Mechanisms of reduced left ventricular filling rate in coronary artery disease.

To identify mechanisms underlying slow left ventricular filling in coronary artery disease, left ventriculograms from 93 patients and 18 normal subjects were digitised frame by frame and global and regional function analysed. In 54 patients peak normalised filling rates were above the lower 95% confidence limit of normal (2 X 9s-1) and in 39 they were below. Patients with slow filling had a lower ejection fraction, a higher end systolic volume, and less overall shape index change, although a larger percentage occurred during isovolumic relaxation owing to asynchronous relaxation. Stroke volume was not significantly different. Slow outward wall motion was associated with increased cavity volume and systolic hypokinesis. Wall motion was also appreciably asynchronous, with wide spreads in the times of peak outward velocity and termination of rapid outward movement between regions. Early outward movement usually started in the anterior region, with peak velocity occurring before mitral valve opening, and significantly earlier than that in the apex or the inferior region. Ventricular oscillations occurred during filling in 23 patients. This asynchronous wall movement was unrelated to the distribution of coronary artery disease, systolic hypokinesis, or Q waves on electrocardiograms but was similar to that occurring in mitral stenosis. The main causes of slow left ventricular filling in patients with coronary artery disease appear to be (a) failure to achieve a normal low end systolic volume, with associated loss of physiological changes in left ventricular cavity shape, and (b) incoordinate wall motion during isovolumic relaxation which dissipates energy normally coupled to rapid ventricular filling. The resulting slow and asynchronous wall motion may have clinical implications especially when the time available for left ventricular filling is short.     

Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia

OBJECTIVE: To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. DESIGN: A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. SUBJECTS: 10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. INTERVENTIONS: Treadmill exercise and dobutamine stress were performed on different days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. RESULTS: Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no difference in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), -5.6 (1.5)%, p < 0.05; and -6.1 (2.2)%, p < 0. 01), and at 30 and 45 minutes after dobutamine (-10.8 (1.8)% and -5. 5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst affected segment 15 and 30 minutes after exercise (-27.9 (7.2)% and -28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (-32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). CONCLUSIONS: In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease.     

Effects of the dipyridamole test on left ventricular function in coronary artery disease.

The dipyridamole stress test is used with thallium-201 to detect areas of inhomogeneity of blood flow that point to coronary artery disease (CAD). It is unclear whether dipyridamole produces inhomogeneous perfusion only or whether it actually decreases net flow in the obstructed vessels and produces true ischemia. It is also unclear what effect dipyridamole has on global and segmental left ventricular function. Therefore, ejection fraction, segmental wall motion and ventricular volume equivalents were measured before and after dipyridamole in 113 patients and 32 normal subjects. Ejection fraction responded in an abnormal fashion in 98 patients (87%), decreasing from 49 +/- 11% to 43 +/- 13% (p less than 0.0001), whereas it increased in 29 normal subjects (90%) from 57 +/- 6% to 64 +/- 10% (p less than 0.0001). Wall motion worsened distinctly in 75 patients (66%), and pressure/volume ratio deteriorated in 72%. The effect of dipyridamole lasted between 10 and 25 minutes, but was promptly reversed by aminophylline. These findings indicate that dipyridamole generally induces true ischemia in CAD. Furthermore, the degree of dysfunction is related to the angiographically assessed severity of CAD. The shortness of breath (seen in 10% of patients) may be partially explained by the findings, and it seems advisable to give aminophylline to every patient in order to promptly correct left ventricular dysfunction.     

Influence of left ventricular asynchrony on filling in coronary artery disease

To evaluate whether the extent of left ventricular (LV) asynchrony plays a role in the impairment of LV rapid filling in patients with coronary artery disease (CAD), 48 patients underwent both radionuclide angiography and cardiac catheterization. Patients were divided into group I (n = 33), with normal LV kinesis or only mild hypokinesia, and group II (n = 15), with LV dyskinesia or akinesia. Radionuclide ejection fraction was higher in group I than in group II (62 +/- 12 vs 44 +/- 20%; p less than 0.001). Peak filling rate was significantly lower in group II (1.9 +/- 0.8 vs 2.6 +/- 0.9 end-diastolic counts/s; p less than 0.01). Time to end-systole coefficient of variation, an index of the extent of LV asynchrony, was significantly higher in group II than in group I (43 +/- 10 vs 35 +/- 6; p less than 0.0002). In group I, a highly significant inverse relation was found between this index of asynchrony and peak filling rate (r = 0.71; p less than 0.0001). This correlation was found even when time to end-systole coefficient of variation was normalized to the RR interval (r = 0.49; p less than 0.01) and when peak filling rate was expressed in stroke counts (r = 0.57; p less than 0.001). The correlation between peak filling rate and index of asynchrony was maintained up to an end-systole coefficient of variation value of approximately 35. In group II patients (most with an asynchrony value greater than or equal to 35) no relation was found between time to end-systole coefficient of variation and peak filling rate.     

