Dual vs. triple antithrombotic treatment after percutaneous coronary intervention in patients with non-valvular atrial fibrillation: a meta-analysis on current evidence.

OBJECTIVE: Combination and duration of antithrombotic therapy in order to prevent both stent thrombosis and thromboembolic complications after coronary artery stenting (PCI) in non-valvular atrial fibrillation (AF) is still debated. This uncertainty can be attributed mainly to the fact that the reference trials were open-label and not adequately powered in order to reach a definitive conclusion on ischemic endpoints (i.e., stent thrombosis). On these grounds, data from real-life studies could support evidence on dual antithrombotic treatment (DAT) safety (bleeding risk) and efficacy (stent thrombosis prevention). The aim of the meta-analysis is to investigate in both randomized controlled trials (RCTs) and observational studies (Obs) the risks and/or benefits related to DAT vs. triple antithrombotic treatment (TAT) regimens in patients affected by AF undergoing PCI. MATERIALS AND METHODS: RCTs and Obs were retrieved through PubMed database. The risk ratio with 95% confidence interval was used to compare the primary and the safety endpoints. RESULTS: Meta-analysis demonstrated no significant differences between DAT vs. TAT for mortality. However, a two-fold higher mortality rate was registered in Obs than in RCTs. The Obs did not confirm the expected significant reduction in bleeding risk shown by the RCTs; however, the bleeding rates in Obs were more than three-fold those of RCTs. In Obs, a significant greater risk for stent thrombosis was observed in DAT than in TAT. CONCLUSIONS: The safety and efficacy outcomes observed in RCTs are unrealistic with respect to the current clinical practice. So, more evidence is needed to have more exhaustive guidelines based on RCTs with homogeneous designs and protocols that should mimic real-life population and practice.

Takotsubo cardiomyopathy and flecainide toxicity: a case report and brief literature review.

OBJECTIVE: Takotsubo syndrome, also known as stress cardiomyopathy, is predominantly reported in postmenopausal women and it is often triggered by a physical or emotional stressor. CASE REPORT: We present the case of a 44-year-old Caucasian woman admitted to the emergency department after voluntary intake of 20 tablets of flecainide 150 mg to commit suicide. During the in-hospital stay in the Cardiac Intensive Care Unit, the patient developed Takotsubo syndrome. CONCLUSIONS: The relative role of flecainide as a possible trigger of the syndrome is discussed in the context of the current literature evidence.

Improving performance of 3D speckle tracking in arterial hypertension and paroxysmal atrial fibrillation by using novel strain parameters.

The function of left atrium (LA) is closely related to LA remodeling and one of the most important mechanisms is an increased deposition of fibrous tissue that often is the basis for LA electro-mechanical changes before the onset of atrial fibrillation (AF). This study evaluated LA shape and function, by investigating standard and novel strain parameters calculated by a new approach based on homologous times derived from 3D speckle tracking echocardiography (3DSTE) in hypertensive (HT) and paroxysmal atrial fibrillation (PAF) patients with or without left ventricular hypertrophy (LVH), compared to control (C) subjects. LA function was assessed using homologous times to compare strain variables among different individuals, acquired at different physiological time periods. Standard global longitudinal (GLS) and circumferential (GCS) strains were measured at peak of atrial diastole, while longitudinal and circumferential strains (GLSh, GCSh), strain rate (GLSr, GCSr), volume (Vh) and volume rate (Vr) were measured during the atrial telediastolic phase (fifth homologous time) and atrial pre-active phase (tenth homologous time). Using ANOVA, we found an impaired LA deformation detected by standard, interpolated strains and strain rates in both HT and PAF groups compared to C. We also performed ROC analysis to identify different performances of each parameter to discriminate groups (GLSr10 + GCSr10: C vs PAF 0.935; C vs PAF_LVH 0.924; C vs HT_LVH 0.844; C vs HT 0.756). Our study showed anatomical and functional LA remodeling in patients with PAF and HT. 3D strains and strain rates derived from the homologous times approach provide more functional information with improved performance to identify among the explored groups, in particular PAF patients.

