[Why Coronary CTA will affect the diagnosis and management of stable coronary artery disease?]. / Pourquoi l'angioscanner va transformer les habitudes dans le diagnostic et la prise en charge de la maladie coronaire stable?

Until recently, the optimal work-up of patients with stable coronary artery disease (CAD) was based on non-invasive functional tests. Coronary CTA (CCTA) now challenges this standard work-up due to its efficacy to exclude significant coronary artery disease. Current indications for CCTA include symptomatic patients with intermediate pre-test probability of CAD with altered ECG (LBBB, repolarization abnormalities) rendering stress tests useless or patients unable to achieve sustained stress effort, and patients with indeterminate or uninterpretable results on ischemic work-up. A more agressive position is to consider CCTA as the cornerstone of patient management because the limitations and pitfalls of non-invasive techniques open the door to an alternative diagnostic imaging technique, either alone, or in combination with other Imaging techniques after reorganizing the sequence of imaging work-up. Without dismissing the dogma of initial détection of CAD along with prognostic stratification using functional tests, the recent availability of a minimally invasive anatomical test in the management of patients with stress angina, given the known limitations of traditional tests, changes the standard work-up algorithms. This suggests that the diagnostic work-up of patients with CAD is likely to be modified to increase the rôle of CCTA.

Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function.

Evidence is increasing for small-vessel disease and disturbance of endothelium-dependent vasodilation in diabetic patients. The aim of this study was to compare coronary circulation in 11 diabetic patients (6 type I and 5 type II) and 7 control subjects. All patients had normal left ventricular systolic function and angiographically normal coronary arteries. To evaluate the maximal area of coronary microcirculation, coronary vascular reserve was determined by intracoronary Doppler and a maximally vasodilating dose of intracoronary papaverine (peak-to-resting coronary flow velocity ratio). To assess coronary endothelial function responses to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) M coronary estimated concentrations) were analyzed on four different segments in each patient by quantitative angiography. Peak-to-resting coronary flow velocity ratio was lower in diabetic patients than in control subjects (3.9 +/- 0.9 and 5.0 +/- 0.7, respectively, P < 0.02). Acetylcholine did not produce any diameter change at 10(-8) and 10(-7) M, but a progressive diameter reduction was observed at 10(-6) and 10(-5) M (-8.0 +/- 15.2%, P < 0.02 and -24.0 +/- 13.6%, P < 0.001, respectively). In control subjects, a progressive diameter dilation was produced from 10(-8) to 10(-6) M acetylcholine (5.1 +/- 3.4, 12.1 +/- 7.0, and 16.4 +/- 7.3%, respectively, all P < 0.001), and a moderate reduction was observed at 10(-5) M (-4.9 +/- 7.5%, P < 0.02). In the two groups, all segments dilated similarly after intracoronary isosorbide dinitrate.(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.

Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.

OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.

Repeated coronary artery occlusions during routine balloon angioplasty do not induce myocardial preconditioning in humans.

OBJECTIVES: The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty induce a myocardial ischemic protective effect. BACKGROUND: In animals, brief coronary artery occlusions preceding a more prolonged occlusion result in reduced infarct size. Whether myocardial protection against ischemia could also occur in humans during angioplasty remains controversial. METHODS: Thirteen patients with a proximal left anterior descending coronary artery stenosis with no angiographic collateral circulation underwent percutaneous transluminal coronary artery balloon angioplasty. Three 120-s balloon inflations separated by a 5-min equilibration period were performed. For each inflation, intracoronary ST segment modifications, septal wall thickening (M-mode echocardiography), left ventricular pressures and time derivatives were measured at baseline and at 30, 60 and 90 s after balloon inflation and 120 s after balloon deflation. RESULTS: Intracoronary electrocardiographic analysis showed that the time course of the maximal ST segment elevation was identical at each inflation, as were wall motion changes assessed by the decrease in septal wall thickening. For the first and last inflations, peak positive dP/dt decreased significantly by 13 +/- 9% (mean +/- SD) and 14 +/- 13%, whereas peak negative dP/dt increased by 23 +/- 15% and 22 +/- 10%, respectively (all p < 0.01 from baseline values). The relaxation time constant, tau, was altered similarly during the different inflations, from 44 +/- 6 to 74 +/- 13 ms and from 57 +/- 13 to 77 +/- 13 ms (all p < 0.001) for the first and last inflations, respectively. Left ventricular end-diastolic pressure increased to the same level after each inflation. In contrast to other hemodynamic variables, tau and left ventricular end-diastolic pressure did not return to baseline values in between the inflations, which may be due to myocardial stunning. CONCLUSIONS: In patients with proximal left anterior descending coronary artery stenosis and no evidence of collateral circulation, brief periods of ischemia, such as those used during routine coronary balloon angioplasty, do not provide any protection against myocardial ischemia.