Improved left ventricular diastolic filling in patients with coronary artery disease after percutaneous transluminal coronary angioplasty

Left ventricular (LV) diastolic filling is abnormal at rest in many patients with coronary artery disease (CAD), even in the presence of normal resting LV systolic function. To determine the effects of improved myocardial perfusion on impaired. LV diastolic filling, we studied 25 patients with one-vessel CAD by high-temporal-resolution radionuclide angiography before and after percutaneous transluminal coronary angioplasty (PTCA). No patient had ECG evidence of previous myocardial infarction. Despite normal regional and global LV systolic function at rest in all patents, LV diastolic filling was abnormal (peak LV filling rate [PFR] less than 2.5 end-diastolic volumes (EDV)/sec or time to PFR greater than 180 msec) in 17 of 25 patients. Twenty-three patients had abnormal LV systolic function during exercise. After successful PTCA, LV ejection fraction and heart rate at rest were unchanged, but LV ejection fraction during exercise increased, from 52 +/- 8% (+/- SD) to 63 +/- 5% (p less than 0.001). LV diastolic filling at rest improved: PFR increased from 2.3 +/- 0.6 to 2.8 +/- 0.5 EDV/sec (p less than 0.001) and time to PFR decreased from 181 +/- 22 to 160 +/- 18 msec (p less than 0.001). Thus, a reduction in exercise-induced LV systolic dysfunction after PTCA, reflecting a reduction in reversible ischemia, was associated with improved LV diastolic filling at rest. These data suggest that in many CAD patients with normal resting LV systolic function and without previous infarction, abnormalities of resting LV diastolic filling are not fixed, but appear to be reversible manifestations of impaired coronary flow.     

Pulsed Doppler assessment of left ventricular diastolic filling in coronary artery disease before and immediately after coronary angioplasty

To determine if left ventricular (LV) diastolic filling abnormalities are detectable by Doppler echocardiography in patients with coronary artery disease (CAD), 34 patients with CAD and 24 normal, age-matched control subjects underwent mitral valve pulsed Doppler examination. At catheterization, all CAD patients had typical angina, at least 70% diameter narrowing of 1 major coronary artery, ejection fraction of 50% or more and no valvular heart disease. Seventeen CAD patients underwent coronary angioplasty and had a Doppler examination 1 day before and 1 day after the procedure. Doppler diastolic time intervals, peak velocities at rapid filling (E velocity), atrial contraction (A velocity) and the ratio peak E/peak A velocities were measured. The following areas under the Doppler velocity envelope and their percentage of the total area were calculated: first third of diastole (0.33 area), triangular area under the peak E velocity (E area), and triangular area under the peak A velocity (A area). Patients with CAD and normal subjects were significantly different (p less than 0.01) in peak E velocity (CAD 0.60 +/- 0.12 m/s, normal 0.68 +/- 0.12 m/s), peak A velocity (CAD 0.59 +/- 0.12 m/s, normal 0.48 +/- 0.11 m/s), ratio peak E/peak A velocities (CAD 1.0 +/- 0.27, normal 1.5 +/- 0.32), A area (CAD 0.052 +/- 0.015 m, normal 0.036 +/- 0.010 m), ratio E area/A area (CAD 1.7 +/- 0.53, normal 2.5 +/- 0.69), and all area fractions. In the CAD patients who had undergone coronary angioplasty, no differences were found in any Doppler index before and immediately after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular diastolic filling in patients with coronary artery disease and normal left ventricular function

Abnormal left ventricular diastolic filling (DF) has been noted in coronary disease (CD) patients with normal left ventricular function (NLVF). Inclusion of patients with regional wall disease, hypertension, and left ventricular hypertrophy may be responsible for abnormal DF. We evaluated left ventricular DF curves derived from gated blood pool scans in 21 normals (group 1), in 38 CD patients with NLVF specifically defined (group 2), and in 28 CD patients with ejection fractions greater than 50% and regional disease (group 3). The peak filling rate (PFR), mean filling rate (MFR), the percentage of stroke volume filled at one third of diastole (%SV-1/3 DT) and at the end of the rapid filling period (%SV-RFP) were determined. Groups 1 and 2 had similar DF parameters. Group 2 patients with 75% obstructive left anterior descending disease (LAD) had a reduced %SV-RFP and PFR (2.56 +/- 0.56 end-diastolic volumes/sec [EDV/S]) as compared to normals (3.11 +/- 0.65 EDV/S, p less than 0.01). Group 3 patients had a reduced PFR (2.14 +/- 0.53 EDV/S, p less than 0.001), MFR, %SV-1/3 DT, and %SV-RFP. DF in CD patients with NLVF was similar to normals in a select group of patients but was abnormal in patients with regional disease and greater than 75% LAD disease with NLVF.     

