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.     

Insensitivity of the cold pressor stimulation test for the diagnosis of coronary artery disease

Cold pressor stimulation (CPS) was compared with supine bicycle exercise during radionuclide ventriculography as a procedure for diagnosing coronary artery disease (CAD). Thirty patients were studied. In the 18 patients with angiographically proved CAD, left ventricular ejection fraction (LVEF) decreased a mean of 5.0 +/- 1.0 ejection fraction units (+/- SEM) in response to CPS. Only two patients developed a new wall motion abnormality. In response to maximal supine exercise, the CAD group showed a mean decrease in LVEF from rest of 1.9 +/- 1.1%. Nine patients developed an exercise-induced wall motion abnormality. In the 12 patients with angiographically proved normal coronary arteries, LVEF decreased a mean of 5.8 +/- 1.3 units in response to CPS and increased a mean of 9.2 +/- 1.2% in response to exercise. Thus, the LVEF response to CPS was not significantly different in the CAD and normal groups (5.0 +/- 1.0 vs 5.8 +/- 1.3, NS). These same patients demonstrated the expected difference in LVEF response to exercise. We conclude that CPS produces similar changes in LVEF in patients with and without CAD, and therefore is not useful in diagnosing ischemic heart disease.     

Left ventricular functional assessment by radionuclide ventriculography during isometric handgrip and bicycle exercise in patients with aortic insufficiency

Twelve patients with chronic aortic insufficiency underwent radionuclide ventriculography performed in conjunction with dynamic bicycle and isometric handgrip exercise. Changes in left ventricular ejection fraction (LVEF) during exercise were measured. In all patients, the degree of regurgitation was determined by catheterization, and in eight patients, left ventricular end-diastolic pressure (LVEDP) was measured. The change in LVEF during either form of exercise was inversely related to the LVEDP. This correlation was somewhat better and more linear for bicycle exercise (R=0.84, p <.005) than for handgrip (R = 0.71, p<.025). By either exercise technique, a decrease in LVEF by >4 points occurred only in patients with 3 to 4 + regurgitation. We conclude that although radionuclide ventriculography with either bicycle or handgrip exercise is useful in determining the effect of aortic insufficiency on left ventricular functional reserve, bicycle exercise correlates better with other criteria of ventricular dysfunction.     

Left ventricular ejection fraction changes during recovery from treadmill exercise: A preliminary report of a new method for detecting coronary artery disease

To test the value of combining treadmill exercise with radionuclide angiography for detecting exercise-induced left ventricular dysfunction, ejection fractions were calculated at rest, peak supine bicycle exercise, and during three supine post-treadmill recovery periods (2-4 min, recovery 1; 4-6 min, recovery 2; 8-10 min, recovery 3) in ten coronary artery disease patients and eight normal subjects. Both the normal subjects and coronary artery disease patients had normal resting ejection fractions (>0.50). In the normal subjects the mean ejection fraction increased significantly (p<0.005) from rest (0.61 ± 0.03) to peak supine bicycle exercise (0.71 ± 0.04), and the mean ejection fraction also remained significantly higher (p<0.005) at rest than during 10 min post-treadmill exercise. However, the coronary artery disease patients did not significantly change the mean ejection fraction from rest (0.59±0.06) to peak supine bicycle exercise (0.55±0.08), and the average ejection fraction during each one of the post-treadmill recovery periods was not significantly different from rest. At the third recovery period all the normals but no coronary artery disease patients had higher ejection fraction than the resting ejection fraction. We thus conclude that the magnitude of change in ejection fraction from rest to 8-10 min post-treadmill exercise in patients with normal resting ejection fraction may be helpful in identifying those with coronary disease.     