Coronary artery response to cold-pressor test is impaired early after operation in heart transplant recipients.

OBJECTIVES: The aim of the present study was to evaluate the coronary vasomotor response to the cold-pressor test within 3 months after heart transplantation. BACKGROUND: Normal epicardial coronary arteries dilate in response to sympathetic stimulation evoked by the cold-pressor test. In transplant recipients, abnormal coronary vasomotion has been described shortly after operation. METHODS: Fourteen heart transplant recipients were compared 52 +/- 15 days (mean +/- SD) after operation with 10 control subjects. All had angiographically normal epicardial coronary arteries. Coronary blood flow velocity was measured with a Doppler catheter placed in the proximal left anterior descending coronary artery. Four segments in each patient were analyzed by quantitative coronary angiography to assess the diameter changes during the cold-pressor test and after intracoronary injection of isosorbide dinitrate. RESULTS: Coronary flow velocity increased similarly during the cold-pressor test in control subjects and in transplant recipients, from 7.5 +/- 2.3 to 11.0 +/- 3.9 cm/s and from 10.3 +/- 3.2 to 13.7 +/- 4.8 cm/s (both p < 0.01). In control subjects, 39 of 40 segments analyzed dilated during the cold-pressor test. In transplant recipients, 48 of 56 segments analyzed did not change or constricted. The mean epicardial coronary diameter increased significantly during the cold-pressor test in control subjects (+13 +/- 6%, p < 0.001), whereas it did not change significantly in transplant recipients (-2 +/- 9%, p = NS). In transplant recipients, isosorbide dinitrate elicited coronary vasodilation similar to that in control subjects. CONCLUSIONS: These data indicate that in human transplanted denervated hearts, coronary vasodilation in response to sympathetic stimulation by cold exposure is impaired shortly after operation.

Effects of time and previous acute rejection episodes on coronary vascular reserve in human heart transplant recipients.

OBJECTIVES: This study examined whether previous rejection episodes may have deleterious effects on coronary vascular reserve of heart transplant recipients months after transplantation. BACKGROUND: Coronary reserve has been demonstrated to be within the normal range in long-term transplant patients without previous episodes of rejection. Conversely, acute rejection is associated with a dramatic reduction of coronary reserve, which is rapidly restored after therapy. METHODS: Coronary flow velocity was measured by intracoronary Doppler catheter before and after a maximally vasodilating dose of intracoronary papaverine in 16 control subjects and in 59 transplant patients classified into three groups with respect to time after transplantation: 1 to 6 months (group 1, n = 17), 7 to 18 months (group 2, n = 22) and > 18 months (group 3, n = 20). Coronary vascular reserve was evaluated through peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index. All patients had normal findings on left ventricular angiography and coronary arteriography and a normal left ventricular mass. RESULTS: Arterial pressure was normal in all groups. Heart rate in the three groups of transplant patients, mean aortic pressure in groups 1 and 2, left ventricular systolic pressure in group 2 and rate-pressure product in groups 1 and 2 were higher than in control subjects. Average number of rejection episodes per patient was similar in the three groups of patients (group 1, 2.4 +/- 1.4; group 2, 2.5 +/- 1.9, and group 3, 2.1 +/- 1.3). Results showed no difference between each group of transplant patients and control subjects for peak/rest coronary flow velocity ratio (control subjects, 5.2 +/- 0.8; group 1, 5.3 +/- 1.5; group 2, 4.9 +/- 1.2, and group 3, 4.4 +/- 1.6) and for minimal coronary vascular resistance index (control subjects, 0.18 +/- 0.03; group 1, 0.18 +/- 0.04; group 2, 0.20 +/- 0.06, group 3, 0.23 +/- 0.11). In addition, patients with zero or one rejection episode had similar values of peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index (4.3 +/- 1.3 and 0.23 +/- 0.10, respectively, n = 22) as did those with one or two rejection episodes (5.1 +/- 1.5 and 0.19 +/- 0.07, respectively, n = 24), and those with four or more episodes (5.2 +/- 1.4 and 0.19 +/- 0.05, respectively, n = 13). CONCLUSIONS: This study showed that coronary vascular reserve remains within normal range and is independent from the number of previous episodes of rejection until late after transplantation in human heart transplant patients with angiographically normal coronary arteries.

