François Guérin

Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis

Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.

Stent implantation in acute myocardial infarction

Among 138 patients treated with coronary angioplasty during acute myocardial infarction (AMI), 35 (25%) had stent implantation. Mean age was 56 years and 83% were men. Mean onset of chest pain was 6.0 +/- 5.3 hours, and previous thrombolytic therapy was given to 10 patients (29%). Infarct location was anterior in 19 (54%), inferior in 14 (40%), and lateral in 2 patients (6%). Thrombolysis in Myocardial Infarction trial flows 0,1, and 2 were seen in 24 (69%), 6 (17%), and 5 patients (14%), respectively. The culprit vessel was the left anterior descending artery in 18 (51%), right coronary artery in 14 (40%), left circumflex in 2 (6%), and left main coronary artery in 1 patient (3%). Mean vessel diameter was 3.3 +/- 0.3 mm. Indications were: primary in 5 (14%), suboptimal result in 8 (23%), nonocclusive dissection in 14 (40%), and occlusive dissection in 8 patients (23%). Angiographic thrombus after initial angioplasty was present in 12 patients (34%). A total of 46 stents were implanted; mean balloon diameter and pressure were 3.4 +/- 0.4 mm and 15.5 +/- 2.2 atm, respectively. Residual diameter stenosis was 4 +/- 7%. There were 2 deaths; sudden 1, and after elective coronary artery bypass grafting in the other; 2 patients (6%) had groin hematomas. Mean hospitalization was 9.9 +/- 5.0 days. Repeat angiography revealed no stent occlusion. With initial intravenous heparin for 3 to 7 days, all patients received aspirin and ticlopidine for 1 month. Thus, AMI is not a contraindication for stent implantation. The benefits of stenting are a high success rte, low residual diameter stenosis, and low incidence of in-hospital recurrent ischemia. Reduction in restenosis rate in this setting is likely but remains to be determined.

Improvement in Exercise Performance by Inhalation of Methoxamine in Patients with Impaired Left Ventricular Function

BACKGROUND Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. METHODS We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design. RESULTS In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). CONCLUSIONS The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long-term benefit in patients with heart failure will require further study.

Pre- and postoperative hemodynamic and cineangiocardiographic assessment of left ventricular function in patients with aortic regurgitation

Abstract Hemodynamic and angiocardiographic analysis was performed prior to and 14 months on the average following valve replacement in 11 patients with severe, isolated, pure, chronic aortic regurgitation. The aortic diastolic pressure, reduced prior to surgery, reverted to normal as did the cardiac index. Left ventricular filling pressure, elevated prior to surgery, returned to normal while aortic systolic pressure did not vary substantially. The markedly increased stroke volume returned to normal as did the net left ventricular stroke work. Left ventricular end-diastolic and end-systolic volumes, also markedly elevated, decreased but did not return to normal levels. The shape of the left ventricle, which was more spherical than normal during end-systole prior to surgery, as evidenced by the decrease in the systolic axis ratio, reverted to normal. The ejection fraction, severely reduced before surgery, increased moderately (46 ± 13 vs 51 ± 19 per cent) as did the extent of circumferential fiber shortening (δD) (21 ± 8 vs 27 ± 12 per cent). The mean velocity of fiber shortening ( VCF ) increased significantly (0.68 ± 0.2 vs 1.03 ± 0.47 circ./sec.), as did the mean left ventricular ejection rate (1.32 ± 0.48 vs 1.91 ± 0.76). Comparative analysis of the evolution of left ventricular function indices and of extramyocardial factors (end-diastolic fiber stretching and impedance to ejection) showed that whereas in some cases myocardial damage appeared to be irreversible, in others dramatic improvement sometimes occurred following surgery. It was not possible, however, to determine the threshold below which the damage was irreversible. It may therefore be concluded that in some patients with severe regurgitation attended by profound myocardial insufficiency, correction of the valvular defect could produce not only clinical and hemodynamic improvement, but also improvement in myocardial contractile status.

