Performance of the failing and nonfailing right ventricle of patients with pulmonary hypertension.

Hemodynamic performance of the right ventricle was measured in 34 patients: 17 with pulmonary hypertension, 9 with pulmonary hypertension and right ventricular failure and 8 control subjects. Among the patients with pulmonary hypertension who did not have right ventricular failure, right ventricular maximal isovolumic rate of development of ventricular pressure (dP/dt) was significantly elevated (P less than 0.001), whereas maximal 1/P dP/dt and maximal velocity of contractile element shortening (Vmax) were comparable with values observed in control subjects. The patients with pulmonary hypertension who had right ventricular failure also showed an augmented right ventricular maximal dP/dt (P less than 0.001) and normal 1/P dP/dt and Vmax. These observations indicate that in pulmonary hypertensive heart disease, even when the right ventricle failed in a clinical sense, the contractile effort was normal. Consequently, right ventricular failure may develop in patients with pulmonary hypertensive heart disease even though the cardiac muscle performs normally as a contractile tissue.     

History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease

The history and physical examination were assessed in 215 patients with acute pulmonary embolism uncomplicated by preexisting cardiac or pulmonary disease. The patients had been included in the Urokinase Pulmonary Embolism Trial or the Urokinase-Streptokinase Embolism Trial. Presenting syndromes were (1) circulatory collapse with shock (10 percent) or syncope (9 percent); (2) pulmonary infarction with hemoptysis (25 percent) or pleuritic pain and no hemoptysis (41 percent); (3) uncomplicated embolism characterized by dyspnea (12 percent) or nonpleuritic pain usually with tachypnea (3 percent) or deep venous thrombosis with tachypnea (0.5 percent). The most frequent symptoms were dyspnea (84 percent), pleuritic pain (74 percent), apprehension (63 percent) and cough (50 percent). Hemoptysis occurred in only 28 percent. Dyspnea, hemoptysis or pleuritic pain occurred separately or in combination in 94 percent. All three occurred in only 22 percent. The most frequent signs were tachypnea (respiration rate 20/min or more) (85 percent), tachycardia (heart rate 100 beats/min or more) (58 percent), accentuated pulmonary component of the second heart sound (57 percent) and rales (56 percent). Signs of deep venous thrombosis were present in only 41 percent and a pleural friction rub was present in only 18 percent. Either dyspnea or tachypnea occurred in 96 percent. Dyspnea, tachypnea or deep venous thrombosis occurred in 99 percent. As a group, the identified clinical manifestations, although nonspecific, are strongly suggestive of acute pulmonary embolism. Conversely, acute pulmonary embolism was rarely identified in the absence of dyspnea, tachypnea or deep venous thrombosis.     

Hemodynamic and anatomic determinants of relative differences in amplitude of the aortic and pulmonary components of the second heart sound

Intraarterial sound and pressure in the region of normal semilunar valves and the physical characteristics of the normal semilunar valves were measured to determine the factors that cause a difference in amplitude of the aortic and pulmonary components of the second heart sound. During cardiac catheterization, intraarterial sound was measured near the aortic valve in 15 normotensive patients and near the pulmonary valve in 13 patients with normal pulmonary arterial pressure and 17 patients with pulmonary hypertension. Both the rate of change of the diastolic pressure gradient and the amplitude of the pulmonary component of the second heart sound were higher in patients with pulmonary hypertension than in those with normal pulmonary arterial pressure. In patients with pulmonary hypertension, the amplitude of the pulmonary component of the second sound was as great as that of the aortic component. However, even in patients with pulmonary hypertension, diastolic pressure and the rate of change of the pressure gradient across the valve were lower than on the left side of the heart. These findings suggest that anatomic as well as hemodynamic factors determine the relative amplitude of the pulmonary and aortic components of the second sound. Examination of valves dissected from 12 patients at autopsy revealed that the normal pulmonary valve had a larger surface area and was thinner and more distensible than the normal aortic valve. These observations indicate that both the pulmonary and aortic components of the second sound are related to the rate of change of the diastolic pressure gradient that develops across the valves. However, a comparable driving pressure across the pulmonary valve would cause the pulmonary component of the second sound to have a greater amplitude than the aortic component because of the larger surface area and greater distensibility of this valve. These physical characteristics of the pulmonary valve permit it to produce more compression and thus more sound-pressure than the somewhat smaller and less distensible aortic valve.     

