Biomedical subjects
Publications and source records attributed to E D Wigle.
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To better understand the pathophysiology of obstruction of left ventricular outflow in hypertrophic cardiomyopathy and to determine the value of intraoperative transesophageal Doppler echocardiography in decision making, 32 consecutive patients undergoing ventriculomyectomy were assessed. The mean preoperative left ventricular outflow gradient was 83 +/- 39 mm Hg and the mean basal septal width was 24 +/- 6 mm. Compared with transesophageal findings in 10 normal control subjects, the mitral leaflets were longer and the coaptation point was abnormal in the patients with obstructive hypertrophic cardiomyopathy (anterior and posterior leaflet lengths in the patients were 31 +/- 4 vs. 22 +/- 3 mm in the control group [p less than 0.00001] and 20 +/- 2 vs. 15 +/- 3 mm in the control group [p less than 0.00001]). The coaptation point in the patient group was in the body of the leaflets at a mean of 9 +/- 2 mm from the anterior leaflet tip, whereas it was at or within 3 mm of the leaflet tip in the normal group. During early systole, the distal third to half of the anterior mitral leaflet angled sharply anteriorly and superiorly (systolic anterior motion), resulting in leaflet-septal contact and incomplete mitral leaflet coaptation in mid-systole. This caused the formation of a funnel, composed of the distal parts of both leaflets, that allowed a jet of posteriorly directed mitral regurgitation to occur in mid- and late systole. The sequence of events in systole was eject/obstruct/leak. Transesophageal echocardiography was also helpful in planning the extent of the resection, assessing the immediate result and excluding important complications. In successful cases, the post-myectomy study showed 1) a dramatic thinning of the septum, with widening of the left ventricular outflow tract to a width similar to that in the normal subjects, 2) resolution of systolic anterior motion and the left ventricular outflow tract color mosaic, and marked reduction or abolition of mitral regurgitation despite persistence of abnormal mitral leaflet length and an abnormal mitral leaflet coaptation point. The routine use of transesophageal echocardiography in patients undergoing surgical myectomy for the treatment of obstructive hypertrophic cardiomyopathy is recommended.
To evaluate scar-type and matrix connective tissue and to assess their role in the diastolic dysfunction of hypertrophic cardiomyopathy, surgically resected subaortic myectomy specimens and several autopsy hearts from patients with hypertrophic cardiomyopathy were studied. Eighteen specimens were differentially stained by a newly developed method that precisely determines relative collagen content; these tissues were compared with postmortem hypertrophied and normal control subaortic specimens. Quantitation revealed a 72% higher level (36.5 vs. 22.1 micrograms collagen/mg protein) of stainable collagen in the hearts with hypertrophic cardiomyopathy than in hypertrophied control hearts. The endocardial plaque was quantitated morphometrically, and it constituted only 4.6 +/- 1.7% of the total increased collagen content in the cardiomyopathy specimens. For the matrix studies, the cardiomyopathy specimens were stained by a silver impregnation technique that identifies connective tissue elements not normally visible with routine histologic methods. There was a marked increase in content of all matrix components, both in areas of pathologic scarring and in "normal" zones. Whorls of matrix connective tissue were noted in regions of myocyte whorls, as well as independent of them. Thus, these studies revealed a striking increase of both scar-type and matrix connective tissue in hypertrophic cardiomyopathy. The extensive scarring and the pronounced interstitial and intercellular matrix connective tissue may contribute to the increased ventricular chamber stiffness and impaired relaxation in this disease.
To examine the "adequacy" of basal coronary flow in ventricular hypertrophy, the relation between proximal coronary artery dimensions and regional ventricular mass in aortic valve stenosis (AS) and hypertrophic cardiomyopathy (HC) was evaluated. Coronary artery size was determined by quantitative coronary arteriography while global/regional ventricular mass was calculated using computer-processed biplane 2-dimensional echocardiography. In comparison to 18 "normal" subjects, left anterior descending coronary dimensions were significantly larger in those with hypertrophy (normal 3.32 +/- 0.54, AS 3.82 +/- 0.71, HC 4.72 +/- 0.81 mm, p less than 0.05), with progressive increases in left anterior descending/circumflex coronary diameter ratios (normal 1.04 +/- 0.14, AS 1.18 +/- 0.19, HC 1.25 +/- 0.31, p less than 0.01). Compared to the AS group, indexed anteroseptal mass was greater in the HC subjects (AS 40.9 +/- 8.9 vs HC 72.1 +/- 21 g/m2, p less than 0.001). Both septal width/left anterior descending coronary diameter ratios (AS 3.61 +/- 1.06 vs HC 4.85 +/- 1.17 mm/mm, p less than 0.05) and indexed anteroseptal mass/left anterior descending coronary diameter ratios (AS 11.2 +/- 3.0 vs HC 15.6 +/- 3.4 g/m2/mm, p less than 0.01) were greater in HC subjects. Increased coronary dimensions were observed in both AS and HC, with the greatest changes noted within the left anterior descending distribution in HC, but when analyzed with respect to regional ventricular mass, these subjects demonstrated relative "inadequate" enlargement in coronary artery diameters. Underdeveloped epicardial coronary arteries may contribute to anteroseptal myocardial ischemia, with resultant angina pectoris, increased ventricular ectopic activity and sudden death in HC.
