Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas' disease: assessment by dobutamine stress echocardiography.

OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium. BACKGROUND: Segmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas' heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas' disease. In addition, chagasic sera may contain autoantibodies against human beta-adrenergic receptors. METHODS: Two groups of patients with Chagas' disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation. RESULTS: Patients with Chagas' disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas' group 1 (54.7+/-6.6%; SD) and in group 2 (35.1+/-12.1%) were significantly lower than control group (66.7+/-2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas' disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001). CONCLUSIONS: Thus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease.

Two-year follow-up after intracoronary gamma radiation therapy.

BACKGROUND: Neointimal hyperplasia and unfavorable remodeling have been demonstrated to be the major limitation to endovascular revascularization procedures. Intracoronary gamma radiation therapy has been shown to reduce the restenosis index. However, the late effects of these novel procedures are unknown. MATERIALS AND METHODS: To evaluate the long-term effects on clinical and angiographic outcome of endovascular gamma radiation therapy following percutaneous transluminal coronary angioplasty (PTCA), serial angiography over a 2-year period was performed in 21 patients (22 lesions) who were treated with 192Ir in doses of 20-25 Gy after PTCA. Angiograms were analyzed using quantitative methods (QCA). RESULTS: The mean late loss between PTCA and 6 months was 0.20 +/- 0.59 and 0.13 +/- 0.84 between 6 months and 2 years. At 6 months, angiographic binary restenosis was present in six arteries (27.2%). At 2 years, binary restenosis was observed in six arteries (27.2%), including one patient who had developed restenosis and excluding one patient with spontaneous regression. Two early pseudoaneurysms and two late aneurysms were observed at 6 months, with little increase at 2 years. No other angiographic complication was observed. None of the patients or medical staff developed complications or illnesses that could be related to the effects of the radiation procedure. CONCLUSIONS: Gamma radiation therapy decreases late luminal loss, is safe and free of unexpected complications at 6 months follow-up, with no significant changes or late complications at 2-years' follow-up.

Long-term angiographic and clinical outcome after percutaneous transluminal coronary angioplasty and intracoronary radiation therapy in humans.

BACKGROUND: Ionizing radiation has been shown to reduce neointimal formation after balloon angioplasty in experimental models of restenosis. This study was designed to evaluate the feasibility, safety, and effectiveness of intracoronary radiation therapy (ICRT) after percutaneous transluminal coronary angioplasty (PTCA) for preventing restenosis in human coronary arteries. METHODS AND RESULTS: Twenty-one patients (22 arteries) with unstable angina underwent standard balloon angioplasty. ICRT was performed with the use of an 192Ir source wire that was hand delivered to the angioplasty site. Angiographic follow-up was performed at 24 hours, between 30 and 60 days, and at 6 months. Angioplasty was successful in 19 of 22 lesions, and insertion of the radioactive source wire was successful at all treated sites. Angiographic study at 24 hours demonstrated early late loss of the luminal diameter from 1.92+/-0.55 to 1.40+/-0.27 mm. Between 30 and 60 days, repeat angiography demonstrated total occlusion in 2 arteries, a new pseudoaneurysm in 1 artery, and significant dilatation at the treatment site in 2 additional vessels. At > or = 6 months' follow-up, all remaining arteries (n=20) maintained patent, with a mean lumen diameter of 1.65+/-0.8 mm. The calculated late lumen loss was 0.27+/-0.56 mm, and the late loss index was 0.19. Clinical events at 1 year included myocardial infarction in 1 patient, repeat angioplasty to the treated site in 3 patients, and persistent angina in 7 patients. CONCLUSIONS: These preliminary results demonstrate that ICRT after coronary intervention is feasible and is associated with an acceptable degree of complications and lower rates of angiographic restenosis indexes.

Basis of endovascular radiation therapy in human coronary arteries.

Restenosis is the major limitation to a full expansion of all revascularization procedures. Elastic coil, unfavorable remodeling and a proliferative response to injury are the more importune mechanisms to restenosis. Ionizing radiation based on the inhibitory effect on cellular proliferation has been widely used in the treatment of numerous neoplastic and non neoplastic conditions. Experimental brachytherapy has demonstrated to reduce restenosis in peripheral arteries and coronary arteries in animal models and gamma-radiation therapy decrease restenosis after stent implantation in femoral-popliteal arteries in patients. We developed to evaluate the feasibility, safety and effects of gamma intracoronary radiation therapy after coronary angioplasty a protocol and used a wire 0.018 and 0.014 inches in diameter and 30 mm active length with 192 Iridium into the closed channel polyethylene catheter was not centered the source within the vessel wall. We prescribed 25 Gy and 20 Gy to the diameter of the reference artery to 21 patients. The 24 hours, two months and after six months angiographic follow up demonstrated that intracoronary radiation therapy was feasible and safe and preliminary analysis point out a reduction in late loss. The efficacy and safety of the different sources and procedures should be well established. There is a great expectation regarding the efficacy and safety of vascular brachytherapy to increasing the use of endovascular recanalization procedures.

Coronary vascular reactivity is abnormal in patients with Chagas' heart disease.

Symptoms of myocardial ischemia, such as chest pain (sometimes with anginal features), acute myocardial infarction, and segmental wall motion abnormalities (including left ventricular apical aneurysm), frequently occur in patients with Chagas' heart disease. Because these clinical findings occur in the presence of normal coronary arteries, it is possible that an abnormality of the coronary vascular reactivity could be present in these patients. Therefore the current study was undertaken to determine whether endothelium-dependent coronary vasodilation is abnormal in Chagas' heart disease. Coronary endothelial function was assessed by infusing the endothelium-dependent vasodilator acetylcholine (10(-8) to 10(-6) mol/L) and the endothelium-independent vasodilator adenosine (10(-4) mol/L) into the left anterior descending coronary artery of nine patients (age 43 +/- 4 years) with Chagas' heart disease. Coronary blood flow was measured with a Doppler flow velocity catheter and by quantitative coronary cineangiography. The left ventricular ejection fraction was 39% +/- 5%; eight patients had a left ventricular apical aneurysm; and one had an area of anteroapical hypokinesis. An impairment of the endothelium-dependent coronary vasodilation was demonstrated by a reduction in coronary blood flow of 41.2% +/- 12.8% produced by the infusion of acetylcholine at 10(-6) mol/L and by a blunted but preserved increase in coronary blood flow of 114.6% +/- 65.0% with the infusion of adenosine at 10(-4) mol/L (p = 0.03). In conclusion, patients with Chagas' heart disease have an abnormality of the coronary endothelium-dependent vasodilation, and this abnormality may play a role in their chest pain syndrome and in the development of segmental wall motion abnormalities.