Size dependence of the end-systolic stress/volume ratio in humans: implications for the evaluation of myocardial contractile performance in pressure and volume overload.

The end-systolic stress/volume ratio is currently recognized as a relatively load-independent index of myocardial contractile performance, but its dependence on ventricular size may limit its value for interpatient comparisons. In this study, the relation between the end-systolic stress/volume ratio and left ventricular end-diastolic volume was angiographically analyzed in 104 patients with normal coronary angiograms. Eighteen patients had a normal ventricle, 24 had aortic stenosis, 18 had aortic regurgitation, 9 had mitral regurgitation and 35 had cardiomyopathy. An inverse relation between the end-systolic stress/volume ratio and left ventricular end-diastolic volume was demonstrated in the normal group (r = 0.72, p less than 0.001); subjects with a larger left ventricle had a reduced index but, presumably, the same degree of contractility as that of subjects with a smaller ventricle. Attempts to normalize values by using end-diastolic volume or body surface area were unsuccessful. A similar inverse relation was demonstrated in the aortic stenosis group (r = 0.48, p less than 0.05), probably because hypertrophy helps to keep wall stress normal or low despite progressive ventricular enlargement in these patients. The end-systolic stress/volume ratio was also inversely related to left ventricular chamber size in patients with volume overload due to aortic regurgitation (r = 0.80, p less than 0.001) and in those with cardiomyopathy (r = 0.84, p less than 0.001). However, at a given left ventricular end-diastolic volume, the end-systolic stress/volume ratio was higher in patients with aortic regurgitation than in those with cardiomyopathy, suggesting better contractile performance for a comparable degree of ventricular dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasodilator reserve in untreated and treated hypertensive patients with and without left ventricular hypertrophy.

OBJECTIVES: This study was initiated to compare the coronary reserve in treated hypertensive patients with and without left ventricular hypertrophy with that in untreated patients. BACKGROUND: Coronary reserve is impaired in hypertensive patients with left ventricular hypertrophy and normal coronary arteries. Moreover, basal coronary resistance is elevated in hypertensive patients without left ventricular hypertrophy. METHODS: Coronary reserve was measured with a coronary Doppler catheter before and after a maximally vasodilating dose of intracoronary papaverine (peak/rest flow velocity ratio) in 16 control subjects and 37 hypertensive patients with normal epicardial coronary arteries. Among 20 untreated hypertensive patients, myocardial mass was increased in 11 (group 2a) and normal in 9 (group 2b). Seventeen patients had been treated effectively for at least 1 year; nine (group 3a) had persistent left ventricular hypertrophy, and eight (group 3b) had no left ventricular hypertrophy before treatment. Left ventricular volumes and ejection fraction were normal in all groups. RESULTS: Coronary reserve was moderately reduced in group 2b (3.5 +/- 0.6 vs. 5.2 +/- 0.8 in control subjects, p < 0.001) and markedly diminished in groups 2a and 3a (2.5 +/- 0.5 and 2.7 +/- 0.4, respectively; all p < 0.001 vs. control subjects). In group 3b, coronary reserve was comparable to that of control subjects (5.1 +/- 1.4). CONCLUSIONS: The reduction in coronary reserve observed in untreated hypertensive patients with normal myocardial mass suggests that structural abnormalities of the coronary microvasculature may occur before left ventricular hypertrophy. Treated patients with normal mass before treatment had a coronary reserve comparable to that of normotensive control subjects, whereas normalization of arterial pressure with persistent left ventricular hypertrophy was associated with a marked impairment of coronary reserve.

Coronary flow and resistance reserve in patients with chronic aortic regurgitation, angina pectoris and normal coronary arteries.

