Detecting abnormalities in left ventricular function during exercise by respiratory measurement

The degree of exercise-induced cardiac dysfunction and its relation to the anaerobic threshold were evaluated in 23 patients with chronic heart disease. A symptom-limited exercise test was performed with a cycle ergometer with work rate increased by 1 W every 6 seconds. Left ventricular function, as reflected by ejection fraction, was continuously monitored with a computerized cadmium telluride detector after the intravenous injection of technetium-labeled red blood cells. The anaerobic threshold (mean, 727 +/- 166 ml/min) was determined by the noninvasive measurement of respiratory gas exchange. As work rate rose, the left ventricular ejection fraction increased but reached a peak value at the anaerobic threshold and then fell below resting levels. Ejection fraction at rest, anaerobic threshold, and peak exercise were 41.4 +/- 11.3%, 46.5 +/- 12.0%, and 37.2 +/- 11.0%, respectively. Stroke volume also increased from rest (54.6 +/- 17.0 ml/beat) to the point of the anaerobic threshold (65.0 +/- 21.2 ml/beat) and then decreased at peak exercise (52.4 +/- 18.7 ml/beat). The slope of the plot of cardiac output versus work rate decreased above the anaerobic threshold. The anaerobic threshold occurred at the work rate above which left ventricular function decreased during exercise. Accurate determination of the anaerobic threshold provides an objective, noninvasive measure of the oxygen uptake above which exercise-induced deterioration in left ventricular function occurs in patients with chronic heart disease.     

Regional myocardial dysfunction in patients with angina at rest and response to isosorbide dinitrate assessed by phase analysis of radionuclide ventriculograms

Left and right ventricular synchrony was assessed in 15 patients with angina at rest but no previous infarction by phase analysis of equilibrium radionuclide ventriculograms. Transient thallium-201 perfusion defects were noted in all during angina at rest and coronary vasospasm was documented in nine of the patients. Radionuclide ventriculograms were performed at control, during the ischemic episodes and after intravenous isosorbide dinitrate. Left and right ventricular phase histograms were quantified by the standard deviation from the mean of the peak (SD). Left ventricular ejection fraction averaged 65 +/- 11% (mean +/- standard deviation) at control, decreased in all patients during angina at rest to 49 +/- 14% (p less than 0.01) and increased in all patients after isosorbide dinitrate to 66 +/- 12%. However, ejection fraction during ischemia was abnormal in only nine patients and changed in two by less than 5% from the control value. Regional wall motion abnormalities were noted in all patients during the ischemic episodes but resolved after isosorbide dinitrate administration. Control left ventricular SD was 14.5 +/- 4 degrees, increased in all patients to 22.8 +/- 5 degrees during angina at rest (p less than 0.01) and returned to control values after isosorbide dinitrate administration (14.2 +/- 4 degrees). In contrast, right ventricular SD did not significantly change during ischemia as compared with control and isosorbide dinitrate. It is concluded that in angina at rest, a normal left ventricular ejection fraction does not exclude severe regional dysfunction; separate left and right ventricular SD is a sensitive index in detecting transient left ventricular dysfunction, and relief of ischemia is associated with rapid normalization of regional left ventricular function.     

Hemodynamically important right ventricular infarction: follow-up evaluation of right ventricular systolic function at rest and during exercise with radionuclide ventriculography and respiratory gas exchange

The prognosis and recovery of right ventricular systolic function in patients with hemodynamically documented right ventricular myocardial infarction (RVMI) is unclear. Therefore 27 patients who met hemodynamic criteria for RVMI were followed for at least 1 year. Four patients died within 1 year and 23 survived. Postmortem examination performed in three of the four patients showed extensive infarction of the right and left ventricles. Survivors underwent early and late follow-up resting radionuclide ventriculograms and late exercise studies. During long-term follow-up (1 to 4 years) resting radionuclide ventriculography demonstrated a significant improvement in right ventricular ejection fraction (30 +/- 7% to 43 +/- 8%; p less than .001) and right ventricular wall motion index (2.2 +/- 0.4 to 1.5 +/- 0.5; p less than .001) in 18 patients who survived longer than 1 year. Fourteen of these patients underwent upright bicycle exercise while off beta-blocking drugs and peak radionuclide ejection fraction was acquired after anaerobic threshold was achieved. Right ventricular ejection fraction increased significantly from 41 +/- 10% to 47 +/- 12% (p less than .001), as did the left ventricular ejection fraction (55 +/- 15% to 60 +/- 12%; p less than .05). The direction and magnitude of change of the right ventricular ejection fraction correlated significantly with the left ventricular ejection fraction (r = .82, p less than .02). Deviations from this correlation occurred in patients who had a decreased forced expiratory volume in 1 sec and an abnormal ventilatory reserve during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of isosorbide dinitrate on response to submaximal and maximal exercise in patients with congestive heart failure.