Sensitivity and specificity of nuclear phase analysis versus ejection fraction in coronary artery disease

Phase standard deviation (SD) and skew characteristics of the first Fourier harmonic of equilibrium radionuclide volume curves were examined and compared during rest and during supine bicycle exercise with ejection fraction (EF) changes and the development of ischemia in 17 control subjects and in 2 groups of patients (n = 57) with coronary artery disease (CAD). Group I comprised 37 patients with CAD; IA was a subgroup of 20 patients with previous myocardial infarction (MI) and IB a subgroup of 17 patients with CAD without MI (all with coronary stenosis greater than 75% diameter narrowing). Group II comprised 20 patients with CAD who had undergone coronary bypass surgery. In the Group I subjects, phase SD was the most sensitive indicator of CAD at rest (Group I, 56%; Group IA, 70%, and Group IB, 29%), and the EF was the most sensitive indicator at submaximal (Group I, 78%; Group IA, 86%, and Group IB, 64%) and maximal exercise (Group I, 70%; Group IA, 93%, and Group IB, 53%). When phase SD and skewness were combined with EF changes, little increase in sensitivity occurred in Group I (rest 61%, submaximal exercise 88% and maximal exercise 76%). The results from Group II subgroups were qualitatively similar to those observed with Group I subgroups. These data reveal a marginally improved sensitivity for detection of CAD during supine bicycle radionuclide ventriculography when phase measurements were added to changes in global EF values.     

Ejection fraction and heart rate correlate with diastolic peak filling rate at rest and during exercise

We investigated the independent variables correlating with the multigated radionuclide peak filling rate (PFR) at rest and during supine bicycle exercise in 20 normal individuals. Independent variables were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), ejection fraction (LVEF), time to PFR (TPFR), peak ejection rate (PER) and time to PER (TPER). Fifteen subjects completed at least five stages of exercise at 25 watts each. Correlating independent variables were selected by a forward-backward stepwise multiple linear regression (BMDP2R). A partial correlation statistical program was also used to allow control of critical independent variables. The final regression equations were: a) resting state, PFR = -2.5 + 0.03HR + 0.05LVEF + 0.02SBP-0.02DBP, and b) exercise state, PFR = -3.8 + 0.04HR + 0.08LVEF. All independent variables mentioned above correlated with PFR (simple correlations designated as zero partials). However, when LVEF and HR were held constant (second order partials), the correlation of PFR with any of the other independent variables disappeared. In summary, the radionuclide global LV PFR is predominantly correlated to LVEF and HR at rest and during exercise. These correlations should be considered when assessing exercise effects of disease states on PFR.     

Radionuclide assessment of a normal left ventricular response to exercise in patients without evidence of heart disease

The aim of this study was to define normal left ventricularperformance at rest and during supine bicycle exercise withequilibrium radionuclide ventriculography in a normal populationother than young healthy volunteers. Thirty-one patients (meanage 45 years ± 9 SD) with chest pain of varying originandno evidence of heart disease proven by means of noninvasiveand invasive techniques were studied. Left ventricular ejectionfraction (LVEF) at rest averaged 0.64 ± 007 SD and increasedwith peak exercise to 0.73 ± 008 SD (P<0.005). Changein LVEF from rest to maximum exercise ranged within 0–0.19.Six patients (19%) failed to augment LVEF with exercise to morethan 0.05; none of the patients dropped LVEF during exercise.Multivariate analysis revealed no significant predictors ofLVEF response to exercise. However, there was a tendency thatresting LVEF and enddiastolic volume index with exercise mightinfluence LVEF response to exercise. Peak left ventricular ejectionrate (LVER) at rest averaged 3.3s^–1 ± 0.6 SD andincreased to 51 s^–1 ± 11 SD (P<0.005) with exercise.Peak left ventricular early filling rate (LVFR) was 2.8s^–1± 0.6 SD at rest and was measured 5.5 s^–1 ±l.3 SD at maximum exercise (P<0.005). Left ventricular enddiastolicvolume (EDV) did not change significantly from rest to maximumexercise, whereas left ventricular endsystolic volume (ESV)decreased to 79% ± 19 SD (P<0.01) of the value atrest. In conclusion, in a normal population other than healthy youngvolunteers LVEF does not necessarily have to increase with exercise.Moreover, besides an augmentation of heart rate a normal leftventricular response to supine exercise is associated with anincrease of LVER and LVFR, a decrease in ESV and no significantchange in EDV, suggesting augmented contractility and a virtuallynegligible role of the Frank-Starling mechanism during exercise.     

