The relationship between left ventricular functional response to isometric exercise and asynergic contraction and diastolic stiffness

Either augmentation or impairment of left ventricular function has previously been reported in different patients, in response to isometric exercise. To identify the mechanisms associated with these disparate responses, the effects of submaximal sustained handgrip upon left ventricular systolic and diastolic properties were studied in 29 patients during diagnostic catheterization. In 16 patients (group I), ejection fraction, mean Vcf, and the mean systolic ejection rate remained constant, while the ratio of peak systolic pressure to end systolic volume increased significantly from 2.81 ± 0.6 to 3.17 ± 0.6 ml/mm Hg. In 13 patients (group II) ejection fraction declined from 0.6 ± 0.03 to 0.51 ± 0.03, Vcf from 0.96 ± 0.09 to 0.85 ± 0.09 circ/sec, mean normalized systolic ejection rate from 1.79 ± 0.1 to 1.50 ± 0.09 sec^?1, and the peak systolic pressure to end systolic volume ratio from 2.23 ± 0.3 to 1.99 ± 0.3 (p < 0.05 for each). Systemic arterial mean pressure increased similarly by 19% and 21 % in groups I and II, respectively (p < 0.05 for each). Systemic vascular resistance increased significantly by 23% in group I and by 5% in group II (p < 0.05). Left ventricular end diastolic volume declined from 85.4 ± 7 to 77.3 ± 11 ml/m² in group I, while end diastolic and end systolic volumes increased by 13% and 35%, respectively in group II (p < 0.05 for each). In both groups, baseline exponential pressure-volume relations were similar, though higher intercepts of the pressure-volume relations upon the Y-axis suggested greater “diastolic tone”, and steeper volume-normalized pressure-volume elasticity relations indicated “stiffer” left ventricular chambers in group II patients. While the incidence of coronary artery disease was similar, both the severity and extent of left ventricular asynergy were greater in group II patients. We conclude that dilatation and deterioration of left ventricular ejection function in response to isometric exercise are causally related to, and comprise a useful predictor of, severe underlying left ventricular asynergy and impaired chamber distensibility.     

Effects of digoxin on left ventricular function in coronary artery disease patients

To assess whether digitalis modifies or prevents the deterioration of the left ventricular ejection fraction and wall motion during acute ischemia, we performed gated blood pool radionuclide ventriculograms in 15 patients with angiographically documented coronary artery disease. All patients were studied in the resting state and during maximal supine bicycle exercise, both before and 1 hour after 1 mg intravenous digoxin.There was no significant difference, pre-digoxin vs post-digoxin, in exercise tolerance (415 ± 84 vs 418 ± 107 seconds), number of segments with abnormal resting wall motion (12 vs 11) or exercise wall motion (21 vs 19). Ten patients developed angina during the same exercise load, irrespective of digoxin administration. Twelve patients had subnormal left ventricular ejection fraction during exercise pre-digoxin, vs 13 patients post-digoxin (P = ns). In the resting state, the left ventricular ejection fraction was higher after digoxin (53 ± 14% pre vs 58 ± 14% post, P < 0.05). During exercise, however, the left ventricular ejection fraction was not significantly improved after digoxin (50 ± 16% pre vs 53 ± 17% post, P = ns).These data indicate that although acute administration of digoxin improves the resting left ventricular function, it does not improve exercise tolerance to angina. Furthermore, intravenous digoxin does not appear to prevent the deterioration of left ventricular wall motion and ejection fraction during exercise induced ischemia.     

