Acute myocardial infarction in a patient with chronic myelocytic leukemia during chemotherapy with hydroxyurea.

BACKGROUND: Cardiac toxicity is a known side effect of chemotherapeutics such as 5-fluorouracil (5-FU) or cisplatin. Chest pain with ECG changes, arrhythmias, acute myocardial infarction (AMI), heart failure and sudden death have been described in the literature. CASE STUDY: We report the first case of AMI in a 59-year-old male patient with chronic myelocytic leukemia (CML) during chemotherapy with hydroxyurea. The patient was not affected by prior heart disease and did not reveal any classic risk factors for coronary heart disease. Because of the severe thrombocytopenia (23000/µl), no acetylsalicylic acid (ASA) or clopidogrel were given but low dose heparin (400 U/h). Urgent coronary angiography revealed complete thrombotic occlusion of the proximal left descending coronary artery. CONCLUSION: This case reveals that AMI can occur during chemotherapy with hydroxyurea in patients without prior heart disease. The pathogenesis of this phenomenon remains hitherto unclear. Coronary artery spasm, lesions of the endothelium as well as coagulation disorders have been postulated to explain this side effect of hydroxyurea.

Levo-alpha-acetylmethadol (LAAM) induced QTc-prolongation - results from a controlled clinical trial.

BACKGROUND: Due to potential proarrhythmic side-effects levo-alpha-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. METHODS: ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1) during a run-in period with all patients on methadone and 2) 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. RESULTS: Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group). No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409s +/- 0.022s versus 0.418s +/- 0.028s, p = 0.046), whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1). CONCLUSIONS: In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended under LAAM medication.

[Sinus node dysfunction with intermittent sinus arrest and AV-nodal escape rhythm as initial manifestation of pheochromocytoma]. / Sinusknotendysfunktion mit intermittierendem Sinusarrest und AV-junktionaler Ersatzrhythmus als Erstmanifestation eines Phäochromozytoms.

A 25-year-old male student complained about episodic palpitations, dizziness, nausea and headache 5 years prior to presentation. No otorhinolaryngic, neurologic or gastrointestinal causes were identified. Several ECG recordings revealed sinus node dysfunction with intermittent sinus arrest and AV-nodal escape rhythm. The patient was given a permanent DDD-pacemaker. Six months later, the clinical symptoms were unchanged. During an attack, physical examination revealed paleness, diffuse sweating and an arterial blood pressure of 250/130 mmHg, which decreased to 120/80 mmHg within a few minutes. Abdominal ultrasound and abdominal computed tomographic scan demonstrated the presence of a large (6.4 x 5.5 cm) left-sided adrenal mass. Two 24-h-urinary collections demonstrated elevated noradrenaline (mean 315 micrograms/24 h, normal < 80 micrograms/24 h) and adrenaline (mean 268 micrograms/24 h, normal < 20 mg/24 h) levels. Blood samples, which were drawn during excessive blood pressure rise, revealed elevation of plasma catecholamines (6.793 pg/ml for adrenaline (normal 50-150 pg/ml) and 10.424 pg/ml for noradrenaline (normal 200-500 pg/ml), so that the diagnosis of pheochromocytoma was considered established. The tumor was successfully removed during laparascopic surgery. After surgery, the patient remained well and normotensive. Three months later, several long-term ECG recordings showed sinus arrhythmia with no evidence of sinus arrest or AV-nodal escape rhythm, so that the DDD pacemaker was turned off. This case underlines that sinus node dysfunction with intermittent sinus arrest and AV-nodal escape rhythm is a potential early manifestation of a pheochromocytoma. These changes seem to disappear after successful removal of the tumor.

Increased heterogeneity of coronary perfusion in patients with early coronary atherosclerosis.

BACKGROUND: In patients with typical angina but angiographically normal coronary arteries, abnormal vasomotor function is assumed to be a major underlying cause. However, data on this issue are conflicting, and recent studies suggest that fluid dynamic abnormalities exist in these patients. The aim of the study was to evaluate whether early stages of atherosclerosis are characterized by alterations of baseline coronary hemodynamics and endothelium-independent vasomotion. Besides established intracoronary Doppler parameters, heterogeneity of perfusion was assessed and related to early signs of atherosclerosis as determined by electron-beam computed tomography (EBCT). METHODS: In 59 patients with typical angina and angiographically normal or near-normal coronary arteries, intracoronary Doppler measurements were performed in all 3 major coronary arteries. Baseline average peak velocity (bAPV) and hyperemic average peak velocity (hAPV) in response to intracoronary injection of adenosine were measured, and coronary flow velocity reserve (CFVR) was calculated. Heterogeneity was assessed as variability of bAPV, hAPV, and CFVR and was calculated as (STD/MEAN). 100. Doppler data were analyzed according to tertiles of the EBCT-derived Agatston calcium score (ie, score 0-1 [lowest tertile], 2-28 [medium tertile], and >28 [highest tertile]). RESULTS: The mean EBCT-derived Agatston calcium score was 49 +/- 107. No coronary calcium was observed in 17 (29%) patients. The mean values of bAPV, hAPV, and CFVR were not different between the calcium score tertiles. However, patients in the highest tertile had a significantly increased variability index of bAPV (29.6% +/- 11.6%) compared with patients in the lowest tertile (13.4% +/- 7.3%, P <.0001). Variability of CFVR was also increased in these patients (15.5% +/- 11.7% vs 10.5% +/- 4.0%, P =.03). CONCLUSION: These results indicate that early stages of atherosclerosis are characterized by microvascular abnormalities that do not uniformly affect the myocardium but are heterogeneous. The high variability of baseline coronary flow velocity with increasing coronary calcium suggests that in patients with early stages of atherosclerosis fluid dynamic effects may play a crucial role even in the absence of angiographically appreciable epicardial stenoses.

