Biomedical subjects
Publications and source records attributed to C P Appleton.
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OBJECTIVES: The purpose of this study was to determine whether left atrial size and ejection fraction are related to left ventricular filling pressures in patients with coronary artery disease. BACKGROUND: In patients with coronary artery disease, left ventricular filling pressures can be estimated by using Doppler mitral and pulmonary venous flow velocity variables. However, because these flow velocities are age dependent, additional variables that indicate elevated left ventricular filling pressures are needed to increase diagnostic accuracy. METHODS: Echocardiographic left atrial and Doppler mitral and pulmonary venous flow velocity variables were correlated with left ventricular filling pressures in 70 patients undergoing cardiac catheterization. RESULTS: Left atrial size and volumes were larger and left atrial ejection fractions were lower in patients with elevated left ventricular filling pressures. Mean pulmonary wedge pressure was related to mitral E/A wave velocity ratio (r = 0.72), left atrial minimal volume (r = 0.70), left atrial ejection fraction (r = -0.66) and atrial filling fraction (r = -0.66). Left ventricular end-diastolic and A wave pressures were related to the difference in pulmonary venous and mitral A wave duration (both r = 0.77). By stepwise multilinear regression analysis, the ratio of mitral E to A wave velocity was the most important determinant of pulmonary wedge (r = 0.63) and left ventricular pre-A wave (r = 0.75) pressures, whereas the difference in pulmonary venous and mitral A wave duration was the most important variable for both left ventricular A wave (r = 0.75) and left ventricular end-diastolic (r = 0.80) pressures. The sensitivity of a left atrial minimal volume > 40 cm3 for identifying a mean pulmonary wedge pressure > 12 mm Hg was 82%, with a specificity of 98%. CONCLUSIONS: Left atrial size, left atrial ejection fraction and the difference between mitral and pulmonary venous flow duration at atrial contraction are independent determinants of left ventricular filling pressures in patients with coronary artery disease. The additive value of left atrial size and Doppler variables in estimating filling pressures and the possibility that left atrial size may be less age dependent than other mitral and pulmonary venous flow velocity variables merit further investigation.
Aside from its more conventional uses as a cardiovascular drug, the calcium channel blocker verapamil has recently been added to chemotherapeutic regimens to reduce drug resistance in B-cell and other neoplasms that express the P-glycoprotein. We recently treated patients with continuous-infusion verapamil (0.15 mg/kg per hour to 0.60 mg/kg per hour) over a 5-day period in combination with continuous-infusion vincristine and doxorubicin plus oral dexamethasone. Seventy-one courses involving 35 hospitalized patients were prospectively studied for cardiovascular and other side effects. Cardiovascular side effects were observed most frequently and consisted of first-degree heart block, hypotension, sinus bradycardia, and junctional rhythms. We observed higher degree heart block, but the QRS interval remained narrow and the ventricular escape rate remained relatively normal. Effects on mean arterial pressure, heart rate, and PR interval were both time and dose related. Severe, symptomatic congestive heart failure was rarely observed. The most common noncardiovascular side effects were constipation, peripheral edema, and weight gain. All systemic toxic effects observed were easily treated or disappeared with either temporary or permanent discontinuation of the verapamil infusion or by a decrease in the dose of verapamil. We conclude that the cardiovascular side effects associated with continuous, high-dose intravenous verapamil therapy are significant and dose limiting but are rapidly reversible. Less cardiotoxic chemosensitizers are needed to reverse multidrug resistance in cancer.
