Myocardial mechanics in young adult patients with diabetes mellitus: effects of altered load, inotropic state and dynamic exercise

The disease entity "diabetic cardiomyopathy" has been extensively described in young patients with diabetes in the absence of ischemic, hypertensive or valvular heart disease. The most convincing data have been a 30% to 40% incidence of decreased radionuclide angiographic left ventricular ejection fraction response to dynamic exercise. In the current study, the hypothesis was tested that this abnormal ejection fraction response was due to alterations in ventricular loading conditions or cardiac autonomic innervation (extrinsic factors), or both, rather than to abnormalities in intrinsic ventricular systolic fiber function (contractility). Twenty normotensive patients with diabetes (mean age 30 +/- 5 years, mean duration 15 +/- 6 years) and 20 age-matched normal subjects were studied. All patients with diabetes had a normal treadmill exercise tolerance test without evidence of myocardial ischemia. By radionuclide angiography, all normal subjects increased ejection fraction with exercise (62 +/- 4% to 69 +/- 6%; p less than 0.001). In contrast, 11 (55%) of 20 patients with diabetes maintained or increased ejection fraction with exercise (group 1; 62 +/- 4% to 69 +/- 6%; p less than 0.001) and 9 (45%) of 20 showed an exercise-induced decrease (group 2; 73 +/- 4% to 66 +/- 6%; p less than 0.001). No difference in the incidence of microangiopathy, as noted by funduscopic examination, was present between the diabetic groups. Despite the abnormal ejection fraction response to exercise in the group 2 patients with diabetes, all patients with diabetes had a normal response to afterload manipulation, normal baseline ventricular contractility as assessed by load- and heart rate-independent end-systolic indexes and normal contractile reserve as assessed with dobutamine challenge. Autonomic dysfunction did not explain the disparate results between the group 2 patients' radionuclide angiographic data and their load-independent tests of ventricular contractility and reserve. In addition, the high ejection fraction at rest in group 2 patients (73 +/- 4% versus 62 +/- 4% for normal subjects; p less than 0.001) was not related to the abnormal tests of autonomic function. Thus, when left ventricular systolic performance was assessed by load- and rate-independent indexes, there was no evidence for cardiomyopathy in young adult patients with diabetes who have normal blood pressure and no ischemic heart disease.     

Evaluation of relationship between myocardial contractile state and left ventricular function in patients with aortic regurgitation

We studied the relationship between myocardial contractile state and left ventricular functional response to exercise in 14 asymptomatic patients with isolated moderate-to-severe aortic regurgitation and six control subjects. The slope of the systolic blood pressure-left ventricular end-systolic volume (pressure-volume) relationship determined by radionuclide ventriculography during angiotensin infusion was used as an indirect measure of myocardial contractility and was compared with left ventricular ejection fraction at rest and during both isometric handgrip and dynamic bicycle exercise. The slope of the pressure-volume relationship was significantly lower in patients with aortic regurgitation than in the control subjects (1.75 +/- 0.57 vs 2.78 +/- 0.42, p less than 0.01). The slope correlated exponentially with resting ejection fraction and was linearly related to changes in left ventricular ejection fraction during both handgrip and bicycle exercise. In patients with aortic regurgitation, resting ejection fraction may overestimate myocardial function. The slope of the pressure-volume relationship measured during afterload stress and left ventricular ejection fraction response to exercise intervention more reliably reflect the degree of left ventricular dysfunction.     

Left ventricular function in hypothyroidism. Responses to exercise and beta adrenoceptor blockade.

The effects of exercise and beta adrenoceptor blockade on left ventricular function were assessed in eight patients with hypothyroidism before and during thyroxine replacement treatment. Left ventricular ejection fraction, measured by radionuclide ventriculography, was reduced in hypothyroid patients at rest and on exercise. The rise in ejection fraction with exercise was, however, similar in both groups. Pretreatment with intravenous propranolol reduced the ejection fraction at rest 9% in both hypothyroid and euthyroid patients and reduced the rise on exercise. Directional changes in a second index of myocardial contractility based on the shape of the ventricular volume curve paralleled the changes in the ejection fraction. Left ventricular function is therefore reversibly depressed by thyroid hormone deficiency but responses to exercise and beta adrenoceptor blockade are normal. There is no evidence of altered adrenergic sensitivity in the control of myocardial contractility in hypothyroidism.     