Isosorbide dinitrate is an effective vasodilator that improves resting left ventricular performance in patients with congestive heart failure, but little is known of the effect of the drug on the response to exercise. Bicycle exercise to symptomatic maximum was performed by 18 patients with class II to IV congestive heart failure before and 90 minutes after administration of isosorbide dinitrate, 40 mg orally. Although resting pulmonary wedge pressure and systemic vascular resistance were significantly reduced after isosorbide dinitrate, exercise duration was not altered and maximal oxygen consumption was not significantly changed (13.6 +/- 1.3 [SEM] standard error of the mean versus 13.8 +/- 1.2 ml/kg per min). At peak exercise pulmonary wedge pressure of 37.1 +/- 1.7 mm Hg, cardiac index of 4.19 +/- 0.35 liters/min per m2, and systemic vascular resistance of 14.7 +/- 1.3 units were not significantly different after nitrate administration. However, at submaximal loads, pulmonary wedge pressure was reduced from 33.6 +/- 1.7 to 27.9 +/- 1.8 mm Hg (P less than 0.01), and systemic resistance from 16.5 +/- 1.5 to 13.7 +/- 1.0 units (P less than 0.01) after administration of isosorbide dinitrate. Thus, short-term administration of nitrates does not improve maximal exercise capacity or left ventricular performance at maximal exercise in patients with congestive heart failure, but it does appear to improve pump function at submaximal work loads and may therefore enable patients to perform limited exercise more comfortably.     

Impaired cardiopulmonary response to exercise in moderate hypertension.

OBJECTIVE: To identify the limiting factors of exercise performance in subjects with hypertension associated with left ventricular hypertrophy. The secondary objective was to establish relationship between peripheral function and exercise capacity. DESIGN: Cardiopulmonary exercise testing was conducted using two protocols: a graded exercise test to maximal effort established maximal exercise capacity, followed by a step-incremental test combining gas-exchange measures and radionuclide angiography. The exercise responses were compared within and between groups. SETTING: All hypertensive subjects were selected from the Toronto Tri-Hospital Hypertension Clinic. Normal subjects were recruited from the surrounding community. PATIENTS: Twelve patients with established hypertension and left ventricular hypertrophy (determined by echocardiography) were studied as a referred/volunteer sample. All had no evidence of coincident diseases and were unmedicated at time of testing. A volunteer sample of normal, healthy subjects acted as a control. INTERVENTIONS: Graded exercise to maximum and step-incremental (submaximal and steady-state) exercise was used to quantify cardiopulmonary function during exercise stress. MAIN OUTCOME MEASURES: These included (for exercise performance) maximal oxygen intake (VO2max), the ventilatory anaerobic threshold, total peripheral resistance and blood lactate. Cardiac function measures included ejection fraction and ventricular volumes. RESULTS: Cardiac function data obtained during exercise in hypertensive subjects included an increase in the pressure to volume ratio, but a blunted ejection fraction response at peak exercise (P less than 0.05). Although end-diastolic volume increased during exercise (P less than 0.05), values were lower during both levels of exercise compared with normal subjects. Mean +/- SD end-systolic volume increased from 39 +/- 22 at rest to 42 +/- 23 mL during peak exercise. Hypertensive subjects had a lower VO2 max (mean 27.4 +/- 4.8 mL/kg/min) compared with normals (40.0 +/- 8.5 mL/kg/min) and a lower ventilatory anaerobic threshold (14.4 +/- 2.9 versus 27.6 +/- 5.8 mL/kg/min, P less than 0.005). Furthermore, hypertensive patients had a significantly elevated total peripheral resistance at rest (2.5 +/- 1.0 versus 1.8 +/- 0.4 peripheral resistance units) and at peak exercise (1.6 +/- 0.7 versus 0.8 +/- 0.2, P less than 0.01) compared with normal subjects (P less than 0.05). A correlation coefficient of 0.92 was found between total peripheral resistance and VO2 max in hypertensive subjects (P less than 0.01). CONCLUSIONS: These data suggest that peripheral factors, specifically a failure to reduce significantly total peripheral resistance, limits exercise performance despite a maintenance of left ventricular function during exercise in patients with moderate hypertension. The use of cardiopulmonary exercise testing can help in identifying the underlying cause of exercise intolerance in this population and limited left ventricular reserve at peak exercise, and may offer a sensitive measure of therapeutic end-points.     

