Vassilios Prassopoulos

Doxorubicin-induced cardiac neurotoxicity: Study with iodine 123-labeled metaiodobenzylguanidine scintigraphy

BackgroundIodine 123-labeled metaiodobenzylguanidine (123I-MIBG) can be used to generate a scintigraphic image of the adrenergic nervous innervation of the heart.Methods and ResultsTo test the hypothesis that doxorubicin may lead to damage of cardiac neurons, we examined 37 patients with various malignant neoplasms, 14 of whom were on therapy with doxorubicin. All patients were examined with 123I-MIBG scintigraphy and radionuclide ventriculography. Cardiac 123I-MIBG uptake was assessed by means of a heart to mediastinum activity ratio (H/M). Left ventricular ejection fraction was not different in patients with or without doxorubicin. In patients receiving doxorubicin, the H/M ratio was significantly lower (1.73±0.25 vs 2.13±0.25, p<0.001) and correlated with doxorubicin cumulative dose (r=−0.51, p<0.001). By using a H/M ratio of 1.73 as a cutoff point, 123I-MIBG uptake was abnormal in none of the 23 patients not receiving and 6 of 14 patients receiving doxorubicin therapy (p<0.001). In 10 patients initially not receiving doxorubicin, 123I-MIBG scintigraphy was repeated after receiving 236±47 mg/m2 of doxorubicin. The H/M became abnormal in 3 of 10 patients, whereas the ejection fraction became abnormal in 2 of 10 patients.Conclusion123I-MIBG cardiac uptake decreases in a doxorubicin dose-dependent way, indicating a cardiac adrenergic neurotoxic effect of doxorubicin. This phenomenon appears early and generally before deterioration of the ejection fraction.

Dobutamine-induced ST-segment elevation in patients with healed myocardial infarction: A marker of myocardial viability

The purpose of this study was to determine the significance of transient ST-segment elevation during dobutamine infusions in patients with healed Q wave myocardial infarction. Twenty-seven patients with previous Q wave myocardial infarction were studied prospectively with dobutamine-thallium-201 single-photon emission computed tomography. The presence of ST-segment elevation in leads with Q waves was related to thallium reversibility at 4-hour redistribution imaging or after reinjection, to residual flow, as well as to wall motion abnormalities in the infarcted zone. ST-segment elevation in infarct-related leads was observed in 15 patients; 11 (73%) showed viability by thallium-201 in the infarcted zone. In patients without ST-segment elevation, viability was shown less frequently (33%, P < .05). Hypokinesis in infarcted segments was present in 60% of patients with ST-segment elevation and in 25% of patients without ST-segment elevation (.05 < P < .1). Finally, infarct-related artery was patent and/or collaterals were present in 10 patients with ST-segment elevation (67%) and in 4 patients without (33%, .05 < P < .1). In conclusion, ST-segment elevation during dobutamine infusion is a marker of residual viability in infarcted segments.

Antimyosin Scintigraphy for Detection of Cardiac Amyloidosis

The diagnostic value of antimyosin scanning in 7 patients with biopsy-proven cardiac amyloidosis was examined in this study. Antimyosin imaging was positive in all amyloid patients, with more intense uptake in patients with heart failure.

Natural evolution of antimyosin scan and cardiac function in patients with acute myocarditis

Indium-111 monoclonal antimyosin antibody imaging is a convenient method to diagnose acute myocarditis. The present study examined the natural evolution of a positive antimyosin scan in 10 patients with acute myocarditis, in relation to left ventricular ejection fraction. All patients underwent myosin-specific monoclonal antibody imaging and radionuclide ventriculography; in all patients endomyocardial biopsy was performed. Repeat assessment of left ventricular function and antimyosin uptake was performed 1, 2 and 6 months later. A heart-to-lung ratio was used to quantify antimyosin uptake. Heart-to-lung ratio in patients with myocarditis was 2.12 +/- 0.31, significantly higher than that observed in eight controls (1.35 +/- 0.08, P < 0.001). During follow-up 2.2 repeat scans per patient were performed. Heart-to-lung ratio normalized (< 1.6) within 1 month in four patients, within 2 months in one patient and within 6 months in two patients; three patients continued to have a positive antimyosin uptake at 6 months, suggesting ongoing myocardial necrosis. At the end of follow-up, ejection fraction improved by > 5% in four patients; normalization or persistence of tracer uptake could not predict an improvement of ejection fraction. It is concluded that antimyosin scintigraphy is useful for diagnosing myocarditis in its subacute or chronic stage during which unknown or immune mechanisms may be in operation. An improvement in left ventricular function cannot be predicted on the basis of persistence or not of tracer uptake.