Coronary artery dimensions in primary and secondary left ventricular hypertrophy

Background. Coronary artery enlargment has been previously described in left ventricular hypertrophy.Objectives. We sought to assess coronary artery dimensions and their relation to left ventricular muscle mass in primary and secondary hyperthropy.Methods. Cross-sectional area of the left and right coronary arteries was determined by quantitative coronary angiography in 52 patients: 12 control subjects and 40 patients (13 with hypertrophic cardiomyopathy, 12 with dilated cardiomyopathy and 15 with aortic valve disease). As a measure of left ventricular hypertrophy, angiographic left ventricular mass and equatorial cross-sectional muscle area were determined.Results. Cross-sectional area of both the left and right coronary arteries is increased in left ventricular hypertrophy (p < 0.05 vs. values in control subjects). There is a curvilinear relation between left coronary artery size and left ventricular muscle mass (r = 0.76) or cross-sectional muscle area (r = 0.75). However, normalization of coronary cross-sectional area for left ventricular muscle mass or muscle area shows insufficient enlargement of the coronary arteries in both primary and secondary hypertrophy.Conclusions. 1) Coronary artery size increases as left ventricular mass increases in both primary and secondary hypertrophy. 2) The enlargement of left coronary cross-sectional area is independent of the cause of the increase in left ventricular mass. 3) The size of the coronary arteries is inappropriate with regard to left ventricular hypertrophy. Thus, the stimulus for growth of the coronary arteries is not influenced by the underlying disease but appears to depend on the degree of left ventricular hypertrophy.     

Assessment of left ventricular performance by on-line pressure-area relations using echocardiographic automated border detection

Objectives. The purpose of this study was to evaluate left ventricular performance by on-line pressure-area relations using echocardiographic automated border detection in the in situ canine heart in a manner similar to pressure-volume analyses.Background. Echocardiographic automated border detection can measure ventricular cavity area as an index of volume and may be interfaced with pressure to construct pressure-area loops on-line.Methods. Eight anesthetized open chest dogs had simultaneous measurement of ventricular pressure, aortic flow and midventricular short-axis area. Pressure-area loops were constructed by a computer workstation interfaced with the ultrasound system. Stroke area (Maximal area — Minimal area) and stroke force (∝P dA [P = pressure; A = area]) values during inferior vena cava (n = 8) and aortic (n = 4) occlusions were compared with stroke volume and estimates of stroke work, respectively. Inotropic modulation was induced with dobutamine infusion (2 to 5 μg/kg body weight per min), followed by propranolol infusion (2 to 5 mg). End-systolic and maximal elastance and preload recruitable stroke force (stroke force versus end-diastolic area) were derived for each period.Results. Changes in stroke area and stroke force were significantly correlated with changes in stroke volume and estimates of stroke work during caval occlusion (n = 8) (r = 0.87 ± 0.02, SEE = 8 ± 1% and r = 0.90 ± 0.03, SEE = 8 ± 2%, respectively). In dogs with aortic occlusion (n = 4), changes in stroke area significantly correlated with changes in stroke volume for pooled data (r = 0.84, SEE = 8%, y = 1.0x + 3). Ventricular performance increased with dobutamine infusion (n = 7): endsystolic elastance 30 ± 11 to 67 ± 24 mm Hg/cm²(p < 0.02 vs. control values); maximal elastance 37 ± 11 to 82 ± 26 mm Hg/cm²(p < 0.02 vs. control values); preload rcruitable stroke force 81 ± 24 to 197 ± 92 mm Hg (p < 0.02 vs. control values). Decreases occurred with propranolol infusion (n = 5) end-systolic elastance 20 ± 4 to 13 ± 4 mm Hg/cm²(p < 0.002 vs. control values); maximal elastance 29 ± 8 to 15 ± 5 mm Hg/cm²(p < 0.002 vs. control values); preload recruitable stroke force 66 ± 14 to 40 ± 9 mm Hg (p < 0.002 vs. control values).Conclusions. On-line pressure-area relations are a potentially useful means to assess left ventricular performance in a manner that is quantitatively similar to the predicted responses of pressure-volume relations.     

Left atrial function and ventricular filling in hypertensive patients with paroxysmal atrial fibrillation