Frequency spectra of the first heart sound and of the aortic component of the second heart sound in patients with degenerated porcine bioprosthetic valves

To determine the usefulness of the frequency of heart sounds in the assessment of porcine bioprosthetic valve degeneration, frequency spectra of phonocardiograms of the first heart sound and the aortic component of the second sound were analyzed in 31 patients with degenerated porcine bioprosthetic valves. Comparisons were made with 35 control patients whose valves were inserted 1 month or less. Among 23 patients with degenerated porcine bioprosthetic valves in the mitral position, the dominant frequency of the first heart sound was 95 ± 11 Hz, which exceeded the first sound in 18 controls (51 ± 3 Hz) (p < 0.01). The degenerated mitral porcine bioprosthetic valves of 14 patients showed calcification or fibrosis and the first heart sound in these patients was 115 ± 16 Hz, which exceeded that of control subjects (p < 0.001). The degenerated mitral porcine bioprosthetic valves of 9 patients showed torn leaflets only, and the first heart sound in these patients was 64 ± 9 Hz, which did not differ from that of control subjects. In the aortic position, 8 valves were degenerated and the aortic component of the second sound was 109 ± 12 Hz, which was higher than that in 17 control subjects (63 ± 4 Hz) (p < 0.001). Only 2 of these degenerated valves showed tears unaccompanied by calcific deposits or fibrosis, and the frequencies were comparable to that of control subjects. These observations indicate that the frequency of heart sounds in patients with degenerated porcine bioprosthetic valves becomes abnormally elevated when degeneration is accompanied by calcification or fibrosis, which causes the cusps to stiffen.     

Role of blood viscosity in the production of innocent ejection murmurs.

The purpose of this study was to investigate factors that may participate in the production of innocent ejection murmurs. Although it is known that ejection murmurs are produced by turbulent flow, the cause of turbulence in subjects with innocent murmurs has not been determined. The viscosity and the density of blood are factors that participate in the production of turbulence. Therefore, their role in the production of innocent ejection murmurs was investigated in 40 healthy young women, aged 18 to 22 years. Fourteen subjects had an innocent murmur; 26 had no murmur. All had a normal hematocrit (37 ml/100 ml or greater); none were anemic. However, the subjects with an innocent murmur had a significantly lower hematocrit (P < 0.01), and consequently the viscosity of blood in these subjects was lower (0.038 ± 0.001 versus 0.042 ± 0.001 poise) (P < 0.001). The density of blood and the estimated stroke volume were similar in both groups. These observations suggest that young women with an innocent murmur may have a lower viscosity of blood than those without a murmur. The increased turbulence caused by the decreased viscosity may contribute to causing inaudible ejection murmurs to exceed the threshold of audibility.     

Aortic origin of innocent murmurs.