The relation between left ventricular asynchrony, relaxation, outward wall motion and filling characteristics during control period and pacing-induced myocardial ischaemia in coronary artery disease

To assess the relation between left ventricular asynchrony, relaxation, outward wall motion and filling in patients with coronary artery disease and normal systolic function, pressure measurements and left ventricular angiography were performed at rest and after pacing. Asynchrony and outward wall motion were quantified by segmental area-time curves. At rest, there were no differences in asynchrony and time constant between 10 patients with coronary artery disease and 10 normal subjects, while the early-filling rate was less in patients with coronary artery disease than in normal subjects. Six coronary artery disease patients with isolated left anterior descending disease displayed anterior outward wall motion which was less than that of normal subjects. In 10 coronary artery disease patients with pacing-induced angina, asynchrony increased, time constant prolonged and the early-filling rate decreased. In 6 coronary artery disease patients with isolated left anterior descending disease, anterior outward wall motion decreased after pacing. Thus, impaired early diastolic filling at rest in patients with coronary artery disease and normal systolic function may result not from asynchrony nor impaired relaxation, but from reduced regional outward wall motion of the affected area supplied by diseased coronary artery during early diastole. However, during ischaemia temporal asynchrony and impaired relaxation possibly add to left ventricular filling impairment in patients with coronary artery disease.     

Left ventricular diastolic filling in patients with coronary artery disease without myocardial infarction

Left ventricular diastolic dysfunction at rest was studied in 24 patients with coronary artery disease but no evidence of previous myocardial infarction. Seven patients with normal coronary arteries were studied as control. Diastolic filling was analyzed by the serial left ventricular volume and 14 radial axes from the gravity point of the left ventricle with cine left ventriculography. There were no differences in the systolic function between coronary artery disease and the normal control. Peak filling rate was decreased significantly in the groups with left anterior descending artery disease (LAD, p less than 0.05) and multivessel disease (MVD, p less than 0.05), but not in the group with right coronary artery disease (RCA). Time to peak filling rate was prolonged in each group of LAD (p less than 0.05), RCA (p less than 0.05), and MVD (p less than 0.001), compared with controls. The time-volume curve showed disturbed rapid filling in the LAD and RCA groups, and also both depressed rapid and slow filling in the MVD group. In the LAD group, the filling fraction was decreased significantly at the time of 25% of the diastolic period (p less than 0.001) and radial distension to the anterior wall was decreased at the time of 25%, 50%, and 75% of the diastolic period, compared with controls. In the RCA group, the filling fraction (p less than 0.001) and radial distension to the posterior wall were decreased only at the time of 25% of the diastolic period. In the MVD group, filling fraction and radial distension to the most wall were decreased at 25%, 50%, and 75% of the diastolic period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacological stress echocardiography in the diagnosis of coronary artery disease and myocardial ischaemia: a comparison between dobutamine and dipyridamole.

The objective of this study was to relate regional wall motion abnormalities assessed by dobutamine and dipyridamole stress echocardiography to quantitative measurements of coronary artery stenoses in consecutive patients referred for coronary angiography, and to compare haemodynamic effects of and complications related to the two agents. Patients underwent stress echoes on separate days in random sequence and had coronary angiography within 3 days of stress echocardiography. Echocardiograms were assessed by two investigators unaware of the patients' coronary anatomy. Coronary angiograms were also assessed quantitatively using the computer-assisted Cardiovascular Angiography Analysis System. There were 46 consecutive patients referred for coronary angiography; 28 were using beta-antagonists. Main outcome measures were sensitivity and specificity for dobutamine and dipyridamole stress echocardiography for detection of coronary artery disease (wall motion abnormalities at rest or stress) and myocardial ischaemia (stress induced new wall motion abnormalities). Sensitivity for the detection of myocardial ischaemia was found to be 57% for dobutamine and 64% for dipyridamole. Specificities were 78% and 89% respectively. Sensitivities for detection of coronary artery disease (lesion > or = 50% diameter stenosis) was 79% for dobutamine and 82% for dipyridamole; specificities were 78% and 89% respectively. These differences between the two agents are not significant. There were no severe side effects with either agent. Mean heart rate rose significantly with both tests but was higher with dobutamine; mean systolic blood pressure rose with dobutamine and fell with dipyridamole. It was concluded that dobutamine and dipyridamole stress echocardiography have similar sensitivities and specificities for detection of myocardial ischaemia and coronary artery disease although the haemodynamic effects of the two agents are different. Both are free from serious complications.     