Effects of bradykinin on coronary blood flow and vasomotion in transplant patients.

OBJECTIVES: To evaluate the effects of exogenous bradykinin on coronary epicardial and microcirculatory tone in transplant patients (HTXs), and to compare them with the effects of acetylcholine. BACKGROUND: Coronary endothelial dysfunction has been reported to occur early after heart transplantation, most notably when acetylcholine was the endothelium-function marker used. The effects of bradykinin on coronary vasomotion are unknown in HTXs. METHODS: Sixteen HTXs were compared 3.6 +/- 1.7 months after transplantation to seven control subjects. Coronary flow velocity was measured using guide-wire Doppler. Diameters (D) of three segments of the left coronary artery and coronary blood flow (CBF) were assessed at baseline, after 3-min infusions of increasing bradykinin doses (50, 150 and 250 ng/min) then of increasing acetylcholine doses (estimated blood concentrations of 10(-8), 10(-7) and 10(-6) M). RESULTS: Bradykinin induced similar dose-dependent increases in D and CBF in both groups: D was 11 +/- 12%, 19 +/- 14% and 22 +/- 16% (all p < 0.0001), and CBF was 50 +/- 40%, 130 +/- 68% and 186 +/- 77% (all p < 0.0001). Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in HTX, as well as a marked increase in CBF in both groups. Acute allograft rejection, present in 8 of the 16 HTXs, did not modify responses to bradykinin, but was associated with a smaller CBF increase in response to acetylcholine (p < 0.05). CONCLUSIONS: The coronary vasodilating effects of bradykinin are preserved early after heart transplantation, even in the presence of acute allograft rejection. Although there is an abnormal vasoconstricting response to acetylcholine reflecting endothelium dysfunction, the endothelium remains a functionally active organ in heart transplant recipients.

Role of coronary artery lumen enlargement in improving coronary blood flow after balloon angioplasty and stenting: a combined intravascular ultrasound Doppler flow and imaging study.

OBJECTIVES: This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting. BACKGROUND: Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in > or = 50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results. METHODS: To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity. RESULTS: The percent diameter stenosis decreased from (mean +/- SD) 84 +/- 13% to 37 +/- 18% after angioplasty and to 8 +/- 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 +/- 0.79 at baseline to 1.89 +/- 0.56 (p = NS) after angioplasty but increased to 2.49 +/- 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 +/- 2.09 vs. 5.10 +/- 2.03 mm2, p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001). CONCLUSIONS: In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.

Coronary artery constriction caused by the cold pressor test in human hypertension.

Hypertensive patients with angiographically normal coronary arteries may have myocardial ischemia when metabolic demand increases. Abnormal epicardial coronary artery vasomotion in response to sympathetic stimulation may contribute to ischemia in such patients. We studied the vasomotor response of smooth coronary arteries to a cold pressor test in 10 hypertensive patients without other risk factors and in 9 control subjects. Vessel dimensions were measured by quantitative angiography, and blood flow was calculated using an intracoronary Doppler catheter in the left anterior descending coronary artery. In response to cold pressor stimulation, arteries of control subjects dilated 13.0 +/- 5.9% (P < .001), and they constricted 8.2 +/- 8.5% in hypertensive patients (P < .001). Rate-pressure product increased from 9466 +/- 1677 to 12,547 +/- 2367 beats per minute (bpm).mm Hg in control subjects (P < .001) and from 13,720 +/- 1823 to 17,353 +/- 2037 bpm.mm Hg in hypertensive patients (P < .001). Coronary blood flow velocity and blood flow increased 51 +/- 26% (P < .05) and 87 +/- 27% (P < .001), respectively, in control subjects and 68 +/- 52% (P < .05) and 36 +/- 33% (P < .01) in hypertensive patients. At peak cold pressor test, despite a significant higher rate-pressure product in hypertensive patients, blood flow was similar in both groups, suggesting an uncoupling between myocardial metabolic demand and supply. Thus, hypertension impairs the vasodilator response of angiographically normal coronary arteries to a cold pressor test. This abnormal response may be due to enhanced catecholamine reactivity and/or impairment of endothelial flow-mediated vasodilator response.