Is it possible a new definition of metabolic syndrome in childhood?

OBJECTIVE: To investigate whether a group of Italian children and adolescents who were diagnosed to have metabolic syndrome (MS) according to a new ethnic age and gender specific definition had, in comparison with a control group, other signs and metabolic risk factors which are commonly associated with MS. PATIENTS AND METHODS: The cross-sectional study population included 300 subjects (51% boys, age range 6-14 years), who were divided into 2 groups according to the presence of MS, diagnosed on the basis of 3/5 factors derived from the age and gender specific quantile distribution of MS components in a large regional Italian population survey (Calabrian Sierras Community Study, CSCS). In all subjects the following data were collected: anthropometric measures, blood pressure, liver function, C-reactive protein (hsCRP), uric acid blood levels, lipid and glucose profile. Triglycerides/HDL-cholesterol (TG/HDL-C) ratio was calculated. RESULTS: There were 38 subjects (13%) with MS, who had higher indices of growth and fat distribution and higher blood levels of uric acid, alanine aminotransferase and gamma-glutamyltransferase. TG/HDL ratio was higher (median 3.11 vs. 1.14, p = 0.00001) in MS subjects who had lower apolipoprotein A and higher apolipoprotein B and non-HDL-C levels. hsCRP was not different between groups. CONCLUSIONS: Our ethnic age and gender specific definition of MS in Italian children and adolescents was able to identify in a youth group different cardiometabolic risk factors related to insulin resistance, endothelial damage and nonalcoholic fatty liver disease, which are commonly associated with MS diagnosis.

Non-invasive assessment of functional strain lines in the real human left ventricle via speckle tracking echocardiography.

A mechanics-based analysis of data from three-dimensional speckle tracking echocardiography is proposed, aimed at investigating deformations in myocardium and at assessing shape and function of distinct strain lines corresponding to the principal strain lines of the cardiac tissue. The analysis is based on the application of a protocol of measurement of the endocardial and epicardial principal strain lines, which was already tested on simulated left ventricles. In contrast with similar studies, it is established that endocardial principal strain lines cannot be identified with any structural fibers, not even along the systolic phase and is suggested that it is due to the capacity of the endocardial surface to contrast the dilation of the left ventricle.

Torsion of the human left ventricle: experimental analysis and computational modeling.

We set a twofold investigation: we assess left ventricular (LV) rotation and twist in the human heart through 3D-echocardiographic speckle tracking, and use representative experimental data as benchmark with respect to numerical results obtained by solving our mechanical model of the LV. We aim at new insight into the relationships between myocardial contraction patterns and the overall behavior at the scale of the whole organ. It is concluded that torsional rotation is sensitive to transmural gradients of contractility which is assumed linearly related to action potential duration (APD). Pressure-volume loops and other basic strain measures are not affected by these gradients. Therefore, realistic torsional behavior of human LV may indeed correspond to the electrophysiological and functional differences between endocardial and epicardial cells recently observed in non-failing hearts. Future investigations need now to integrate the mechanical model proposed here with minimal models of human ventricular APD to drive excitation-contraction coupling transmurally.

ECHO and magnetic resonance imaging in a patient with high bleeding risk and ventricular perforation: a case report and literature review.

Myocardial perforation is a complication following pacemaker implantation that may cause cardiac tamponade. We present an original case of myocardial lead perforation not complicated by acute cardiac tamponade. The patient with an acute myocardial infarct had a high bleeding risk both in the acute phase of lead insertion (anticoagulant and triple platelet anti-aggregation therapy) and after few days, the percutaneous extraction lead for the double platelet antiaggregant therapy. Torrent-Guasp's theory is considered for explaining the clinical course of patient. Echocardiography and magnetic resonance imaging (MRI) evaluation showed a diffuse pericardial non-hemorrhagic fibrinous effusion and guide the clinical management.

[Anthracycline cardiotoxicity]. / Cardiotossicità da antracicline.

