Massimo Ciavolella

Verapamil versus acebutolol for syndrome X

Abstract The precise mechanism responsible for angina pectoris in patients with syndrome X has not been completely identified. Recent evidence suggests that angina in these patients is probably due to an abnormal vasodilatory reserve of coronary microcirculation.1,2 This evidence and the clinical observation of an abnormally high pressure and heart rate response to low workload often seen in some patients with syndrome X suggest a role of an inappropriate sympathetic response in the pathogenesis of exercise-induced angina. To evaluate this aspect further, we carried out a randomized, double-blind, crossover study with acebutolol (a β1-specific blocking agent) and verapamil.

Differences of regional coronary flow reserve assessed by adenosine thallium-201 scintigraphy early and six months after successful percutaneous transluminal coronary angioplasty or stent implantation

This study assesses regional coronary flow reserve using adenosine thallium-201 scintigraphy early and 6 months after angiographically successful percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Seventeen consecutive men with a significant isolated left anterior descending coronary artery stenosis were scheduled for repeat coronary angiography and adenosine-planar thallium-201 scintigraphy within 24 hours and 6 months after successful PTCA (n = 8) or stent implantation (n = 9). After background subtraction, left ventricular segmental uptake was semiquantitatively assessed on thallium images. The perfusion defect severity was scored from 0 (normal) to 3. Coronary angiograms were analyzed using an automated edge contour detection computer analysis system. Data are expressed as mean value +/- 1 SD, and proportions as percentage. The residual narrowing was 17 +/- 8% after PTCA and 9 +/- 2% after stent implantation (p = 0.02). Twenty-four hours after the procedure, hypoperfused segments were detected in all patients (100%) and in 4 patients (44%) (p = 0.05), respectively. The total number of hypoperfused segments was greater after PTCA than after stent implantation (16 [40%] vs 7 [16%], p = 0.001, respectively) as was the perfusion defect severity (4.4 +/- 3.1 vs 1 +/- 1.2, p = 0.006). Six months after the procedure, 3 of the 5 patients who had undergone PTCA without restenosis still had reversible perfusion defects. None of the stent-treated patients had restenosis or reversible perfusion defects (p = 0.05). Among PTCA-treated patients without restenosis, the total number of hypoperfused segments and the perfusion defect severity were 9 of 25 (36%) and 0.8 +/- 0.8, respectively. Thus, a regional reduction in coronary flow reserve, occasionally observed early after successful stent implantation, is probably due to a transient alteration of small coronary vessels, as was also supported by the absence of perfusion defects 6 months after the procedure. The more severe impairment of regional coronary flow reserve observed early after successful PTCA is probably also due to angiographic underestimation of the residual stenosis, as suggested also by the persistence of reversible perfusion defects 6 months after the procedure in a few patients.

Recovery of contractility of viable myocardium during inotropic stimulation is not dependent on an increase of myocardial blood flow in the absence of collateral filling

OBJECTIVES The purpose of this study was to determine whether contractile recovery induced by dobutamine in dysfunctioning viable myocardium supplied by nearly occluded vessels is related to an increase in blood flow in the absence of collaterals. BACKGROUND Dobutamine is used to improve contractility in ventricular dysfunction during acute myocardial infarction. However, it is unclear whether a significant increase in regional blood flow may be involved in dobutamine effect. METHODS Twenty patients with 5- to 10-day old anterior infarction and > or =90% left anterior descending coronary artery stenosis underwent 99mTc-Sestamibi tomography (to assess myocardial perfusion) at rest and during low dose (5 to 10 microg/kg/min) dobutamine echocardiography. Rest echocardiography and scintigraphy were repeated >1 month after revascularization. Nine patients had collaterals to the infarcted territory (group A), and 11 did not (group B). RESULTS Baseline wall motion score was similar in both groups (score 15.9+/-1.3 vs. 17.4+/-2.0, p = NS), whereas significant changes at dobutamine and postrevascularization studies were detected (F[2,30] = 409.79, p < 0.0001). Wall motion score improved significantly (p < 0.001) in group A both at dobutamine (-5.3+/-2.2) and at postrevascularization study (-5.5+/-1.9), as well as in group B (-3.9+/-2.8 and -4.5+/-2.4, respectively). Baseline 99mTc-Sestamibi uptake was similar in both groups (62.9+/-9.7% vs. 60.3+/-10.4%, p = NS), whereas at dobutamine and postrevascularization studies a significant change (F[2,30] = 65.17, p < 0.0001) and interaction between the two groups (F[2,30] = 33.14, p < 0.0001) were present. Tracer uptake increased significantly in group A both at dobutamine (+ 10.9+/-7.9%, p < 0.001) and at postrevascularization study (12.1+/-8.7%, p < 0.001). Conversely, group B patients showed no change in tracer uptake after dobutamine test (-0.4+/-5.8, p = NS), but only after revascularization (+8.8+/-7.2%, p < 0.001). CONCLUSIONS The increase in contractility induced by low dose dobutamine infusion in dysfunctional viable myocardium supplied by nearly occluded vessels occurs even in the absence of a significant increase in blood flow.

