Early and subtle abnormalities of left ventricular function in clinically stable coronary artery disease patients with normal ejection fraction

BACKGROUND: It has been reported that, in the initial phase of ischemic cardiomyopathy, the earliest alterations of left ventricular function are detected during the relaxation phase. The aim of this study was to look for precocious abnormalities in the early stage of ischemic cardiomyopathy in both left ventricular systolic and diastolic phases. METHODS AND RESULTS: Using simultaneous left ventricular catheterization and echo-Doppler techniques, we studied both systolic and diastolic function in 44 (37 males and 7 females, mean age 55.7+/-8) normotensive, clinically stable, coronary artery disease patients with normal left ventricular ejection fraction in comparison to 9 age- and sex-matched normal control subjects (7 males and 2 females, mean age 54.7+/-9). Mean values of E deceleration time, tau, left ventricular end-diastolic volume and pressure, and end-systolic volume and lowest diastolic pressure were significantly higher (from P<.05 to P<.01), whereas mean dP/dt/P values significantly lower (P<.05) in coronary artery disease patients than in controls. A strict relationship (P<.001) between dP/dt/P and tau, left ventricular lowest and end-diastolic pressure was found in all subjects studied. CONCLUSION: Early and subtle abnormalities in parameters of both systolic and diastolic function can be found in the majority of coronary artery disease patients with normal ejection fraction.     

Impact of left ventricular ejection fraction on endothelial function in patients with coronary artery disease

BACKGROUND: Endothelial dysfunction is present in patients with coronary artery disease (CAD) or with congestive heart failure. HYPOTHESIS: This study was performed to evaluate the impact of systolic heart function on endothelial function in patients with CAD. METHODS: The study population consisted of 283 consecutive patients (mean age 59 years, 176 men) undergoing coronary angiography. Endothelial function was assessed by measuring flow-mediated vasodilation (FMD) of the brachial artery. RESULTS: Patients (n = 236) with an ejection fraction (EF) > or = 55% on routine echocardiogram were younger (mean age 58 vs. 62 years), showed a lower prevalence of diabetes (15 vs. 38%) and myocardial infarction (13 vs. 66%), and showed a higher FMD (4.8 +/- 2.4 vs. 4.0 +/- 2.0%, p < 0.05) than patients (n = 47) with an EF < 55%. The correlation coefficient between FMD/endothelial function and EF/systolic heart function was 0.149 (p < 0.02) in the overall study population. Multivariate analysis showed that of age, gender, frequency of diabetes mellitus, myocardial infarction, and CAD extent, EF was the only significant independent parameter correlating with FMD in patients with CAD. CONCLUSIONS: Compared with the other tested risk factors, EF surprisingly was the only significant independent parameter correlating with endothelial function in patients with CAD. Our results support the view that endothelial function is an independent prognostic factor in patients with CAD.     

Effect of exercise on left ventricular ejection fraction in men with coronary artery disease.

Left ventricular ejection fraction (LVEF) was measured at rest and during supine bicycle exercise in 31 men with arteriographically defined coronary disease and in 15 normal men. LVEF was calculated from a left ventricular time vs activity curve (collimated scintillation probe, 99m Technetium) as the fracitonal fall in count-rate divided by the background-corrected left ventricular end-diastolic count-rate. In normal men LVEF at rest averaged .59 +/- .06 (+/-SD) and during exercise was .72 +/- .08. LVEF did not increase with exercise in men with coronary disease (.55 +/- .03 to .57 +/- .03; N = 31; AVE +/-SEM; NS). In 17 men with coronary disease who had ST segment depression with exercise, LVEF either decreased or was unaltered in all (55 +/- .04 to .49 +/- .03; P less than 0.05); whereas in 14 without ST depression, LVEF increased in 10 (71 per cent) and was unaltered in 4 (29 per cent) (.54 +/- .04 to .66 +/- .04; P less than 0.01). Results suggest that LVEF during exercise normally increases, but in men with coronary disease LVEF either fails to increase or actually decreases. In addition there appears to be a relationship between ST segment changes during exercise and ejection fraction.     

Effects of anger on left ventricular ejection fraction in coronary artery disease.