Ventriculoarterial coupling and left ventricular efficiency in heart transplant recipients.

BACKGROUND: In heart transplants, left ventricular function may be impaired in the absence of rejection or graft atherosclerosis. Matching between left ventricle and arterial receptor, i.e., ventriculoarterial coupling, and left ventricular efficiency have never been studied. METHODS: Left ventricular pressure-volume loops and single beat analysis were used to determine effective arterial elastance (Ea) and the slope of the end-systolic pressure-volume relation (end-systolic elastance; Ees). Left ventricular efficiency was evaluated by determination of external work (EW), pressure-volume area (PVA), coronary blood flow (continuous thermodilution), and myocardial oxygen consumption (MVO2). Measurements were made at baseline in 11 control subjects and 9 heart transplant recipients (HTX) without rejection and were repeated after phenylephrine in the latter group. RESULTS: At baseline, Ees, Ees/Ea, and work efficiency (EW/PVA) were lower in HTX than in control subjects (2.51+/-0.87 vs. 3.70+/-1.15 mmHg/ml/m2, P<0.01; 0.96+/-0.21 vs. 1.47+/-0.31, P<0.001; and 0.53+/-0.08 vs. 0.59+/-0.09, P<0.01, respectively). Energy conversion efficiency (PVA/MVO2) and mechanical efficiency (EW/ MVO2) were higher in HTX (0.58+/-0.08 vs. 0.45+/-0.14, P<0.001; and 0.31+/-0.05 vs. 0.26+/-0.06, P<0.001, respectively). In HTX, phenylephrine infusion increased Ees, Ea, EW, PVA, and MVO2 without modifying Ees/Ea, EW/PVA, PVA/MVO2, and EW/MVO2. CONCLUSIONS: In heart transplants, (1) left ventricular contractility is moderately depressed; (2) elevation of energy conversion efficiency compensates for the decrease in work efficiency, allowing normal mechanical efficiency; and (3) alpha 1 adrenergic stimulation does not impair ventriculoarterial coupling and mechanical efficiency.

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 the effects of exercise and cold pressor test on the vasomotor response of normal and atherosclerotic coronary arteries and their relation to the flow-mediated mechanism.

This study was designed to assess the vasomotor response of coronary arteries to exercise and the cold pressor test, and its relationships with the endothelium-mediated dependent mechanism. Twenty-two patients were entered in the study. Group I was composed of 12 patients with a total cholesterol level < 200 mg/dl associated with angiographically smooth, normal coronary arteries. Group 2 consisted of 10 patients with both a cholesterol level > 240 mg/dl and angiographic luminal irregularities of the left anterior descending coronary artery. Coronary blood flow was assessed by a 0.018-inch tip guidewire during Doppler ultrasonography, and analysis of the coronary arterial dimension of the midportion of the left anterior descending coronary artery was performed by quantitative coronary angiography. Catecholamine concentrations were assessed at the different stages of the protocol. The rate-pressure product increased during both the cold pressure test and exercise (p < 0.001). Coronary blood flow velocity increased during the cold pressor and exercise tests by 24.5 +/- 10% and 72 +/- 42%, respectively (p < 0.001), and by 127 +/- 62% (p < 0.0001) after administration of papaverine. In group 1, the cold pressor test had a more pronounced vasodilating effect on epicardial coronary arteries (+11.2 +/- 16%) compared with group 2 (-2 +/- 9%, p < 0.05). Similarly, exercise had a vasodilating action in group 1 (11.3 +/- 15%) compared with group 2 (-1.9 +/- 8%, p < 0.05). Both responses were highly correlated (r = 0.92, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary microcirculation and cardiovascular pathology.

The recent arrival of new techniques for exploring the coronary microcirculation has facilitated assessment of both the incidence and consequences of disorders of this network in a large number of cardiovascular diseases. The microcirculation is affected in numerous cardiomyopathies in the presence of different cardiovascular risk factors and also following cardiac transplantation. Dysfunction of the microcirculation may correspond to a reduction in the surface of the maximum section of coronary arterioles, which involves multiple mechanisms, although this phenomenon does not appear to play a role in ischaemic heart disease. Reduced coronary flow is most frequently related to vascular rarefaction of multifactorial origin, including greater or lesser degrees of intimal proliferation, perivascular fibrosis, hypertrophy of the media and extrinsic compression.