Handgrip increases endothelin-1 secretion in normotensive young male offspring of hypertensive parents.

OBJECTIVES We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents. BACKGROUND It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension. METHODS Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery. RESULTS Group A had higher norepinephrine levels than group B throughout the test (baseline 181+/-32 [SEM] vs. 96+/-12 pg/ml, p < 0.05; peak HG 467+/-45 vs. 158+/-12 pg/ml, p < 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p < 0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07+/-0.14 vs. 0.59+/-0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p < 0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square=7.59, p=0.0059) and ET-1 changes during HG (chi-square=4.23, p=0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not. CONCLUSIONS The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.

Acute oral trimetazidine administration increases resting technetium 99m sestamibi uptake in hibernating myocardium

BackgroundTrimetazidine is an antiischemic drug protecting the myocardium from ischemic damage through the preservation of mitochondrial oxidative metabolism, without any hemodynamic effect. 99mTc-sestamibi is accumulated by myocytes according to mitochondrial function. As mitochondrial metabolism is thought to be present in hibernating myocardium, the aim of the study was to investigate trimetazidine effects on infarcted and eventually hibernating myocardial areas by means of 99mTc-sestamibi perfusional scintigraphy, comparing them to postoperative recovery of wall motion.Methods and ResultsTwelve patients with previous myocardial infarction underwent 2 perfusion imaging tomographic studies at rest with 99mTc-sestamibi, receiving placebo or trimetazidine (60 mg orally), and subsequently underwent revascularization procedures. An echocardiographic study was carried out before and >3 months after revascularization. At polar map analysis of placebo scan, infarcted vascular territories (wall motion score index: 2.65±0.31) showed 73.7%±10.4% of the territory with activity <2.5 SD from the mean of normals, for a severity (expressed as the sum of the standard deviations below average normal values in all abnormal pixels) of 833.8±345.7. Polar map analysis of the trimetazidine scan showed tracer uptake increased significantly in 11 of them, by 8.2%±3.0% (p<0.001) and by 180.3±111.0 SD (p<0.001), respectively. Postoperative wall motion score index improved significantly in 9 of these territories (−0.9±0.4, p<0.001).ConclusionsTrimetazidine-associated increase in 99mTc-sestamibi uptake in infarcted but viable myocardial areas is probably related to an improvement in mitochondrial oxidative metabolism that is essential to 99mTc-sestamibi retention. Additionally, coupling trimetazidine administration to 99mTc-sestamibi perfusional scintigraphy may represent a means of detecting viable myocardium.

Nitroglycerin-induced changes in myocardial sestamibi uptake to detect tissue viability: radionuclide comparison before and after revascularization

BackgroundNitroglycerin (NTG) is known to increase the blood supply to the myocardium, and would thus increase the delivery of a perfusional tracer such as sestamibi (MIBI) to the tissue. The latter, in turn, would take up and concentrate the tracer to a greater extent than in basal conditions only if energy-dependent mechanisms were still available — that is, only if the cells were still viable. MethodsWe evaluated the changes that intravenous administration of NTG induced on the uptake of MIBI by akinetic myocardial areas, using tomographic perfusional imaging in 23 patients with previously ascertained anterior myocardial infarction who were undergoing myocardial revascularization procedures. Changes in uptake were compared with echocardiographic and perfusional changes occurring after operation. ResultsThe improvement of MIBI uptake after NTG correctly identified 12 of the 16 patients (75%) showing postoperative wall motion improvement; they comprised 12 of the 14 (86%) patients with NTG-induced increase in MIBI uptake who showed improved wall motion after operation. A close correlation (r = 0.88, P< 0.001) was found between the increase in myocardial MIBI uptake induced by NTG infusion and that induced by revascularization. The presence of collaterals to the akinetic area was associated with a significantly (P<0.01) greater increase in MIBI uptake both during NTG infusion and after operation. ConclusionsThe results of this study suggest that MIBI perfusional myocardial scintigraphy during infusion of NTG is capable of detecting viable but chronically hypoperfused myocardium, predicting postoperative wall motion and perfusional improvement, and reflecting the postoperative pattern of perfusion. The best results were achieved in patients with evidence of collateral circulation supplying the infarcted area.