Left ventricular hypertrophy has been found to be associated with a reduction of coronary vascular reserve, which could be responsible for episodes of myocardial ischemia. To evaluate coronary flow and resistance reserve in patients with chronic aortic regurgitation, coronary sinus blood flow and coronary resistance were measured before and after an intravenous dipyridamole infusion (0.14 mg/kg per min X 4 min) in eight control subjects and eight patients with aortic regurgitation, exertional angina pectoris and normal coronary arteriograms. Coronary flow reserve, evaluated by the dipyridamole/basal coronary sinus blood flow ratio, and coronary resistance reserve, evaluated by the basal/dipyridamole coronary resistance ratio, were both significantly reduced in patients with aortic regurgitation (1.67 +/- 0.40 versus 4.03 +/- 0.52 in control subjects, p less than 0.001 and 1.71 +/- 0.50 versus 4.38 +/- 0.88 in control subjects, p less than 0.001, respectively). In patients with aortic regurgitation, basal coronary sinus blood flow was higher than in control subjects (276 +/- 81 versus 105 +/- 24 ml/min, respectively, p less than 0.001) and basal coronary resistance was lower (0.31 +/- 0.13 versus 0.95 +/- 0.17 mm Hg/ml per min, respectively, p less than 0.001), but coronary blood flow and resistance after dipyridamole were not significantly different in the two groups (461 +/- 159 versus 418 +/- 98 ml/min in control subjects, 0.19 +/- 0.11 versus 0.22 +/- 0.04 mm Hg/ml per min in control subjects, respectively). These data demonstrate that coronary reserve is severely reduced in patients with chronic aortic regurgitation and exertional angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine-induced coronary vasoconstriction in young, heavy smokers with normal coronary arteriographic findings.

PURPOSE: Cigarette smoking is a major coronary risk factor. Acetylcholine dilates coronary arteries in normal subjects, but acetylcholine-induced coronary constriction has been reported in patients with normal coronary arteriographic findings and other risk factors for coronary artery disease. The purpose of the present study was to evaluate the epicardial coronary artery response to acetylcholine in young, heavy smokers. SUBJECTS AND METHODS: Responses to stepwise infusion of acetylcholine (10(-8)M, 10(-7)M, 10(-6)M, and 10(-5)M) into the left coronary artery were studied in five young, heavy smokers and in five age-matched nonsmokers. All subjects were normotensive and had normal left ventricular function and coronary arteriographic findings. Levels of serum cholesterol, triglycerides, and low-density lipoprotein levels were within normal ranges. Vessel dimensions were measured on four different segments in each subject, with quantitative digital-substracted arteriography. RESULTS: In smokers, no change was produced at the 10(-8) M and 10(-7) M concentrations of acetylcholine, but progressive diameter reduction was observed at 10(-6) M and 10(-5) M acetylcholine (-26.6% +/- 13.6%, p < 0.001; -42.2% +/- 9.5%, p < 0.001, respectively). In nonsmokers, a progressive diameter dilation was produced from 10(-8) M to 10(-6) M acetylcholine (+5.3% +/- 3.6%, p < 0.001; +12.4% +/- 6.5%, p < 0.001; +15.9% +/- 6.9%, p < 0.001, respectively), and no change was observed at 10(-5) M acetylcholine. In the two groups, all segments dilated after infusion of intracoronary isosorbide dinitrate. CONCLUSION: The abnormal coronary vasoconstriction induced by acetylcholine in young, heavy smokers with angiographically normal coronary arteries suggests an endothelial vasodilator dysfunction. This mechanism may contribute to the pathogenesis of coronary artery disease in cigarette smokers.

Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis.

PURPOSE: In order to clarify the significance of anginal pain and myocardial thallium-201 scan defects in cardiac sarcoidosis, the pharmacologic effect of dipyridamole on myocardial perfusion was assessed by planar thallium-201 myocardial scintigraphy in patients with sarcoidosis. PATIENTS AND METHODS: Thallium-201 myocardial scintigraphy was performed at rest and after 0.56 mg/kg intravenous dipyridamole during four minutes in 16 patients with sarcoidosis. The myocardial scan (45-degree and 70-degree left anterior oblique, and anterior views) was divided into 15 segments. Results were evaluated by the number of segmental defects and with a global perfusion score (from 0 to 60) by a semi-quantitative index depending on the size and severity of myocardial thallium-201 defects. RESULTS: Thirteen of the 16 patients showed partial or total reversion of their thallium-201 defects on redistribution scanning either at rest or after dipyridamole. The mean (+/- SD) number of myocardial perfusion defects that were present in all the patients decreased from 5.31 +/- 1.78 at rest to 3.25 +/- 2.52 after redistribution (p less than 0.001) and to 2.19 +/- 2.10 after dipyridamole (p less than 0.001). The mean global perfusion score increased from 53.2 +/- 3.0 at rest to 56.2 +/- 2.9 after redistribution (p less than 0.001) and to 57.2 +/- 2.7 after dipyridamole (p less than 0.001). A significant correlation (r = 0.82, p less than 0.001) was found between the increase of global perfusion score on redistribution and after dipyridamole. CONCLUSION: The reversibility of myocardial scan defects is a common finding in sarcoidosis. It makes unlikely the role of scar fibrosis or extensive confluent granulomas as a mechanism for such defects. The effect of dipyridamole suggests the presence of reversible disorders lying at the coronary microvascular level.