To determine the effect of increasing heart rate on mitral flow velocity variables, the time constant of left ventricular isovolumic relaxation and the transmitral pressure gradient, 16 lightly sedated, conscious dogs were studied with Doppler echocardiography during incremental right atrial pacing (n = 16) or the administration of atropine (n = 8) or isoproterenol (n = 8). With increasing heart rate, similar changes were seen with all three interventions and included: 1) mitral flow velocity in early diastole and the early diastolic transmitral pressure gradient either changed minimally or did not change; 2) mitral flow velocity at the start of and as a result of atrial contraction progressively increased; 3) the "absolute" increase in mitral flow velocity and transmitral pressure gradient at atrial contraction demonstrated a biphasic response, initially decreasing as heart rate increased, but then increasing again when atrial contraction occurred in close proximity (less than 70 ms) to mitral valve opening; 3) mitral flow velocity at atrial contraction did not exceed mitral flow velocity in early diastole until atrial contraction was within 70 ms of mitral valve opening and the two velocity peaks were nearly fused; and 4) the largest transmitral pressure gradient and mitral flow velocity occurred at the fastest heart rates, when left atrial contraction preceded mitral valve opening. Major differences among methods included: 1) variable changes in PR interval (+14.2 +- 8.9 ms with atrial pacing versus -74 +/- 26 ms with isoproterenol at peak heart rate compared with baseline); 2) variable changes in the speed of left ventricular relaxation (-2.8 +/- 2.8 ms with pacing versus -7.6 +/- 2.4 ms with isoproterenol at peak rate); and 3) the heart rate at which equalization of mitral flow velocity in early diastole and mitral flow velocity at atrial contraction velocity occurred (128 +/- 12 beats/min with pacing versus 185 +/- 19 beats/min with isoproterenol). These results show that regardless of method, qualitatively similar changes in mitral flow velocity and transmitral pressure gradient occur as heart rate increases. However, for any given heart rate, mitral flow velocity variables and late diastolic pressure gradient can be markedly different, depending on whether atrial pacing, withdrawal of parasympathetic tone or sympathetic stimulation is the cause of the increase in heart rate. These differences among methods appear most related to their effect on PR interval and to a lesser extent the rate of letf ventricular isovolumic relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)
Pericardial effusion is associated with an abnormal increase in respiratory variation in mitral flow velocity. However, the relation of the changes in flow velocity to pericardial pressure, hemodynamics and two-dimensional echocardiographic findings is not established. Therefore, 11 sedated dogs with extensive hemodynamic instrumentation were studied with two-dimensional and Doppler echocardiography during four stages of progressively larger pericardial effusion. During all stages of effusion, respiratory variation in peak mitral flow velocity in early diastole and left ventricular isovolumetric relaxation time was increased compared with baseline (p less than 0.05). This increase was seen at the earliest stage of effusion (mean pericardial pressure 4.2 +/- 1.4 versus -0.8 +/- 0.9 mm Hg at baseline, p less than 0.05), and preceded the appearance of unequivocal diastolic right heart collapse in every dog. Maximal respiratory variation coincided with the appearance of right atrial collapse (mean pericardial pressure 7.1 +/- 2.4 mm Hg; mean inspiratory decrease in aortic pressure 9.5 +/- 2.6 mm Hg; mean aortic pressure 88.2 +/- 15.2 versus 102.2 +/- 11.2 mm Hg at baseline, p less than 0.05; and cardiac output 3.8 +/- 1.2 versus 5.5 +/- 1.3 liters/min at baseline, p less than 0.05), but did not increase at stages associated with more severe hemodynamic compromise. In addition, the respiratory changes in peak mitral flow velocity in early diastole were associated with simultaneous changes in the diastolic transmitral pressure gradient. It is concluded that in this model of acute pericardial effusion 1) increased respiratory variation in early diastolic mitral flow velocity, peak mitral flow velocity in early diastole and left ventricular isovolumetric relaxation time occurs almost immediately as pericardial pressure increases and persists at all stages of increasing pericardial effusion; 2) the abnormal respiratory variation occurs before equalization of intracardiac pressures and before the onset of unequivocal right heart collapse; 3) the respiratory variation occurs as a result of changes in the diastolic transmitral pressure gradient; and 4) the magnitude of the respiratory change is not necessarily predictive of pericardial pressure or severity of hemodynamic compromise, especially at the more severe stages of pericardial effusion.