This study examined the comparative potency of several psychological stressors and exercise in eliciting myocardial ischemia as measured by left ventricular (LV) ejection fraction (EF) changes using radionuclide ventriculography. Twenty-seven subjects underwent both exercise (bicycle) and psychological stressors (mental arithmetic, recall of an incident that elicited anger, giving a short speech defending oneself against a charge of shoplifting) during which EF, blood pressure, heart rate and ST segment were measured. Eighteen subjects had 1-vessel coronary artery disease (CAD), defined by greater than 50% diameter stenosis in 1 artery as assessed by arteriography. Nine subjects served as healthy control subjects. Anger recall reduced EF more than exercise and the other psychological stressors (overall F [3.51] = 2.87, p = .05). Respective changes in EF for the CAD patients were -5% during anger recall, +2% during exercise, 0% during mental arithmetic and 0% during the speech stressor. More patients with CAD had significant reduction in EF (greater than or equal to 7%) during anger (7 of 18) than during exercise (4 of 18). The difference in EF change between patients with CAD and healthy control subjects was significant for both anger (t25 = 2.23, p = 0.04) and exercise (t25 = 2.63, p = 0.01) stressors. In this group of patients with CAD, anger appeared to be a particularly potent psychological stressor.     

Non-invasive quantification of exercise-induced changes in regional left ventricular function in normals and patients with one vessel coronary artery disease using radionuclide ventriculography

To quantitate changes in regional left ventricular functioninduced by ischemia or scar, rest and exercise equilibrium radionuclidestudies of 26 patients with one vessel coronary artery diseaseand 12 normal individuals were analysed with a new method forregional ejection fraction determination. A computer algorithmprovided observer-independent segmental analysis from a centreof gravity of the left ventricular activity at end-diastole(left anterior oblique projection). Special segments were assignedfor anteroseptal, inferoapical and posterolateral areas correspondingto the three main coronary arteries. Reproducibility using anunchanged camera positioning was excellent even for 2 min acquisitionstudies (r=0.93) and still good after repositioning (r=0.80to 0.87). In normal areas, regional ejection fraction increasedor showed no change during exercise. In contrast, it decreasedsignificantly in regions supplied by stenosed coronary arteries(ischemia) and remained depressed in scar zones. The methodproved to be valid for regional changes induced by left anteriordescending and left circumflex coronary obstructions, but lessfor right coronary artery lesions. Global ejection fractionreflected a sum of all regional changes implying that regionalanalysis should be more sensitive in detecting coronary arterydisease.     

Reproducibility of the angiographic left ventricular ejection fraction in patients with coronary artery disease

Quantitative analysis of the single and repeated cine left ventriculogram was performed in 20 patients with coronary artery disease to determine both the intrinsic variance of individual beats separated by different time intervals and variance between analyses of different observers. In addition, ventriculograms obtained from left ventricular injections of contrast medium prior to coronary arteriography were compared to ventriculograms obtained from either left ventricular or pulmonary artery injections after arteriography. The time period between studies varied from 30 minutes to 90 minutes to four days. Analysis of the same ventriculogram by different observers resulted in an average difference in ejection fraction of 0.05 (pNS). The average difference in ejection fraction was 0.02 between two early beats of the same ventriculogram (pNS). The average difference between sequential ventriculograms was 0.07 (pNS), but individual variations greater than 0.10 were not uncommon, particularly between studies done before and after arteriography, or several days apart. Patients exhibiting wide variance in ejection fractions between two studies either had wide variance in other hemodynamic measurements or degree of asynergy, or both. This study provides a frame of reference for analysis of sequential ventriculograms in patients with coronary artery disease, especially in evaluating changes in the state of the disease or the effects of therapy. It is especially important that: (1) standard hemodynamic measurements be made before ventriculography, (2) the same radiographic techniques repeated whenever possible, and (3) the same person analyze the two ventriculograms.     

