Systemic toxic effects associated with high-dose verapamil infusion and chemotherapy administration.

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.

Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study.

BACKGROUND: Noninvasive assessment of diastolic filling by Doppler echocardiography provides important information about left ventricular (LV) status in selected subsets of patients. This study was designed to assess whether mitral annular velocities as assessed by tissue Doppler imaging are associated with invasive measures of diastolic LV performance and whether additional information is gained over traditional Doppler variables. METHODS AND RESULTS: One hundred consecutive patients referred for cardiac catheterization underwent simultaneous Doppler interrogation. Invasive measurements of LV pressures were obtained with micromanometer-tipped catheters, and the mean LV diastolic pressure (M-LVDP) was used as a surrogate for mean left atrial pressure. Doppler signals from the mitral inflow, pulmonary venous inflow, and TDI of the mitral annulus were obtained. Isolated parameters of transmitral flow correlated with M-LVDP only when ejection fraction <50%. The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/E') showed a better correlation with M-LVDP than did other Doppler variables for all levels of systolic function. E/E' <8 accurately predicted normal M-LVDP, and E/E' >15 identified increased M-LVDP. Wide variability was present in those with E/E' of 8 to 15. A subset of those patients with E/E' 8 to 15 could be further defined by use of other Doppler data. CONCLUSIONS: The combination of tissue Doppler imaging of the mitral annulus and mitral inflow velocity curves provides better estimates of LV filling pressures than other methods (pulmonary vein, preload reduction). However, accurate prediction of filling pressures for an individual patient requires a stepwise approach incorporating all available data.

Influence of incremental changes in heart rate on mitral flow velocity: assessment in lightly sedated, conscious dogs.

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)

Hemodynamic determinants of Doppler pulmonary venous flow velocity components: new insights from studies in lightly sedated normal dogs.

OBJECTIVES: We sought to define the hemodynamic determinants of pulmonary venous (PV) flow velocities to assess how these are affected by respiration, heart rate and loading conditions. BACKGROUND: Pulmonary venous flow velocity (PVFV) recorded with pulsed wave Doppler technique is currently used in the noninvasive evaluation of left ventricular (LV) diastolic function and filling pressures. Although previous studies in both animals and humans have shown that PV flow is pulsatile, the hemodynamic determinants of the individual components of this flow remain controversial. Understanding the physiologic mechanisms should help to better define the clinical utility of these Doppler techniques. METHODS: PV flow velocities obtained with transesophageal pulsed wave Doppler imaging were recorded together with PV, left atrial (LA) and LV pressures in 10 sedated, spontaneously breathing normal dogs. PVFV and hemodynamic data were analyzed during apnea, inspiration and expiration, at atrial paced heart rates of 60, 80, 100 and 120 beats/min and mean LA pressures of 6, 12, 18 and 24 mm Hg. RESULTS: The data showed that 1) PV pressure varied depending on recording site, resembling pulmonary artery pressure closer to the pulmonary capillary bed and LA pressure closer to the venoatrial junction; 2) PVFV qualitatively followed changes in the PV-LA pressure gradient; 3) four PVFV components exist under normal conditions-three of which follow phasic changes in LA pressure and one of which (the late systolic component) is more influenced by RV stroke volume and the compliance of the pulmonary veins and left atrium; 4) normal respiration and changes in heart rate significantly alter PVFV variables--in particular, reverse flow velocity at atrial contraction; and 5) increasing LA pressure results in larger PV A wave and PV early systolic flow velocities, as well as an earlier peak in PV late systolic flow velocity and a more prominent velocity minimum before PV diastolic flow. CONCLUSIONS: Using transesophageal pulsed wave Doppler technique, four PVFV components are identifiable and determined by PV-LA hemodynamic pressure gradients. These gradients appear to be influenced by a combination of physiologic events that include RV stroke volume, the compliance of the pulmonary vasculature and left atrium and phasic changes in LA pressure. PV flow velocity components are significantly influenced by heart rate, respiration and LA pressure. These findings have implications for the interpretation of LV diastolic function and filling pressures by current Doppler echocardiographic techniques but require further clinical investigation.