Diastolic mitral regurgitation is a common finding that can be detected with use of Doppler echocardiographic techniques in patients with atrioventricular (AV) conduction abnormalities. With use of simultaneous hemodynamic and Doppler techniques, mitral flow velocity, mitral valve motion and transmitral pressure gradient were studied during 50 cardiac cycles each of spontaneous or atrial paced first- and second-degree AV block in five lightly sedated dogs. Diastolic mitral regurgitation was detected during atrial relaxation on all beats in which ventricular contraction was delayed greater than 190 ms. In all dogs the diastolic regurgitation was associated with a reverse transmitral pressure gradient (3.7 +/- 1.1 mm Hg in first-degree AV block and 3.2 +/- 1.5 mm Hg in second-degree AV block) that occurred primarily as the result of a decrease in atrial pressure with atrial relaxation. These reverse pressure gradients were as large as the maximal forward transmitral gradients in early diastole (2.9 +/- 0.9 mm Hg in first-degree AV block and 3.1 +/- 0.7 mm Hg in second-degree AV block) and larger than the maximal forward pressure gradients at atrial contraction (1.7 +/- 0.5 and 1.4 +/- 0.6 mm Hg, respectively, p less than 0.05). The maximal reverse pressure gradient during atrial relaxation was also as large as the reverse pressure gradient in mid-diastole (2.7 +/- 0.9 and 2.8 +/- 1.0 mm Hg, respectively), associated with deceleration of early diastolic mitral flow. Peak diastolic mitral regurgitation velocity coincided with the maximal reverse transmitral gradient and was usually larger than anterograde mitral flow velocity.(ABSTRACT TRUNCATED AT 250 WORDS)
A hallmark of cardiac tamponade is pulsus paradoxus. However, the exact mechanism of pulsus paradoxus and the relation of left and right ventricular ejection dynamics remain controversial, with some studies suggesting an inverse relation in ventricular filling and ejection and others citing a more important role for the effects of right heart ejection dynamics delayed by transit through the pulmonary artery bed. To specifically reexamine this issue, six sedated but spontaneously breathing dogs were studied during experimental cardiac tamponade with use of extensive hemodynamic instrumentation and Doppler methods. During cardiac tamponade, left ventricular systolic pressure decreased from 125.8 +/- 12.1 to 81.7 +/- 26.7 mm Hg (p less than 0.01) and cardiac output from 5.86 +/- 1.48 to 2.34 +/- 0.98 liters/min (p less than 0.001); mean pericardial pressure increased from -1.2 +/- 0.8 to 10.5 +/- 3 mm Hg (p less than 0.001) and pulsus paradoxus from 4.3 +/- 1.6 to 10.7 +/- 1.2 mm Hg (p less than 0.001) compared with baseline values. An inverse relation in left and right ventricular ejection dynamics that was very close to 180 degrees out of phase was seen throughout the respiratory cycle in multiple hemodynamic and Doppler variables including peak systolic pressures, aortic and pulmonary flow velocities and ventricular ejection times. Simultaneous recording of the transmitral pressure gradient provided indirect evidence that the ventricular ejection dynamics were directly related to changes in ventricular filling. However, the magnitude of ventricular pressure or output flow velocity for each respiratory cycle was variable, depending on the exact timing of filling and ejection in relation to the phase of respiration. Variation in left ventricular output due to changes in right ventricular output delayed by transit through the pulmonary vasculature was not recognized in any animal. It is concluded that in spontaneously breathing dogs with acute cardiac tamponade, peak ventricular pressures, ventricular ejection times and pulmonary and aortic flow velocities have an inverse relation that is very close to 180 degrees out of phase.