Objectives. We evaluated left atrial dimensions and function, as well as left ventricular structure and filling, in hypertensive patients with paroxysmal atrial fibrillation.Background. In hypertensive patients, left atrial dilation and enhanced volume transport may facilitate arrhythmias.Methods. Left ventricular two-dimensional and M-mode echocardiograms and pulsed Doppler echocardiography of transmitral flow were performed in 17 consecutive primary hypertensive patients with paroxysmal atrial fibrillation (group EHf) and in 34 patients with high blood pressure without this arrhythmia (group EH). Seventeen normal subjects (group N) were also investigated. Groups were matched for age and gender.Results. The EH and EHf groups had similar systolic arterial pressures ([mean ± SD] group EH 185 ± 27, group EHf 173 ± 25 mm Hg, p = NS) and left ventricular mass index (group EH 154 ± 55, group EHf 131 ± 57.8 g/m², p = NS), and their M-mode left ventricular systolic wall stress and fractional shortening were comparable to those of normal subjects. M-mode left atrial maximal (group N 37.8 ± 6, group EH 37.9 ± 4.6, group EHf 44.6 ± 6.7 mm, p < 0.05 for group EHf vs. groups N and EH) and minimal diameters and the diameter preceding atrial contraction (group N 31 ± 3.6, group EH 34.5 ± 5, group EHf 40.4 ± 6.9 mm, p < 0.001 for group EHf vs. group N; p < 0.05 for group EHf vs. group EH) were greater in group EHf than in group EH and group N subjects, whereas only the latter diameter was increased in group EH (p < 0.05 vs. group N), so that left atrial fractional shortening was higher than normal only in group EH (group N 10.8 ± 4.4%, group EH 14.6 ± 5.5%, group EHf 9.3 ± 5.3%; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). The pulsed Doppler ratio of early to late transmitral flow rates (E and A wave velocity/time integrals × mitral annulus area) was lower than normal in group EH (group N 2.9 ± 2.2, group EH 1.75 ± 0.8, group EHf 2.8 ± 0.8; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.001; group EHf vs. group N, p = NS) and was “normalised” in group EHf, early flow being increased in this group (group N 42 ± 13, group EH 39 ± 29, group EHf 60 ± 17 ml; group EHf vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05).Conclusions. These results suggest that the occurrence of paroxysmal atrial fibrillation in hypertension is associated with enlargement of the left atrium, depression of its contractile function and “normalization” of the pattern of left ventricular filling and is independent of left ventricular hypertrophy and systolic wall stress. The mechanisms linking these variables remain undefined.     

Beneficial effect of amrinone on myocardial oxygen consumption during acute left ventricular failure in dogs

In 11 dogs ischemic left ventricular failure characterized by a 30 percent reduction In cardiac output and a left ventricular end-dlastolic pressure of 18 mm Hg or more was produced by proximal occlusion of the left anterior descending coronary artery followed by serial occlusions of the distal left circumflex coronary artery. Administration of amrlnone In an Intravenous bolus injection followed by a constant Infusion produced Improvements in cardiac output (from 1.62 ± 0.50 to 2.19 ± 0.52 Itters/min [mean ± standarddeviation], p <0.05), left ventricular end-dlastolic pressure (from 21.6 ± 3.5 to 11.0 ± 5.4 mm Hg, p <0.05) and peak positive rate of rise of left ventricular pressure [dP/dt](from 1,264 ± 241 to 1,800 ± 458 mm Hg·^?1, p <0.05). These Improvements were maintained throughout the 20 minute period of therapy. No significant alteration in heart rate or arterial pressure was noted. In parallel with the hemodynamic improvement myocardial oxygen consumption improved to 0.094 ± 0.05 and 0.092 ± 0.04 vol·^?1?^?1 after 2 and 20 minutes; respectively, of amrinone compared with 0.124 ± 0.05 during left ventricular failure (both <0.05). The effects of amrinone on left ventricular failure are due to augmented contractility and mild systemic vasodllatation. The reduction in myocardial oxygen consumption during amrlnone-treated left ventricular failure presumably results from a reduction in ventricular wall tension that more than offsets the effect of an Increase in contractility.     

Effects of transluminal coronary angioplasty on left ventricular systolic and diastolic function at rest and during exercise