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To determine the clinical course of apical hypertrophic cardiomyopathy, 26 patients (mean age 45 years) with asymmetric apical hypertrophy diagnosed by echocardiography or angiography were followed up for an average of 7.3 years (range 1 to 22). Presenting symptoms included atypical chest pain (n = 10), typical angina (n = 6), dyspnea (n = 5) and palpitation (n = 8). Ten patients were asymptomatic. At follow-up all patients had inverted precordial T waves, and 14 had the syndrome of "giant T wave negativity" (greater than or equal to 10 mm). In six patients with electrocardiographic follow-up of greater than 10 years (mean 13.4), precordial T wave inversion had progressed from -0.8 +/- 3.9 to -11.2 +/- 8.0 mm in lead V4 in association with increased QRS amplitude. Episodic atrial fibrillation occurred in 4 of 10 patients with echocardiographic left atrial enlargement. Although left ventricular systolic function was normal, diastolic relaxation was impaired in comparison with values in 10 healthy control subjects: in all 18 patients studied peak filling rate was decreased (4.44 +/- 0.44 versus 6.13 +/- 1.54 stroke volumes/s); time to peak filling was increased (174 +/- 40 versus 147 +/- 32 ms); and atrial systolic contribution to ventricular end-diastolic volume was increased (21.5 +/- 6.8 versus 11.5 +/- 4.6 stroke volume %). During follow-up, 21 of the 26 patients remained in stable condition or were asymptomatic. One patient with normal coronary arteries had an apical myocardial infarction with development of a discrete apical aneurysm and loss of "giant T wave negativity." This patient was the only one to have documented life-threatening ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
This article discusses the central role of cardiac ultrasonography-- two dimensional echocardiography, Doppler echocardiography, continuous-wave Doppler, pulsed-wave Doppler--in the clinical assessment and management of patients with hypertrophic cardiomyopathy.
This study was designed to evaluate the relation between severity of obstruction to left ventricular outflow and left ventricular ejection time in hypertrophic obstructive cardiomyopathy. With dual catheters across the left ventricular outflow tract, the pressure gradient and corresponding left ventricular ejection time were measured in 10 patients as the pressure gradient was pharmacologically provoked or abolished, or both. The patients were studied during constant atrial pacing to avoid the potential errors introduced with heart rate correction equations. The pressure gradient was pharmacologically provoked or reduced over a range of greater than or equal to 62 mm Hg per patient. In each patient the left ventricular ejection time varied directly with the pressure gradient (mean r = 0.97, range 0.92 to 1.00). The change in magnitude of the pressure gradient varied directly with the corresponding change in the measured ejection time (mean r = 0.98, range 0.97 to 1.00). When the data from all 10 patients were pooled with use of Weissler's heart rate correction equation, the relation between the corrected left ventricular ejection time and the pressure gradient was still significant and linear (r = 0.86), but less so than in individual patients. This difference was the result of marked interpatient variability in the slope of this linear relation reflecting interpatient differences in other important factors, such as underlying myocardial contractility and stroke volume, that influence left ventricular ejection time. This study demonstrates a clear, direct and highly significant relation between the magnitude of the pressure gradient and the left ventricular ejection time in hypertrophic obstructive cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Surgical ventriculomyectomy and ventriculomyotomy by the aortic approach are safe and effective methods of relieving symptoms and obstruction to left ventricular outflow in patients with hypertrophic obstructive cardiomyopathy. With the addition of Doppler ultrasound to the routine follow-up assessment of these patients an unexpectedly high occurrence of aortic regurgitation was found in the postoperative patients. Because aortic regurgitation has been reported to rarely accompany this condition, 67 patients with hypertrophic obstructive cardiomyopathy were studied clinically and with Doppler echocardiography for the presence and severity of aortic regurgitation. Severity of the regurgitation was quantitated by pulsed or color Doppler echocardiography according to the length and width of the regurgitant jet in at least two views. In 37 patients with hypertrophic obstructive cardiomyopathy who did not undergo surgery, aortic regurgitation was detected in only 1 (3%) by Doppler ultrasound and in none clinically. In 52 patients who did undergo surgery and were studied a mean of 7.8 years postoperatively, aortic regurgitation of trivial to moderate degree was common, being detected in 28 (54%) by Doppler ultrasound and in 6 (12%) clinically. In a subgroup of 22 patients who were studied preoperatively and again early postoperatively (mean 6 weeks), new aortic regurgitation was found in 8 (36%) and was graded as trivial in all. Aortic regurgitation is a common complication related to ventriculomyectomy and ventriculomyotomy in patients with hypertrophic obstructive cardiomyopathy. Although initially trivial, the regurgitation may progress in severity over time. The regurgitation has been well tolerated in all patients studied to date.