Experimental cardiac tamponade: a hemodynamic and Doppler echocardiographic reexamination of the relation of right and left heart ejection dynamics to the phase of respiration.

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.

Demonstration of restrictive ventricular physiology by Doppler echocardiography.

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.

Cardiac tamponade and pericardial effusion: respiratory variation in transvalvular flow velocities studied by Doppler echocardiography.

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.

Diastolic mitral and tricuspid regurgitation by Doppler echocardiography in patients with atrioventricular block: new insight into the mechanism of atrioventricular valve closure.

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.

Superior vena cava and hepatic vein Doppler echocardiography in healthy adults.

Pulsed wave Doppler ultrasound recordings of blood flow velocity in the superior vena cava were made in 40 healthy adults (aged 22 to 69 years) during both normal respiration and 10 second episodes of apnea. The forward flow velocity pattern was biphasic, with systolic flow velocity greater than diastolic flow velocity. During apnea, peak flow velocities ranged from 32 to 69 cm/s (mean 45.7 +/- 8.4) during systole and from 6 to 45 cm/s (mean 27.2 +/- 8.3) in early diastole. Systolic flow velocity integrals also exceeded diastolic values. With atrial systole (A wave), forward flow velocities were reduced or flow was reversed. Thirty-nine of 40 subjects had A wave flow reversal during apnea, and in these the ratio of reverse to total forward flow velocity integrals ranged from 1 to 16% (mean 6 +/- 4%). Compared with values during apnea, there were higher mean values with inspiration and lower values with expiration for velocities and flow velocity integrals. Hepatic vein tracings, when adequate (12 of 40 subjects), showed forward flow characteristics similar to those from the superior vena cava, but with more frequent and larger A wave and ventricular end-systole (atrial V wave) flow reversals. Superior vena cava flow velocity variables were calculated in subgroups to assess the effects of age, respiratory pattern and increased venous return. This study defines normal Doppler ultrasound superior vena cava and hepatic vein flow velocities and their variation with respiration in healthy adults. These results can be used for comparison with patterns found in disease states.

Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study.

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.

Diastolic mitral regurgitation with atrioventricular conduction abnormalities: relation of mitral flow velocity to transmitral pressure gradients in conscious dogs.

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)

Experimental pericardial effusion: relation of abnormal respiratory variation in mitral flow velocity to hemodynamics and diastolic right heart collapse.

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.

Utility of preload alteration in assessment of left ventricular filling pressure by Doppler echocardiography: a simultaneous catheterization and Doppler echocardiographic study.

OBJECTIVES: The aim of this study was to demonstrate the usefulness of preload alterations in assessing left ventricular filling pressures with transmitral Doppler velocity curves. BACKGROUND: Doppler mitral inflow velocities, used to estimate left ventricular filling pressures noninvasively, are limited in predicting left ventricular filling pressures, especially in patients with normal systolic function and a "pseudonormal" mitral filling pattern. METHODS: Forty-nine patients were studied in the cardiac catheterization laboratory with simultaneous Doppler echocardiography using high fidelity catheters to compare left ventricular diastolic filling pressures (pre-A wave left ventricular pressure) and Doppler mitral inflow at baseline and during reduction of preload during the strain phase of the Valsalva maneuver (n = 27) or sublingual nitroglycerin (n = 36), or both (n = 14). Doppler measurements consisted of E (initial peak velocity), A (velocity at atrial contraction), deceleration time (time from E velocity to deceleration of flow extrapolated to baseline) and absolute A wave velocity (A' [peak A wave velocity minus velocity at onset of atrial contraction]). RESULTS: In patients with high pre-A wave pressure (> or 15 mm Hg), there was a greater change in the E/A' ratio during the Valsalva maneuver than in patients with a normal pre-A wave pressure (-1.22 +/- 1.1 vs. -0.35 +/- 0.17; p = 0.02). A similar change was seen when comparing the change in the E/A' ratio after administration of nitroglycerin in patients with a high versus a normal pre-A wave pressure (0.81 +/- 0.49 vs. 0.18 +/- 0.17; p < 0.001). These differences were present in patients with a normal E/A ratio at baseline. CONCLUSIONS: Alterations in preload during assessment of Doppler echocardiographic indexes may be useful in noninvasively assessing left ventricular filling pressures.