The immediate effects of isosorbide dinitrate on right ventricular function in patients with acute hypoxemic respiratory failure. A combined invasive and radionuclide study

We administered 20 mg of isosorbide dinitrate sublingually to 16 patients with acute hypoxemic respiratory failure (ARF) complicated by pulmonary artery hypertension (PAH) and evaluated its effects 20 to 30 min later using a combination of invasively measured pressures and flows and ECG-gated cardiac scintigraphy. We measured the right and left ventricular ejection fractions and a simultaneous thermodilution stroke volume index; we then calculated respective end-diastolic (EDVI) and end-systolic (ESVI) volume indexes. An initially depressed mean right ventricular ejection fraction (RVEF) increased modestly after the administration of isosorbide dinitrate (35 +/- 10 to 41 +/- 10%; p less than 0.02), whereas both the mean right ventricular end-diastolic (-27 +/- 50 ml/M2; p less than 0.04) and end-systolic (-27 +/- 44 ml/M2; p less than 0.03) volume indexes fell. The RVEF increased in 11 of 16 patients: within this subgroup, a decrease in the RVEDVI and RVESVI was associated with a decrease in both cardiac index (delta 0.3 L/min/M2) and LVEDVI (delta -15 +/- 21 ml/M2; p less than 0.01); hence, O2 delivery also fell (delta -36 +/- 56 ml/min/M2; p less than 0.05). In some patients with ARF complicated by PAH, sublingually administered nitrates may improve right ventricular systolic function when globally depressed. However, left ventricular "pump" function appears to be depressed when a concurrent depression in right ventricular "pump" function ensues.     

Clinical response and effects on left ventricular function of isosorbide dinitrate added to propranolol or diltiazem monotherapy in patients with chronic stable angina

Twenty-four patients were randomized to a double-blind, triple placebo controlled, latin square protocol to examine the relative efficacy of propranolol or diltiazem given as monotherapy or in combination with isosorbide dinitrate. Treatment phases were preceded and followed by placebo control periods. At the end of each phase, symptom-limited treadmill exercise stress tests were performed, as well as rest and exercise radionuclide ventriculography. Both forms of monotherapy were effective in reducing episodes of angina and nitroglycerin use, and in improving exercise tolerance. Diltiazem monotherapy was associated with slightly higher treadmill times (509.9 +/- 123 s) compared to propranolol (462.7 +/- 131 s, P less than 0.05). The addition of isosorbide dinitrate to either form of monotherapy allowed no further improvement in any of the measured clinical responses. Radionuclide ventriculography showed no significant difference in resting left ventricular function. The addition of isosorbide dinitrate to propranolol showed a reduction in end diastolic volume in keeping with a reduction in preload. In response to exercise, stress-induced left ventricular dysfunction was equal in all groups except for the diltiazem-nitrate combination, which was associated with a higher ejection fraction (56.2 +/- 8.6%) compared to monotherapy (52.6 +/- 10.9%, P less than 0.01). A higher cardiac output could be achieved in the groups treated with diltiazem; this was related to increased heart rate and maintenance of stroke volume. It was concluded that diltiazem is equally effective as propranolol for the treatment of chronic stable angina and, in terms of exercise capacity and cardiac output, superior to beta-blockade. The addition of isosorbide dinitrate appears to impart no overt benefits, but some evidence suggests a reduction in left ventricular decompensation in the face of stress.     