Intraarterial sound was measured just distal to the aortic and pulmonary valves of 10 subjects with no apparent valve disease. Six patients had no audible murmur; four had grade 1 to 2 innocent murmurs. At rest, during normal sinus rhythm, the intensity of intraarterial sound was greater above the aortic than above the pulmonary valve (0.41+/-0.14 versus 0.02+/-0.01 ergs/sec per cm2 [mean+/-standard error of the mean]) (P less than 0.02). In all patients with an audible murmur, the murmur was of greater amplitude within the aorta than within the pulmonary artery. The two patients with a grade 1 murmur had a murmur near the aortic valve and no murmur near the pulmonary valve. To examine the effects of increased flow, the six patients with inaudible murmurs were studied during the first beat immediately after a premature ventricular contraction. The intensity of intraarterial sound after premature contractions in these six patients was 1.41+/-0.38 ergs/sec per cm2 above the aortic valve and 0.10+/-0.04 above the pulmonary valve (P less than 0.01). The intensity of murmurs in the aorta during postextrasystolic beats was in the range that occurs with grade 1 to 2 murmurs, whereas murmurs within the pulmonary artery were in the range of inaudible murmurs. Comparable observations were made in dogs in which instantaneous flow was also measured. These observations suggest that innocent murmurs are produced at the aortic rather than the pulmonary valve, possibly because of the greater compliance of the pulmonary artery, which may have a damping effect upon turbulence.     

Determinants of the amplitude of the aortic component of the second heart sound in aortic stenosis

The characteristics of the aortic component of the second heart sound in calcific and congenital noncalcific aortic stenosis were studied to determine a cause for observed differences. Intraarterial pressure and sound were measured above the aortic valve in 20 patients utilizing catheter-tip micromanometers. Ten patients had a normally functioning aortic valve, six had calcific aortic stenosis and four had congenital noncalcific aortic stenosis. As expected, the aortic sound was diminished in patients with calcific aortic stenosis compared with that in patients with a normal valve (600 ± 200 versus 2,600 ± 200 dynes/cm² (P < 0.001). In patients with congenital aortic stenosis, sound amplitude was not reduced compared with that in patients with a normal valve. Measurement of sound produced by closure of normal and stenotic valves in an in vitro model of the circulatory system yielded comparable results. In vitro high speed (2,000 frames/sec) motion pictures of the diastolic motion of the closed cusps showed vibrations of comparable magnitude in the normal porcine and the simulated congenitally stenotic valve. The calcified stenotic valve showed no noticeable diastolic vibrations. These observations indicate an association between the amplitude of the second heart sound and diastolic vibrations of the closed cusps. A calcified stenotic valve, being thick and stiff, would have a diminished ability to vibrate and would therefore produce a diminished sound. A congenitally stenotic valve, in contradistinction, if not yet damaged by degenerative changes, would not be limited in its ability to vibrate during diastole and would therefore produce a normal second sound.     

Blood velocity in the right coronary artery: relation to the distribution of atherosclerotic lesions

Vascular endothelial injury by high shear stresses and adverse effects of low shear rates on mass transfer across the arterial wall have been suggested as factors in atherogenesis. This study describes differences in blood velocity, and therefore differences of shear rate, across the lumen of the right coronary artery (RCA) of man. Selective coronary arteriograms of 30 patients without obstructive RCA disease were reviewed. Velocity was assessed qualitatively based on the rate of clearance of contrast material. There was a rapid clearing of contrast material along the outer wall of the RCA as it curved around the border of the heart. A much slower clearing occurred along the inner wall, bordering the myocardium, which persisted 2 to 6 cardiac cycles after the outer wall had cleared. This suggests that velocity, and therefore shear rate, is much lower along the inner wall of the RCA. To determine the relation of the distribution of atherosclerotic plaques in the RCA to local blood velocity, the RCA in 17 randomly selected human subjects who died of noncardiac disease were studied histologically. There was an uneven distribution of atherosclerotic plaques in the RCA with greater involvement of the inner wall. These observations demonstrate an association between the lower shear rate along the inner wall of the RCA and the site of higher concentration of atherosclerosis.     