Exponential fit of QT interval-heart rate relation during exercise used to diagnose stress-induced myocardial ischemia

The aim of this study was to analyze the dynamic changes of QT interval--heart rate relation during exercise, fitting their reciprocal variations to an exponential formula (QT = A - B.exp(-k.RR], in order to see whether diagnostic contributions might so be derived. The authors studied 139 patients who underwent a simultaneous assessment of regional myocardial perfusion and ventricular function by means of two injections of 99mTc-methoxy-isobutyl-isonitrile at rest and at peak of a submaximal exercise test, using first pass radionuclide angiography with multielement gamma-camera and single photon emission computerized tomography, in order to detect and localize the presence of stress-induced myocardial ischemia. According to radionuclide results, patients were divided into three groups: group A, 7 individuals with no sign of stress-induced myocardial ischemia; group B, 79 patients with evidence of ischemia in 1 (16.5%), 2 (65.5%), or 3 (17.7%) main coronary territories; and group C, 53 patients with previous infarction and evidence of ischemia in other territories. Conventional analysis of the exercise test (greater than or equal to 0.1 mV ST depression) showed a pathological response in no individual of group A, in 34 patients of group B (43%), and in 27 patients of group C (50.9%); overall sensitivity was 46.2%, specificity 100%, and diagnostic accuracy 48.9%. Exponential coefficients A, B, and k showed wide overlap of values among the three groups, although a significant difference was present in mean k values between groups A and B (p less than 0.001), and group C (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

ST/HR slope and improved exercise ECG detection of myocardial ischemia in patients with suspected coronary artery disease

Predictive values of ST/HR slope and ST-segment displacement during symptom-limited exercise were determined in 85 patients who underwent coronary angiography for suspected coronary artery disease, using perfusional and functional radionuclide images with 99mTc-2-methoxy-isobutil-isonitrile as an index of stress-induced myocardial ischemia. ST/HR slope showed a better sensitivity than conventional stress-induced changes of ST-segment displacement (96% vs. 73%, respectively). In patients with clinical suspicion of coronary artery disease, the main result was the negative predictive value of ST/HR slope when compared with conventional ST-segment displacement (98% vs. 41%). ST/HR slope was unable to perfectly separate patients with different degrees of ischemia, however, subjects without scintigraphic signs of stress-induced ischemia and patients with ischemic impairment in three myocardial regions were correctly identified as distinct populations. In patients with a previous myocardial infarction, no difference was found between the two criteria and a wide overlap of ST/HR slope values was present. The authors conclude that ST/HR slope is useful to detect the rate of change in electric parameters during exercise and might therefore more adequately be used to separate normal from definitely abnormal responses to exercise.

Preoperative Identification of Viable Myocardium: Effectiveness of Nitroglycerine-Induced Changes in Myocardial Sestamibi Uptake

In order to predict tissue viability in infarcted myocardial areas, changes induced by nitroglycerine infusion on Sestamibi myocardial uptake were evaluated in 37 patients with previously confirmed myocardial infarction undergoing coronary artery bypass grafting, and compared with echocardiographic and perfusional changes occurring after the operation. The improvement of Sestamibi uptake after nitroglycerine correctly classified 24/26 (92%) patients showing postoperative improvement of wall motion in the infarcted area, whereas 24/31 (77%) patients with nitroglycerine-induced increase in Sestamibi uptake had improved wall motion after operation. The presence of collateral flow to the infarcted area was associated with a significantly (P < 0.01) higher increase in Sestamibi uptake both during nitroglycerine infusion and postoperatively. An increase in wall motion score after operation was associated with a significantly higher (P < 0.05) increase in Sestamibi uptake score during nitroglycerine infusion. Thus, the results of this study suggest that Sestamibi perfusional myocardial scintigraphy during nitroglycerine infusion is capable of assessing viable but chronically hypoperfused myocardium and predicting postoperative wall motion and perfusional improvement, to yield the best results in patients with evidence of collateral circulation that supplies the infarcted area.

Growth Hormone and Insulin‐Like Growth Factor 1 in Normopituitaric Patients with Various Degrees of Heart Failure

Among biological systems activated in congestive heart failure, increased plasma levels of growth hormone (GH) are hypothesized to be secreted by adenohypophysis, in response to catecholamines’ and atrial natriuretic factor (ANF).2 Additionally, GH, through somatomedins or insulin-like growth factor1 (IGFl), exerts a positive inotropic effect on heart r n u ~ c l e . ~ ~ The aim of the present study was: 1) to investigate the bahavior of the GH-IGF1 axis in normopituitaric patients with various degrees of heart failure; 2) to assess whether GH and IGFl plasma levels are linked to ventricular mass; and 3) to investigate the behavior of the GHIGFl axis after clinical improvement.