Multifactorial determinants of reduced coronary flow reserve after dipyridamole in dilated cardiomyopathy.

Coronary sinus blood flow (ml/100 g left ventricular [LV] mass/min) and coronary resistance (mean aortic minus LV mean diastolic pressures/coronary sinus blood flow, mm Hg/[ml/100 g/min]) were studied in 7 control patients and in 11 patients with severe dilated cardiomyopathy (DC) and normal coronary arteriograms. Basal coronary sinus blood flow was not different in the 2 groups. After intravenous administration of dipyridamole (0.14 mg/kg/min X 4 min), coronary sinus blood flow and dipyridamole/basal coronary sinus blood flow ratio were significantly (p less than 0.001) lower in the DC group than in the normal group (coronary sinus blood flow 188 +/- 48 vs 408 +/- 58, respectively; blood flow ratio 1.78 +/- 0.35 vs 4.01 +/- 0.56, respectively), and the coronary resistance was higher in the DC group than in the control group (0.39 +/- 0.15 vs 0.22 +/- 0.03, respectively, p less than 0.01). After administration of dipyridamole in patients with DC, no correlation could be found between coronary sinus blood flow and LV mean diastolic, mean aortic or coronary driving pressures, i.e., mean aortic minus LV mean diastolic pressures. Thus, in DC patients, neither an elevated LV diastolic pressure nor a low coronary perfusion pressure can totally account for the restriction of the coronary flow reserve after dipyridamole.

Maximal coronary vasodilator capacity of orthotopic heart transplants in patients with and without rejection.

In cardiac allograft rejection, histopathologic changes suggesting that myocardial ischemia is a component of the rejection process have been documented. To further define the coronary vascular reactivity of human heart transplant, coronary sinus blood flow and coronary resistance were measured before and after intravenous dipyridamole within the first year after transplantation in 8 patients without rejection (group II) and in 5 patients with rejection (group III). All had normal coronary arteriograms. Results were compared to those of 8 control subjects (group I). After dipyridamole, coronary sinus blood flow was increased in groups I, II and III by 303, 212 (p less than 0.01 vs group I) and 45%, respectively (p less than 0.001 vs groups I and II). Coronary resistance was reduced by 77, 73 (not significant vs group I) and 36%, respectively (p less than 0.001 vs groups I and II). Concomitantly, coronary sinus blood oxygen content was increased by 172, 145 (not significant vs group I) and 78%, respectively (p less than 0.001 vs group I, not significant vs group II). Thus, the coronary flow reserve evaluated by the dipyridamole/basal coronary sinus blood flow ratio and the coronary resistance reserve evaluated by the basal/dipyridamole coronary resistance ratio were dramatically impaired in group III (1.56 +/- 0.09 and 1.63 +/- 0.30, respectively, p less than 0.001 vs groups I and II). In contrast, they were almost normal in group II (3.11 +/- 0.42 vs 4.03 +/- 0.52 in group I, p less than 0.02, and 3.83 +/- 0.78 vs 4.45 +/- 0.81 in group I, difference not significant). Thus, the impairment of coronary reserve during heart rejection should be linked to abnormalities of the coronary microvaculature. This emphasizes the important involvement of the coronary circulation in the rejection process.

Comparison of left ventricular responses to the six-minute walk test, stair climbing, and maximal upright bicycle exercise in patients with congestive heart failure due to idiopathic dilated cardiomyopathy.