[Electromechanically controlled versus roengenologically guided percutaneous transluminal laser myocardial revascularization]. / Elektromechanisch gesteuerte versus röntgenologisch geführte perkutane transluminale Lasermyokardrevaskularisation.

Transmyocardial laser revascularization is a modern therapeutic concept for patients with end-stage coronary artery disease not eligible for bypass surgery, percutaneous coronary interventions or heart transplantation. Although the principal idea of creating additional myocardial perfusion from the cavum of the left ventricle was derived from observations in reptile hearts, histological investigations suggest that channel patency is not the underlying mechanism for improved clinical symptoms. Sympathetic denervation and angioneogenesis may be additional explanations for improvement of angina and stress tolerance. The first experiences with transmyocardial laser revascularization were made using a surgical approach. Two randomized multicenter trials could show a significant improvement in angina and stress tolerance 12 months after creating channels using laser technique. While these results were obtained by performing thoracotomy, catheter-based systems have been designed for a less invasive approach of this technique. A further advantage of these new systems is that regions like the septum can be treated which are not eligible for a surgical approach. Using percutaneous transluminal catheter-based systems channels of up to 6 mm length can be created. Beside the fluoroscopic guided creation of myocardial channels a new mapping system has been applied using electromechanical features of viable myocardial tissue. This system is based on the observation that endocardial electrograms recorded from an infarcted area are characterized by very low amplitude and fractionated morphology. This system allows online mapping of viable myocardium and provides spatial, electrical, and mechanical information of the myocardium. This method of electromechanical mapping highly correlates with results obtained from myocardial perfusion scans. Recent preliminary clinical trials demonstrated that catheter-based creation of myocardial channels is a feasible and successful alternative to the surgical laser revascularization. Also with this approach a significant improvement in angina and stress tolerance can be achieved. The results of the PACIFIC study, the first randomized multicenter study using percutaneous transluminal laser revascularization, demonstrates that after 3 and 6 months more than half of the patients presented improved angina of at least 1 Canadian-Cardiovascular-Society class. Whether electromechanical guided myocardial laser revascularization is more efficient than fluoroscopic guided has not been proven yet. Further studies will have to evaluate this issue.

Corrected coronary flow velocity reserve: a new concept for assessing coronary perfusion.

OBJECTIVES: In order to limit the variability of coronary flow velocity reserve (CFVR), we analyzed which factors independently affect CFVR and established a new parameter integrating these factors. BACKGROUND: Coronary flow velocity reserve (CFVR) is a frequently used parameter for evaluating the physiological significance of epicardial stenosis and microvascular function. Since CFVR measurements are done in substantially different hemodynamic and clinical situations, interpretation of CFVR requires correction for major influencing factors. METHODS: In 141 patients with angina-like symptoms and angiographically unobstructed coronary arteries, intracoronary Doppler measurements were performed in at least two coronary vessels. Coronary flow velocity reserve was calculated as the ratio of hyperemic average peak velocity (hAPV), after intracoronary bolus of adenosine, to baseline average peak velocity (bAPV). RESULTS: Analysis of covariance revealed that only bAPV (p < 0.0001) and age (p < 0.0001) were independent factors influencing CFVR. Based on a regression model for estimation of predicted CFVR values, individual CFVR values (CFVRind) obtained at different bAPV and age were transformed in corrected CFVR values (CFVRcorr) by relating them to a mean bAPV of 15 cm/s and a mean age of 55 years. The transformation from CFVRind into CFVRcorr for the left anterior descending artery can be done by using the following equation: CFVRcorr = 2.85*CFVR(ind)*10(0.48*log(bAPV)+(0.0025*age)-1.16). When applying this new parameter to conditions assumed to cause microvascular dysfunction, analysis showed that only patients with diabetes showed a significant decrease of traditional CFVR and CFVRcorr, whereas a history of hypertension and current smoking habit had no influence on CFVRcorr. CONCLUSIONS: The concept of CFVRcorr standardizes CFVR for bAPV and age as the major physiological determinants. Especially in patients with microvascular dysfunction, this approach may help to discriminate between conditions directly affecting vasodilator reserve and conditions primarily affecting bAPV.