Cardiac performance in thyrotoxicosis: analysis of 10 untreated patients

This study attempts to define cardiac performance at rest and during exercise in patients with untreated thyrotoxicosis. We studied 7 women and 3 men, aged 23 to 59 years (40 +/- 10, mean +/- standard deviation [SD]) and compared the results with those obtained in 12 normal subjects. In patients with thyrotoxicosis, the rhythm was sinus and the only untoward symptom was palpitations; the resting electrocardiographic results were normal in 8 patients and showed left ventricular hypertrophy in 2 patients; the left ventricular ejection fraction and volumes (measured by radionuclide ventriculography) were normal at rest. During exercise, 1 patient had dyspnea and 7 had leg fatigue; 2 were asymptomatic. Also, 7 patients had greater than or equal to 5% increase in left ventricular ejection fraction, 2 had no change, and 1 had a decrease. In all 10 patients, the exercise ejection fraction was greater than or equal to 60%. All normal subjects had a greater than or equal to 5% increase in ejection fraction during exercise. There were no significant differences at rest between patients with thyrotoxicosis and normal subjects in blood pressure, ejection fraction, end-diastolic volume, stroke volume, end-systolic volume, or cardiac output, but the heart rate was significantly higher in patients with thyrotoxicosis (91 +/- 10 versus 80 +/- 12 beats/min, p less than 0.05). During exercise, there were no significant differences between patients with thyrotoxicosis and normal subjects in blood pressure, end-diastolic volume, stroke volume, end-systolic volume, or cardiac output. The exercise ejection fraction was significantly lower in patients with thyrotoxicosis than in normal subjects (68 +/- 10% versus 75 +/- 4%, p less than 0.05). Cardiac performance is normal at rest in patients with thyrotoxicosis, but during exercise abnormal left ventricular reserve occurs in some patients.     

Cardiac function and plasma catecholamines during upright exercise in healthy young subjects

Radionuclide left ventricular ejection fraction, left ventricular volume changes and plasma catecholamines were recorded in six healthy untrained male subjects at rest and during upright exercise at increasing work loads. During mild submaximal exercise mean left ventricular ejection fraction increased 10% because of end-diastolic dilation, while a further 4% increase of left ventricular ejection fraction was recorded at heavy submaximal exercise mainly due to increased end-systolic contraction. Great individual changes were recorded during maximal exercise.

Alterations in plasma catecholamines were most pronounced at the high exercise levels indicating that changes in cardiac contractility are not linearly correlated with changes in sympathetic nervous activity.

Repeat studies showed only minor variations of mean left ventricular ejection fraction and plasma catecholamines indicating an acceptable reproducibility of the measurements. Variations of both left ventricular ejection fraction and catecholamines were smaller during exercise than at rest.     

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.     

Impaired left ventricular functional reserve in hypertensive patients with left ventricular hypertrophy

To determine whether patients with hypertension and especially those with left ventricular hypertrophy have subtle changes in cardiac function, we measured the increase in left ventricular ejection fraction and in systolic blood pressure to end-systolic volume index ratio with exercise in 40 hypertensive patients and 16 age-matched normotensive volunteers. Twenty-two hypertensive patients without hypertrophy had normal end-systolic wall stress at rest and exercise responses. In contrast, the 18 patients with echocardiographic criteria for left ventricular hypertrophy demonstrated a significant increase in end-systolic wall stress at rest compared with normal subjects (69 +/- 16 vs. 55 +/- 15 10(3) x dyne/cm2, p less than 0.05) despite having normal resting left ventricular size and ejection fraction. In patients with left ventricular hypertrophy, the increase in ejection fraction with exercise was less than in the normotensive control subjects (7 +/- 7 vs. 12 +/- 8 units, p less than 0.05), and delta systolic blood pressure to end-systolic volume with exercise was reduced (3.3 +/- 3.8 vs. 8.3 +/- 7.7 mm Hg/ml/m2, p less than 0.05). The hypertensive patients with hypertrophy displayed a shift downward and to the right in the relation between systolic blood pressure to end-systolic volume ratio and end-systolic wall stress compared with control subjects and hypertensive patients without left ventricular hypertrophy. Thus, hypertensive patients with left ventricular hypertrophy by echocardiography and normal resting ejection fraction exhibit abnormal ventricular functional responses to exercise. This finding may have implications in identifying patients at higher risk for developing heart failure.     