Submaximal exercise tests have been advocated to assess exercise capacity in chronic heart failure, but hemodynamic responses have not been characterized. To determine left ventricular (LV) responses during submaximal exercise, the LV ejection fraction (EF) and volumes were evaluated by using an ambulatory radionuclide detector in 13 patients with idiopathic dilated cardiomyopathy during upright maximal graded bicycle exercise, stair climbing and a 6-minute walk test. The 3 tests elicited different responses in volumes and, to a lesser degree, in LVEF. The maximal bicycle exercise led to a decrease in LVEF from 22 +/- 9% to 17 +/- 8% (p <0.05), with marked increases in both end-diastolic volume (EDV) (+15 +/- 10%, p <0.001) and end-systolic volume (ESV) (+23 +/- 18%, p <0.001). Stair climbing tended to reduce LVEF (from 24 +/- 11% to 21 +/- 10%, p = 0.05), with a lesser increase in volumes, which was more marked for ESV (+8 +/- 9%, p <0.01) than for EDV (+4 +/- 4%, p <0.01). The 6-minute walk test did not significantly change LVEF (23 +/- 10% vs 22 +/- 10%), but increased both EDV (+10 +/- 6%, p <0.001) and ESV (+8 +/- 8%, p <0.01) moderately and proportionally. Exercise capacity indexes (peak oxygen consumption, maximal bicycle work rate, stair climbing time, and the distance covered during the 6-minute walk test) correlated significantly with one another. There was no correlation between submaximal exercise tolerance indexes and resting or exercise LVEF. This study shows that (1) LVEF changes are inadequate to report on LV volume changes during exercise; (2) the 3 tests induce different LV volume changes; (3) the 6-minute walk test induces significant changes in LV volumes but no change in LVEF.

Nonlimited exercise test combined with high-dose dipyridamole for thallium-201 myocardial single-photon emission computed tomography in coronary artery disease.

Clinical, electrocardiographic, and thallium-201 single-photon emission computed tomography data were evaluated in 397 consecutive patients divided into 3 groups according to coronary hyperemic stimulation: 186 patients (group I; Ex) had maximal symptom-limited exercise ergometric stress testing, 93 patients (group II; Dip) had intravenous dipyridamole (0.7 to 0.8 mg/kg) stress testing, and 118 patients (group III; Dip+Ex) had dipyridamole (0.7 to 0.8 mg/kg) plus nonlimited (i.e., symptom-limited) exercise stress testing, achieving a maximal workload (mean +/- SD) of 102 +/- 37 W. Clinical tolerance was higher in Ex than in Dip groups (p < 0.01), and tended to be higher in Dip+Ex than in Dip groups (p = NS). Image quality--as judged by signal-to-noise ratios--was superior in Ex and Dip+Ex groups when compared with the Dip group (p < 0.01). Chest pain and electrocardiographic positivity were more frequent in the Dip+Ex group than in the Dip group (p < 0.05), despite more extensive coronary artery disease (CAD) in the Dip group; and reversible scintigraphic defects were more frequent in Dip+Ex versus Dip (p < 0.01) and in Ex versus Dip groups (p < 0.05) in patients with established CAD, as well as for the whole group. We conclude that, in patients unable to achieve 85% of their maximal predicted heart rate, the combination of high-dose dipyridamole plus nonlimited exercise stress testing is superior to dipyridamole stress testing alone, and comparable to maximal exercise testing.

[Coronary reserve: a dynamic evaluation of coronary circulation]. / La réserve coronaire: une évaluation dynamique de la circulation coronaire.

Measuring the coronary reserve is a way of evaluating pathologies of the large coronary vessels as well as of coronary microcirculation. In man, measurement of the coronary sinus blood flow by the thermodilution method can be used to determine the increase in flow induced by selective injection of a contrast medium into the left coronary artery or by intravenous injection of dipyridamole. Such measurements have been performed in subjects with normal coronary blood flow and left ventricular function, in patients with cardiac or systemic diseases likely to alter coronary perfusion (e.g. atheromatous coronary disease, dilated cardiomyopathy, scleroderma, sarcoidosis) and in patients who had undergone heart transplantation. Flow and resistance reserves have been calculated from the maximal/basal coronary flows ratio and from the minimal/basal coronary resistance ratio. The results obtained provided information on the repercussions of coronary stenosis on myocardial perfusion and on alterations of coronary microcirculation in pathologies respecting the main coronary arteries. In addition, changes in coronary reserve induced by some pharmacological agents may be used to evaluate the effects of certain cardiovascular therapies.