The left ventricular global and regional systolic function, ventricular volumes, and peak diastolic filling rate (PDFR) were studied in 30 patients with coronary artery disease, before and 2 to 5 days after transluminal coronary angioplasty (PTCA), utilizing equilibrium radionuclide angiography at rest and during exercise. At rest, the global ejection fraction (EF) was unchanged before (60 ± 9%) and after PTCA (62 ± 10%). During exercise, global EF increased from 59 ± 11% pre PTCA to 67 ± 10 post PTCA (p < 0.001). Twenty-two patients had abnormal EF response to exercise pre PTCA, versus seven post PTCA (p < 0.001). Improvements in exercise regional EF paralleled the changes in global EF. End-systolic volume was unchanged at rest but decreased significantly with exercise post PTCA (60 ± 36 ml pre vs 49 ± 32 ml post PTCA, p < 0.01). At rest, the PDFR was unchanged post PTCA (2.4 ± 0.9 end-diastolic volume (EDV)/sec pre vs 2.5 ± 0.8 EDV/sec post). During exercise, PDFR increased from 2.1 ± 0.7 EDV/sec pre PTCA to 2.5 ± 0.7 EDV/sec post PTCA (p < 0.02). In conclusion, in patients with coronary artery disease, successful PTCA improves global and regional systolic function during exercise. Diastolic function is improved during exercise, a fact not previously demonstrated.     

Echocardiographic prediction of left ventricular function after correction of mitral regurgitation: Results and clinical implications

Objectives. This study attempted to determine the incidence, prognosis and predictability of postoperative left ventricular dysfunction in patients undergoing correction of mitral regurgitation.Background. Left ventricular fonction in patients with mitral regurgitation is altered by loading conditions and is difficult to assess. Predictive value of preoperative variables on postoperative left ventricular function and the role of echocardiography are uncertain.Methods. In 266 patients undergoing correction of mitral regurgitation between 1980 and 1989, left ventricular fonction was echocardiographically assessed preoperatively (within 6 months) and postoperatively (within 1 year).Results. After correction of mitral regurgitation, left ventricular ejection fraction decreased significantly ([mean ± SD] 50% ± 14% vs. 58% ± 13%, p < 0.0001). Postoperative left ventricular dysfunction (ejection fraction < 50%) was frequent (41% of patients) and carried a poor prognosis (at 8 years survival, 38% ± 9% vs. 69% ± 8%, p < 0.0001). Four preoperative echocardiographic variables showed good correlation with postoperative ejection fraction: preoperative ejection fraction (r = −0.70), systolic diameter (r = −0.63), diameter/thickness ratio (r = − 0.64) and end-systolic wall stress (r = −0.62) (all p < 0.0001). With multivariate analysis, ejection fraction (p = 0.0001) and systolic diameter (p = 0.0005) were independent predictors of postoperative ejection fraction, and angiographic variables provided no incremental predictive power. In addition to echocardiographic variables, recent regurgitation, functional class and coronary artery disease were also independent predictors of postoperative ejection fraction.Conclusions. After surgical correction of mitral regurgitation, left ventricular dysfunction is frequent and carries a poor prognosis. Postoperative ejection fraction can be predicted by echocardiographic preoperative ejection fraction and systolic diameter. Recent onset of regurgitation, mild or no symptoms, and absence of coronary artery disease are independent and favorable predictors of postoperative ejection fraction. These results should lead to consideration of surgical correction at an earlier stage.     

Prevalence of left ventricular hypertrophy in Type I diabetic patients with diabetic nephropathy

Summary The increased mortality of patients with diabetic nephropathy is mainly due to cardiovascular disease and end stage renal failure. Left ventricular hypertrophy is an independent risk factor for myocardial ischaemia and sudden death. The aim of our cross-sectional study was to evaluate left ventricular structure and function in Type I (insulin-dependent) diabetic patients with diabetic nephropathy. M-mode and Doppler echocardiography were done on 105 Type I diabetic patients with diabetic nephropathy [61 men, age (means ± SD) 44 ± 9 years, and albuminuria [median(range)] 567(10–8188) mg/24 h, serum creatinine 109 (53–558) μmol/l], and 140 Type I diabetic patients with persistent normoalbuminuria [79 men, 47 ± 10 years, urinary albumin excretion rate 8 (0–30) mg/24 h, and serum creatinine 81 (55–121) μmol/l]. Patients with and without nephropathy were comparable with respect to sex, body mass index, and duration of diabetes. Arterial blood pressure was slightly higher in patients with nephropathy: 140/79 ± 17/9 mm Hg vs 134/78 ± 15/8 mm Hg, p < 0.01, and the majority of proteinuric patients received antihypertensive drugs, 84 vs 17 %, respectively, p < 0.001. Left ventricular mass index was increased in the nephropathic group (means ± SD) 100.6 ± 23.9 g/m² compared with the normoalbuminuric group 91.4 ± 21.9 g/m², p = 0.002. Left ventricular hypertrophy was found more often in patients with nephropathy 23 (14–31)% compared with patients with normoalbuminuria 9 (5–14)%, p < 0.005. Diastolic function, assessed by the ratio between the peak diastolic velocity and the peak atrial systolic velocity (E/A ratio) and isovolumic relaxation time, was reduced in patients with vs without nephropathy: 1.17 ± 0.29 vs 1.34 ± 0.32, and 81.7 ± 16.5 vs 74.6 ± 14.5, p < 0.001 and p = 0.002, respectively. Systolic function was about the same and normal in both groups. Our study suggests that an increase in left ventricular mass index and a decrease in diastolic function occurs early in the course of diabetic nephropathy. [Diabetologia (1999) 42: 76–80] Received: 16 April 1998 and in final revised form: 5 August 1998     