Radionuclide assessment of cardiac performance in cystic fibrosis. Reproducibility and effect of theophylline on cardiac function

A study was designed to evaluate the reproducibility of right and left ventricular ejection fraction measurements (RVEF, LVEF) by equilibrium radionuclide angiography in cystic fibrosis (CF) and to determine the effect of the acute administration of aminophylline on RVEF and LVEF in this disease. Both RVEF and LVEF were measured at rest and during incremental supine bicycle exercise by equilibrium radionuclide angiography in 18 patients with CF. In 9 of these patients, radionuclide studies were repeated after an infusion of aminophylline (9 mg/kg), whereas the remaining patients had radionuclide studies repeated after a placebo infusion. No significant increase in mean RVEF or LVEF values either at rest or at peak exercise was seen after aminophylline infusion. In the patients who underwent sequential radionuclide studies without intervening active drug intervention, the mean (+/- standard deviation) variability in RVEF and LVEF measurements between the 2 studies was 2.6 +/- 2% and 3.6 +/- 2.9%, respectively. We conclude that (1) equilibrium radionuclide angiography is a reasonably reproducible technique for serial assessment of biventricular function at rest and during exercise in CF, and that (2) the acute administration of aminophylline does not augment cardiac function either at rest or during exercise in this disease.     

Comparison of effects of isometric and supine bicycle exercise on left ventricular performance in patients with aortic regurgitation and normal ejection fraction at rest

The effects of handgrip and supine bicycle exercise on hemodynamics and left ventricular (LV) performance were compared in 25 patients with moderate to severe aortic regurgitation (AR) and normal LV ejection fraction at rest (greater than or equal to 50%) and in 10 control subjects. In both groups, heart rate, systolic blood pressure, rate-pressure product, and LV output were higher during supine bicycle exercise. Compared with the controls, in patients with AR, stroke volume was unchanged during supine bicycle exercise. LV end-diastolic volume increased during handgrip exercise but was unchanged during supine bicycle exercise. LV end-systolic volume increased and ejection fraction decreased during both forms of exercise. Of 25 patients with AR, 15 (60%) during handgrip exercise and 19 (76%) during supine bicycle exercise had an abnormal ejection fraction response (p less than 0.05). In patients with moderate to severe AR and normal LV ejection fraction at rest, both handgrip and supine bicycle exercise induced LV dysfunction. An abnormal LV ejection fraction response occurred more often with supine bicycle exercise. Handgrip exercise may be a useful alternative method for detecting LV dysfunction in patients with AR in whom adequate bicycle exercise cannot be accomplished.     

Response to exercise after withdrawal from chronic alcoholism

To test for early evidence of alcoholic cardiomyopathy and to assess changes in exercise response after abstinence, 12 asymptomatic alcoholic men (group 1) underwent maximal upright bicycle exercise radionuclide ventriculography two to six days after alcohol withdrawal. Six of these patients (group 1A) had similar testing two to four weeks later. Six control subjects (group 2) had repeated exercise tests without isotope study. Group 1 left ventricular ejection fraction response (LVEF) was normal. LVEF at similar workloads did not differ in group 1A (p = NS). However, unlike group 2 results, the linear regression line relating double product to exercise stage in group 1A was higher at first exercise (p less than 0.05), probably due to the effects of alcohol withdrawal. We conclude that radionuclide left ventriculographic findings in these patients do not support the concept of a preclinical alcoholic cardiomyopathy made apparent by exercise, and exercise very early after alcohol withdrawal is associated with an increased myocardial oxygen demand at any given workload.     

Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects

Serial hemodynamic and plasma catecholamine responses were compared among 10 healthy men (27 +/- 3 years) (+/- 1 standard deviation) during symptom-limited handgrip (33% maximal voluntary contraction for 4.4 +/- 1.8 minutes), cold pressor testing (6 minutes) and symptom-limited supine bicycle exercise (22 +/- 5 minutes). Plasma catecholamine concentrations were measured by radioenzymatic assays: ejection fraction and changes in cardiac volumes were assessed by equilibrium radionuclide angiography. During maximal supine exercise, plasma norepinephrine and epinephrine concentrations increased three to six times more than during either symptom-limited handgrip or cold pressor testing. Additionally, increases in heart rate, systolic blood pressure, rate-pressure product, stroke volume, ejection fraction and cardiac output were significantly greater during bicycle exercise than during the other two tests. A decrease in ejection fraction of 0.05 units or more was common in young normal subjects during the first 2 minutes of cold pressor testing (6 of 10 subjects) or at symptom-limited handgrip (3 of 10), but never occurred during maximal supine bicycle exercise. The magnitude of hemodynamic changes with maximal supine bicycle exercise was greater, more consistent and associated with much higher sympathetic nervous system activation, making this a potentially more useful diagnostic stress than either handgrip exercise or cold pressor testing.     