We examined vena cava Doppler flow velocity tracings from 69 fetuses between 22 and 40 weeks' gestation. Twenty-three fetuses had arrhythmias. Fifteen fetuses had absent end-diastolic Doppler velocities in the umbilical artery, a condition associated with intrauterine growth retardation, and 15 normal fetuses with normal umbilical artery Doppler velocity ratios were matched by gestational age. In studies in 16 additional fetuses, inferior vena cava Doppler velocity waveforms were compared with superior vena cava Doppler velocity waveforms. Peak velocities and time-velocity integrals of forward or reverse flow during systole, early diastole, and atrial contraction were measured. In addition, the time-velocity integral during flow coincident with atrial contraction (a wave) was expressed as a percent of the time-velocity integral of total forward flow during both systole and early diastole. Systolic-to-diastolic ratios of inferior vena cava forward time-velocity integrals were not significantly different from systolic-to-diastolic ratios of superior vena cava forward time-velocity integrals (p = 0.86), but the percent of blood moving in a reverse direction during atrial contraction in the inferior vena cava was greater than the percent of blood moving in a reverse direction in the superior vena cava (p less than 0.05). Relative forward flow in early diastole in the group of normal fetuses increased with advancing gestational age (r = 0.60, p less than 0.05). During premature atrial contractions flow in the inferior vena cava was reversed, and the percent of reverse flow during atrial systole increased significantly from 4.5 +/- 0.3% to 28.3 +/- 3.7% (mean +/- SEM, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Studies in instrumented adults have shown an association between Doppler echocardiography-derived atrioventricular valve deceleration times and ventricular function. To determine how gestational age affects deceleration time in the tricuspid and mitral valve, pulsed Doppler ultrasonographic examinations were performed in 54 normal human fetuses. In addition, 26 fetuses with growth retardation and the absence of end-diastolic Doppler velocities in the umbilical artery were examined. Measurements were obtained from strip chart recordings; between three and five beats were used to obtain an average heart rate, ratio of peak velocity at atrial contraction to peak velocity in early diastole, and deceleration time in early diastole. Deceleration times increased during gestation from 86 +/- 27 to 116 +/- 18 msec in the tricuspid valve and from 98 +/- 25 to 132 +/- 21 msec in the mitral valve. Fetuses with growth retardation and the absence of end-diastolic Doppler velocities in the umbilical artery had longer deceleration times than those of normal fetuses (p less than 0.01). The increase in deceleration time across both atrioventricular valves in normal fetuses may be related to heart rate, an increased rate of ventricular relaxation, or an increase in ventricular compliance. The fetuses with intrauterine growth retardation and the absence of end-diastolic velocities in the umbilical artery have abnormally increased deceleration times; in the abnormal fetus this may be a result of impaired ventricular relaxation or decreased ventricular compliance.
Conventional hemodynamic measurements and Doppler echocardiography were used to assess ventricular physiology of the human cardiac allograft and to examine the influence of pertinent clinical factors on chronic myocardial performance. Sixty-four patients (18-55 years old; mean, 39 years) undergoing routine annual hemodynamic assessment were studied. Blood-flow velocity properties across the mitral, tricuspid, and aortic valves were analyzed from Doppler ultrasound recordings. Ten of these patients had elevated diastolic pressures associated with a sharp early diastolic dip followed by an exaggerated and abrupt rise in pressure, consistent with restrictive-constrictive ventricular physiology. Left ventricular dP/dt and stroke volume were lower in these patients compared with the other 54 patients. Doppler echocardiographic indexes of left ventricular filling and ejection in these 10 patients differed significantly. Isovolumic relaxation time and pressure half-time were shorter, peak early mitral and tricuspid flow velocities were higher, and mean aortic flow velocity and acceleration were lower. A higher rejection incidence was the only demonstrable clinical factor associated with impaired ventricular function. Doppler echocardiography may, therefore, noninvasively identify patients with hemodynamic evidence of restrictive-constrictive physiology. This abnormality occurs in approximately 15% of allograft recipients, is associated with impaired systolic performance, and may be related to rejection incidence.