Silent left ventricular dysfunction during routine activity after thrombolytic therapy for acute myocardial infarction

To investigate prospectively the occurrence and significance of postinfarction transient left ventricular dysfunction, 33 ambulatory patients who underwent thrombolytic therapy after myocardial infarction were monitored continuously for 187 +/- 56 min during normal activity with a radionuclide left ventricular function detector at the time of hospital discharge. Twelve patients demonstrated 19 episodes of transient left ventricular dysfunction (greater than 0.05 decrease in ejection fraction, lasting greater than or equal to 1 min), with no change in heart rate. Only two episodes in one patient were associated with chest pain and electrocardiographic changes. The baseline ejection fraction was 0.52 +/- 0.12 in patients with transient left ventricular dysfunction and 0.51 +/- 0.13 in patients without dysfunction (p = NS). At follow-up study (19.2 +/- 5.4 months), cardiac events (unstable angina, myocardial infarction or death) occurred in 8 of 12 patients with but in only 3 of 21 patients without transient left ventricular dysfunction (p less than 0.01). During submaximal supine bicycle exercise, only two patients demonstrated a decrease in ejection fraction greater than or equal to 0.05 at peak exercise; neither had a subsequent cardiac event. These data suggest that transient episodes of silent left ventricular dysfunction at hospital discharge in patients treated with thrombolysis after myocardial infarction are common and associated with a poor outcome. Continuous left ventricular function monitoring during normal activity may provide prognostic information not available from submaximal exercise test results.     

Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance

Exercise stress testing is routinely used for the noninvasive assessment of coronary artery disease and is considered a safe procedure. However, the provocation of severe ischemia might potentially cause delayed recovery of myocardial function. To investigate the possibility that maximal exercise testing could induce prolonged impairment of left ventricular function, 15 patients with angiographically proved coronary disease and 9 age-matched control subjects with atypical chest pain and normal coronary arteries were studied. Radionuclide ventriculography was performed at rest, at peak exercise, during recovery and 2 and 7 days after exercise. Ejection fraction, peak filling and peak emptying rates and left ventricular wall motion were analyzed. All control subjects had a normal exercise test at maximal work loads and improved left ventricular function on exercise. Patients developed 1 mm ST depression at 217 +/- 161 s at a work load of 70 +/- 30 W and a rate-pressure product of 18,530 +/- 4,465 mm Hg x beats/min. Although exercise was discontinued when angina or equivalent symptoms occurred, in all patients diagnostic ST depression (greater than or equal to 1 mm) developed much earlier than symptoms. Predictably, at peak exercise patients showed a decrease in ejection fraction and peak emptying and filling rates. Ejection fraction and peak emptying rate normalized within the recovery period, whereas peak filling rate remained depressed throughout recovery (p less than 0.002) and was still reduced 2 days after exercise (p less than 0.02). In conclusion, in patients with severe impairement of coronary flow reserve, maximal exercise may cause sustained impairement of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular function in dilated cardiomyopathy. Noninvasive determination of end-systolic stress-diameter and shortening fraction-stress relations

The ejection fraction and fractional shortening are parameters of left ventricular function dependent on the conditions of load. They are not perfect indices of myocardial contractility. The study of the relationships between stress and diameter and fractional shortening and stress in end-systole provides a better means of assessing the contractile state of the myocardium. The relationships between end-systolic stress-diameter and end-systolic stress-fractional shortening were studied non-invasively in 10 normal subjects (Group I) and 7 patients with severe dilated cardiomyopathy (Group II). End-systolic longitudinal stress of the left ventricle was calculated from Grossman's formula by coupling automatic measurement of blood pressure (cuff method) with simultaneous M mode recordings guided by 2D echocardiography. The line of regression of end-systolic stress-end-systolic diameter was determined in all cases from a series of 14 points obtained after sublingual administration of 10 mg of isosorbide dinitrate. The line of regression of fractional shortening-end-systolic stress was established in both groups by using the values observed under basal conditions and at the peak of action of the isosorbide dinitrate. The following results obtained: Under basal conditions, patients in Group II had greater end-diastolic diameters (69 +/- 8 vs 49 +/- 4 cm, p less than 0.01), greater end-systolic diameters (61 +/- 8 vs 33 +/- 4 mm, p less than 0.001) and higher end-systolic stress (140 +/- 54 vs 67 +/- 13 10(3) dyn/cm2, p less than 0.001). Fractional shortening was lower in Group II than in Group I (12 +/- 5 vs 33 +/- 5%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Resistance to isosorbide dinitrate in patients with severe chronic heart failure: incidence and attempt at hemodynamic prediction