Estimation of left ventricular filling pressures using two-dimensional and Doppler echocardiography in adult patients with cardiac disease. Additional value of analyzing left atrial size, left atrial ejection fraction and the difference in duration of pulmonary venous and mitral flow velocity at atrial contraction.

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.

Intraventricular flow during isovolumic relaxation: description and characterization by Doppler echocardiography.

This study describes the characteristics of a prominent Doppler flow velocity signal representing intraventricular flow during left ventricular isovolumic relaxation. The flow during the isovolumic relaxation period was demonstrated in 60 subjects, including 7 with a normal heart, 26 with hypertrophic cardiomyopathy, 10 with aortic valve disease, 9 with a transplanted heart and 8 others. All had normal to hyperdynamic left ventricular systolic function with some degree of cavity obliteration as seen in the apical two-dimensional echocardiographic views. In contrast, this isovolumic relaxation period flow could not be demonstrated in the absence of cavity obliteration in any of 20 patients with either normal or diminished left ventricular systolic function. Isovolumic relaxation period flow was best recorded from the apical transducer position and was directed toward the apex in all patients. By pulsed wave, and with two-dimensional Doppler ultrasound, the isovolumic relaxation period flow originated within a narrow area in the medial portion of the left ventricle along the middle or basal segments of the interventricular septum, but was recorded over a larger area toward the apex. The peak isovolumic relaxation period flow velocity was recorded just basal to the area of cavity obliteration, usually at the level of the papillary muscles, and ranged from 0.4 to 2.3 m/s (mean of 1.0 m/s). This isovolumic relaxation period flow started with aortic valve closure and, in 50 of the 60 patients, it lasted throughout isovolumic relaxation until mitral valve opening. In the other 10 patients (all with hypertrophic cardiomyopathy), it lasted for only a part (mean 63%) of this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler evaluation of patients with constrictive pericarditis: use of tricuspid regurgitation velocity curves to determine enhanced ventricular interaction.

OBJECTIVES: This study sought to examine the value of analyzing Doppler echocardiographically derived tricuspid regurgitation signals during respiration in relation to the diagnosis of constrictive pericarditis. BACKGROUND: A physiologic hallmark of constrictive pericarditis is enhanced ventricular interdependence, which produces reciprocal changes in right and left ventricular filling and ejection dynamics during the respiratory cycle. It was hypothesized that these changes could be detected noninvasively by analyzing Doppler echocardiographically derived tricuspid regurgitation signals and that this information could assist in noninvasively diagnosing constrictive pericarditis. METHODS: Simultaneous Doppler echocardiography and catheterization studies of the right and left sides of the heart with high fidelity pressure manometers were performed in 5 patients with surgically confirmed constrictive pericarditis and 12 patients (control subjects) with heart failure due to other causes. RESULTS: Changes observed in tricuspid regurgitation Doppler echocardiographic variables from onset to peak inspiration in patients with constrictive pericarditis were significantly different from those in control subjects. Mean (+/- SD) percent change in maximal tricuspid regurgitation velocity was 13% +/- 6% and -8% +/- 7% in the constrictive pericarditis and control groups, respectively (p < 0.0001); mean percent change in tricuspid regurgitation signal duration was 18% +/- 2% and -2% +/- 7%, respectively (p < 0.0001); mean percent change in tricuspid regurgitation time velocity integral was 27% +/- 15% and -10% +/- 12%, respectively (p < 0.0001). CONCLUSIONS: Respiratory changes in Doppler echocardiographically derived tricuspid regurgitation peak velocity and velocity duration are increased in patients with constrictive pericarditis and may be helpful in diagnosing this condition noninvasively.

Determination of left ventricular filling pressure by Doppler echocardiography in patients with coronary artery disease: critical role of left ventricular systolic function.