Effect of turbulent blood flow on systolic pressure contour in the ventricles and great vessels: Significance related to anacrotic and bisferious pulses

The effect of turbulent blood flow on the contour of systolic pressure in the left and right ventricles and great vessels was investigated in 64 patients undergoing diagnostic cardiac catheterization. Intracardiac pressure and sound were recorded using a catheter-tip micromanometer. Measurements were made in normal subjects and patients with a variety of disorders including aortic stenosis, hypertrophic obstructive cardiomyopathy, coarctation of the aorta and atrial septal defect. Observations showed a consistent association of the intracardiac murmur, which is indicative of turbulence, with a transient reduction of the centrally recorded systolic pressure. The resultant abnormal systolic pressure contour can be explained on the basis of fluid dynamic considerations related to turbulence.     

Mechanism of a musical systolic murmur caused by a degenerated porcine bioprosthetic valve

The cause of a musical (cooing) murmur produced by a degenerated bioprosthetic valve in the mitral position was investigated. Spectral analysis of the murmur recorded at the chest wall at the site of the maximum palpable impulse showed virtually all sound in a narrow frequency band around the dominant frequency of 158 hertz. The same valve, surgically removed and mounted in the mitral position in a pulse duplicating system, produced an audible musical murmur detected by a phonocatheter in the atrial chamber. Nearly all of the sound-pressure occurred in a narrow band of frequency around 145 hertz. High speed motion pictures (500 frames/s) showed systolic flutter of a flail leaflet. The frequency of this leaflet flutter was 142 hertz. Hot film anemometry showed minimal turbulence, all located near the margin of the regurgitant leaflet. The intensity of the murmur was unrelated to the intensity of turbulence. A second degenerated bioprosthetic valve that produced in vivo a typical blowing holosystolic mitral regurgitant murmur produced in vitro a murmur with a broad range of frequencies (20 to 500 hertz). With this valve, the intensity of the murmur was related to the intensity of the turbulence. Motion pictures showed no leaflet flutter. Flutter of an insufficient valve leaflet causing uniform and periodic high frequency fluctuating pressures therefore appeared to be the cause of the musical quality of the systolic murmur in a degenerated bioprosthetic valve.     

Valve origin of the aortic incisura

The occurrence and magnitude of the incisura of the central aortic pressure were shown in 66 patients to depend on the functional state of the aortic valve. In normal subjects and children with congenital aortic stenosis (with thin flexible leaflets), the incisura ranged between 6 and 14 mm Hg. With aortic regurgitation, the incisura diminished as the severity of regurgitation increased. With calcific aortic stenosis, the incisura was smaller or absent. These observations imply a valve mechanism productive of the incisura. In vitro studies of human aortic valves confirmed these observations. Additional in vitro studies with high speed cinematography (2,000 frames/sec) of a stented normal porcine valve also showed that early diastolic stretch and recoil of the leaflets occurs. These results indicate that in the presence of a normal or diseased aortic valve the aortic incisura is produced primarily by valve distension or recoil, respectively. Distension and rebound of the aortic walls do not appear to contribute significantly in the presence of a normal or a diseased valve. Because acquired aortic valve disease affects the magnitude of the central aortic incisura, inspection of the incisura may be of ancillary value in evaluating the pathologic state of the aortic valve.     

Hemodynamic determinants of the frequency and amplitude of a musical murmur produced by a regurgitant mitral bioprosthetic valve

The purpose of this study was to assess the hemodynamic determinant of the amplitude and frequency of a musical murmur produced by a regurgitant degenerated bioprosthetic valve in the mitral position. The prosthetic valve, obtained at surgery, was studied in the mitral position of an in vitro pulse duplicating system. In vitro, the valve produced a musical murmur that was caused by flutter of a flail leaflet. When the peak pressure difference between the left ventricle and left atrium was increased from 95 to 150 mm Hg, the fundamental frequency of the musical murmur increased from 91 to 187 hertz and the amplitude increased from 2,080 to 11,420 dynes/cm². The fundamental frequency of the musical murmur was linearly related to the peak systolic pressure difference between the left ventricle and the left atrium (correlation coefficient [r] = 0.99). Similarly, the fundamental frequency of the musical murmur was linearly related to the magnitude of regurgitant flow across the valve (r = 0.99); and the regurgitant flow as expected was linearly related to the systolic pressure difference between the left ventricle and left atrium. The amplitude of the musical murmur was also related to both the peak systolic pressure difference between the left ventricle and left atrium (r = 0.99) and the magnitude of regurgitant flow (r = 0.99). These results indicate that the magnitude of regurgitant flow, determined by the systolic pressure difference between the left ventricle and left atrium, was a determinant of both the amplitude and the frequency of the musical murmur.     