Pulmonary versus systemic hemodynamics in determining exercise capacity of patients with chronic left ventricular failure

Right, but not left ventricular ejection fraction correlates with exercise capacity in patients with left ventricular failure, suggesting an important role of the pulmonary circulation. Hemodynamics were measured at rest and during bicycle exercise to symptomatic maximum in 41 patients with chronic left ventricular failure. Maximal oxygen consumption averaged only 12.8 ± 5.2 ml/min/kg. Pulmonary wedge pressure rose from 21.9 ± 8.2 to 35.9 ± 9.3 mm Hg during exercise, while pulmonary arterial mean pressure rose from 31.8 ± 10.9 to 50.4 ± 12.9 mm Hg (both p < 0.0001). Resting cardiac index and resting systemic arterial mean pressure did not correlate with maximal oxygen consumption (r = 0.23 and 0.20, respectively), which, however, did correlate with pulmonary wedge pressure (r = −0.54, p < 0.001). Maximal oxygen consumption did not correlate with resting systemic vascular resistance (r = −0.20) or resting pulmonary vascular resistance (r = −0.26). During exercise, total pulmonary resistance remained unchanged at 6.5 ± 3.8 U while systemic vascular resistance fell significantly. The relation between total pulmonary resistance and exericise capacity and the failure of total pulmonary resistance to fall during exercise suggest that afterload on the right ventricle may be an important determinant of exercise capacity in patients with chronic left ventricular failure.     

Ineffectiveness of sublingual nitroglycerin in acute left ventricular failure in the presence of massive peripheral edema

Although it has been postulated that peripheral edema may reduce venous compliance in patients with congestive heart failure, this possibility has not yet been Investigated. Sublingual nitroglycerin, 1.6 to 2.4 mg, was administered to 15 patients with acute left ventricular failure, including 8 patients without peripheral edema (group I) and 7 patients with massive peripheral edema (group II). Baseline hemodynamic variables were similar in the two groups. In group I, sublingual nitroglycerin decreased the left ventricular filling pressure from 28 ± 2 (mean ± 1 standard deviation) to 14 ± 3 mm Hg (p < 0.005), whereas cardiac output increased from 3.3 ± 0.4 to 4.3 ± 0.3 liters/min (p < 0.005) because of an increase in stroke volume. Right atrial pressure decreased from 28 ± 3 to 13 ± 3 mm Hg (p < 0.005). In group II, no significant hemodynamic changes were induced by nitroglycerin despite the elevated baseline left ventricular filling pressure of 30 ± 5 mm Hg and right atrial pressure of 29 ± 4 mm Hg. Five patients from group II were rechallenged with sublingual nitroglycerin 18 days after furosemide therapy, when the peripheral edema had cleared (6 kg weight loss). At this time there were significant decreases in left ventricular filling pressure (from 13 ± 2 to 9 ± 2 mm Hg; p < 0.025) and right atrial pressure (from 13 ± 1 to 9 ± 2 mm Hg; p < 0.005); cardiac output was not increased, probably because of the normal baseline left ventricular filling pressure. These results indicate that through various mechanisms massive peripheral edema decreases venous compliance and therefore prevents nitroglycerin from reducing preload.     