Peak systolic blood pressure/end-systolic volume ratio: Assessment at rest and during exercise in normal subjects and patients with coronary heart disease

To assess the utility of a recently proposed index of left ventricular performance, the ratio of peak left ventricular systolic pressure to end-systolic volume, equilibrium radionuclide angiography was used to determine end-systolic volume and the systolic blood pressure obtained by cuff sphygmomanometer to determine peak systolic pressure. Data were analyzed at rest and during supine bicycle exercise in 15 normal subjects (Group 1), 50 patients with coronary artery disease (Group II) and 9 patients with obstructive lung disease and no evidence of coronary artery disease on clinical examination including exercise thallium imaging (Group III). In 15 subjects the correlation between the resting angiographic and radionuclide pressure/volume ratio was excellent (r = 0.929, p <0.005).Forty-seven (94 percent) of the 50 patients in Group II had a depressed pressure/volume ratio at rest or an abnormal change in this ratio during exercise, whereas only 43 (86 percent) of this group had an abnormal ejection fraction at rest or during exercise. Additionally, 3 of 15 subjects in Group I had an abnormal ejection fraction response, defined as less than 0.05 ejection fraction unit increase with exercise (specificity 80 percent), whereas all subjects in Group I had a normal increase in pressure/volume ratio (specificity 100 percent). At rest, neither index identified more patients with coronary artery disease than the other. Of the nine patients in Group III, six had an abnormal ejection fraction response to exercise, whereas only one had an abnormal pressure/volume ratio response.It is concluded that the end-systolic pressure/volume ratio is a useful index of left ventricular performance. In some patients during supine exercise stress it may be more sensitive than the ejection fraction response alone in identifying the presence of coronary artery disease.     

Assessment of right ventricular function at rest and during exercise in patients with coronary heart disease: A new approach using equilibrium radionuclide angiography

To evaluate a new method of calculating right ventricular ejection fraction by equilibrium radionuclide angiography and to assess its response during supine bicycle exercise, 20 normal persons and 50 patients with angiographically documented coronary artery disease were studied. Each subject underwent a resting equilibrium and first pass right ventricular study as well as symptom-limited graded bicycle exercise while supine. The correlation between the two methods in all 70 cases was good (r = 0.81). Inter- and intraobserver variability was small (3.9 ejection fraction units or less) and serial reproducibility (two studies performed 2 weeks apart) was also good (4 ejection fraction units or less). There was no difference in the right ventricular ejection fraction at rest when normal subjects and patients with coronary disease were compared (0.49 ± 0.10 versus 0.46 ± 0.08). Ejection fraction increased with exercise in normal subjects (0.49 ± 0.10 to 0.64 ± 0.12, p < 0.005). As a group, patients with right coronary stenosis (alone or in combination with other lesions) showed no change in ejection fraction with exercise (0.46 ± 0.13 to 0.45 ± 0.12); and ejection fraction increased with exercise in patients with coronary disease without right coronary stenosis (0.46 ± 0.08 to 0.53 ± 0.11, p < 0.05). Among patients with both significant right and left coronary artery disease more severe right ventricular dysfunction during exercise was seen in the presence of more severe left ventricular dysfunction. It is concluded that during exercise the right ventricle shows dysfunction caused in part by local ischemia as well as by altered loading conditions due to left ventricular dysfunction. Equilibrium angiography is a useful and reliable method for evaluating right ventricular function in man.     

Incidence of arrhythmias induced by isometric and dynamic exercise.