Oral isosorbide dinitrate has been widely used to lower elevated left ventricular filling pressure in patients with chronic heart failure. Although the recommended dose of this drug is 40 mg every 6 h, failure to respond to this dose has been observed in many patients with heart failure. In the present study the incidence of resistance to isosorbide dinitrate was evaluated and an attempt was made to identify baseline hemodynamic predictors for this phenomenon in 50 patients with severe chronic heart failure due to left ventricular systolic dysfunction (mean left ventricular ejection fraction 0.23 +/- 0.08). Twenty-seven (54%) of the 50 patients responded to 40 mg of isosorbide dinitrate (greater than 20% decrease in mean pulmonary artery wedge pressure sustained greater than or equal to 1 h) and 23 patients (46%) failed to respond. Nonresponders to 40 mg of isosorbide dinitrate had a significantly higher baseline right atrial pressure than did responders (14 +/- 5 versus 10 +/- 6 mm Hg, p less than 0.02). In addition, all 7 patients with a baseline right atrial pressure of less than 7 mm Hg and 12 of 14 patients with a baseline right atrial pressure less than 10 mm Hg responded to 40 mg. No significant differences were noted between responders and nonresponders in any other baseline hemodynamic or clinical variables, or in peak isosorbide dinitrate serum levels (32 +/- 19 ng/ml in nonresponders versus 44 +/- 36 ng/ml in responders). Of the 23 nonresponders to 40 mg, 22 received a higher dose (80 to 120 mg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic effects of isosorbide dinitrate in patients with congestive cardiac failure at rest and during submaximal supine exercise.

Eight patients with chronic congestive cardiac failure secondary to ischaemic heart disease performed submaximal supine exercise before and after 5 mg sublingual isosorbide dinitrate (ISDN) at the time of cardiac catheterisation. Exercise before ISDN produced a poor response in left ventricular performance. After ISDN this response was significantly improved. Compared with the control exercise period cardiac index (CI) increased from mean 2.9 to 3.5 l/mn/m2 (p = less than 0.0025), stroke volume index (SVI) from mean 24 to 29 ml/m2 (p = less than 0.0005) and left ventricular stroke work index (LVSWI) from mean 22 to 28 g-m/m2 (p = less than 0.0025). Although ISDN reduced LVEDP significantly at rest, there were associated small but significant falls in CI, SVI and LVSWI. The improvement in exercise cardiac index was related to the ejection fraction, or the ejection fraction of the contractile section where a left ventricular aneurysm was present. ISDN may be effective in improving exercise tolerance in ambulant patients with chronic congestive cardiac failure.     

Left ventricular function in chronic asymptomatic aortic insufficiency. Angioscintographic study

More accurate information is needed on the usefulness of radionuclide angiography performed during exercise for the assessment of left ventricular function in chronic aortic regurgitation and on its value compared with echocardiography. Between January, 1985 and January, 1988, we studied 23 asymptomatic patients presenting with severe, isolated and pure aortic regurgitation. Nine patients who were not operated upon during that period (group N) had the following characteristics: age 39.4 +/- 12.3 years, left ventricular end-diastolic diameter 67.3 +/- 4.7 mm, left ventricular end-systolic diameter 43.4 +/- 3.2 mm, left ventricular fibre shortening fraction 0.36 +/- 0.05, left ventricular radionuclide ejection fraction 0.67 +/- 0.10 at rest and 0.66 +/- 0.09 during maximum exercise. Compared with the values obtained in 8 controls of the same age (ejection fraction 0.65 +/- 0.07, p less than 0.05, at rest and 0.76 +/- 0.09, p less than 0.05, during maximum exercise), the behaviour of group N patients during exercise was perturbed. Fourteen patients who underwent surgery presented with the following characteristics: age 53.3 +/- 13.3 years (p less than 0.05), left ventricular end-diastolic diameter 71.4 +/- 8.7 mm (p less than 0.05), left ventricular end-systolic diameter 49.4 +/- 6.5 mm (p less than 0.05), fibre shortening fraction 0.31 +/- 0.03 (p less than 0.01), ejection fraction 0.53 +/- 0.08 at rest (p less than 0.001) and 0.40 +/- 0.08 during maximum exercise (p less than 0.001). These results suggest that radionuclide angiography performed during exercise is effective in the early detection and accurate evaluation of myocardial dysfunction in patients with chronic aortic regurgitation at the asymptomatic stage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of captopril on left ventricular end-systolic pressure-volume and stress-shortening relations in severe cardiac failure