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.     

Left ventricular function in patients with coronary heart disease in the presence or absence of angina pectoris during exercise radionuclide ventriculography

This study compares left ventricular (LV) performance during exercise in patients with angiographically documented coronary artery disease (CAD) based on the presence or absence of angina pectoris during the index exercise tests. The patients were divided into 2 groups: Group I included 31 patients who had angina pectoris during the test and Group II included 43 who did not. Multivessel CAD was present in 21 patients (68%) in Group I and 26 patients (60%) in Group II (difference not significant [NS]). There were no significant differences between the 2 groups in age, sex, history of diabetes mellitus, history of myocardial infarction and in the exercise duration, work load, heart rate and systolic blood pressure. Exercise-induced ST-segment depression was present in 48% of the patients in Group I and in 40% in Group II (NS). The mean LV ejection fraction at rest was 52 ± 12% in Group I and 50 ± 17% in Group II (NS). There were significant differences in the 2 groups in the change from rest to exercise in ejection fraction (?4.5 ± 7.6% in Group I vs 1 ± 9.4% in Group II, p < 0.01), end-systolic volume (29 ± 38 ml in Group I vs 9 ± 23 ml in Group II, p < 0.005), the change in systolic blood pressure-to-end-systolic volume ratio (?0.1 ± 0.5 mm Hg/ml in Group I vs 0.3 ± 1.1 mm Hg/ml in Group II, p < 0.05), and wall motion score (?0.4 ± 0.6 in Group I vs 0.09 ± 0.7 in Group II, p < 0.05).Thus, asymptomatic myocardial ischemia may occur in patients with extensive CAD and be associated with abnormal exercise LV function; however, patients with symptomatic CAD have worse exercise LV function than those with asymptomatic CAD.     

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

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

Effect of nifedipine on exercise-induced left ventricular dysfunction and myocardial hypoperfusion in stable angina

To assess the effects of nifedipine on left ventricular function and regional myocardial perfusion, exercise radionuclide ventriculography was performed in 15 men (median age 59 years) and exercise thallium-201 scintigraphy was done in 11 of them, before and 90 minutes after the oral administration of 20 mg of nifedipine. All patients had stable angina and angiographically proved coronary artery disease without evidence of spasm. Exercise tolerance after administration of nifedipine increased from 343 ± 42 seconds to 471 ± 50 seconds (p < 0.01), whereas the peak exercise double product remained essentially unchanged (difference not significant). Ejection fraction improved significantly at rest (from 49 ± 3.6% to 52 ± 3.3%, p < 0.05) and at peak exercise (42 ± 3.3% to 47 ± 3.7%, p < 0.05). Nifedipine also resulted in an improved segmental wall motion score (4.3 ± 2.3 to 3.0 ± 2.3, p < 0.05; 0 = normal and 4 = worst degree of dysfunction). The ejection fraction increased by more than 5% in one third of the patients at rest, and in more than half of the patients at peak exercise. Improved exercise myocardial perfusion occurred in 5 of 11 patients (45%) and in 7 of 28 segments (25%) with reversible hypoperfusion. Thus, nifedipine produces significant improvement in global and regional left ventricular function in patients with coronary artery disease and stable angina. This may be accounted for, at least in part, by improvement in myocardial perfusion.     

Hemodynamic and metabolic effects of diltiazem during coronary sinus pacing with particular reference to left ventricular ejection fraction