The incidence of arrhythmias during isometric sustained handgrip exercise and during dynamic graded bicycle exercise was compared in a group of 45 patients with various forms of heart disease on no antiarrhythmic therapy. Atrial arrhythmias were equally common during handgrip and bicycle exercise but ventricular arrhythmias were more frequent during handgrip exercise. Of the 45 patients, 38 per cent developed ventricular arrhythmias during isometric exercise, with ventricular tachycardia occurring in 15 per cent. During dynamic exercise 22 per cent of the 45 patients developed ventricular arrhythmias, with ventricular tachycardia occurring in 2 per cent. Patients with coronary artery disease and/or depressed left ventricular function developed twice the incidence of ventricular arrhythmias with isometric than with dynamic exercise. Thus, isometric exercise testing is of more value than dynamic exercise testing in unmasking latent ventricular arrhythmias in patients with heart disease.     

Incidence of arrhythmias induced by isometric and dynamic exercise.

The incidence of arrhythmias during isometric sustained handgrip exercise and during dynamic graded bicycle exercise was compared in a group of 45 patients with various forms of heart disease on no antiarrhythmic therapy. Atrial arrhythmias were equally common during handgrip and bicycle exercise but ventricular arrhythmias were more frequent during handgrip exercise. Of the 45 patients, 38 per cent developed ventricular arrhythmias during isometric exercise, with ventricular tachycardia occurring in 15 per cent. During dynamic exercise 22 per cent of the 45 patients developed ventricular arrhythmias, with ventricular tachycardia occurring in 2 per cent. Patients with coronary artery disease and/or depressed left ventricular function developed twice the incidence of ventricular arrhythmias with isometric than with dynamic exercise. Thus, isometric exercise testing is of more value than dynamic exercise testing in unmasking latent ventricular arrhythmias in patients with heart disease.     

Exercise-Induced Decrease in Myocardial High-Energy Phosphate Metabolites in Patients With Chagas Heart Disease

BackgroundThe influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood.Methods and ResultsChanges in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with ³¹P magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac ³¹P-MRS. The myocardial phosphocreatine to [β-phosphate]adenosine triphosphate ratio (PCr/β-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc–sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/β-ATP was decreased in all Chagas groups (1.23 ± 0.37) versus group C (1.88 ± 0.08; P < .001) and was lower in group I (0.89 ± 0.24) versus groups II (1.44 ± 0.23) and III (1.40 ± 0.37; P < .001). There was no stress-induced change in cardiac PCr/β-ATP (1.88 ± 0.08 at rest vs 1.89 ± 0.08 during exercise; P = NS) in group C. Mean cardiac PCr/β-ATP was 0.89 ± 0.24 and 0.56 ± 0.21 at rest and during exercise, respectively, in group I (37% decrease; P < .001). In group II, PCr/β-ATP was 1.44 ± 0.23 at rest and 0.97 ± 0.37 during exercise (33% decrease; P < .001). In group III, PCr/β-ATP was 1.40 ± 0.37 at rest and 0.60 ± 0.19 during exercise (57% decrease; P < .001).ConclusionsMyocardial high-energy phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac high-energy phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.     

Effects of severity of mitral stenosis on left and right ventricular function at rest and during exercise

Few studies have assessed the effect of severity of mitral stenosis (MS) on ventricular function. Using equilibrium radionuclide ventriculography to measure ejection fraction and volume changes, 63 patients were studied during supine, symptom-limited exercise. To more carefully assess the 12 patients with MS and impaired left ventricular function, 2 groups of patients were formed. Group I (n = 51) had a normal (less than 50%) resting left ventricular (LV) ejection fraction (EF) and group II (n = 12) had an abnormally low (less than 50%) resting LVEF. Both groups were divided into mild (greater than 1.4 cm2), moderate (1.1-1.4 cm2) and severe (less than 1.0 cm2) MS. There were no differences in mean rest or exercise LVEF for group I. Exercise LVEF increased significantly (p less than 0.05) from rest with mild MS, but not with moderate or severe MS. The decrease in exercise LVEF was due to a decrease in exercise end-diastolic volume of 9 +/- 23% and 15 +/- 18% for moderate and severe MS, respectively. Exercise end-systolic volume decreased normally for all degrees of MS severity. Exercise right ventricular (RV)EF did not increase for any degree of MS severity due to an increase in end-systolic volume. All patients in group II had an RVEF of less than 40%. For this group, severity of MS had no effect on resting LVEF and the response to exercise was similar to group I. We conclude that in patients with MS, resting LVEF is unaffected by MS severity whereas exercise LVEF decreases with increased severity of MS due to impaired diastolic filling.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial dysfunction and abnormal left ventricular exercise response in autonomic diabetic patients