Mental stress-induced myocardial ischemia in coronary artery disease patients with left ventricular dysfunction.

BACKGROUND: Reduced left ventricular ejection fraction (LVEF) is a risk factor for poor outcomes in patients with coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) also identifies a subset of CAD patients at increased risk for future cardiovascular events. Susceptibility to MSIMI in patients with CAD and reduced LVEF is unknown. METHODS AND RESULTS: We enrolled 182 patients (67 women) with a mean age of 64 years and a documented history of CAD in this study. Baseline resting ejection fraction was determined by use of technetium 99m sestamibi gated single photon emission computed tomography. Abnormal LVEF was defined as less than 45% for men and less than 50% for women (based on published norms for our software [Cedars-Sinai Medical Center]). All participants underwent mental stress testing with a public speaking task. Rest/stress myocardial perfusion single photon emission computed tomography was performed via conventional methodology. Images were visually compared for number and severity of perfusion defects by use of a scoring method from 0 to 4. A summed difference score was calculated as the difference between summed stress and rest scores. A score of greater than 3 was considered abnormal. MSIMI developed in 19% of patients with normal LVEF and 31% of those with reduced LVEF. There is no statistically significant difference between the two groups (P = .11). CONCLUSIONS: CAD patients with left ventricular dysfunction are equally susceptible to MSIMI as those with normal LVEF.     

Correction of myocardial ischaemia after transcatheter embolisation of a small left coronary artery venous fistula.

A 50 year old woman presented with a history of angina and palpitation. She had a positive exercise test and thallium scintigraphy showed reversible ischaemia in the territory of the left anterior descending coronary artery. Coronary angiography showed a small coronary arteriovenous fistula arising from the bifurcation of the left main stem--that is, the origin of the left anterior descending and circumflex coronary arteries--with no evidence of coronary stenosis. The aberrant coronary artery was embolised with platinum microcoils delivered by a percutaneous, transcatheter, coaxial technique. The patient was subsequently symptom free with no evidence of ischaemia on exercise testing or thallium scintigraphy. This case suggests that when there is clear evidence of myocardial ischaemia even small coronary arteriovenous fistulas should be treated by embolisation.     

Effects of acute K-strophantidin administration on left ventricular relaxation and filling phase in coronary artery disease.

In 10 patients with coronary artery disease, preserved left ventricular (LV) performance and absence of previous myocardial infarction, the effects of an acute intravenous administration of k-strophantidin (0.005 mg/kg over 10 minutes) on selected parameters of both LV systolic and diastolic function, including relaxation, were evaluated. An increase in positive first derivative of LV pressure (dP/dt) and in the ratio between dP/dt and the pressure developed (dP/dt/P) (1,530 +/- 287) 1,600 +/- 329 mm Hg/s [p less than 0.05], and 30 +/- 6 to 34 +/- 8 s-1 [p less than 0.05], respectively) demonstrated the inotropic effect of k-strophantidin, whereas volumetric parameters of systolic function (end-systolic and stroke volume indexes, and ejection fraction) did not show any significant change. However, LV relaxation was impaired by k-strophantidin injection; in fact, mean values of T constant were significantly increased from 50 +/- 12 to 55 +/- 13 ms (p less than 0.01). Lowest LV and end-diastolic pressures increased from 8 +/- 4 to 11 +/- 4 mm Hg (p less than 0.05) and from 17 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05), respectively. The end-diastolic volume and maximal rate of volumetric increase during the early and late filling phases were not modified by k-strophantidin. Mean aortic pressure increased from 110 +/- 10 to 120 +/- 12 mm Hg (p less than 0.001). Therefore, in patients with coronary artery disease and LV preserved performance, an acute intravenous administration of k-strophantidin appears to stimulate contractility and to worsen relaxation, and minimal LV and end-diastolic pressures.     