Hemodynamics of multiple versus single 50 percent coronary arterial stenoses

The purpose of this study was to compare coronary blood flow in the presence of multiple fixed coronary arterial stenoses with that in the presence of a single stenosis of equivalent length and diameter. The study was performed using an in vitro pulse duplicating system. The aortic root section consisted of an acrylic mold of the root of the aorta of a calf. The coronary system was designed to produce coronary flow with physiologic magnitudes and phasic patterns. Aortic and left ventricular pressures as well as the reduction in pressure across the coronary test section containing the stenotic segments were measured with catheter-tip micromanometers. Coronary flow was measured with a cannulating electromagnetic flow transducer. The fluid viscosity was 0.04 poise. Studies were performed sequentially with one 2 mm long arterial segment with a stenosis of 50 percent of luminal diameter, two such stenotic segments and three such stenotic segments in series. A single 4 mm long, 50 percent diameter stenotic segment and a 6 mm long, 50 percent diameter stenotic segment were also studied. The heart rate was 71 beats/min, stroke volume 80 ml and aortic pressure $\text{140}\text{75}\text{mm Hg}$. A single 2 mm long, 50 percent stenotic segment caused a 6 percent reduction of coronary flow; three such stenoses in series caused a 19 percent reduction of coronary flow. In contrast, a single 6 mm long, 50 percent diameter stenotic segment caused only an 8 percent reduction of coronary flow. The results suggest that in a maximally dilated coronary bed, a greater reduction of coronary flow would occur in the presence of multiple short stenoses than in the presence of a single stenosis of equivalent length and diameter.     

Evaluation of platelet reactivity in patients with valvular heart disease

Transmission electron microscopy with a standardized in vitro method was used to evaluate the degree of blood platelet reactivity in 72 normal subjects and 72 patients with valvular heart disease. Among the patients with abnormal natural heart valves, 51 had either aortic insufficiency or aortic stenosis, and 21 patients showed either mitral insufficiency or mitral stenosis. For normal subjects, the platelet differential counts were dominated by the dendritic type platelet, and only a few platelets showed cytoplasmic spreading between adjacent pseudopodia (spread type). A hyperactive response was defined as greater than 20% of the spread type platelet or more than 93 aggregates per 100 single platelets counted, or both. Only 6 (8%) of the 72 normal subjects showed hyperactive platelets. In contrast, 45 (62%) of the 72 patients with valvular heart disease had hyperactive platelets (p less than 0.01). For patients with abnormal valves, the mean percent of the spread type platelet was 35% with a mean value of 105 platelet aggregates. The increased level of platelet reactivity was independent of both the position of the valve (aortic versus mitral) and its functional status (insufficient versus stenotic). Disturbed flow and the exposure of subendothelial thrombus-producing materials are features associated with abnormal heart valves. These factors, which usually occur in combination, may explain the hyperactive platelet response found in these patients.     

