Cardiovascular adverse events complicating the administration of rituximab: report of two cases.

Rituximab is a murine/human chimeric monoclonal antibody directed against the CD20 antigen. It is widely used in combination with polychemotherapy regimens for the treatment of hematological disorders. There is no evidence of direct cardiotoxicity of the drug but a few cases of cardiovascular adverse events have been reported in the literature. We report on two patients affected by stage IV non-Hodgkin lymphoma with bone marrow infiltration and peripheral blood involvement who experienced cardiovascular accidents temporally related to rituximab infusion. In both cases the monoclonal antibody was administered in association with a polychemotherapy regimen but administration was postponed several days later in order to avoid severe cytokine release syndrome because of the high tumor burden. The first case concerns an episode of atrial fibrillation in a patient with a diagnosis of small B-cell lymphoma. The episode happened immediately after rituximab infusion. In the second case there was an episode of chest pain associated with fever and chills during rituximab infusion in a patient with a diagnosis of mantle cell lymphoma. In both cases we noticed an unusual correlation between symptom recurrence and the speed of rituximab infusion. Both patients presented several cardiovascular risk factors but preliminary cardiac function assessment excluded signs of heart dysfunction. The pathogenesis of cardiovascular events during rituximab infusion remains unclear. A key role might be played by cytokine release from B cells as a consequence of rituximab activity. Moreover, pre-existing silent cardiac damage could be co-responsible for the clinical manifestations we reported. We consider our clinical experience relevant because it raises an issue of good clinical practice: despite rituximab's good tolerability profile, patients with cardiovascular risk factors should undergo accurate cardiac assessment so that silent heart disease can be detected. If the suspicion of cardiac damage is high, more extensive cardiac assessment is recommended.

Weekly standard doses of rh-EPO are highly effective for the treatment of anemic patients with low-intermediate 1 risk myelodysplastic syndromes.

For more than 20 years erythropoietin (rHEPO) has largely been used to treat anemia in myelodysplastic syndromes (MDS). Early clinical trials showed erythroid responses in no more than 15-25% of patients. In the last decade, a better selection of MDS patients suitable for a therapeutic challenge with rHEPO, alone or in combination with G-CSF, allowed for an increased response-rate, averaging around 40%. More recently, an even higher percentage of responses have been obtained using higher-doses of rHEPO (up to 80,000 IU/weekly) in lower-risk MDS patients. This treatment however, especially at such high doses, is costly and not easily affordable for prolonged periods. The aim of this study was to verify if the use of "standard" doses of rHEPO could induce a satisfying response-rate with a less expensive treatment schedule in IPSS-defined "lower-risk" MDS anemic patients. From January 2005 to December 2009 a total of 55 consecutive anemic (Hb ≤ 10 g/dL) patients (29 males, 26 females, median age 78 years) with low-intermediate-1 risk MDS were treated after informed consent with rHEPO (40,000 IU once a week subcutaneously) for at least 3 months; at the end of this period, erythroid response was assessed, and responders were allowed to continue the treatment indefinitely, whereas non-responders were considered "off study". Both efficacy and safety of the treatment were recorded and evaluated. After 3 months of treatment, 36 out of 55 (65.5%) patients achieved an erythroid response to rHEPO according to IWG 2006 criteria. Higher response-rates to rHEPO were related with both lower IPSS and particularly WPSS scores. Treatment was safe, and only 1 patient had to discontinue the treatment because of unmanageable side-effects. Among the 36 responders, 28 (77%) maintained the response after a median follow-up of 46 months. Our data indicate that standard doses of rHEPO are at least as effective as higher-doses for correcting anemia in lower-risk MDS patients; in this clinical scenario, this schedule allows for a consistent reduction of costs without precluding the achievement of a durable erythroid response.

Orthostatic hypotension as cause of syncope in patients older than 65 years admitted to emergency departments for transient loss of consciousness.