Radionuclide analysis of right and left ventricular response to exercise in patients with atrial and ventricular septal defects

In patients with ventricular or atrial septal defect, the ventricle which is chronically volume overloaded might not appropriately respond to increased demand for an augmentation in output and thereby might limit total cardiac function. In this study we simultaneously measured right and left ventricular response to exercise in 10 normal individuals, 10 patients with ventricular septal defect (VSD), and 10 patients with atrial septal defect (ASD). The normal subjects increased both right and left ventricular ejection fraction, end-diastolic volume, and stroke volume to achieve a higher cardiac output during exercise. Patients with VSD failed to increase right ventricular ejection fraction, but increased right ventricular end-diastolic volume and stroke volume. Left ventricular end-diastolic volume did not increase in these patients but ejection fraction, stroke volume, and forward left ventricular output achieved during exercise were comparable to the response observed in healthy subjects. In the patients with ASD, no rest-to-exercise change occurred in either right ventricular ejection fraction, end-diastolic volume, or stroke volume. In addition, left ventricular end-diastolic volume failed to increase, and despite an increase in ejection fraction, left ventricular stroke volume remained unchanged from rest to exercise. Therefore, cardiac output was augmented only by the heart rate increase in these patients. Right ventricular function appeared to be the major determinant of total cardiac output during exercise in patients with cardiac septal defects and left-to-right shunt.     

Exercise-induced cardiac dysfunction in sickle cell anemia. A radionuclide study

Cardiac performance was studied by radionuclide angiography at rest and during exercise in 22 adolescents with sickle cell (SC) anemia and the results were compared with those in 12 control subjects. At rest, cardiac contractility was normal; cardiac output and end-diastolic volume were increased. At maximal exercise, heart rate, cardiac output response, and work capacity were reduced; the reduction was related to the degree of anemia. Left ventricular end-diastolic volume decreased with exercise most markedly in patients with ischemic exercise electrocardiograms. An abnormal ejection fraction response to exercise occurred in 4 patients; electrocardiographic signs of ischemia developed in all 4, and wall motion abnormalities in 2. Those patients who had electrocardiographic signs of ischemia had a significantly lower heart rate, ejection fraction, and cardiac output response to exercise, and a lower hematocrit level than subjects with normal results on exercise electrocardiography. The increase in cardiac output was not sufficient to maintain a normal level of exercise. The decrease in end-diastolic volume suggests that diastolic function was abnormal during exercise. Cardiac dysfunction was manifested by an abnormal ejection fraction response, wall motion abnormalities, and incomplete left ventricular filling during exercise.     

Haemodynamic adaptation to exercise in asymptomatic patients with severe aortic regurgitation

Thirty-six patients with severe aortic regurgitation and 10 normal subjects underwent radionuclide angiography to examine the cardiovascular adaptations to exercise. Patients were sub-divided into four groups based on the directional change of ejection fraction with exercise. Group A (15 patients) showed normal ejection fraction at rest and peak exercise (0.65 +/- 0.05 and 0.73 +/- 0.06 respectively). Group D (six patients) showed significant abnormalities in left ventricular function at rest with further deterioration during exercise (0.44 +/- 0.09 to 0.35 +/- 0.07 respectively). In patients with good left ventricular function left ventricular end-diastolic and end-systolic volume decreased progressively with exercise and at peak exercise end-systolic volume was within normal limits. In patients with poor left ventricular function both end-diastoic and end-systolic volume progressively increased with exercise. Both net and total stroke volume were significantly higher at rest in patients with normal left ventricular function but net stroke volume increased with exercise only in those with good myocardial function and was quantitatively similar to that seen in normal subjects. The severity of aortic regurgitation as judged by regurgitant fraction was reduced during exercise in all except four patients, by an average of 22% in all groups. The major factor determining increasing cardiac output with exercise was found to be the status of myocardial function. Although reduction in the severity of aortic regurgitation may favourably influence distribution of stroke volume in those with normal myocardial function, it failed to contribute significantly to increasing cardiac output in those with poor left ventricular function.     