Predictors of right ventricular dysfunction in patients with coronary artery disease and reduced left ventricular ejection fraction

BACKGROUND: The frequency and determinants of right ventricular (RV) dysfunction in patients with coronary artery disease (CAD) and reduced left ventricular (LV) function have not been thoroughly investigated. METHODS: The study population consists of 80 consecutive patients, invasively evaluated at our centre. Entry criteria were: LV ejection fraction < 45%; angiographic evidence of obstructive CAD; disease history of more than 3 months' duration. Exclusion criteria were: recent myocardial infarction and unstable angina. All patients underwent cardiac catheterization with coronary, LV and RV angiography. RV dysfunction was defined as a RV ejection fraction < 35%, which corresponds to the mean-three standard deviations of controls. RESULTS: Sixty-five patients (81%) had multi-vessel disease and 57 (71%) had a previous myocardial infarction. Mean LV ejection fraction was 31 +/- 8%. Mean RV ejection fraction was 46 +/- 11%. Right ventricular dysfunction was present in 14 patients (18%). An occluded proximal right coronary artery was associated with significantly lower RV ejection fraction (38 +/- 12% versus 47 +/- 10%; P = 0.009) but not LV ejection fraction (30 +/- 8% versus 32 +/- 9%; P = 0.444). However, at multivariate analysis, only pulmonary hypertension was an independent significant predictor of RV dysfunction (P < 0.001; OR: 1.13; CI: 1.06 -1.22). CONCLUSION: Right ventricular dysfunction in patients with chronic ischaemic LV dysfunction is detected in less than 20% of cases. Proximal right coronary artery occlusion is associated with a reduced RV ejection fraction. However, the role of right coronary artery disease is overwhelmed by the haemodynamic burden of pulmonary hypertension, which represents the only independent predictor of RV dysfunction in our population.     

Global and regional left ventricular response to bicycle exercise in coronary artery disease. Assessment by quantitative radionuclide angiocardiography.

The left ventricular response to bicycle exercise was evaluated in 60 patients with coronary artery disease and in 13 normal control subjects. Left ventricular ejection fraction, mean normalized ejection rate and regional wall motion were determined using first-pass radionuclide angiocardiograms obtained at rest and again during peak graded bicycle exercise. All normal subjects demonstrated improved left ventricular function with exercise. Left ventricular ejection fraction increased significantly from 67 ± 3 per cent (mean ± SE) at rest to 82 ± 4 per cent with exercise (p < 0.001). Similarly, the left ventricular ejection rate increased significantly from 3.47 ± 0.31 sec^?1 to 6.53 ± 0.42 sec^?1(p < 0.001). In contrast, in 44 of 60 patients with coronary artery disease, the ejection fraction or ejection rate either decreased or remained the same with exercise. New or exaggerated regional wall motion abnormalities were detected in 28 of 60 patients with coronary artery disease. Over-all, global or regional evidence of compromised left ventricular reserve was found in 48 of 60 patients with coronary artery disease.The major determinant of an abnormal left ventricular response to exercise was the presence or absence of electrocardiographic evidence of myocardial ischemia. Left ventricular ejection fraction decreased or remained the same with exercise in all patients with coronary artery disease and electrocardiographic ischemia. New regional wall motion abnormalities were detected in 20 of these patients. In this group, the left ventricular ejection fraction decreased from 66 ± 2 per cent at rest to 58 ± 2 per cent with exercise (p < 0.001), whereas the ejection rate was unchanged by exercise (rest 3.33 ± 0.21 sec^?1; exercise 3.34 ± 0.22 sec^?1, p > 0.05). Of the 30 patients with coronary artery disease who exercised to symptom-limiting fatigue without electrocardiographic ischemia, 18 demonstrated compromised left ventricular reserve with exercise. Twelve of the remaining patients with coronary artery disease had normal left ventricular reserve, in eight of whom ventricular function was completely normal both at rest and during exercise. In this group exercised to fatigue, the left ventricular ejection fraction increased from 53 ± 4 per cent at rest to 58 ± 2 per cent with exercise (p < 0.001). The ejection rate also increased from 2.48 ± 0.24 sec^?1 to 3.67 ± 0.39 sec^?1 (p < 0.001). The direction and magnitude of the left ventricular responses to exercise were not affected by long-term oral propranolol administration in 22 patients. Based upon either abnormal exercise left ventricular reserve or abnormal global and regional left ventricular function at rest, the over-all sensitivity of this radionuclide technic for the detection of coronary artery disease was 87 per cent (52 of 60 patients). These data demonstrate that exercise ventricular performance studies provide important physiologic insights into left ventricular functional reserve as well as a sensitive noninvasive approach for the detection of coronary artery disease.     

