Association between Epicardial Adipose Tissue and Atrial Fibrillation in Patients with Transfusion-Dependent ß-Thalassemia.

Background: Modern treatments for transfusion-dependent ß-thalassemia (TDßT) have allowed patients to reach high life expectancy with no iron overload. Despite survival improvement, atrial fibrillation (AF) has emerged as a relevant issue. AF pathophysiology and characteristics in TDßT are different than in the general population. Epicardial adipose tissue (EAT) may play a role but its relationship with AF in patients with TDßT has not been explored. Methods: A monocentric, cross-sectional study, enrolling consecutive patients with TDßT. Epicardial adipose tissue (EAT) was evaluated at magnetic resonance. Characteristics of patients with and without history of AF were investigated. Factors independently associated with AF prevalence were analyzed. Results: A total of 116 patients were enrolled. All patients were treated with regular chelation therapy. The prevalence of AF was 29.3% (34/116). Cardiac T2* and liver iron concentration were no different between patients with and without AF. EAT thickness was significantly higher in patients with AF at left atrium, right atrium and right ventricle (5.0 vs. 4.0 mm, p < 0.01, 4.4 vs. 4.0, p = 0.02 and 5.0 vs. 4.3, p = 0.04). Patients with AF presented with older age, (53 vs. 49 years, p < 0.01), more hypothyroidism (44.1 vs. 20.7%, p = 0.01), pulmonary hypertension (23.5 vs. 2.4% p < 0.01), splenectomy (88.2 vs. 64.6%, p = 0.01), higher right and left atrial volume (61 vs. 40 and 74 vs. 43 mL, both p < 0.01). At multivariable analysis, hypothyroidism, left atrial volume and left atrial EAT were independently associated with AF (odds ratio 9.95, 1.09 and 1.91, respectively). Conclusions: In a contemporary cohort of patients with TDßT, treated with regular chelation therapy, prevalence of AF was unrelated to iron overload. EAT was independently associated with AF.

Non-Vitamin K Antagonist Oral Anticoagulants in Patients with ß-Thalassemia.

Background. Patients with ß-thalassemia have a high incidence of atrial fibrillation (AF) and other supraventricular arrhythmias. The use of non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prophylaxis in patients with ß-thalassemia has not been systematically evaluated. Methods. We enrolled patients with transfusion-dependent ß-thalassemia, who were on treatment with NOACs for thromboembolic prophylaxis of supraventricular arrhythmias. Data on thromboembolic and bleeding events were collected. Results. Eighteen patients were enrolled. The patients had a history of AF (sixteen), typical atrial flutter (five), and atypical atrial flutter (four). The patients were treated with dabigatran (seven), apixaban (five), rivaroxaban (four) or edoxaban (two). The mean follow-up duration was 22 ± 15 months. No thromboembolic events were reported. No major bleedings were observed. Three patients had non-major bleeding events. Two patients reported dyspepsia during treatment with dabigatran and were shifted to a different NOAC. Conclusions. Our study suggests the efficacy and safety of NOACs in patients affected by transfusion-dependent ß-thalassemia.

[Heavy metal! A case of severe iron overload and supraventricular arrhythmias in a thalassemia major patient]. / Heavy metal! Un caso di severo accumulo di ferro e aritmie sopraventricolari in paziente con talassemia major.

Cardiovascular complications are among the main causes of mortality and morbidity in patients with thalassemia major. Iron-chelation therapy is essential to prevent the chronic iron overload linked to the need for transfusions and the consequent cardiac hemosiderosis. Despite the wide use of iron-chelation drugs, today it is still possible to find cases of severe iron accumulation. Furthermore, even regardless of iron overload and cardiac dysfunction, the thalassemic patient has a high arrhythmic burden, especially for supraventricular arrhythmias. There are still many doubts and open questions about the management of such patients, especially regarding the correct use of anticoagulant therapy and the best utilization of therapeutic strategies available for rhythm control. The case presented shows how the interventional approach with catheter ablation can be useful also in the acute phase when antiarrhythmic drugs are ineffective and it is not possible to wait for the iron-chelation therapy to take effect.

Atrial Fibrillation in ß-Thalassemia: Overview of Mechanism, Significance and Clinical Management.

Thalassemia is an inherited blood disorder with worldwide distribution. Transfusion and chelation therapy have radically improved the prognosis of ß-thalassemic patients in the developed world, but this has led to the development of new chronic cardiac complications like atrial fibrillation (AF). Prevalence of AF in patients with ß-thalassemia is higher than in the general population, ranging from 2 to 33%. Studies are lacking, and the little evidence available comes from a small number of observational studies. The pathophysiology is not well understood but, while iron overload seems to be the principal mechanism, AF could develop even in the absence of iron deposition. Furthermore, the clinical presentation is mainly paroxysmal, and patients are highly symptomatic. The underlying disease, the pathophysiology, and the clinical presentation require a different management of AF in ß-thalassemia than in the general population. Rhythm control should be preferred over rate control, and the most important antiarrhythmic therapy is represented by chelation drugs. Thromboembolic risk is high, but the available risk scores are not validated in ß-thalassemia, and the choice of anticoagulation therapy should be considered early. The main purpose of this review is to summarize the actual knowledge about AF in ß-thalassemia, with a specific focus on the clinical management of these complex patients.

Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage.

BACKGROUND: Intracranial haemorrhage is a serious and potentially fatal complication of oral anticoagulant therapy. Prothrombin complex concentrates can substantially shorten the time needed to reverse the effects of oral anticoagulants. The aim of this study was to determine the efficacy and safety of a prothrombin complex concentrate for rapid reversal of oral anticoagulant therapy in patients with intracranial haemorrhage. METHODS: Patients receiving oral anticoagulant therapy and suffering from acute intracranial haemorrhage were eligible for this prospective cohort study if their International Normalised Ratio (INR) was higher than or equal to 2.0. The prothrombin complex concentrate was infused at doses of 35-50 IU/kg, stratified according to the initial INR. RESULTS: Forty-six patients (25 males; mean age: 75 years; range 38-92 years) were enrolled. The median INR at presentation was 3.5 (range, 2-9). At 30 minutes after administration of the prothrombin complex concentrate, the median INR was 1.3 (range, 0.9-3), and the INR then declined to less than or equal to 1.5 in 75% of patients. The benefit of the prothrombin complex concentrate was maintained for a long time, since the median INR remained lower than or equal to 1.5 (median, 1.16; range, 0.9-2.2) at 96% of all post-infusion time-points up to 96 hours. No thrombotic complications or significant adverse events were observed during hospitalisation; six patients (13%) died, but none of these deaths was judged to be related to administration of the prothrombin complex concentrate. CONCLUSIONS: Prothrombin complex concentrates are an effective, rapid and safe treatment for the urgent reversal of oral anticoagulation in patients with intracranial haemorrhage. Broader use of prothrombin complex concentrates in this clinical setting appears to be appropriate.

Temporal variation of heart failure hospitalization: does it exist?

Congestive heart failure (CHF) is the end stage of many cardiac diseases, and one of the leading causes of mortality and morbidity around the world. Coronary heart disease and hypertension (either singly or together) are the main etiology for CHF. It has been reported that major acute cardiovascular events (myocardial infarction, sudden death, cardiac arrest, ischemic and hemorrhagic stroke, pulmonary embolism, rupture/dissection of aortic aneurysms) do not occur randomly through time, but exhibit a specific temporal periodicity characterized by seasonal (winter), weekly (Monday), and circadian (morning) patterns of onset. Thus, because the major causes of CHF present a temporal pattern, in the past several years some studies have investigated the temporal variation of CHF hospitalization and mortality, with results indicating the possibility of a preference for winter months, Mondays, and nighttime, respectively.

Seasonal and weekly patterns of hospital admissions for nonfatal and fatal myocardial infarction.

OBJECTIVE: This retrospective study, based on the database of hospital admissions of the region Emilia-Romagna [RER], Italy, was aimed to confirm the existence of a seasonal or weekly pattern of hospital admission of acute myocardial infarction (AMI) and to verify possible differences between nonfatal or fatal cases. METHODS: The study included all cases of patients with AMI hospitalized between 1998 and 2006. Day of admission was categorized, respectively, into four 3-month intervals, into twelve 1-month intervals, and into seven 1-day intervals for statistical analysis, performed by chi(2) test goodness of fit and partial Fourier series on total cases, males, females, and nonfatal and fatal cases. RESULTS: The database included 64 191 cases of AMI (62.9% males, 12.3% fatal). Acute myocardial infarction was most frequent in winter and least in summer (P < .0001). The highest number of cases was recorded in January and the lowest in July (P < .0001). Chronobiologic analysis showed winter peaks for total cases (January, P = .035), females (December, P = .009), and fatal cases (January, P < .001). Acute myocardial infarction was most frequent on Monday and least on Sunday (P < .0001). Comparing observed vs expected events, there was a significantly higher frequency of cases on weekdays and reduced on weekends, for total (P < .0001), nonfatal (P < .0001), and fatal cases (P = .0001). CONCLUSIONS: This study confirms a significantly higher frequency of AMI admissions in winter and on a Monday. No difference in the frequency of nonfatal vs fatal events, depending of patients' admissions on weekdays or weekends, was found.

Pancytopenia associated with levetiracetam treatment.

Levetiracetam is a pyrrolidine derivate that is approved for the treatment of seizures. It has a favourable pharmacokinetic profile, no clearly established pharmacological interactions, good tolerability and offers the possibility of rapid treatment. We describe a case of pancytopenia and multiple infections observed in the context of levetiracetam treatment. A 65-year-old woman who underwent surgical removal of a meningioma developed progressive pancytopenia complicated by pneumonia and multiple liver abscesses after starting levetiracetam therapy. Bone marrow aspiration and biopsy confirmed the diagnosis. A gradual spontaneous recovery of normal haematopoiesis followed discontinuation of levetiracetam.

An unusual case of hyperammonemia in a 83-year-old woman.

Hyperammonemia, with confusion and lethargy, developed in a 83-year-old woman during a urinary tract infection by Morganella morganii, a urea-splitting Gram-negative bacillus. In this patient, it is thought to have resulted from the production of excessive amounts of ammonia due to bacterial urease and its subsequent reabsorption into systemic circulation. The patient was treated with specific antibiotic therapy, with resolution of the urinary tract infection, progressive reduction in ammonia blood levels, and a parallel improvement in her consciousness and cognitive status.