PURPOSE: To provide specialists and general practitioners with a review of the more recent data about anthracycline-induced cardiotoxicity and diagnostic methods utilized to reveal it. DESIGN: Reviewers identified studies concerning anthracycline cardiotoxicity, with special emphasis to those dealing with its pathogenesis and tools utilized for diagnosing it, by searching MEDLINE and reviewing references for retrieved articles. RESULTS: Three different clinical patterns of cardiotoxicity were described: acute, chronic and late. Highly sensitive tests are necessary for evaluating, during the time, the cardiotoxic effects associated with anthracycline-based therapy and to predict the development of cardiac dysfunction. For this reason, endomyocardic biopsy and radionuclide-based angiocardiography are considered the "gold standard". However, the bidimensional echocardiography is the most commonly performed because of its high specificity and sensitivity combined with low costs. CONCLUSIONS: The peer review of the most recent scientific literature clearly demonstrate that cardiotoxicity is an important complication of anthracycline-based therapy and that the cumulative dose greater than 550 mg/m2 is the main independent risk factor. For the evaluation of anthracycline-related cardiotoxicity, bidimensional echocardiography remains still the easier and faster method.

How long can we give interleukin-2? Clinical and immunological evaluation of AML patients after 10 or more years of IL2 administration.

We have treated 20 patients, affected by acute myelogenous leukemia in advanced phase of the disease, with intravenous high-dose recombinant interleukin-2 (IL2) as induction treatment, achieving a complete remission (CR) in 11/20 of patients (55%). All CR patients were planned to receive a maintenance program with lower subcutaneous doses of IL2 until relapse. Currently, 5/11 patients are alive in continuous complete remission with a minimum follow-up of 9 years from IL2 induction. In the aim to investigate the treatment's side-effects during or after prolonged IL2 therapy, we decided to submit these patients to a clinical and immunological evaluation. Four patients have been evaluated as one, who independently stopped IL2 after 6 years, refused the check-up. No organ-specific treatment sequelae that may decrease the quality of life or may be life-threatening were found, concerning renal, liver and cardiovascular function. Endocrine abnormalities were detected in three patients, the most serious being a severe hypothyroidism, which prompted cessation of IL2 maintenance after 6 years and required thyroid supplementation treatment. Immunological studies were carried out prior to the last IL2 cycle and showed high levels of CD3-positive T cells expressing the IL2 receptor alpha chain (CD25), both in the peripheral blood and in the bone marrow. Our study shows that low-dose IL2 can be given for a prolonged period of time without serious organ-specific late sequelae and with a good quality of life.

High dose of idarubicin-based regimen for diffuse large cell AIDS-related non-Hodgkin's lymphoma patients: a pilot study.

BACKGROUND AND OBJECTIVES: Intensive chemotherapy (CHT) in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL patients) is a vexing problem. Our purpose was to evaluate the feasibility of a high dose idarubicin (HD-IDA)-based regimen in diffuse large cell (DLC) AIDS-NHL patients. DESIGN AND METHODS: Fourteen stage I-IV untreated DLC AIDS-NHL patients with a performance status <3 and no prior AIDS-related diseases received CIOD: cyclophosphamide, HD-IDA (25 mg/m2 in 8 patients, 20 mg/m2 in 6 patients) vincristine and dexamethasone plus granulocyte colony-stimulating factor (G-CSF) and prophylaxis against infections. The outcomes measured were: rate of response, disease-free survival (DFS), overall survival (OS) and the impact of chemotherapy on immunologic and virological parameters. RESULTS: Complete response was achieved in 13/14 cases (response rate: 93%). The median time of response and survival was 33 (range 5-79) and 35.5 (range 6-84) months, respectively. At 60 months the DFS and OS were 71% and 44%, respectively. CIOD with idarubicin 20 mg/m2 was better tolerated than that with 25 mg/m2 and was administered with a higher mean average-relative-dose-intensity (95.38+/-7% vs 83.35+/-15.59%, p=0.0001). Opportunistic infections were more frequent in patients with a baseline CD4 <100 than those with >100 cells/microL (4/5 vs 1/9: p=0.0229). After 3 CIOD courses the mean CD4 cells/microL was significantly lower (p=0.001) and the mean HIV.1 RNA load was significantly higher (p=0.045) than at baseline. INTERPRETATION AND CONCLUSIONS: The proposed chemotherapeutic regimen for AIDS-related non-Hodgkin's lymphoma is feasible in an outpatient setting in selected patients with relatively well-preserved immune function.