[Coronary vasoconstriction induced by acetylcholine in young smokers with normal angiographic coronary vessels]. / Vasoconstriction coronaire induite par l'acétylcholine chez les jeunes fumeurs à coronaires angiographiquement normales.

UNLABELLED: Cigarette smoking is a major risk of coronary artery disease. Acetylcholine-induced coronary artery constriction has been reported in patients with normal coronary arteries and other risk factors. To evaluate coronary artery endothelial function in smokers, coronary artery responses to acetylcholine (10(-8) M to 10(-5) M) were analyzed by quantitative angiography in 5 young heavy-smokers and in 5 age-matched nonsmokers. All patients were normotensive, had normal left ventricular function and coronary arteries. Cholesterol, triglycerides, high- and low-density lipoproteins were within normal range. Vessel dimensions were measured on 4 segments of left coronary artery in all patients. In smokers, no change was produced at 10(-8) M and 10(-7) M acetylcholine concentration, but progressive diameter reduction was observed at 10(-6) M and 10(-5) M acetylcholine concentration. In nonsmokers, a dose-dependent dilation was produced from 10(-8) M to 10(-6) M acetylcholine concentration. No change was observed at 10(-5) M acetylcholine concentration. In the 2 groups, all segments dilated similarly after intracoronary isosorbide dinitrate. CONCLUSION: This study reveals that in heavy-smokers the response of normal coronary arteries to acetylcholine is altered. Thus, endothelial dysfunction may be an early marker for coronary events in cigarette smokers.

[Coronary reserve in treated hypertension with persistent left ventricular hypertrophy]. / Réserve coronaire dans l'hypertension artérielle traitée avec hypertrophie ventriculaire gauche persistante.

UNLABELLED: It has been demonstrated that coronary reserve (CR) is impaired in hypertensive patients with left ventricular hypertrophy and normal epicardial coronary arteries. The present study was undertaken in order to determine if CR returns to normal level after antihypertensive therapy in patients with persistent left ventricular hypertrophy, when the decrease of arterial blood pressure induces a reduction of LV wall stress (LVWS). In 26 patients with normal coronary arteriography, end-diastolic wall thickness (EDWT), LV mass (LVM) and peak systolic LVWS were determined on 30 degrees right anterior oblique LV angiography with simultaneous recording of LV pressure (micromanometer). Coronary flow velocity was measured with a coronary doppler catheter before and after a maximally vasodilating dose of intracoronary papaverine (12 mg). The study group included 6 untreated (G1) and 7 treated (G2) hypertensive patients with LV hypertrophy, and 13 control subjects (C). The peak-to-resting coronary flow velocity ratio (P/R) and a minimal coronary vascular resistance index (MCVRI) calculated as the quotient of mean aortic pressure at peak flow velocity to peak flow velocity and mean aortic pressure at resting flow velocity to resting flow velocity were assessed. Results evidenced that in hypertensive patients with LV hypertrophy, levels of P/R and MCVRI were similar in treated and untreated groups. Thus, in treated patients P/R remained lower and MCVRI remained higher than in control subjects despite the normalization of arterial pressure that resulted in a low peak systolic LVWS. [table: see text] CONCLUSION: this study demonstrates that anti-hypertensive therapy does not restore a normal coronary vascular reserve in patients with persistent LV hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Restoring normal coronary reserve in treated hypertension without left ventricular hypertrophy]. / Restauration d'une réserve coronaire normale dans l'hypertension artérielle traitée sans hypertrophie ventriculaire gauche.