BACKGROUND: Syncope due to orthostatic hypotension (OH) refers to loss of consciousness caused by hypotension induced by the upright position; it is an important risk factor for fall-related physical injuries, especially in the elderly adults. We evaluated the prevalence of OH syncope and the clinical characteristics of patients older than 65 years with syncope due to OH in the Evaluation of Guidelines in Syncope Study 2 group population. METHODS: Two hundred fifty nine patients older than 65 years consecutively admitted to the emergency department because of loss of consciousness in a period of a month were submitted to a standardized protocol approved by the European Task Force for the diagnosis of syncope; all the patients were studied by a trained physician who interacted with a central supervisor as the management of syncope was concerned, using a decision-making software. RESULTS: Prevalence of OH syncope was 12.4%. Patients with OH syncope were more likely to be affected by Parkinson's disease and by other neurological diseases. ST changes and longer values of QTc were found in OH syncope group, and they took a greater number of diuretics, nitrates, and digoxin. In multivariate analysis, Parkinson's disease (p = .001) and use of nitrates (p = .001) and diuretics (p = .020) were independently related to OH syncope. CONCLUSIONS: In patients older than 65 years, Parkinson's disease and neurological comorbidity are strictly related to OH syncope. Moreover, this study suggests the independent link between OH syncope and the use of vasoactive drugs, identifying the majority of cases as adverse drug reaction, a preventable risk factor for syncope and falls in the older population.

Standardized-care pathway vs. usual management of syncope patients presenting as emergencies at general hospitals.

AIMS: The study hypothesis was that a decision-making approach improves diagnostic yield and reduces resource consumption for patients with syncope who present as emergencies at general hospitals. METHODS AND RESULTS: This was a prospective, controlled, multi-centre study. Patients referred from 5 November to 7 December 2001 were managed according to usual practice, whereas those referred from 4 October to 5 November 2004 were managed according to a standardized-care pathway in strict adherence to the recommendations of the guidelines of the European Society of Cardiology. In order to maximize its application, a decision-making guideline-based software was used and trained core medical personnel were designated-both locally in each hospital and centrally-to verify adherence to the diagnostic pathway and give advice on its correct application. The 'usual-care' group comprised 929 patients and the 'standardized-care' group 745 patients. The baseline characteristics of the two study populations were similar. At the end of the evaluation, the standardized-care group was seen to have a lower hospitalization rate (39 vs. 47%, P=0.001), shorter in-hospital stay (7.2+/-5.7 vs. 8.1+/-5.9 days, P=0.04), and fewer tests performed per patient (median 2.6 vs. 3.4, P=0.001) than the usual-care group. More standardized-care patients had a diagnosis of neurally mediated (65 vs. 46%, P=0.001) and orthostatic syncope (10 vs. 6%, P=0.002), whereas fewer had a diagnosis of pseudo-syncope (6 vs. 13%, P=0.001) or unexplained syncope (5 vs. 20%, P=0.001). The mean cost per patient and the mean cost per diagnosis were 19 and 29% lower in the standardized-care group (P=0.001). CONCLUSION: A standardized-care pathway significantly improved diagnostic yield and reduced hospital admissions, resource consumption, and overall costs.

A new management of syncope: prospective systematic guideline-based evaluation of patients referred urgently to general hospitals.

AIMS: The guidelines of the European Society of Cardiology (ESC) define the current standard for the management of syncope, but are still incompletely applied in the clinical setting. METHODS AND RESULTS: Prospective systematic evaluation, on strict adherence to the guidelines, of consecutive patients referred for syncope to the emergency departments of 11 general hospitals. In order to maximize the application, a decision-making guideline-based software was used and trained core medical personnel were designated-both locally in each hospital and centrally-to verify adherence to the diagnostic pathway and give advice on its correction. A diagnostic work-up consistent with the guidelines was completed in 465/541 patients (86%). A definite diagnosis was established in 98% (unexplained in 2%): neurally mediated syncope accounted for 66% of diagnosis, orthostatic hypotension 10%, primary arrhythmias 11%, structural cardiac or cardiopulmonary disease 5%, and non-syncopal attacks 6%, respectively. The initial evaluation (consisting of history, physical examination, and standard electrocardiogram) established a diagnosis in 50% of cases. Hospitalization for the management of syncope was appropriate in 25% and was required for other reasons in a further 13% of cases. The median in-hospital stay was 5.5 days (interquartile range, 3-9). Apart from the initial evaluation, a mean of 1.9+/-1.1 appropriate tests per patient was performed in 193 patients and led to a final diagnosis in 182 of these (94%). CONCLUSION: The results of this study assess the current standard for the management of syncope on the basis of a rigorous adherence to guidelines of the ESC and provide a frame of reference for daily activity when dealing with syncope.