The effects of captopril on cardiovascular dynamics and left ventricular (LV) contractility were studied in 11 patients with severe congestive heart failure and very poor global LV function. Pressures were measured using a flow-guided catheter, cardiac output by thermodilution, and LV contraction and ejection fraction by simultaneous radionuclide angiography. Ventricular loading conditions were altered by sublingual isosorbide dinitrate to facilitate construction of LV pressure-volume and stress-shortening curves. Captopril decreased mean arterial pressure (p less than 0.02) and systemic vascular resistance, while stroke and cardiac index increased in most patients. Left ventricular ejection fraction increased from 18 +/- 5 to 22 +/- 7% (p less than 0.05), but contractility, assessed from end-systolic pressure-volume and end-systolic pressure-shortening relations, was unchanged or decreased slightly. Heart rate and double product also tended to decrease. In contrast, arteriovenous oxygen difference widened and calculated total oxygen consumption increased during captopril therapy (p less than 0.05). The study showed that captopril improved forward blood flow, total oxygen extraction, and LV ejection fraction following the decrease impedance to LV emptying but not at the expense of an increase in ventricular contractility. This makes captopril an attractive drug for patients with end-stage cardiac failure and a severely damaged myocardium.     

Noninvasive measurement of the rest and exercise peak systolic pressure/end-systolic volume ratio: a sensitive two-dimensional echocardiographic indicator of left ventricular function

Thirty-five patients with previous myocardial infarction and 25 normal subjects underwent subcostal view two-dimensional echocardiography at rest and at peak up-right bicycle exercise. The purpose was to assess changes in left ventricular volume with maximal upright bicycle exercise and to compare the utility of the peak systolic pressure/end-systolic volume index ratio and ejection fraction as indicators of left ventricular function. With exercise, normal subjects had a decrease in end-systolic volume index (22 +/- 8 to 11 +/- 3 ml/m2) (p less than 0.001); the normal ejection fraction (59 +/- 9 to 72 +/- 8%, p less than 0.001) and the pressure/volume ratio (6 +/- 3 to 18 +/- 6, p less than 0.001) increased. In patients with prior myocardial infarction there was no change in end-systolic volume index, ejection fraction or pressure/volume ratio with exercise. Although at peak exercise significant differences between normal subjects and patients with prior infarction were demonstrated in end-systolic volume index (p less than 0.001), ejection fraction (p less than 0.001) and pressure/volume ratio (p less than 0.001), the pressure/volume ratio provided sharper delineation between the two groups than did ejection fraction. The exponential relation of the pressure/volume ratio and ejection fraction at peak exercise demonstrates that the pressure/volume ratio is more sensitive as an indicator of normal or borderline left ventricular function and that ejection fraction is more sensitive in quantifying the degree of left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improvement in exercise haemodynamics by isosorbide dinitrate in patients with severe congestive cardiac failure secondary to ischaemic heart disease.