Possible Bromocriptine-Induced Myocardial Infarction

Bromocriptine is commonly used for the suppression of lactation in the postpartum period. Bromocriptine mesylate (2-bromo-ergocryptine monomethanesulfonate) is an ergopeptine derivative [1] and has dopaminergic agonist properties. Postpartum myocardial infarction has been reported in women receiving bromocriptine [2-4]; however, a direct cause and effect relation has not previously been shown, and the pathophysiologic mechanism of the ischemia has not been elucidated. We report a case of postpartum myocardial infarction in a multiparous woman receiving bromocriptine in whom evidence of bromocriptine-induced coronary spasm was obtained using angiography. Case Report A 32-year-old woman, gravida 7, para 7, had an uncomplicated pregnancy and a full-term spontaneous vaginal delivery. The patient was given oral bromocriptine mesylate (Parlodel, Sandoz Pharmaceuticals, Ruell-Malmaison, France; 1.25 mg four times a day) to suppress lactation. When discharged on the fifth postpartum day, she continued taking bromocriptine (2.5-mg tablets twice daily). Then she developed visual hallucinations and severe headache. All these symptoms disappeared when she withheld the drug for 1 day. She took bromocriptine again on day 9 and developed the same symptoms. On day 10 she had an episode of severe chest pain. Her electrocardiogram showed marked ST-segment elevation in leads II, III, and aVF, a Q wave in lead III, and anterior ST depression. Electrocardiogram (ECG) abnormalities did not change after intravenous nitroglycerin. Thrombolytic therapy was not administered because she had recently given birth. Coronary angiography was done 5 hours after the onset of symptoms, and it showed a total occlusion of the midportion of the right coronary artery; the left coronary artery was normal. Test results from ventriculography showed a limited zone of akinesia of the inferior wall. Percutaneous transluminal coronary angioplasty was immediately done, and the right coronary artery was reopened. Serial test results of myocardial enzymes and serial electrocardiograms confirmed acute inferior transmural infarction. The peak serum creatine phosphokinase level was 1100 IU. The patients past history was not significant. She never used bromocriptine before. She smoked 1 pack per day. Blood glucose and lipid profile test results were within normal limits. The patient was discharged on calcium-antagonists, nitrates, and aspirin. One month later, she was tested with bromocriptine, after informed consent, to elucidate the mechanism of her previous myocardial infarction. Calcium-antagonists and nitrates were withdrawn 36 hours before the test. Smoking was prohibited during the test day. With the patient in a supine position, bromocriptine was given orally, at a dose of 2.5 mg. Two hours later, at the peak of action of bromocriptine, she had coronary angiography. A severe narrowing [> 70%] of the right coronary artery occurred; the constriction was 2 cm distal from the tip of the catheter (Figure 1, left). After intracoronary nitroglycerin was administered, this constriction disappeared (Figure 1, right), which indicated that bromocriptine might have caused the vasospasm. The patient said she did not have chest pain during the test. Her ECG remained unchanged compared with the basal ECG, which showed a Q wave in leads III and aVF. The patient was discharged on calcium antagonists, and the subsequent clinical course was uneventful. Figure 1. Coronary angiogram of the right coronary artery. Left. arrow Right. Discussion Postpartum myocardial infarction is a rare event. Only 24 reports including our case have been found in the literature. In 11 cases, this life-threatening complication appeared after treatment with ergot derivatives and in 5 cases, with bromocriptine treatment [2-4 and our study]. A reasonable mechanism for the myocardial infarction in our patient would be coronary artery spasm with possible thrombus formation at the site of spasm. However, coronary atherosclerosis on angiogram was not evident. Additionally, the patient did not have conditions such as mitral stenosis, cardiomyopathy, patent foramen ovale, endocarditis, or atrial fibrillation, which might have caused coronary embolization. To our knowledge, direct evidence of bromocriptine-induced coronary spasm has not been previously reported. The spasm seen after bromocriptine was distinct from catheter tip spasm, for several reasons. We used a soft-tip Schneider JR4 catheter (Schneider AG, Pfizer Hospital Products Group, Zurich, Switzerland), and the operator was careful not to intubate deeply the right coronary artery. The spasm was clearly distal to the catheter tip, and it was 1.5 cm long; catheter-induced spasms usually involve a shorter arterial length. The fact that the spasm was not accompanied by chest pain and electrocardiographic changes is not surprising because it involved an artery supplying an infarcted area. The mechanism whereby bromocriptine could have precipitated coronary artery spasm is not clear. Bromocriptine activates D2-dopamine receptors. D2 receptors are associated with inhibition of adenylate cyclase, and they are located on postganglionic sympathetic nerve terminals [5] where they mediate inhibition of norepinephrine release. There is some evidence [6] that D2 receptors are also located postsynaptically on the arterial wall; however, the properties of these postsynaptic D2 receptors are not known. In normal conditions, bromocriptine does not have serotoninergic or -adrenergic agonist properties, in contrast to other ergot derivatives such as ergonovine maleate commonly used as a provocative agent for coronary spasm. It is possible that in our patient the stimulation of D2-dopaminergic receptors could have resulted in a paradoxical constrictive response as shown with exogenous dopamine in a previous study or that a decreased sensitivity of peripheral dopaminergic receptors could have unmasked the vasoconstrictor effects of bromocriptine that are mediated by other receptors [7]. This might be due to an unusual pathologic reactivity of the arterial coronary wall present in our patient. Vasospasm could have been provoked by both activation of -adrenergic and serotoninergic receptors as previously described [7] in a patient with dopamine-induced coronary spasm. Our study suggests that bromocriptine should be considered as a possible etiologic agent causing postpartum myocardial infarction and should be used with caution in patients with predisposing factors.