Left ventricular contractility related to the state of the coronary bed

The authors studied total and segmental contractility of the left ventricular (LV) myocardium in patients with acute myocardial infarction with single and multiple coronary artery (CA) disease. The group included 75 patients with acute transmural myocardial infarction; coronary arteriography was performed in 56 of them. All patients underwent echocardiography (sector scanning), on the basis of which total (ejection fraction) and segmental parameters (segmental ejection fraction, fraction of segmental wall shortening, velocity of change of segmental area, velocity of change in segmental wall thickness) of LV contractility were calculated. Patients with single CA affection display only a moderate decrease in total ejection fraction, and an insignificant number of complications of myocardial infarction. Segmental contractility data showed severe hyperkinesis of the intact segments of the left ventricle. Multiple CA disease is associated with a marked decrease in both total and segmental contractility of the LV myocardium, and there is no hyperkinesis of the intact segments of the heart.     

Radionuclide assessment of regional differences in left ventricular wall motion and myocardial perfusion in idiopathic dilated cardiomyopathy

Regional variations in left ventricular contractility and myocardialperfusion are frequent in idiopathic dilated cardiomyopathyand might result from an increase in left ventricular wall stressresponsible for regional wall motion abnormalities. The aimof the study was to perform radionuclide studies in patientswith idiopathic dilated cardiomyopathy to assess regional leftventricular wall motion and myocardial perfusion abnormalitiesin this myocardial disease. We studied 29 men referred withidiopathic dilated cardiomyopathy and normal coronary angiograms.Rest radionuclide left ventriculography and exercise thallium-201tomography were performed in all patients. The thallium-201tomograms were divided into 20 segments for each patient. Meanleft ventricular ejection fraction was 27±11%; 17 patientshad diffuse hypokinesia (mean left ventricular ejection fraction:24±9%) and 12 patients had predominant regional hypokinesia(mean left ventricular ejection fraction: 32±12%). Ofall 580 tomographic segments, 186 had a reduction of thallium-201uptake at exercise. Among them, reversibility was found in 53%.On the whole, 68% (158/232) of anterior, inferior and apicalsegments had a perfusion abnormality, compared with 8% (28/348)of septal and lateral segments (P<0.0001). Left ventricular wall motion and myocardial perfusion abnormalitiesare heterogeneous and not evenly distributed in dilated cardiomyopathy.The alterations are predominant on the myocardial regions delineatingthe antero-posterior axis of the left ventricle. These findingssuggest the possible role of increased left ventricular wallstress on this axis.     

Relation between postexercise abnormal heart rate recovery and myocardial damage evidenced by gated single-photon emission computed tomography

Abnormal heart rate recovery (HRR) after exercise has been associated with increased cardiac mortality. The ability of gated myocardial perfusion single-photon emission computed tomography (SPECT) to evaluate myocardial perfusion and function simultaneously might make it helpful in determining possible mechanisms that are involved in this finding. This study investigated the association between abnormal HRR and other indicators of risk for cardiovascular events. Patients (n = 1,296, 784 men; 57 +/- 11 years of age) who underwent exercise/technetium-99m sestamibi gated myocardial perfusion SPECT at rest were prospectively enrolled. Exercise treadmill testing was performed according to a symptom-limited Bruce's protocol. HRR was obtained from the subtraction of heart rate in the first minute of recovery after exercise treadmill testing from maximal heart rate during exercise. Myocardial perfusion SPECT was semi-quantitatively analyzed using a 17-segment left ventricular model. Left ventricular ejection fraction was automatically calculated using quantitative gated SPECT software. In our study, patients with abnormal HRR were older, more frequently diabetic, and hypertensive and had previous myocardial infarction and myocardial revascularization, higher heart rate at rest and perfusion defect quantification scores, lower left ventricular ejection fraction, and larger left ventricular volumes than did patients with normal HRR. In multivariable analysis, age (p <0.0001), heart rate at rest (p <0.0001), left ventricular ejection fraction (p <0.0001), and perfusion defect extent and severity at rest (p = 0.038) were independent predictors of abnormal HRR. In conclusion, abnormal HRR was significantly associated with lower left ventricular ejection fraction and with perfusion defect extent and severity at rest, but not with gated SPECT markers of myocardial ischemia. Therefore, abnormal HRR may reflect myocardial damage.     