Impaired left ventricular filling and regional diastolic asynchrony at rest in coronary artery disease and relation to exercise-induced myocardial ischemia

Impaired left ventricular (LV) diastolic filling at rest is frequently observed in patients with coronary artery disease (CAD) who have normal LV systolic function and no previous infarction. To test the hypothesis that abnormal diastolic function at rest might reflect the functional severity of CAD, as estimated by exercise-induced ischemia, the relation between regional and global LV diastolic function at rest and during exercise-induced ischemia was evaluated in 49 patients with radionuclide angiography. All patients had normal systolic function at rest. Group 1 (n = 26) patients manifested a normal ejection fraction response to exercise and group 2 (n = 23) patients an abnormal response. Data obtained from 22 age-comparable normal volunteers were used for comparison. Although regional and global diastolic function were not different between normal subjects and group 1 patients, peak filling rate was lower in group 2 patients than in normal subjects (2.5 +/- 0.8 vs 3.2 +/- 0.6 end-diastolic counts/s; p less than 0.01). Moreover, regional diastolic asynchrony, as assessed from the radionuclide data by using a regional sector analysis of the LV region of interest, was greater in group 2 patients (46 +/- 44 ms) than in both normal subjects (25 +/- 16 ms; p less than 0.05) and group 1 patients (23 +/- 16 ms; p less than 0.05). Thus, among patients with CAD and with normal LV systolic function at rest, impaired LV filling and regional asynchrony predict a greater degree of exercise-induced ischemia, suggesting a greater extent of jeopardized myocardium.     

Impaired left ventricular filling dynamics during percutaneous transluminal angioplasty for coronary artery disease

The effects of brief periods of major coronary artery occlusion on global and regional peak left ventricular (LV) filling rates were studied during angioplasty in 10 patients. No patient had had a previous myocardial infarction. High-fidelity LV pressure and volume were determined by angiography before and 20 and 50 seconds after the onset of transluminal coronary occlusion and soon after the last balloon inflation. Segmental wall motion was analyzed frame by frame along 20 hemiaxes. Global peak filling rate decreased significantly both after 20 (29%, p less than 0.05) and 50 seconds (27%, p less than 0.05) from the onset of the occlusion. The term sigma delta t1 was defined as the sum of the absolute values of the time differences from the occurrence of global peak filling rate and the segmental peak filling rate in 20 segments. This variable increased significantly during both periods of transluminal occlusion (by 73% and by 72% [both p less than 0.005], respectively), indicating asynchrony in the occurrence of regional peak filling rate. Simultaneously, the sum of intervals between aortic valve closure (end systole) and occurrence of peak segmental shortening, sigma delta t2, measured in the 20 segments, increased by 63% after 20 seconds and by 87% after 50 seconds (both p less than 0.005), showing major asynchrony in segmental contraction. A significant negative correlation was found between global peak filling rate and both sigma delta t1 and sigma delta t2 (r = 0.64, p less than 0.001 and r = 0.70, p less than 0.0001, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Asynchronous left ventricular regional function and impaired global diastolic filling in patients with coronary artery disease: reversal after coronary angioplasty

Left ventricular diastolic filling is impaired in many patients with coronary artery disease and normal left ventricular systolic function, and is improved in many patients after coronary angioplasty (PTCA). To investigate the mechanisms for this improvement, we studied regional asynchrony by radionuclide angiography in 26 patients with single-vessel coronary artery disease before and after successful PTCA. Before PTCA, all patients had normal ejection fractions at rest and normal qualitative left ventricular regional wall motion, as determined by radionuclide and contrast angiography. Quantitative left ventricular regional function was assessed by dividing the left ventricular region of interest into 20 sectors. Phase analysis was performed on each sector's time-activity curve, and the average intersector phase difference was used as an index of left ventricular regional synchrony. Before PTCA, average intersector phase difference was increased compared with normal (6.0 +/- 2.2 vs 4.0 +/- 1.7 degrees, p less than .005), indicating asynchronous regional function. After PTCA, ejection fraction at rest was unchanged, but peak left ventricular filling rate at rest increased from 2.5 +/- 0.6 to 3.0 +/- 0.6 end-diastolic volume/sec (p less than .001) and was associated with a decrease in average intersector phase difference from 6.0 +/- 2.2 to 5.1 +/- 2.3 degrees (p less than .05). Average intersector phase difference decreased in 16 of 21 patients in whom peak filling rate increased after PTCA (p less than .005), compared with one of five patients in whom peak filling rate was unchanged or decreased. Hence, improved global left ventricular filling after PTCA was associated with more synchronous left ventricular regional behavior. To identify the cause of regional asynchrony before PTCA, we then generated time-activity curves from each of four left ventricular quadrants. These data indicated that the asynchrony was caused by regional variation in timing of diastolic rather than systolic events and that PTCA resulted in reduction in regional diastolic asynchrony. These data suggest that in many patients with coronary artery disease and normal left ventricular systolic function, impaired global diastolic filling may result from asynchronous left ventricular regional diastolic function, which is a reversible manifestation of myocardial ischemia or reduced coronary flow.