Nicardipine in the Treatment of Raynaud's Phenomenon: A Randomized Double-Blind Trial

The efficacy of the calcium-channel blocker nicardipine in the treatment of Raynauds phenomenon was assessed in a prospective, double-blind, randomized, crossover trial in 20 patients. Each patient received nicardipine 20 mg or placebo three times a day for two weeks and then was crossed over for two weeks. Nicardipine significantly decreased the frequency and severity of Raynauds phenomenon as compared with placebo. The authors conclude that nicardipine is effective in the treatment of Raynauds phenomenon.

Rotational atherectomy with adjunctive balloon angioplasty versus conventional percutaneous transluminal coronary angioplasty in type B2 lesions: Results of a randomized study

A randomized pilot study was performed comparing conventional balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA] group) and rotational atherectomy (RA) with a medium size burr (50% to 70% burr/artery ratio) with systematic adjunctive balloon angioplasty (RA group) in type B2 stenosis. A total of 64 patients were included. Primary success was 93.7% in the RA group and 87.5% in the PTCA group (p = NS). Technical failure with no complication occurred once in each group. Acute complications occurred in three patients in the PTCA group and in one in the RA group. Angiographic restenosis rates were similar (RA group: 39%, PTCA group: 42%, p = NS) with a follow-up rate of 93%. In type B2 lesions, when compared with conventional angioplasty, RA with systematic balloon angioplasty does not seem to increase procedural success, and the restenosis rate remains comparable. However, these results must be confirmed in a larger series of patients.

Systemic alkalosis as a provocative test for coronary artery spasm in patients with infrequent resting chest pain

Systemic alkalosis was used to detect coronary spasm in 237 patients with infrequent, resting, angina-compatible chest pain. The provocative test was performed without previous coronary arteriography but only in patients with negative submaximal exercise test results. Rapid infusion of alkaline solution followed by maximal hyperventilation raised arterial pH above the 7.65 value necessary for diagnostic significance in 196 (83%) patients. In 24 (12%) of these patients the provocative test induced significant ischemic ST segment changes. In all patients with a positive response, coronary artery disease, which was predominantly vasospastic (19 patients) or atheromatous with a vasospastic contribution (five patients), was demonstrated by coronary arteriography followed, if necessary, by ergot derivative injection. Chest pain and ECG changes were always reversed within 5 minutes by intravenous nitroglycerin. Coronary arteriography was not performed in all patients with a negative response; therefore, the sensitivity of the procedure could not be assessed. However, 36 patients with a negative response to hyperventilation underwent coronary arteriography; 33 (92%) had normal arteriograms and a negative response to ergot derivatives. Hyperventilation appears to be a safe and specific diagnostic procedure in a subset of patients in whom the probability of coronary artery disease may not be judged sufficient to warrant coronary arteriography as a primary diagnostic approach.

Surgical treatment of an atherosclerotic aneurysm of the left main coronary artery.

10. coronary arteries: notes on technical aspects. Cathet Cardiovast Diagn 1990,21:106-11. Bass TA, Miller AB, Rubin RM, Stowers SA, Perryman RA. Transluminal angioplasty of anomalous coronary arteries. AM HEART J 1986;112:610-3. Goulah RD, Goldstein JE, Hart JI. PTCA in anomalous coronary artery. New NJ Med 1989;86:548-50. Schwartz L, Aldridge HE, Sesrle C, Csepio R. Percutaneous transluminal angioplasty of an anomalous left circumflex coronary artery arising from the right sinus of Valsaiva. Cathet Cardiovasc Diagn 1982;8:623-4. Kimbiris D, Lo E, Iskandrian A. Percutaneous transluminal coronary angioplasty of anomalous left circumflex artery. Cathet Cardiovasc Diagn 1987;13:407-10. Rivitz SM, Garratt KN. Stenotic anomalous circumflex artery causing myocardial infarction following angioplasty of a right coronary artery stenosis. Cathet Cardiovasc Diagn 1989;17: 105-8.

Assessment of plexectomy in the treatment of severe coronary spasm in patients with normal coronary arteries

Abstract Surgical denervation of the heart by plexectomy was performed in 3 patients with variant angina, documented coronary spasm, and normal findings on coronary angiography. In all cases, spasm had already been responsible, preoperatively, for myocardial infarction and recurred thereafter in another territory despite medical therapy with a combination of nitrates and calcium antagonists. Plexectomy was performed using a standardized technique. The effectiveness of surgical suppression of cardiac autonomic innervation was confirmed postoperatively by pharmacologic tests. In 2 patients inferior myocardial infarction developed in the early postoperative period; in the third patient, coronary spasm recurred 3 weeks after plexectomy. Thus plexectomy, despite an adequate suppression of autonomic innervation, was ineffective in all cases and may even have been harmful in 2 patients. These data contradict the good results obtained by plexectomy associated with aortocoronary bypass in patients with variant angina and fixed stenotic coronary arteries. This discrepancy may be accounted for by a different pathophysiologic mechanism of vasospasm in normal coronary arteries and in diseased arteries at the site of the atheromatous stenosis. Thus, plexectomy should not be considered in the treatment of vasospasm involving normal coronary arteries, even if medical therapy fails to achieve satisfactory control of variant anginal attacks.