In diabetic patients, the pathophysiologic mechanisms of exercise-induced left ventricular (LV) dysfunction remain controversial. In this study, the role of myocardial contractility recruitment in determining an abnormal LV response to isometric or dynamic exercise has been investigated in 14 diabetic patients with autonomic dysfunction. Ischemic heat disease was excluded by the absence of LV wall motion abnormalities induced by isotonic and isometric exercise and by coronary angiography. Left ventricular and myocardial function were studied at rest, and during isometric and isotonic exercise, by two-dimensional echocardiography; moreover, recruitment of an inotropic reserve was assessed by postextra-systolic potentiation at rest and at peak handgrip. An abnormal response of LV ejection fraction to isometric (9/14) or to dynamic (8/14) exercise was frequent in study patients. In these patients, baseline myocardial contractility was normal, and the significant increase in ejection fraction by postextrasystolic potentiation indicated a normal contractile reserve (65 ± 7% vs. 74 ± 6%, p=0.001). Nevertheless, the downward displacement of LV ejection fraction-systolic wall stress relationships during exercise suggests an inadequate increase in myocardial contractility. However, the abnormal ejection fraction at peak handgrip was completely reversed by postextrasystolic potentiation (67 ± 6% vs. 58.1 ± 10%, p=0.008), a potent inotropic stimulation independent of the integrity of adrenergic cardiac receptors. A defective inotropic recruitment, despite the presence of a normal LV contractile reserve, plays an important role in deexercise LV dysfunction in diabetic patients with autonomic neuropathy.     

Myocardial Dysfunction and Adrenergic Cardiac Innervation in Patients With Insulin-Dependent Diabetes Mellitus

Background. Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested.Objectives. This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease.Methods. Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [±SD] age 28.5 ± 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 ± 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation.Results. Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 ± 7%), and group B (n = 7), with a normal response (72 ± 8%). Baseline LVEF was normal in both group A and B patients (60 ± 6% vs. 61 ± 7%, p = NS). In group A patients, the LV circumferential wall stress–LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 ± 6% vs. 64 ± 10%, p = NS), whereas PESP significantly increased LVEF (60 ± 6% vs. 74 ± 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 ± 7% vs. 72 ± 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 ± 0.30 vs. 2.98 ± 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 ± 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients.Conclusions. Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.     

Relation of right ventricular ejection fraction to exercise capacity in chronic left ventricular failure

Although the left ventricle is traditionally viewed as the heart's main pumping chamber, no correlation has been shown between left ventricular (LV) ejection fraction (EF) at rest and exercise capacity in patients with chronic LV failure. Because vasodilators with venodilating activity increase exercise capacity more than predominant arterial dilators in patients with LV failure, right ventricular (RV) function may relate to exercise capacity in these patients. In 25 patients with chronic LV failure, caused by coronary artery disease in 12 patients and idiopathic dilated cardiomyopathy in 13 patients, RVEF and LVEF at rest were measured by radionuclide angiography. Maximal upright bicycle exercise testing was also performed to determine maximal oxygen consumption, which averaged only 13 ± 4 ml/min/kg. The LVEF at rest was 26 ± 10% and did not correlate with maximal oxygen consumption (r = 0.08). However, the RVEF was 41 ± 12% and correlated with maximal oxygen consumption (r = 0.70, p < 0.001) in the same patients. The correlation was stronger (r = 0.88) in patients with coronary artery disease than in those with idiopathic dilated cardiomyopathy (r = 0.60). Thus, RVEF at rest is more predictive of exercise capacity than LVEF in the same patients with chronic LV failure. These results are consistent with the clinical observation that only venodilating agents increase exercise capacity of patients with chronic LV failure.