OBJECTIVES: This study was designed to determine the usefulness of transthoracic Doppler measurements in detecting increased left ventricular (LV) end-diastolic pressure in patients with coronary artery disease, specifically examining the influence of systolic function on the accuracy of these methods. BACKGROUND: Studies that have correlated Doppler indexes with LV filling pressures primarily involved patients with LV systolic dysfunction. The reliability of Doppler indexes in estimating filling pressures in patients with coronary artery disease and preserved systolic function is unclear. METHODS: Pulsed wave Doppler transmitral and pulmonary venous flow velocity curves and LV pressure were recorded in 83 patients with coronary artery disease. RESULTS: Conventional Doppler indexes (deceleration time of mitral E wave velocity, ratio of peak mitral E to A wave velocities and pulmonary venous systolic fraction) correlated with LV filling pressure in patients with an ejection fraction (EF) < or = 50% but not in those with an EF > 50%. Previously published regression analysis for prediction of LV filling pressure was accurate in patients with an EF < or = 50% but not in those with an EF > 50%. The difference between flow duration with atrial contraction in the pulmonary veins and transmitral flow duration with atrial contraction correlated with LV filling pressure in both groups. CONCLUSIONS: Analysis of the early diastolic portion of the transmitral or pulmonary venous flow velocity curves can be used to predict LV filling pressures in patients with systolic dysfunction, but are inaccurate in patients with preserved systolic function. The combined analysis of both flow velocity curves at atrial contraction is a reliable, feasible predictor of increased LV filling pressure, irrespective of systolic function.

Ratio of left ventricular peak E-wave velocity to flow propagation velocity assessed by color M-mode Doppler echocardiography in first myocardial infarction: prognostic and clinical implications.

OBJECTIVES: To determine the ability of the ratio of peak E-wave velocity to flow propagation velocity (E/Vp) measured with color M-mode Doppler echocardiography to predict in-hospital heart failure and cardiac mortality in an unselected consecutive population with first myocardial infarction (MI). BACKGROUND: Several experimental studies indicate color M-mode echocardiography to be a valuable tool in the evaluation of diastolic function, but data regarding the clinical value are lacking. METHODS: Echocardiography was performed within 24 h of arrival at the coronary care unit in 110 consecutive patients with first MI. Highest Killip class was determined during hospitalization. Patients were divided into groups according to E/Vp <1.5 and > or =1.5. RESULTS: During hospitalization 53 patients were in Killip class > or =II. In patients with E/Vp > or =1.5, Killip class was significantly higher compared with patients with E/Vp <1.5 (p < 0.0001). Multivariate logistic regression analysis identified E/Vp > or =1.5 to be the single best predictor of in-hospital clinical heart failure when compared with age, heart rate, E-wave deceleration time (Dt), left ventricular (LV) ejection fraction, wall motion index, enzymatic infarct size and Q-wave MI. At day 35 survival in patients with E/Vp <1.5 was 98%, while for patients with E/Vp > or =1.5, it was 58% (p < 0.0001). Cox proportional hazards model identified Dt <140 ms, E/Vp > or =1.5 and age to be independent predictors of cardiac death, with Dt < 140 ms being superior to age and E/Vp. CONCLUSIONS: In the acute phase of MI, E/Vp > or =1.5 measured with color M-mode echocardiography is a strong predictor of in-hospital heart failure. Furthermore, E/Vp is superior to systolic measurements in predicting 35 day survival although Dt <140 ms is the most powerful predictor of cardiac death.

Comparison of mitral inflow and superior vena cava Doppler velocities in chronic obstructive pulmonary disease and constrictive pericarditis.