To determine the systemic and coronary hemodynamic effects of diltiazem at rest and during pacing, 14 patients with stable angina pectoris undergoing coronary angiography were studied before and after 0.165 mg/kg (n = 7) and 0.25 mg/kg (n = 7) of intravenously administered diltiazem. Hemodynamic variables, metabolic measurements and left ventricular (LV) ejection fraction (EF) were obtained at rest and during coronary sinus (CS) pacing before and during diltiazem administration. Lactate production during control pacing turned into extraction after diltiazem (p < 0.05). At rest, systemic resistance was reduced by 21% (p > 0.01) and mean arterial pressure by 12% (p < 0.01); cardiac index increased from 2.4 ± 0.4 to 2.6 ± 0.4 liters/min/m² (p < 0.01), with no significant change in heart rate. The mean pulmonary artery pressure increased from 17 ± 2 to 19 ± 3 mm Hg (p < 0.01), but other hemodynamic variables were not affected. Diltiazem given during pacing reduced the mean aortic pressure (from 112 ± 15 to 104 ± 15 mm Hg, p < 0.05), but other hemodynamic variables were not affected significantly. LVEF decreased 16%, from 0.63 ± 0.9 to 0.53 ± 0.8 with CS pacing (p < 0.01); when the pacing was performed after diltiazem administration the 8% decrease in LVEF from 0.64 ± 0.09 to 0.59 ± 13 was less marked (p < 0.01). Diltiazem had no significant effect on LVEF at rest. The overall data suggest that the ischemic manifestations of CS pacing are attenuated by diltiazem in doses of the drug that exert no significant depressant effect on LV function in patients with coronary artery disease.     

Improvement of left ventricular function after percutaneous transluminal coronary angioplasty

Cardiac function and left ventricular dynamics were measured in seven consecutive patients 1 day before and 6 months after percutaneous transluminal balloon angioplasty of subtotal proximal stenosis of the left anterior descending coronary artery. Before angioplasty all patients had obvious left ventricular dysfunction during exercise and to a smaller degree during isoproterenol infusion; the condition of all patients was greatly improved 6 months after angioplasty. After angioplasty, left ventricular end-diastolic pressure was normal at rest and decreased from a mean (± standard error of the mean) of 33.8 ± 1.6 to 19.2 ± 0.5 mm Hg on exercise. Left ventricular ejection fraction, measured by a gated blood pooling technique with technetium-99m, improved on exercise from 46 ± 5.0 percent to 69 ± 1.0 percent. Cardiac output and stroke volume index increased significantly with exercise after angioplasty. The peak negative rate of pressure reduction in the left ventricle (dP/dt/min), an index of left ventricular relaxation, was highly abnormal on exercise before (2,307 ± 260 mm Hg/s) and increased to the normal range (3,154 ± 200 mm Hg/s) after angioplasty. The improvement in left ventricular function after transluminal angioplasty in these cases of proximal left anterior descending coronary arterial stenosis is extremely encouraging.     

Effect of nitrates on left ventricular size and function during exercise: Comparison of sublingual nitroglycerin and nitroglycerin paste

To compare the effects of sublingual nitroglycerin and nitroglycerin paste on left ventricular size and performance during supine bicycle exercise, equilibrium radionuclide angiography was performed in 36 persons classified into two groups of normal subjects and two groups of patients with angiographically proved coronary heart disease. Each group underwent a control exercise study, and then one group of normal subjects and one group of patients were restudied after the administration of 0.6 mg of nitroglycerin or 2 inches (5 cm) of nitroglycerin paste (but not both). Data were collected at rest and at peak exercise.In normal subjects exercise resulted in increased ejection fraction, decreased end-systolic volume and little change in end-diastolic volume. After either drug, volumes at rest markedly decreased, and during exercise, ejection fraction increased to levels comparable with pre-drug levels. After nitroglycerin paste the reduction in volume seen at rest persisted during exercise, but after sublingual nitroglycerin end-diastolic volume increased during exercise (88 ± 43 to 113 ± 30 ml [mean ± standard deviation]; p < 0.01). Peak exercise end-diastolic volume after nitroglycerin was still lower than that before nitroglycerin (113 ± 30 versus 120 ± 28 ml, p < 0.05).In patients with coronary disease, ejection fraction did not change during exercise, but both end-diastolic and end-systolic volumes increased. After either drug ejection fraction at rest was unchanged, although ventricular volumes were markedly lower (p < 0.05). Ejection fraction increased with exercise in both groups with coronary disease after either drug. After sublingual nitroglycerin, volumes increased during exercise although the peak exercise end-diastolic volume was still lower than the control value (113 ± 31 versus 145 ± 34 ml; p < 0.01). After paste administration, end-diastolic volume did not change during exercise, and end-systolic volume decreased (41 ± 20 to 36 ± 22 ml; p < 0.05).Thus, sublingual nitroglycerin and nitroglycerin paste improved left ventricular function during exercise. The effect of paste on end-diastolic volume appeared sustained, whereas that of sublingual nitroglycerin was transient, confirming the hypothesis that reduction in end-diastolic volume and, by implication, left ventricular wall tension, is a major mechanism of nitrate action.     