The hemodynamic effects of intravenous disopyramide were determined in 43 patients with hypertrophic cardiomyopathy and pressure gradients at rest (resting obstruction). The basal subaortic pressure gradient decreased in all patients by a mean of 61 mm Hg (range 16 to 123); in 35 patients the gradient was abolished (less than 20 mm Hg). The reduction in pressure gradient was achieved through a decrease in left ventricular systolic pressure, from 178 to 135 mm Hg (p less than 0.0001), and a rise in aortic systolic pressure, from 105 to 123 mm Hg (p less than 0.0001). Left ventricular ejection time was reduced from 326 to 273 ms (p less than 0.0001). Left ventricular end-diastolic pressure decreased from 19 to 16 mm Hg (p less than 0.0001). In a subgroup of 13 patients, cardiac output was unchanged after disopyramide, despite a prolongation of the pre-ejection period from 104 to 137 ms (p less than 0.0001) indicating a decrease in contractility. The maintenance of cardiac output, despite a decrease in contractility, may reflect a decrease in mitral regurgitation resulting from the reduction of systolic anterior motion of the mitral valve by disopyramide. These results indicate that disopyramide produces predictably favorable hemodynamic effects in patients with hypertrophic cardiomyopathy and resting obstruction to left ventricular outflow.
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Hypertrophic cardiomyopathy is a diverse clinical and pathophysiologic disorder of unknown cause that principally involves the left ventricle and is manifested as asymmetric or concentric hypertrophy. If asymmetric, the hypertrophy is usually greatest in the ventricular septum, but variations occur in which the hypertrophy may be maximal at the mid-ventricular level, at the apex, or rarely, in the free wall of the left ventricle. Right ventricular involvement is usually less evident. The principal abnormality in systole is the obstruction to left ventricular outflow caused by systolic anterior motion (SAM) of the anterior or posterior mitral leaflet(s) with mitral leaflet-septal contact. SAM occurs as the result of the Venturi forces created by the rapid ejection of blood through an outflow tract that is narrowed by upper septal hypertrophy, drawing the mitral leaflet(s) anteriorly. The time of onset and duration of mitral leaflet-septal contact determine the magnitude of the pressure gradient. Mitral regurgitation invariably accompanies the obstruction to outflow. Ventriculomyectomy surgery, by thinning the septum and widening the outflow tract, abolishes the abnormal mitral leaflet motion and, consequently, the obstruction to outflow and the mitral regurgitation. In symptomatic patients with resting obstruction this form of surgery more dramatically relieves the systolic abnormalities and the accompanying symptoms than any form of medical therapy currently available. The extent of hypertrophy is believed to be the principal determinant of impaired left ventricular relaxation and increased chamber stiffness that characterize diastole in hypertrophic cardiomyopathy. Diastolic dysfunction is common to most such patients irrespective of the presence or absence of outflow obstruction. Calcium entry blockers may improve the left ventricular relaxation process and relieve symptoms in patients with hypertrophic cardiomyopathy, particularly the subgroup with no obstruction to outflow. Atrial and ventricular arrhythmias are responsible for a significant proportion of the morbidity and mortality, and their prevalence appears to depend on the presence of obstruction and the extent of hypertrophy. Thus, the major manifestations of hypertrophic cardiomyopathy in systole and diastole, as well as the disturbances in rhythm, appear to be related to the site and/or extent of the hypertrophic process. We have learned much about hypertrophic cardiomyopathy in the 30 years since its modern description. The vast majority of symptomatic patients can now be improved with specific medical or surgical therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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In obstructive hypertrophic cardiomyopathy (muscular or hypertrophic subaortic stenosis), there is rapid early systolic ejection through an outflow tract that is narrowed by ventricular septal hypertrophy. This results in Venturi forces acting on the mitral leaflets, which cause mitral leaflet systolic anterior motion. Subsequent mitral leaflet-septal contact results in obstruction to left ventricular outflow and concomitant mitral regurgitation. Evidence is provided that the subaortic pressure gradient in obstructive hypertrophic cardiomyopathy reflects true obstruction to left ventricular outflow. It is important to distinguish this truly obstructive subaortic pressure gradient, due to mitral leaflet-septal contact, from an early systolic impulse gradient, as well as from the intraventricular pressure difference that may be encountered in midventricular obstruction or cavity obliteration.