OBJECTIVE: This study was conducted to determine whether Doppler recording of superior vena cava flow velocities can differentiate chronic obstructive pulmonary disease from constrictive pericarditis in patients with a respiratory variation of > or = 25% in mitral inflow E velocity. BACKGROUND: Although respiratory variation (> or = 25%) in mitral E velocity is the main diagnostic criterion for constrictive pericarditis by Doppler echocardiography, it can also be present in chronic obstructive pulmonary disease. Because the respiratory variation is due to increased change in intrathoracic pressure with respiration in chronic obstructive pulmonary disease, and to dissociation of intrathoracic-intracardiac pressure changes in constriction, it was hypothesized that the Doppler flow velocity pattern in the superior vena cava (affected by intrathoracic pressure) would be different in these two conditions. METHODS: Pulsed-wave Doppler recording of mitral and superior vena cava flow velocities in 20 patients with chronic obstructive pulmonary disease who had > or = 25% respiratory variation in mitral E-wave velocity were compared with those of 20 patients who had surgically proved constrictive pericarditis. RESULTS: Constrictive pericarditis and chronic obstructive pulmonary disease had similar respiratory variation in mitral E velocity (41% versus 46%). In the latter, the E/A ratio was lower (inspiration, 0.8+/-0.3 versus 1.5+/-0.7 [p < 0.0001]; expiration, 1.0+/-0.3 vs. 1.9+/-0.7 [p < 0.0001]) and deceleration time longer (inspiration, 198+/-53 ms versus 137+/-32 ms; expiration, 225+/-43 ms vs. 161+/-33 ms [p < 0.0001]). Inspiratory superior vena cava systolic forward flow velocity was significantly higher in chronic obstructive pulmonary disease (72.9+/-22.6 cm/s versus 36.2+/-9.3 cm/s, p < 0.0001), while expiratory systolic forward flow velocity was similar. Hence, there was a significantly greater respiratory variation in superior vena cava systolic forward flow velocity in chronic obstructive pulmonary disease without an overlap with constrictive pericarditis (39.5+/-18.8 cm/s vs. 4.2+/-3.4 cm/s, p < 0.0001). CONCLUSIONS: Despite a similar respiratory variation in mitral E wave velocities, mitral inflow variables in chronic obstructive pulmonary disease are less restrictive compared with those in constrictive pericarditis. More importantly, patients with chronic obstructive pulmonary disease show a marked increase in inspiratory superior vena cava systolic forward flow velocity, which is not seen in patients with constrictive pericarditis.

Noninvasive doppler echocardiographic evaluation of left ventricular filling pressures in patients with cardiomyopathies: a simultaneous Doppler echocardiographic and cardiac catheterization study.

OBJECTIVES: The purpose of this study was to examine the relation of the mitral flow velocity curves to left ventricular filling pressures in patients with two different types of myocardial problems: hypertrophic cardiomyopathy and severe left ventricular systolic dysfunction. BACKGROUND: Previous studies have suggested that assessment of Doppler-derived mitral flow velocity curves can be used to predict left ventricular filling pressures in specific disease entities. However, it is unclear whether information derived from specific mitral flow velocity curves obtained from one disease entity can be valid in other disease states. METHODS: The study group consisted of 42 patients with left ventricular systolic dysfunction (group A) and 55 patients with hypertrophic cardiomyopathy (group B); both groups underwent simultaneous cardiac catheterization and were studied by Doppler echocardiography. High fidelity measures of left atrial and left ventricular pressures were obtained simultaneously with mitral flow velocity curves. RESULTS: There was a significant relation between the Doppler echocardiographic variables and mean left atrial pressure in group A patients. The left atrial pressure was directly related to the E/A ratio (r = 0.49, p = 0.004) and inversely related to the deceleration time (r = 0.73, p < 0.001). The sensitivity and specificity of the deceleration time, < 180 m/s, which indicated a mean left atrial pressure > or = 20 mm Hg, were both 100%. In group B patients, there was no significant relation between mean left atrial pressure and deceleration time. CONCLUSIONS: Doppler echocardiographic mitral flow velocity curves are useful in predicting and estimating left ventricular filling pressures in patients with left ventricular dysfunction. However, because of the complexity of the multiple interrelated factors that determine diastolic filling of the left ventricle, these flow velocity curves cannot be used in patients with other disease entities, such as hypertrophic cardiomyopathy. Future studies of different disease states are necessary to fully understand the role of Doppler echocardiography in the assessment of diastolic filling.