Myocardial adrenergic denervation in patients with primary (AL) amyloidosis

Three patients, 2 women and 1 man, with primary (AL) amyloidosis without congestive heart failure are described; all 3 patients presented reduced 1–123 metaiodo-benzylguanidine(MIBG) myocardial uptake suggesting marked cardiac sympathetic denervation. This is the first time myocardial adrenergic denervation is described in patients with AL amyloidosis without evidence of congestive heart failure; the observed denervation could be implicated in the pathogenesis of cardiac conduction disturbances which are common in this disease.

Indium-111 monoclonal antimyosin cardiac scintigraphy in men with idiopathic dilated cardiomyopathy

This study examined the prognostic value and the evolution of the heart-to-lung ratio of monoclonal antimyosin antibody (MAA) uptake in patients with a diagnosis of idiopathic dilated cardiomyopathy (IDC). Uptake of indium-111-labeled MAA occurs when the myocytes become irreversibly damaged. The study included 29 men with IDC followed up for 3 years. The diagnosis was verified by endomyocardial biopsy in all patients. Patients who survived beyond 1 year were restudied. Baseline heart-to-lung ratio of MAA was 1.74+/-0.22. Multivariate Cox regression analysis revealed that MAA and New York Heart Association class were independent predictors of late mortality, with a hazard ratio of 4.4 (95% confidence interval 1.1 to 17.9, p = 0.036) and 7.5 (95% confidence interval 2.0 to 28.4, p = 0.003), respectively, when heart-to-lung ratio of MAA uptake was > 1.74 and New York Heart Association class was >11. When these patients were divided into those with chronic IDC (group I [n = 19]) and those with subacute IDC (group II [n = 10]), baseline heart-to-lung ratio was 1.7+/-0.2 and 1.86+/-0.25, respectively (p = NS). In the surviving patients, on restudy, the heart-to-lung ratio of MAA uptake was unchanged in group I (1.64+/-0.20, p = NS), but had decreased to the level of group I (1.66+/-0.21 [p = 0.008]) in group II. Thus, men with IDC and a high heart-to-lung ratio of MAA uptake have a worse long-term prognosis than patients with a lower ratio. The heart-to-lung ratio of MAA decreases comparably over time in subacute IDC and remains stable in chronic IDC.

DETECTION OF MICROINFARCTION IN PATIENTS WITH UNSTABLE ANGINA : STUDY BY 111IN-ANTIMYOSIN IMAGING

To examine the incidence of a positive indium-111 antimyosin scintigraphy in patients with unstable angina, we prospectively examined 25 patients with unstable angina and 11 patients with stable angina. All patients were injected with 2 mCi of indium-111 on admission and planar scintigraphy was performed 48 h later. Symptoms and signs of ischemia indicating severity of ischemia were monitored during the period between injection and scanning. None of the patients developed a rise in cardiac enzymes suggesting myocardial necrosis. Seven (28%) of the 25 patients with unstable angina had positive antimyosin scanning; no stable patients had positive scanning. All seven patients with unstable angina and positive scanning had signs of severe ischemia (four patients had multiple episodes of > 2/day, three patients had prolonged episodes of > 15 min, three patients had ST depression in > 3 EKG leads) while only one of the eighteen unstable patients with negative scannings had signs of severe ischemia (P < 0.001). In conclusion, (1) a significant number of unstable angina patients present positive antimyosin scanning without an elevation of cardiac enzymes and (2) these patients usually present multiple or severe episodes of ischemia indicating that during these episodes, minor myocardial necrosis, undetected by enzymes, may occur.