To assess the influence of mitral prosthesis malfunction on various Doppler echocardiographic indexes, we studied the changes in the peak mitral flow velocity during early diastolic filling phase (Vmax), the mean transprosthesis pressure drop from the simplified Bernoulli equation, the mitral valve area by the pressure half-time method, and the left ventricular isovolumic relaxation time in 15 patients before and after replacement of the malfunctioning mitral prosthesis using continuous wave Doppler echocardiography. Examination of the 15 replaced prostheses revealed a torn or perforated leaflet in 12 valves and a sewing ring dehiscence in one valve. Additional restricted leaflet motion (classified as mild obstruction) was seen in three of these 13 valves. In the remaining two valves, severe prosthesis obstruction was noted. Changes in the Doppler indexes between the preoperative and postoperative study were present in all patients regarding Vmax (mean, 2.2 +/- 0.3 versus 1.6 +/- 0.2 m/sec; p less than 0.001), mean gradient (mean, 9 +/- 5 versus 5 +/- 0.8 mm Hg; p less than 0.001), and isovolumic relaxation time (mean, 47 +/- 12 msec versus 80 +/- 13 msec; p less than 0.001). The mean mitral valve area remained virtually unchanged (2.3 +/- 0.9 versus 2.6 +/- 0.3 cm2; p = NS) but increased postoperatively in each patient with preoperative mild or severe prosthesis obstruction without concomitant aortic regurgitation. Our conclusion is that the peak mitral flow velocity, the mean gradient, and the isovolumic relaxation time are useful parameters in the differentiation of normal and abnormal mitral prosthesis function but may not define the underlying lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Doppler ultrasound recordings of mitral, tricuspid, aortic, and pulmonary flow velocities, and their variation with respiration, were recorded in 12 patients with a restrictive cardiomyopathy and seven patients with constrictive pericarditis. Twenty healthy adults served as controls. The patients with constrictive pericarditis showed marked changes in left ventricular isovolumic relaxation time and in early mitral and tricuspid flow velocities at the onset of inspiration and expiration. These changes disappeared after pericardiectomy and were not seen in patients with restrictive cardiomyopathy or in normal subjects. The deceleration time of early mitral and tricuspid flow velocity was shorter than normal in both groups, indicating an early cessation of ventricular filling, but only patients with restrictive cardiomyopathy showed a further shortening of the tricuspid deceleration time with inspiration. Diastolic mitral and tricuspid regurgitation was also more common in the patients with restrictive cardiomyopathy. These results suggest that patients with constrictive pericarditis and restrictive cardiomyopathy can be differentiated by comparing respiratory changes in transvalvular flow velocities. In addition, although baseline hemodynamics in the two groups were similar, characteristic changes were seen with respiration that suggest differentiation of these disease states may also be possible from hemodynamic data.
The purpose of this study was to prospectively determine the incidence of diastolic mitral and tricuspid regurgitation in atrioventricular (AV) block using Doppler echocardiography. The temporal relation between mitral and tricuspid diastolic insufficiency and the diastolic murmur recorded in patients with complete heart block was also investigated. Twenty-two consecutive patients with AV block (referred to the Echo-Doppler laboratory for routine clinical studies), aged 18 to 87 years, were enrolled in the study. Eleven patients had third degree AV block and a ventricular-inhibited (VVI) pacemaker, two patients had second degree AV block, seven patients had first degree AV block, one patient had blocked premature atrial complexes and one patient had atrial flutter with 4:1 AV block. Diastolic mitral regurgitation was detected in 20 patients, and diastolic tricuspid regurgitation in 21. A mid-diastolic murmur was detected in all patients except in the three youngest. The murmur occurred before diastolic regurgitation and coincided with peak forward flow through the AV valve after atrial contraction. M-mode mitral valve echocardiograms obtained in nine patients demonstrated near closure of some portions of the mitral valve after atrial contraction. Effective closure of the valve, however, did not occur unless ventricular systole supervened. In conclusion, diastolic mitral and tricuspid regurgitation are almost universally present in patients with AV block and are associated with a diastolic murmur. The murmur coincides with forward AV valve flow. Diastolic regurgitation is silent. Effective AV valve closure is not established until ventricular systole occurs, as demonstrated by M-mode echocardiographic recording of the mitral valve.
In patients with restriction of cardiac filling of various origins, cardiac catheterization has been traditionally used as part of the diagnostic evaluation to verify the presence of restrictive/constrictive hemodynamics. In an attempt to determine whether this "restrictive" physiology could be demonstrated noninvasively, 14 patients who had a history, physical examination, two-dimensional echocardiogram and catheterization data compatible with a restrictive myocardial process were studied with pulsed wave Doppler ultrasound. Forty normal subjects served as a control group. The Doppler ultrasound evaluation included measurement of peak mitral and tricuspid flow velocities and flow velocity integrals, mitral and tricuspid deceleration times and central venous flow patterns during apnea and inspiration. The flow velocity recordings across the mitral and tricuspid valves in patients manifesting restriction were markedly different from those in normal subjects, showing shortened deceleration times across both valves, which indicated both an abrupt premature cessation of ventricular filling and the presence of a diastolic dip-plateau contour in ventricular pressure recordings. In addition, abnormal central venous flow velocity reversals with inspiration and diastolic mitral and tricuspid regurgitation were frequently observed, also suggesting the reduced myocardial compliance characteristic of a restrictive myocardial process.