Reproducibility of equilibrium radionuclide ventriculography in patients with coronary artery disease: Response of left ventricular ejection fraction and regional wall motion to supine bicycle exercise

To evaluate the reproducibility of ejection fraction (EF) and regional wall motion (RWM) analyses by rest and exercise equilibrium radionuclide ventriculography (RNV) in the presence of coronary artery disease (CAD), 18 patients underwent two maximum, multistage supine bicycle exercise studies separated by an interval of 2 weeks. There were no significant differences in EF between the two studies, both at rest (56.0 ± 13.8% vs 58.2 ± 11.7%, p = NS) and with exercise (51.1 ± 17.6% vs 54.3 ± 17.6%, p = NS) and a highly significant correlation was shown between the two groups of values (rest r = 0.90, exercise r = 0.93, p < 0.001). There was no significant difference in the change from rest to exercise (?4.9 ± 12.0% vs ?3.8 ± 11.5%, p = NS) between the two studies and the correlation was highly significant (r = 0.69, p < 0.01). The interstudy variabilities were 2.2 ± 6.1% and 1.2 ± 7.3% for rest and exercise, respectively, and 2.0 ± 9.2% for the change from rest to exercise. Ninety-four percent of both rest and exercise regions had similar RWM. Eighty-one percent of the abnormally contracting regions were common to both exercise studies. Utilizing conventional criteria for the diagnosis of CAD, 11 patients had abnormal EF response and nine had abnormal RWM response to exercise on both studies. Combining EF and RWM criteria resulted in the diagnosis of CAD in 15 patients in both studies. We conclude that: (1) there were no significant differences in rest and exercise radionuclide EF and RWM between two supine bicycle exercise studies performed 2 weeks apart in patients with stable CAD and there were significant correlations between the two studies; (2) despite these correlations, the interstudy variabilities emphasize the need for the inclusion of reproducibility studies in all evaluations of interventions by exercise radionuclide ventriculography; and (3) the variations in EF and RWM response to exercise result in a lack of uniformity between the two studies regarding the diagnosis of CAD based on conventional RNV criteria.     

Effects on hemodynamics and left ventricular ejection fraction of intravenous bepridil for impaired left ventricular function secondary to coronary artery disease

To define the hemodynamic effects of bepridil in patients with depressed left ventricular (LV) function, 22 patients with an LV ejection fraction (EF) of 0.45 or less were studied before and after 2 mg/kg (n = 11) and 4 mg/kg (n = 11) of intravenous bepridil. Maximal hemodynamic effects were evident between 15 and 30 minutes after drug infusion. After 2 mg/kg, heart rate decreased 9% (p less than 0.01), cardiac index 17% (p less than 0.01), LV dP/dt max 16% (p less than 0.01), stroke work index 14% (p less than 0.01) and mean aortic pressure 8% (difference not significant). Right atrial pressure increased 8% (not significant), pulmonary arterial wedge pressure 24% (p less than 0.01) and systemic vascular resistance 17% (p less than 0.01). After administering 4 mg/kg of bepridil the changes in heart rate, cardiac index, right atrial pressure, LV dP/dt max, mean aortic pressure and systemic vascular resistance were almost identical to those after the smaller dose. The larger dose produced a 40% (p less than 0.01) increase in pulmonary arterial wedge pressure and a 22% decrease in stroke work index (p less than 0.01), but only the change in wedge pressure was significantly greater (p less than 0.01) than that produced by the lower dose. Radionuclide-determined LVEF decreased 6% (p less than 0.05), from 0.33 +/- 0.14 after 2 mg/kg and 11% (p less than 0.05) from 0.27 +/- 0.11 after 4 mg/kg of bepridil. The data indicate that bepridil exerts significant negative inotropic and chronotropic effects in patients with impaired LV function.     