The role of all-trans-retinoic acid (ATRA) treatment in newly-diagnosed acute promyelocytic leukemia patients aged > 60 years.

BACKGROUND: To evaluate the role and toxicity of ATRA therapy in newly-diagnosed APL patients aged > 60 yrs, the outcome of 16 consecutive elderly APL patients observed between January 1990 and June 1996 were analyzed. PATIENTS AND METHODS: Their median age was 65.5 yrs (range 60-81 years), the male/female ratio was 7:9, and molecular biology analysis showed a PML/RARa rearrangement in all patients. Seven patients had a concomitant cardiovascular disease. ATRA 45 mg/sqm/day was given to all patients, and in 11 was associated with idarubicin (AIDA protocol); in two patients ATRA was associated with mitoxantrone + ara-C, while the remaining three patients received ATRA alone. RESULTS: Fourteen patients (87.5%) achieved CR, and two patients (12.5%) died during induction. Despite the high CR rate, eight episodes of severe cardiovascular complication were observed in seven patients, three of whom had previously had cardiovascular disease; in addition, three patients had sepsis (two bacterial and one fungal). As of 31 March 1997, 9 of 14 patients were still in first CR after a 19-month (range 7-64 months) median follow-up since attainment of the CR. One patient died in CR of a fungal complication and four patients relapsed after 8, 9, 23 and 35 months following CR: two of them achieved a second CR lasting seven and +15 months with ATRA alone. Of the nine patients still in first CR, only three have received the planned consolidation therapy and five have been in CR for more than 24 months (+25, +33, +34, +38, +63). CONCLUSIONS: Despite the fact that most of these patients received shorter consolidation treatments than do younger patients, the good results achieved in them might be considered an indication for modifying treatment schedules in order to reduce severe toxicity and improve protocol compliance.

P-VABEC: a prospective study of a new weekly chemotherapy regimen for elderly aggressive non-Hodgkin's lymphoma.

PURPOSE: To evaluate, in a prospective trial, a new combination chemotherapy specifically designed for elderly patients. PATIENTS AND METHODS: From October 1988 to December 1990, 60 previously untreated patients older than 60 years of age with aggressive non-Hodgkin's lymphoma (NHL) were treated at our institution with a new weekly alternating six-drug chemotherapy regimen, P-VABEC. The schedule consisted of doxorubicin, etoposide, and cyclophosphamide alternated weekly with vincristine and bleomycin. Oral prednisone was administered daily during the entire treatment period. Twenty-six of 60 patients were treated for a total of eight courses and 34 of 60 for 12 courses. RESULTS: A total of 45 patients (75%) achieved a complete response (CR), 10 (17%) a partial response (PR), and five (8%) no response. So far, 20 of 45 CR patients have relapsed, four of 10 PR patients have progressed, and three patients have died while in CR. Twenty-eight patients are still alive and responding (22 CRs, six PRs) after a median follow-up of 25 months. The projected overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) rates at 2 years were 64%, 57%, and 55%, respectively. The outcome of patients treated with eight courses was similar to that of those who received 12 courses of P-VABEC in terms of CR rate and actuarial curves of OS, DFS, and EFS. Hematologic toxicity was mild in all patients. CONCLUSION: The P-VABEC regimen is active, well tolerated, and one of the briefest first-line chemotherapy regimens so far reported in the treatment of elderly patients with aggressive NHL. However, prospective randomized trials are needed to establish the real advantage of this regimen compared with other standard chemotherapy regimens.

Coexistent multiple myeloma and myelofibrosis.

Although the association of bone marrow fibrosis with plasma cell dyscrasias has already been described in several reports, the close relationship between these entities still remains unclear. In this report we describe a patient with clinical and pathologic findings which initially suggested a diagnosis of myelofibrosis, subsequently shown to be coexistent with multiple myeloma. Possible explanations for this association are discussed.