Predicting cardiac mortality after uncomplicated myocardial infarction by exercise radionuclide ventriculography and exercise-induced ST segment elevation.

In 183 consecutive patients with recent, uncomplicated myocardial infarction, the following variables were associated with 4-year cardiac death: haemodynamic decompensation with exercise (P = 0.01), left ventricular ejection fraction at rest (P = 0.004) and at peak exercise (P = 0.003), persistent ST segment elevation at rest in the area of infarction = (P = 0.004), exercise-induced ST segment elevation (P = 0.02), and late aneurysmal evolution (P = 0.01). Exercise left ventricular ejection fraction was the sole variable selected by Cox regression analysis as an independent predictor of cardiac death. In 40 patients with ST segment elevation at rest, left ventricular ejection fraction was 42 +/- 17% at rest and 40 +/- 18% at peak exercise, versus 52 +/- 12% and 52 +/- 14% in the remaining patients (both P less than 0.01). Among these 40, 16 (all with anterior infarction) also had exercise-induced ST segment elevation; their ejection fraction was 32 +/- 13% at rest, 30 +/- 13% during exercise, versus 53 +/- 15% and 53 +/- 15% in 129 patients with no ST segment elevation either at rest, or during exercise (both P less than 0.01). The 4-year risk of death was 20% in the former 40 patients, 36% in the latter 16, while in the complete absence of ST segment elevation, such risk was 3%. All 14 patients with ST segment elevation only during exercise were alive after 4 years: their left ventricular ejection fraction was 47 +/- 12% at rest, 45 +/- 13% with exercise. ST segment elevation was associated with late aneurysmal evolution but not with exercise-induced ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased exercise ejection fraction and reversed remodeling after long-term treatment with metoprolol in congestive heart failure: a randomized, stratified, double-blind, placebo-controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy

BACKGROUND: the effects of long-term administration of beta-blockers on left ventricular (LV) function during exercise in patients with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM) are controversial. PATIENTS AND METHODS: patients with stable congestive heart failure (CHF) (New York heart association [NYHA] class II and III) and ejection fraction (EF) < or =0.40 were randomized to metoprolol, 50 mg t.i.d. or placebo for 6 months. Patients were divided into two groups: ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM). The mean EF was 0.29 in both groups and 92% were taking angiotensin-converting enzyme (ACE) inhibitors. In the IHD group, 84% had suffered a myocardial infarction (MI) and 64% had undergone revascularization at least 6 months before the study. LV volumes were measured by equilibrium radionuclide angiography. Mitral regurgitation was assessed by Doppler echocardiography. All values are changes for metoprolol subtracted by changes for placebo. RESULTS: metoprolol improved LV function markedly both at rest and during sub-maximal exercise in both groups. The mean increase in EF was 0.069 at rest (P<0.001) and 0.078 during submaximal exercise (P<0.001). LV end-diastolic volume decreased by 22 ml at rest (P=0.006) and by 15 ml during exercise (P=0.006). LV end-systolic volume decreased by 23 ml both at rest (P=0.001) and during exercise (P=0.004). Exercise time increased by 39 s (P=0.08). In the metoprolol group, mitral regurgitation decreased (P=0.0026) and only one patient developed atrial fibrillation vs. eight in the placebo group (P=0.01). CONCLUSION: metoprolol improves EF both at rest and during submaximal exercise and prevents LV dilatation in mild to moderate CHF due to IHD or DCM.     

