructive cardiomyopathy (HOCM), following the lead of Goodwin and associates³at the Royal Postgraduate School of Medicine in London. A term that includes subaortic stenosis is unfortunate, since the disorder may be expressed without left ventricular outflow obstruction and since patients have been described as having isolated infundibular subpulmonic stenosis. It is more accurate and potentially less confusing to refer to the disorder as hypertrophic cardiomyopathy and add the word "obstructive" if either left or right ventricular outflow obstruction can be demonstrated.⁴The historical aspects of

Ventricular septal defect associated with left ventricular outflow tract obstruction below the defect

Muscular subaortic stenosis associated with ventricular septal defect (VSD) is a rare but important anomaly. Two types of left ventricular outflow tract (LVOT) obstruction should be distinguished on the basis of morphologic as well as hemodynamic differences, depending on whether the stenosis is localized above (Type I) or below (Type II) the defect. The five cases presented are all in the latter category. In the first two cases the correct diagnosis was not made until after repair of the VSD. Two patients had previously undergone banding of the pulmonary artery (PAB). Marked carotid shudder and a vertical QRS axis in the frontal plane were presented in all cases. For the diagnosis to be established by catheterization, the catheter tip must be maneuvered into the apical part of the left ventricular cavity in order to detect the stenosis on the withdrawal curve. It is difficult to visualize the stenosis by angiography. The surgical approach through the VSD via a right atriotomy is highly recommended for Type II subaortic stenosis.

The treatment of muscular subaortic stenosis : W. G. Bigelow, A. S. Trimble, E. D. Wigle, A. G. Adelman, and C. H. Felderhof. J. Thorac. Cardiovasc. Surg. 68:384–392 (September), 1974

The treatment of muscular subaortic stenosis : W. G. Bigelow, A. S. Trimble, E. D. Wigle, A. G. Adelman, and C. H. Felderhof. J. Thorac. Cardiovasc. Surg. 68:384–392 (September), 1974

The treatment of muscular subaortic stenosis

Of 100 patients with muscular subaortic stenosis, 26 have been followed prospectively with no treatment, 55 have had a trial of propranolol therapy, and 39 were operated upon prior to July, 1973. Transaortic ventriculomyotomy can abolish the outflow gradient, the abnormal systolic anterior movement of the anterior mitral leaflet, and the mitral regurgitation, and it can reduce the left ventricular end-diastolic pressure. Thus the operation produces symptomatic improvement in most patients. This report analyzes the hospital deaths, complications, late deaths, and clinical failures in our series. We have reached the following conclusions: Ventriculomyotomy through the aorta, with or without resection of muscle, is a simple and effective method of treating most patients with muscular subaortic stenosis who have resting obstruction. However, in some of these patients, the gradient is eliminated by angiotensin, but the degree of mitral insufficiency is either increased or else not lessened by the drug. Such patients should have a ventriculomyotomy and mitral valve replacement, provided that the mitral insufficiency is significant. In patients with far-advanced disease, surgical therapy may be of limited value.

Aorticopulmonary septal defect coexisting with ventricular septal defect.

Three cases, in each of which an aorticopulmonary septal defect (AP window) coexisted with a ventricular septal defect, are described. In two the ventricular septal defect was of the usual variety, and in one it was part of the tetralogy of Fallot. The patients presented as examples of congestive cardiac failure with a large left-to-right shunt in infancy. Aortography was the most reliable method for identification of the AP window when a ventricular septal defect was associated. Associated features included a right aortic arch with mirror image branching in the first case and tetralogy of Fallot with muscular subaortic stenosis in the third case. In the case with the tetralogy of Fallot, the effects of pulmonary stenosis were masked by the left-to-right shunt through the AP window.