Seven patients with severe chronic congestive cardiac failure secondary to ischaemic heart disease performed submaximal supine exercise before and after 5 mg sublingual isosorbide dinitrate at the time of cardiac catheterisation. Exercise before isosorbide dinitrate produced a poor response in left ventricular performance. After isosorbide dinitrate this response was significantly improved. Compared with the control exercise period, cardiac index increased from mean 2.6 to 3.1 1/min per m2 (P less than 0.0025), stroke volume index from mean 22 to 27 ml/m2 (P less than 0.0025), and left ventricular stroke work index from mean 21 to 30 g m/m2 (P less than 0.01). Mean left ventricular filling pressure fell from 37 to 26 mmHg (P less than 0.01). Although isosorbide dinitrate reduced left ventricular filling pressure at rest from mean 26 to 17 mmHg (P less than 0.005), there was no significant change in mean cardiac index or stroke volume index, while left ventricular stroke work index decreased from mean 29 to 22 g m/m2 (P less than 0.05). Isosorbide dinitrate effectively reduces left ventricular filling pressure in the resting patient with congestive cardiac failure but produces a more comprehensive improvement in left ventricular performance during exercise.     

Assessment of function of contractile segments in patients with left ventricular aneurysms by quantitative first pass radionuclide ventriculography. Haemodynamic correlation at rest and exercise.

Thirteen patients with left ventricular aneurysms complicating myocardial infarction were studied by contrast angiography and by first pass radionuclide ventriculography. The ejection fraction of the contractile segment (EFCS) was measured from both studies using a double hemishperoid model, and the values correlated closely. There was a monotonic relation between EFCS and stroke volume index measured from thermodilution cardiac outputs carried out simultaneously with the radionuclide study. When radionuclide ventriculography was performed at submaximal supine exercise, changes in EFCS paralleled changes in the total left ventricular ejection fraction in 10 of the 13 cases. In nine patients, changes in EFCS paralleled changes in stroke volume index and the relation between EFCS and stroke volume index was maintained at exercise. After administration of the vasodilator isosorbide dinitrate to 12 patients, repeat exercise radionuclide ventriculography showed an improvement in left ventricular ejection fraction and in eight patients EFCS improved. First pass radionuclide ventriculography can accurately estimate EFCS, which may be an important factor in predicting the likely response to aneurysmectomy. Changes in EFCS on exercise are reflected in changes in total left ventricular ejection fraction and stroke volume index. Isosorbide dinitrate may improve contractile segment function on exercise.     

Improvement in supine bicycle exercise performance in refractory congestive heart failure after isosorbide dinitrate: radionuclide and hemodynamic evaluation of acute effects

The acute effects of oral isosorbide dinitrate on exercise performance in congestive heart failure were evaluated in 11 patients. All patients underwent rest and supine bicycle exercise equilibrium radionuclide ventriculography and hemodynamic measurements before and after oral administration of isosorbide dinitrate, 40 mg four times a day for 24 hours. Ninety minutes after the last dose, isosorbide dinitrate increased the duration of exercise (+ 28 percent, probability [p] < 0.01) and the total work performed (+ 32 percent, p < 0.01); with this drug, significantly (p < 0.05) fewer patients terminated exercise because of dyspnea. At rest, the left ventricular ejection fraction increased after administration of isosorbide dinitrate (+ 14 percent of value before administration, p < 0.02); there were decreases in mean pulmonary arterial pressure (? 23 percent, p < 0.02), mean arterial pressure (? 8 percent, p < 0.05), systemic vascular resistance (? 18 percent, p < 0.005) and pulmonary vascular resistance (? 46 percent, p < 0.001). During comparable levels of exercise, isosorbide dinitrate decreased pulmonary capillary wedge pressure (? 19 percent, p < 0.001), mean pulmonary arterial pressure (? 23 percent, p < 0.001), mean arterial pressure (? 7 percent, p < 0.001), heart rate (? 5 percent, p < 0.01), systemic vascular resistance (? 20 percent, p < 0.01) and pulmonary vascular resistance (? 37 percent, p < 0.01), and increased cardiac index (+ 15 percent, p < 0.02), stroke volume index (+ 19 percent, p < 0.01) and stroke work index (+ 16 percent, p < 0.05). Ejection fraction did not change significantly (+ 7 percent, difference not significant [NS]). During maximal exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (? 15 percent, p = 0.05), mean pulmonary arterial pressure (? 15 percent, p < 0.01), systemic vascular resistance (? 23 percent, p < 0.05) and pulmonary vascular resistance (? 30 percent, p < 0.01) and increases in cardiac index (+ 30 percent, p < 0.001), stroke volume index (+ 31 percent, p < 0.001) and stroke work index (+ 40 percent, p < 0.001). Ejection fraction did not change significantly (+ 9 percent, p = NS). Ten minutes after exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (? 34 percent, p < 0.02), mean pulmonary arterial pressure (? 23 percent, p < 0.02), mean arterial pressure (? 10 percent, p < 0.01) and systemic vascular resistance (? 24 percent, p < 0.001) and increases in stroke volume index (+ 18 percent, p < 0.05) and ejection fraction (+ 12 percent, p < 0.05). It is concluded that oral isosorbide dinitrate, by causing reductions in preload and afterload, produces significant beneficial acute effects on left ventricular performance during exercise in patients with refractory chronic congestive heart failure.     

Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): Baseline characteristics,prognosis and response to therapy in the vasodilator in heart failure trials (V-HeFT)

Objectives. This analysis sought to evaluate the clinical characteristics and outcome in heart failure with mild systolic dysfunction.Background. Although heart failure with mild systolic dysfunction occurs commonly, this is an understudied area because clinical trials have usually excluded patients with ejection fraction >35%.Methods. The 422 patients with left ventricular ejection fraction ⩽35% were compared with 172 with a left ventricular ejection fraction > 35% in the Vasodilator in Heart Failure Trial (V-HeFT I), whereas in V-HeFT-II 554 patients with a left ventricular ejection fraction ⩽ 35% were compared with 218 patients with a left ventricular ejection fraction > 35% for mortality and clinical care. For a left ventricular ejection fraction >35%, treatment with hydralazine/isosorbide dinitrate was compared with prazosin and placebo therapy in V-HeFT I, and hydralazine/isosorbide dinitrate was compared with enalapril in V-HeFT II for mortality, clinical course and change in physiologic variables: ejection fraction, plasma norepinephrine levels, ventricular tachycardia and echocardiographic variables.Results. In both studies, patients with a left ventricular ejection fraction > 35% differed principally in hypertensive history, higher functional capacity and radiographic and echocardiographic cardiac dimension from patients with a left ventricular ejection fraction ⩽35%, and plasma norepinephrine levels differed in V-HeFT II (p < 0.01). Patients with a left ventricular ejection fraction >35% had a lower cumulative mortality than those with a left ventricular ejection fraction ⩽35% (p < 0.0001) and less frequent hospital admissions for heart failure (p < 0.014, V-HeFT I; p < 0.005, V-HeFT II). Although cumulative mortality and morbidity did not differ between treatment groups in V-HeFT I, enalapril decreased overall mortality versus hydralazine/isosorbide dinitrate (p < 0.035) in V-HeFT II. For physiologic variables in V-HeFT II, enalapril decreased ventricular tachycardia at follow-up (p < 0.05).Conclusion. In V-HeFT, heart failure with mild systolic dysfunction was associated with different characteristics and a more favorable prognosis than heart failure with more severe systolic dysfunction. Enalapril decreased overall mortality and sudden death compared with hydralazine/isosorbide dinitrate. Prospective trials are needed to address therapy for heart failure with mild systolic dysfunction.     

Responses of left and right ventricular ejection fractions to aerobic and anaerobic phases of upright and supine exercise in normal subjects

The effects of aerobic and anaerobic exercise on ventricular performance were studied in 13 normal subjects who underwent simultaneous pulmonary gas exchange evaluation and exercise radionuclide ventriculography in the supine and upright postures. Right and left ventricular ejection fraction was measured serially at 2-minute intervals during exercise. The anaerobic threshold occurred at 74% and 80% of maximum heart rate, respectively, during upright and supine exercise. Left and right ventricular ejection fractions rose from rest to the anaerobic threshold (p less than 0.01, p less than 0.01, respectively) and there was a further increase between the anaerobic threshold and maximum exercise (p less than 0.01, p less than 0.01, respectively). The rate of rise of ejection fraction beyond the anaerobic threshold was slightly blunted compared with the rise prior to attaining the anaerobic threshold. There was no significant difference in ventricular performance between supine and upright exercise. The data demonstrate that ventricular performance increases steadily during exercise and is not limited by the conversion of aerobic to anaerobic metabolism.