In an effort to determine what clinically useful information regarding left ventricular diastolic function can be inferred noninvasively with pulsed wave Doppler echocardiography, mitral flow velocity patterns and measured variables were correlated with hemodynamic findings in 70 patients: 30 with coronary artery disease, 20 with idiopathic congestive cardiomyopathy, 14 with a restrictive myocardial process and 6 without significant cardiac disease. The effect of sudden changes in hemodynamics on the mitral flow velocity pattern was also investigated in a subgroup of patients who had simultaneous recording of mitral flow velocity and left ventricular pressure before and after left ventriculography. Mitral flow velocity recordings from 30 healthy adults served as a reference group. This analysis suggests that 1) the majority of patients with these cardiac disorders demonstrate abnormal mitral flow velocity patterns or variables; 2) markedly different flow velocity patterns can be seen in patients with impaired left ventricular relaxation; 3) the different mitral patterns appear to relate more to myocardial function and hemodynamic status than to the type of disease process present; 4) certain mitral patterns suggest different filling pressures and rates of early diastolic left ventricular filling; 5) an increase in left atrial pressure can "normalize" an abnormal mitral flow velocity pattern and "mask" a left ventricular relaxation abnormality; and 6) the different patterns appear to represent a dynamic continuum with the potential to change from one to another as a result of disease progression, medical therapy or sudden changes in hemodynamics. It is concluded that, despite the indirect method of estimation and certain limitations, mitral flow velocity recordings have clinical potential in assessing left ventricular diastolic function that merits further investigation.
Cardiac tamponade has been associated with an abnormally increased respiratory variation in transvalvular blood flow velocities. To determine whether this finding is consistently present in cardiac tamponade, seven patients were studied prospectively with Doppler echocardiography before and after pericardiocentesis and the results were compared with those found in 20 normal adults and 14 asymptomatic patients with pericardial effusion who did not have definite clinical evidence of tamponade. Doppler ultrasound evaluation included measurement of mitral, tricuspid, aortic, pulmonary and central venous flow velocities, as well as left ventricular ejection and isovolumic relaxation times during inspiration, expiration and apnea. In the patients with severe cardiac tamponade, respiratory variation in transvalvular flow velocities and left ventricular ejection and isovolumic relaxation times were markedly increased compared with values in normal subjects and those obtained after pericardiocentesis. In the 14 asymptomatic patients with pericardial effusion but without overt tamponade, 7 showed respiratory variation in flow velocity similar to that of normal subjects. The other seven patients demonstrated increased respiratory change compared with normal, but less than that in the patients with tamponade. Clinical and hemodynamic data in this latter group suggest that these patients may represent an intermediate stage of pericardial effusion with an element of hemodynamic compromise.
To determine the value of transesophageal ultrasound in the assessment of cardiac valve prostheses, 14 patients with clinically suspected mitral prosthesis malfunction were studied by transthoracic and transesophageal two-dimensional imaging as well as by color Doppler flow velocity mapping (color Doppler). Patients underwent left ventricular angiography (n = 13), surgery (n = 11), or both angiography and surgery (n = 10). Nine patients had only mitral valve replacement, four patients had both mitral and aortic valve replacement, and one patient had mitral, aortic, and tricuspid valve replacement. There were 16 biological and four mechanical prostheses. The degree of mitral regurgitation was graded by both transthoracic and transesophageal color Doppler according to the area of the regurgitant jet visualized and was compared with a three-point classification of mitral regurgitation by left ventricular angiography judged by observers blinded to the echocardiographic results. All transesophageal studies were performed without complication and were well tolerated. The pathological morphology of the mitral prosthesis was additionally or more clearly visualized by transesophageal two-dimensional imaging and subsequently proven at surgery in three patients with flail leaflets and one patient with a vegetation compared with images obtained by the transthoracic approach. Valvular regurgitation was graded by the transthoracic approach as absent in four patients, mild in two patients, moderate in five patients, and severe in only three patients. The transesophageal assessment showed absence of mitral regurgitation in two patients, moderate regurgitation in two patients, and severe regurgitation in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)