Anomalies in left ventricular systolic function disclosed by exercise testing in chronic aortic insufficiency. Study by cavitary scintigraphy

Fifty-two patients with a symptomatic chronic aortic insufficiency underwent radionuclide angiography. The following parameters were measured at rest and at peak exercise: ejection fraction, regurgitant fraction, ventricular volumes, stroke volume, cardiac output and an index of systemic arterial resistance. The ventricular dimensions, the thickness of the septal and posterior walls, left ventricular myocardial mass and endsystolic stress were determined by 2D echocardiography. The patients were divided into 3 groups based on left ventricular changes on exercise: the first group (18 patients) had physiological left ventricular adaptation to exercise (increased ejection fraction, reduced endsystolic volume); a second group of 18 patients had moderate left ventricular dysfunction (absence of increase in ejection fraction and a reduction of less than 20% of endsystolic volume with respect to basal values); a third group of 17 patients had what was considered to be severe left ventricular dysfunction (decreased ejection fraction of over 5% and increased endsystolic volume of over 20% with respect to basal values). There was no significant difference between the three groups with respect to basal values of ejection fraction, ventricular volumes and systemic arterial resistance. On exercise, the heart rate, blood pressure and systemic arterial resistances varied in a comparable manner in each of the three groups. The left ventricular dimensions and myocardial mass were identical in the three groups. Only left ventricular endsystolic strain tended to be higher in the third group of patients compared with the other two, but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease

To compare acute effects of nitroglycerin (0.8 mg sublingually), nifedipine (5 ng/kg/min i.v.) and metoprolol (0.15 mg/kg i.v.) on normal, ischemic and scarred myocardial segments in man, we performed simultaneous hemodynamic and radionuclide measurements of left ventricular functions. Sixteen patients with isolated left anterior descending (LAD) disease were studied at rest and during exercise. Nine patients had angina and exercise-induced ischemia (LAD stenosis) and seven patients had previous transmural myocardial infarction and no ischemic changes during thallium imaging (LAD occlusion). The effects of the drugs on regional ejection fraction of the involved anteroseptal region and the normal posterolateral area were compared. Global ejection fraction at rest did not change after nitroglycerin, increased after nifedipine and decreased after metoprolol. In patients with ischemia, the exercise ejection fraction improved after all drugs due to increased regional ejection fraction in ischemic segments: i.e., a regional antiischemic effect evidenced by improved regional function could be demonstrated with all three agents. Regional ejection fraction increased from 35.8 +/- 19.5% to 66.2 +/- 15.2% (+/- SD) after nitroglycerin (p less than 0.001), to 61.7 +/- 8.7% after nifedipine (p less than 0.001), and to 48.4 +/- 7.0% after metoprolol (p less than 0.01). In regions of myocardial scar, regional ejection fraction was not changed after any drug. In normal areas, regional ejection fraction remained unchanged after nitroglycerin and nifedipine, but decreased after metoprolol. Despite similar antiischemic effects of all three drugs, underlying hemodynamic mechanisms were quite different and may provide a rationale for combined forms of treatment. These results may help to select optimal drug combinations to improve myocardial performance in patients with chronic ischemic heart disease.     

Left Ventricular Response to Exercise after Transmural Anterior Myocardial Infarction*