High doses of ara-C and m-AMSA in the treatment of refractory acute non lymphocytic leukemia.

From November, '85 to March, '87, 17 patients (12 males and 5 females, median 28 years) with resistant or relapsed ANLL received HiDAC (3 g/m2 c.i. 3 hs every 12 hs, day 1-4) + m-AMSA (100 mg/m2 i.v. day 5-7) as salvage therapy: 8/17 patients (47.1%) achieved CR, 7/17 (41.1%) were resistant and 2/17 (11.8%) died during induction; 8/10 relapsed patients achieved a 2nd CR, while all 7 primary resistant patients failed to. Median period of PMN less than 0.5 x 10(9)/l was 28 days, median period of PLTS less than 30 x 10(9)/l was 25 days. All patients had infections during aplasia. Median CR duration was 6.6 months, while median survival of responders was 10.6 months. Two patients with severe induction-related complications relapsed after 2 and 5 months, respectively: 1 patient underwent BMT and relapsed after 21 months; 5 patients, 4 of whom had received a prior ABMT during 1st CR, underwent ABMT: 3 died from ABMT related toxicity and 2 relapsed after 8 and 18 months, respectively. We conclude that HiDAC + m-AMSA is highly effective in relapsed, but not in resistant patients with acceptable hematologic and extra-hematologic toxicity. The role and modalities of ABMT in prolonging a 2nd CR are at present controversial.

Therapy of essential thrombocythemia with alpha-interferon: results and prospects.

Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long-term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha-interferon (IFN) exerts a dose-dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non-mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha-IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1-3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9-12 months). Also patients resistant to cytotoxic drugs may respond to alpha-IFN, suggesting a lack of cross-resistance between the two treatment modalities. Side-effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low-dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha-IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.

Interferon alpha-2b as treatment for Philadelphia-negative chronic myeloproliferative disorders with excessive thrombocytosis.

We treated 32 patients with Ph1-negative chronic myeloproliferative disorders (CMD) with excessive thrombocytosis with Interferon alpha-2b (IFN alpha-2b): 26 had essential thrombocythaemia, ET (18 previously untreated, eight pretreated); one thrombocythaemia after treatment for Hodgkin's disease (HD); two thrombocythaemia associated with non-Hodgkin's lymphoma (NHL); three stage II idiopathic myelofibrosis (IM). IFN was given at daily doses of 1-4 x 10(6) IU. Twenty-seven patients (84%) responded, 17 (53%) achieved complete haematologic response after a median time of 12 weeks, and 10 (31%) partial haematologic response. Median platelet levels declined in complete haematologic response patients from 1,190 to 335 x 10(9)/l. Normalization of megakaryocyte (MK) levels was observed in 8/17 complete haematologic response patients treated for 9-12 months, with decreased bone marrow (BM) cellularity. Side effects requiring dose reduction or discontinuation of treatment occurred in 28% of cases with IFN doses of 2 or 4 x 10(6) IU. After 1 year of continuous IFN treatment, responses were maintained with conventional chemotherapy or low-dose IFN. This study demonstrates that IFN has definite therapeutic activity in CMD with excessive thrombocytosis. This biological agent, either alone or in combination with other antineoplastic treatment, may represent a new therapeutic approach for these disorders.

Risk of iron overload and 'hemochromatosis allele(s)' in patients on maintenance hemodialysis.

In the present study, we have evaluated the relationship between serum ferritin (SF) levels, 'hemochromatosis allele(s)', blood transfusions and iron parenteral administration in 69 hemodialysis patients. We demonstrated significantly higher SF levels in patients with hemochromatosis allele(s) (HA+) than in patients without hemochromatosis alleles (HA-). In addition, HA+ patients who had received blood transfusions up to 15 months prior to the study had SF levels even higher than those without blood transfusions. On the other hand, HA- patients had normal levels of SF, independent of blood transfusions. After intravenous administration of 1 g iron saccharate, SF levels were significantly higher only in HA+ transfused patients. In conclusion, our study demonstrated that HA+ patients are at a higher risk of iron overload and therefore the use of transfusional and/or parenteral iron should be strictly limited.