Coronary microcirculation and cardiovascular pathology.

The recent arrival of new techniques for exploring the coronary microcirculation has facilitated assessment of both the incidence and consequences of disorders of this network in a large number of cardiovascular diseases. The microcirculation is affected in numerous cardiomyopathies in the presence of different cardiovascular risk factors and also following cardiac transplantation. Dysfunction of the microcirculation may correspond to a reduction in the surface of the maximum section of coronary arterioles, which involves multiple mechanisms, although this phenomenon does not appear to play a role in ischaemic heart disease. Reduced coronary flow is most frequently related to vascular rarefaction of multifactorial origin, including greater or lesser degrees of intimal proliferation, perivascular fibrosis, hypertrophy of the media and extrinsic compression.

Early impairment of acetylcholine-induced endothelium-dependent coronary vasodilation is not predictive of secondary graft atherosclerosis.

STUDY OBJECTIVE: To test the hypothesis that the magnitude of early constriction of coronary arteries to acetylcholine might be a useful predictor of secondary graft atherosclerosis. DESIGN: The responses of epicardial coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8)M to 10(-5)M) were compared in 7 control subjects and in 18 patients who had undergone transplants within 2 months after surgery. MEASUREMENTS AND RESULTS: Vessel dimensions (percent basal diameter) were measured by quantitative angiography. Follow-up at 1 year showed angiographically normal coronary arteries in 12 patients (group 1) and coronary atherosclerosis in 6 patients (group 2). In control subjects, acetylcholine induced a dose-dependent dilation from 10(-8)M to 10(-6)M. No significant variation was observed at 10(-5)M. In patients with transplants early after surgery, diameters did not vary significantly from base at 10(-8)M in either group and constricted significantly at higher concentrations. Vasodilator responses to intracoronary isosorbide dinitrate were similar in both groups with transplants early after surgery, and at 1 year in group 1, but significantly lower than in control subjects. CONCLUSIONS: In patients who had undergone transplants, acetylcholine-induced endothelium-dependent coronary artery dilation is similarly impaired early after surgery (within 2 months) in patients with and without coronary atherosclerosis at 1-year follow-up. Thus, response to acetylcholine is not a predictor of secondary atherosclerosis in patients with heart transplants.

Myocardial high-energy phosphate depletion in allograft rejection after orthotopic human heart transplantation.

The present study was designed to assess whether acute rejection affects myocardial energy content of the human orthotopically transplanted heart. Adenosine triphosphate content was measured in one tissue sample obtained during 46 routine right ventricular endomyocardial biopsies 6 to 455 days (98 +/- 110) after transplantation in 19 cyclosporine-treated transplant recipients. Tissue samples were immediately frozen in liquid nitrogen within 10 seconds after excision. Adenosine triphosphate analysis was performed with high performance liquid chromatography. Three groups of biopsy specimens were classified according to the standardized cardiac biopsy grading system. Group 1: Eight biopsy specimens without rejection; group 2: 24 biopsy specimens with mild rejection; group 3: 14 biopsy specimens with moderate or severe rejection. Graft systolic function evaluated by echocardiographic fractional shortening was in the normal range the day of biopsy. All patients had normal coronary angiograms within 1 month of the study. In the presence of mild rejection (grade 1A or 1B), adenosine triphosphate content was not significantly different from that of nonrejecting hearts (26.15 +/- 7.1 and 28.57 +/- 8.23 nmol/mg protein, respectively). By contrast, a significant decrease in adenosine triphosphate content was observed when moderate or severe rejection with focal or diffuse aggressive infiltrates were present (10.46 +/- 4.11 nmol/mg protein; p < 0.01 versus two other groups). In seven cases, sequential analysis showed a significant increase in adenosine triphosphate content after rejection therapy concomittant with histologic improvement: 10.19 +/- 2.9 before and 30.13 +/- 7.0 nmol/mg protein after treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic events and long-term survival after combined heart and kidney transplantation: a 12-year single-center experience.