Abstract: Left ventricular response to exercise after transmural anterior myocardial infarction. A. T. H. Tan, N. Sadick, P. J. Harris, J. Morris and D. T. Kelly. Aust. N.Z. J. Med., 1982, 12 , pp. 489–494. The purpose of this study was to determine the effect of a previous myocardial infarction on the left ventricular response to exercise and to see how this response is modified by the presence of multivessel versus single vessel coronary artery disease. Twenty-seven patients with a past history of transmural anterior myocardial infarction underwent rest and exercise gated equilibrium blood pool imaging. All 27 patients had a total occlusion of the left anterior descending coronary artery and akinesis of the anterior wall of the left ventricle. Sixteen patients had isolated, left anterior descending artery occlusion (Group A). Eleven patients had multivessel disease with 70% or greater stenosis of one or more major coronary arteries in addition to the total left anterior descending artery occlusion (Group B). Seventeen subjects with atypical chest pain and normal exercise test were selected as controls. Seven Group B patients but no Group A patients developed angina and/or ischaemic ST changes with exercise. Control subjects achieved an average 94±2% (mean) of their predicted work capacity whereas the post-infarct patients had a diminished work capacity (Group A 73±6%, P <0.001; Group B 65±5%, p< 0.001). Control subjects showed an increase in ejection fraction (EF) from rest (0.53 ±0.02) to peak exercise (0.63±0.02). This increase was primarily due to a 33±6% decrease in end systolic volume since the end diastolic volume did not change significantly from rest to peak exercise (-1.4±4%). In Group A patients, EF did not change from rest (0.32±0.03) to peak exercise (0.30±0.03) because there was a similar increase in end-diastolic volume (76±4%) and end-systolic volume (19±4%). However, in Group B patients EF decreased from 0.32±0.03 to 0.23±0.02 (p<0.01) because of a disproportionate increase in endsystolic volume (45 ± 13%) compared to enddiastolic volume (27± 7%). When patients with abnormal resting left ventricular function due to previous myocardial infarction exercise there is little change in the ejection fraction and the increase in cardiac output is heart rate dependent. If additional myocardial ischaemia develops the ejection fraction and stroke volume decrease due to a disproportionate increase in endsystolic volume.     

Relationships of left ventricular systolic time intervals with hemodynamic variables in intact and failing hearts.

Deviation of systolic time intervals (STI) from the regression lines obtained from 122 normal subjects was studied in 22 healthy adults (Group 1), 18 N.Y. functional class I cardiac patients (Group II) with ischemic (IHD) or primary myocardial disease (PMD), and 15 similar patients (pts) but N.Y. functional class II with prior heart failure (Group III). STIc (corrected for heart rate) were normal in Groups I and II. Supine exercise caused shortening of pre-ejection period PEPc and prolongation of left ventricular ejection time ETc in both groups. Group III pts had a significantly longer PEPc and shorter ETc at rest. Supine exercise caused further prolongation of PEPc and a slight prolongation of ETc in this group. In 8 mongrel dogs, the effect of controlled changes of hemodynamic variables on STI was studied with intact hearts and repeated after myocardial impairment has been induced by pentobarbital. Doubling of venous return while the heart was intact produced changes in STI similar to the effects of supine exercise in Groups I and II human subjects. With myocardial impairment, comparable increase in venous return had an effect on STI similar to the effect of supine exercise Group III patients. Controlled increase in each of heart rate or blood pressure, with other hemodynamic variables kept constant, produced changes in STI different from the effect of supine exercise on human subjects. The study suggests that the value of supine exercise induced changes in STI in reflecting left ventricular performance is attributable primarily to increased volume load. In this resepct supine exercise is probably superior to other forms of exercise in disclosing impaired left ventricular performance.     

Is functional capacity related to left atrial contractile function in nonobstructive hypertrophic cardiomyopathy?

The mechanisms underlying reduced exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (NHCM) could include perturbations of ventricular relaxation, diastolic compliance, or compensatory atrial systolic function. We hypothesized that a loss of atrial contractility in NHCM patients leads to reduced functional capacity. To test this hypothesis, we compared resting noninvasive left atrial ejection phase indices in 49 consecutive patients with NHCM (ages 36+/-10 years; 41% female) and normal left ventricular ejection fraction (mean, 68%+/-8%) with objective metabolic exercise parameters. Left atrial active emptying fraction, ejection force, and kinetic energy failed to predict exercise capacity. Only left atrial total and active emptying volumes correlated weakly with minute volume/CO2 production slope (r=0.31 and r=0.33; p<0.05 for both). Furthermore, when subjects were stratified by New York Heart Association symptomatology, exercise parameters--but not atrial contractility--differed between groups. These data, obtained at rest, fail to suggest that NHCM-related heart failure symptoms are due to an atrial myopathy.