Echocardiographic evaluation of porcine bioprosthetic valves: Experience with 309 normal and 59 dysfunctioning valves

To determine the clinical value of echocardiographic evaluation of porcine bioprosthetic valves, the findings in all patients who had porcine bioprosthetic valve replacement and adequate quality echocardiographic studies from 1978 to 1982 were analyzed. The study includes 309 normal and 59 dysfunctioning valves. Valve dysfunction resulted from spontaneous cusp degeneration in 39 (34 valve regurgitations, 5 stenoses), infective endocarditis in 12, paravalvular regurgitation in 5, regurgitation of redundant cusps, mitral valve thrombi, and aortic stent stenosis in 3 others. Echocardiographic findings were correlated with gross surgical pathologic or autopsy findings in 45 of the 59 dysfunctioning valves. Echocardiographic abnormalities were demonstrated in 41 of 59 (69%) dysfunctioning valves. A systolic mitral or diastolic aortic valve flutter was diagnostic of a regurgitant valve caused by a torn or unsupported cusp margin and was observed in 28 of 34 (82%) regurgitant valves with no false-positive studies. Echocardiographic cusp thickness of ≥ 3 mm correctly identified all regurgitant and stenotic valves with gross anatomic evidence of localized or generalized cusp thickening or calcific deposits. Echocardiographic valve abnormalities were observed in only 4 of 12 patients with infective endocarditis and in 1 of 5 with paravalvular regurgitation.Thus, echocardiography provides important information regarding the function of porcine bioprosthetic valves and is of value in the decision to replace these valves, especially when dysfunction is due to spontaneous cuspal degeneration. Echocardiography is neither sensitive nor specific in patients with infective endocarditis and paravalvular regurgitation.     

Some clinical considerations regarding the relation of coronary vasospasm to coronary atherosclerosis: A hypothetical pathogenesis

This study explores the relation between coronary arterial spasm and the development of coronary atherosclerosis. The clinical history and coronary angiographic and electrocardiographic data in 212 consecutive patients with ischemic heart disease were correlated. These patients were classified into four groups: Group 1, patients without angiographic evidence of atherosclerosis; Group 2, patients with single vessel disease; Group 3, patients with double vessel disease; and Group 4, patients with significant narrowing of major coronary arteries. Although spontaneous angina occurred in all four groups, it was more common (55 percent) in the patients in Group 1, who were predominantly female and young. Spontaneous angina was confirmed in Group 1 with several techniques, including thallium-201 scintigraphy, ergonovine administration and electrocardiography during attacks of pain. Prior myocardial infarction was present with similar frequency in all four groups. A patient is discussed whose spontaneously occurring coronary arterial spasm later progressed to fixed arteriosclerotic narrowing requiring coronary bypass surgery. These observations and a review of the literature lend support to the hypothesis that coronary arterial spasm can be a possible antecedent leading to the later development of fixed atherosclerotic coronary arterial obstruction.     

Comparison of radionuclide and enzymatic estimate of infarct size in patients with acute myocardial infarction

A comparison was made of the estimated size of the myocardial infarction occurring in 26 patients with a first infarction using creatine kinase (CK) enzyme release between radionuclide gated blood pool measurement of total and regional ventricular function and thallium-201 scintigraphic measurement of myocardial perfusion defects. Creatine kinase estimates of infarct size (enzymatic infarct size) correlated closely with the percent of abnormal contracting regions, left ventricular ejection fraction and thallium-201 estimates of percent of abnormal perfusion area (r = 0.78, 0.69 and 0.74, respectively, p less than 0.01). A close correlation also existed between percent abnormal perfusion area and percent of abnormal contracting regions (r = 0.81, p less than 0.01) and left ventricular ejection fraction (r = 0.69, p less than 0.01). Enzymatic infarct size was larger in anterior (116 +/- 37 CK-g-Eq) than inferior (52 +/- 29 CK-g-Eq) myocardial infarction (p less than 0.01) and was associated with significantly more left ventricular functional impairment as determined by left ventricular ejection fraction (33 +/- 7 versus 60 +/- 10%) (p less than 0.01) and percent abnormal perfusion area (58 +/- 14 versus 13 +/- 12) (p less than 0.01). No significant correlation was observed between enzymatic infarct size and right ventricular ejection fraction. These different methods of estimating infarct size correlated closely with each other in these patients with a first uncomplicated myocardial infarction.