Isolated stenosis of left anterior descending or right coronary artery: Relation between site of stenosis and ventricular dysfunction and therapeutic implications

Indications for coronary arterial bypass surgery in single vessel coronary artery disease are unresolved. To determine the extent of myocardium at risk with stenosis (70 percent or more) of a single coronary artery, left ventricular angiograms of 200 patients with stenosis confined to either the left anterior descending or right coronary artery and of 15 normal control subjects were assessed. Among patients without myocardial infarction, ejection fraction was unchanged (p > 0.05 versus normal values) in (1) those with stenosis of the proximal (above first septal branch, n = 19), mid (between septal and first diagonal branches, n = 14) and distal (within 2 cm distal to diagonal branch, n = 15) left anterior descending coronary artery, and (2) those with stenosis of the proximal (above acute marginal branch, n = 16) and distal (between acute marginal and posterior descending branches, n = 16) right coronary artery. In contrast, ejection fraction was depressed (p < 0.001 versus normal values) In left anterior descending arterial stenosis with anterior myocardial Infarction: proximal (38 ± 10 percent, n = 33), mid (46 ± 12 percent, n = 24; p < 0.01 versus proximal), and distal (56 ± 9 percent, n = 15; p < 0.01 versus mid). Ejection fraction was similar with proximal and distal stenosis of the right coronary artery and inferior Infarction: 54 ± 11 percent versus 55 ± 9 percent, p > 0.05; both p < 0.05 versus normal value. Shortening velocity was assessed in three anterior (I to III, base to apex) and three inferior (IV to VI, apex to base) equidistant hemichords perpendicular to the long axis, 30 ° right anterior oblique view. With anterior Infarction and left anterior descending stenosis, shortening of hemichords I to V, I to IV and II to III with proximal, mid and distal stenosis, respectively, was depressed (p < 0.05 versus normal value). Septal excursion and thickening on M mode echocardiography with proximal left anterior descending stenosis and infarction were depressed (p < 0.05 versus mid and distal stenosis with infarcts). Hemichordal shortening with Inferior infarction was similarly depressed (p > 0.05) with proximal and distal stenoses.In conclusion, stenosis of the left anterior descending coronary artery is a heterogenous disease, the extent of jeopardized myocardium is highly dependent on the site of stenosis, and the criteria for surgery cannot be applied uniformly. When the surgical goal is myocardial preservation, these data provide an objective rationale for bypass of stenosis of the proximal left anterior descending coronary artery. In stenosis confined to the right coronary artery, left ventricular preservation alone should not be considered an indication for coronary bypass grafting.     

The influence of age and gender on left ventricular response to supine exercise in asymptomatic normal subjects

The performance of normal subjects during radionuclide ventriculography has been related to age, but the combined effects of age and sex on exercise ventricular function are not well described. We studied 55 normal volunteers, 27 men (age = 30 ± 10 years) and 28 women (age = 33 ± 14 years), free of chest pain syndromes, during supine rest/exercise radionuclide ventriculography performed to fatigue. Resting left ventricular ejection fraction did not differ between male and female subjects (64 ± 5.4 vs 64 ± 6.1; p = NS). Both the peak left ventricular ejection fraction (78 ± 4.4 vs 72 ± 9.2; p < 0.001) and the change in ejection fraction with exercise (14 ± 4.0 vs 7.9 ± 7.0; p < 0.001) were significantly greater in men compared to respective values in women. Regression analysis showed that sex (r = 0.51; p < 0.001) but not age (r = −0.18; p = 0.19) was a significant predictor of change in ejection fraction with exercise. Data on left ventricular volume response to exercise, available in 43 subjects, revealed that men had a greater percentage of decline in end-systolic volume with exercise than women (−47 ± 15 vs −24 ± 26; p < 0.001). It is concluded that sex exerts a significant influence on normal left ventricular response to fatigue-limited supine exercise and that the gender difference is mediated, in part, by left ventricular end-systolic volume response to exercise.