BACKGROUND: In this study we compare the incidence of cardiac rejection and long-term survival after combined heart and kidney transplantation (HK) and single heart transplantation (H). Combined HK transplantation is a surgical option for patients with irreversible cardiac and renal failure. However, long-term results of combined HK transplantation on immunologic events and patient survival remain unknown. METHODS: Between 1988 and 1997, 12 consecutive patients underwent combined HK transplantation (HK group) at a single institution. A control group (H group) of 24 single heart transplant recipients operated on within the same period was matched for age, pre-operative pulmonary vascular resistance, hepatic insufficiency and gender mismatch. Recipients and donors were ABO compatible without HLA antigen matching. All patients received immediate triple immunosuppression that included cyclosporine. Because of early renal dysfunction, cyclosporine was switched to anti-thymocyte globulin in 5 patients from the HK group and in 1 patient from the H group (p = 0.01). RESULTS: Actuarial freedom from heart rejection at 6 months and at 1 year following transplantation averaged 90 +/- 9% and 70 +/- 14% in the HK group, and 65 +/- 10% and 49 +/- 11% in the H group, respectively (p = 0.023). Actuarial survival at 1, 5 and 12 years was not significantly different between groups, at 66%, 55% and 28% in the HK group, and 66%, 44% and 32% in the H group, respectively (p = 0.66). CONCLUSION: The incidence of cardiac rejection was significantly lower. Long-term survival in the HK group was similar to that in the H group. Putative mechanisms of decreased cardiac rejection in the HK group include allogeneic stimulation, donor-derived dendritic cells and induction by anti-thymocyte globulins. The need for long-term immunosuppression may be reduced after combined heart and kidney transplantation.

Impairment of flow-dependent coronary dilation in hypertensive patients. Demonstration by cold pressor test induced flow velocity increase.

In normal coronary arteries, increased flow velocity induces endothelium-dependent dilation, and dilation in response to sympathetic stimulation evoked by the cold pressor test is partly due to increased flow velocity. In arterial hypertension, angiographically normal coronary arteries were constricted by acetylcholine, an endothelium-dependent vasodilator. To assess the epicardial coronary artery response to the increase blood flow velocity induced by the cold pressor test in hypertensive patients with angiographically normal coronary arteries, coronary artery diameters and flow velocity were measured during cold pressor test in 12 untreated hypertensive patients and in 10 control subjects. Diameters were determined by quantitative angiography on proximal and distal segments of the left anterior descending coronary artery, and flow velocity measurements were made by Doppler testing in the distal segment. In control subjects, the proximal and distal segments dilated during cold pressor test by 12.0 +/- 4.5% and 13.9 +/- 6.5%, respectively (both P < .001), when flow velocity increased by 46.7 +/- 26.1% (P > .05). In hypertensive patients, segments were constricted, respectively, by 10.3 +/- 8.5% (P < .001) and 7.9 +/- 8.6% (P < .01), when the flow velocity was increased by 68.3 +/- 48.2% (P < .001). Intracoronary injection of an endothelium-independent dilator resulted in similar dilation in control subjects (proximal: +30.0 +/- 12.9%; distal: +32.4 +/- 15.2%) and in hypertensive patients (proximal: +22.3 +/- 7.5%; distal: +28.8 +/- 15.4%). In conclusion, in hypertensive patients with angiographically normal coronary arteries and without any other coronary risk factors, endothelium-dependent flow-mediated coronary dilation evoked by the cold pressor test is impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility, safety, cost-effectiveness and 1 year follow-up of coronary stenting without predilation: a matched comparison with the standard approach.

BACKGROUND: We evaluated the feasibility, safety, procedural cost-effectiveness, radiation dose and time and 1-year target vessel revascularization rate of direct unprotected mounted stenting without previous balloon dilatation (DS) in native coronary artery lesions. METHODS: DS was attempted in 119 patients; 39 had a recent myocardial infarction, 62 had unstable angina, and 18 had stable angina. The clinical follow-up was obtained at 14+/-5 months (range 6 to 24 months). These results were compared with those for a consecutive group of 160 patients matched for type and length of lesions and who had a stent only if the post-balloon residual stenosis was >30%. RESULTS: The feasibility of DS was 112/119 (94%). The number of inflations, the length of the stent/length of the lesion ratio, the time and the dose of radiation were dramatically lower in the DS group (P<0.001). DS conferred a slight reduction in procedure-related cost [$820+/-157 for DS vs. 894+/-427 for standard dilatation (SD) per patient]. The 1-year target vessel revascularization rate was similar in both groups [nine (8%) for DS vs. 17 (11%) patients for SD, ns]. CONCLUSIONS: DS is feasible and safe in selected coronary lesions. This method provides a low rate of repeat revascularization and reduces the time and the dose of radiation compared with the standard approach.