Relation between radionuclide angiographic regional ejection fraction and left ventricular regional ischemia in awake dogs

Multigated equilibrium radionuclide angiography was used to quantitate global and regional ejection fraction (EF) in 26 awake dogs 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD) or left circumflex (LC) coronary artery. Changes in global and regional EF were correlated with simultaneous measurements of the extent of acute left ventricular (LV) ischemia measured by radioisotope-labeled microspheres. The extent of ischemia, defined as the percentage of LV mass with greater than 25% reduction in blood flow from normal regional flow, was linearly related to the percent change in global EF after LAD (r = 0.84) and LC (r = 0.77) occlusions. The extent of ischemia also correlated with regional EF (r = 0.47 to 0.88 for LAD and r = 0.41 to 0.69 for LC occlusions). In 24 of 25 LAD occlusions and in all 20 LC occlusions that produced a measurable ischemic zone, the maximal percent change in regional EF exceeded the percent change in global EF. Two LAD occlusions and 2 LC occlusions reduced regional EF but not global EF. Thus, global and regional EF decreased in direct proportion to the extent of acute myocardial ischemia; regional ischemia produced greater changes in regional than in global EF.     

Regional ejection fraction: a quantative radionuclide index of regional left ventricular performance.

Radionuclide measurements of regional left ventricular ejection fraction were evaluated as a quantitative index of regional left ventricular function. Left ventricular regional ejection fractions were derived from background-corrected, time-activity curves in 43 patients assessed by both gated equilibrium radionuclide angiocardiography and left ventricular contrast angiography. From a single, modified left anterior oblique projection, the regional change in background corrected counts was determined in each of three anatomic regions. The normal range for regional radionuclide ejection fraction was determined in 10 patients with normal contrast ventriculograms and without obstructive coronary artery disease at coronary arteriography. Regional ejection fraction was compared with percent segmental axis shortening and extent of akinetic segments in corresponding regions of the contrast ventriculogram. Radionuclide and roentgenographic methods were in agreement as to the presence or absence of abnormal wall motion in 83 of 99 left ventricular regions (84%) in 33 patients evaluated prospectively. Comparison of regional ejection fraction demonstrated significant differences between regions with roentgenographically determined normokinesis (75 +/- 3%, mean +/- SEM), hypokinesis (44 +/- 3%, p less than 0.0005) and akinesis (24 +/- 5%, p less than 0.005). We conclude that the left ventricular regional ejection provides a reliable quantitative assessment of regional left ventricular performance.     

The impact of coronary artery disease and left ventricular ejection fraction on the prognosis of patients with peripheral artery disease

The impact of the severity of coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) on the prognosis of patients with peripheral artery disease (PAD) has not been systematically studied. We retrospectively analysed 622 patients with PAD (intermittent claudication (IC): n = 446; critical limb ischaemia (CLI): n = 176). The association of SYNTAX score and LVEF with mortality was analysed using the Cox proportional hazard model. In patients with IC, a high SYNTAX score was significantly associated with mortality, whereas reduced LVEF was significantly associated with mortality in patients with CLI. The prognostic impact of CAD and LVEF appears different between patients with IC and CLI.     

右冠状动脉狭窄程度对左冠状动脉狭窄患者左室射血分数的影响

目的研究右冠状动脉不同程度狭窄对左冠状动脉狭窄患者左室射血分数（LVEF）的影响。方法根据左冠状动脉病变部位不同,将1 000例左冠状动脉狭窄患者分为左前降支（LAD）狭窄,左回旋支（LCX）狭窄,左主干（LM）狭窄,左前降支+左回旋支（LAD+LCX）狭窄4个系列。每个系列再根据右冠状动脉（RCA）病变程度不同分为RCA正常组（直径狭窄<50%）、RCA非闭塞组（99%>直径狭窄≥50%）和RCA闭塞组（直径狭窄≥99%）,比较分析3组间LVEF的差异。结果在LAD,LCX,LM,LAD+LCX狭窄时,与RCA正常组LVEF相比,RCA非闭塞组LVEF分别下降0.9%,0.3%,3.4%和2.8%;RCA闭塞组LVEF分别下降10.9%,3.7%,6.5%和5.2%。LAD狭窄时,RCA非闭塞组和RCA闭塞组之间LVEF有统计学差异（P<0.01）。结论右冠状动脉病变可在左冠状动脉狭窄的基础上使左室射血分数进一步下降;当左冠状动脉狭窄为闭塞性病变时,影响更为明显。