Between 1971 and March 1986, 61 patients underwent surgery for hypertrophic obstructive cardiomyopathy. Age at operation varied from 3.5 to 76 years (mean 38). The standard approach was a generous transaortic myectomy. One-quarter of the patients underwent concomitant repair of associated lesions. There was one operative and two late deaths, for an actuarial 5 years survival 93% (+/- 8%). Average follow-up is 3 years per patient. Sixty-four percent of these patients are asymptomatic and another 30% were in New York Heart Association class II. Persistent symptoms were usually related to arrhythmias. Early atrioventricular block did not occur, but two patients were paced for complex arrhythmias 3 and 4 years after surgery. Hemodynamic studies (n = 22), two-dimensional echocardiographic (n = 47), and Doppler assessments (n = 23) demonstrated a left ventricular outflow tract pressure gradient of 70 and 14 mm Hg before and after surgery, respectively, left ventricular diastolic pressure of 18 and 14 mm Hg, percent of patients with mitral regurgitation of 70% and 30%, percent of patients with systolic anterior motion of 100% and 35%, and percent of patients with aortic insufficiency of 9% and 49%. Eight-six percent of the patients catheterized had no resting obstruction. Subaortic myectomy produces symptomatic improvement by reducing the left ventricular outflow tract pressure gradient, mitral regurgitation, and left ventricular end-diastolic pressure, and probably improves longevity.
The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested. Sixty family physicians were randomised to two treatment strategies. "Test" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing. Computer feedback on management was mailed to the doctors. This encouraged doctors to apply the "stepped care" protocol, supplied charts of diastolic blood pressure v time, and ranked patients' diastolic blood pressures by percentile. Letters were mailed to patients to remind them of appointments. "Control" doctors filled out the same data collection forms as test physicians, but neither doctors nor patients received computer feedback. Physicians who used the computer saw more patients per practice than control doctors (test 50 patients, control 40). For all patients the length of follow up was significantly longer in test practices (test 199 days, control 167), and a smaller percentage dropped out of active treatment in test practices (test 37.5%, control 42.1%). For patients with "moderate" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practices (88.5 mm Hg), but it failed to reach this goal in control practices (93.3 mm Hg). A greater average reduction of diastolic pressure was achieved in test practices (test 21.7 mm Hg, control 16.7 mm Hg). Though patients with "moderate" hypertension were better controlled in test practices than in control practices, the patients in test practices visited their doctors less often (test 13.3 visits per patient-year, control 17.4 visits). Among patients with newly detected hypertension test practices achieved a greater reduction in diastolic pressure than control practices (test 15.1 mm Hg v control 11.3 mm Hg) and more sustained control of hypertension (test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days).
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.
Echocardiography has greatly simplified the diagnosis of hypertrophic cardiomyopathy and routine haemodynamic studies are usually only required in patients being considered for myectomy or the assessment of coexistent coronary disease. A complete echo Doppler study should be performed in all patients with hypertrophic cardiomyopathy to define the degree of obstruction, the degree of asymmetric hypertrophy and abnormalities of diastolic function. In this manner the patient can be classified according to haemodynamic subgroup, thus influencing the choice of treatment and helping to determine prognosis. These studies also provide a simple quantitative method of assessing the beneficial effects of medical or surgical therapy.