UNLABELLED: It has been previously demonstrated that coronary vascular reserve (CVR) was severely impaired in hypertensive patients with left ventricular hypertrophy (LVH), even after anti-hypertensive therapy. To assess if CVR was similarly depressed in hypertensive patients without LVH, peak-to-resting coronary flow velocity ratio (P/R) and a minimal coronary vascular resistance index (MCVRI) were determined with a coronary Doppler catheter placed into the left anterior descending coronary artery and maximally vasodilating dose of intracoronary papaverine (12 mg) in 16 control subjects (C), 7 untreated hypertensives without LVH (G1), and 7 hypertensives without LVH treated for at least one year (G2). All subjects and patients had normal left ventricular angiography and coronary arteriography. Left ventricular and aortic pressures, rate-pressure-product (RPP) were significantly elevated in G1 and were similar to those of control subjects in G2. Results evidenced that P/R was reduced and that MCVRI was increased in G1. However, these alterations were moderate. In G2, these two indices were similar to those of control subjects: [table: see text] CONCLUSIONS: These results suggest: 1) that alterations of coronary microcirculation occur before left ventricular hypertrophy in hypertensive patients; 2) that anti-hypertensive therapy may restore a normal coronary vascular reserve in hypertensive patients without LVH, when coronary vascular reserve remained severely impaired despite normalization of arterial pressure in patients with persistent LVH.

[Analysis of the complications of coronarography. Apropos of a series of 2,300 consecutive tests]. / Analyse des complications de la coronarographie. A propos d'une série de 2,300 examens consécutifs.

The coronarographic risk is 3 deaths per thousand and 2 non-fatal complications per cent. Fatal cases are always related to severe coronary lesions, particularly stenosis of main trunk. Their incidence is equivalent during catheterization by the humeral or femoral routes whereas local complications are more frequent by the humeral approach. In the series of 2,300 successive coronarography examinations reported there were less than 4 deaths per thousand and 1.82 complications per cent. Four factors contribute to the reduction in high risk coronarography mortality when the following protocol is used. First, routine coronary opacification at start of investigations after determination of left ventricular pressures allowing, in patients with very severe coronary lesions and/or markedly altered left ventricular function, the ventriculography to be postponed until the following day or even cancelled. Second, use of a new contrast medium of lower osmolarity possessing advantages over older products. Third, and principally, institution of a very strict pre- and per-coronarography drug protocol, controlled use of an intraaortic diastolic counter-current balloon, and notably placed in position during examination in patients with very pronounced stenosis of main trunk. In these cases the arterial desilet is left in place for 24 hours after examination to delay vagal reflex provoked by compression and to allow urgent insertion if necessary of an intra-aortic diastolic counter-current balloon catheter. Fourth, use of Diltiazem intracoronary in case of major spasm and Streptokinase and possible metallic guide to obtain repermeability of a thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Myocardial thallium scintigraphy after administration of dipyridamole. Application to the diagnosis and evaluation of coronary insufficiency]. / Scintigraphie myocardique au thallium après administration de dipyridamole. Application au diagnostic et à l'évaluation de l'insuffisance coronaire.

Myocardial thallium scintigraphy performed after intravenous injection of dipyridamole is a non-invasive method to diagnose and evaluate coronary disease. It can be used as an alternative to postexercise scintigraphy, both methods having similar sensitivity and specificity. The dipyridamole test is contraindicated in patients with a history of bronchospasm and uncontrolled angina pectoris. Close clinical and electrocardiographic monitoring is required. The wide use of tomographic techniques has notably improved this examination.

[Coronary vascular reserve in heart transplantation. Normalization after therapy for rejection]. / Réserve vasculaire coronaire dans la transplantation cardiaque. Normalisation après traitement du rejet.

Acute rejection is associated with severe impairment of coronary reserve in heart transplants. To evaluate the effects of rejection therapy, coronary reserve was assessed in 6 patients before and after treatment of an acute episode of rejection. Coronary reserve was significantly enhanced after rejection therapy (4.7 +/- 0.8, vs 2.3 +/- 0.5, P less than 0.001) and was not significantly different from that of transplanted patients without rejection (5.4 +/- 0.8). This study provides evidence that alterations of coronary reserve due to acute rejection are reversible after treatment of the rejection episode.