[Severe acquired aplastic anemia: historical outcome of patients treated by allogeneic bone marrow transplantation from matched sibling donors. A study by the Spanish Group for Bone Marrow Transplantation in Children (GETMON)]. / Aplasia medular grave adquirida: evolución histórica de los resultados obtenidos con trasplante de progenitores hematopoyéticos de donante familiar. Estudio del Grupo Español para el Trasplante de Médula Osea en Niños (GETMON).

INTRODUCTION: Allogeneic haematopoietic stem-cell transplantation is the treatment of choice for acquired aplastic anaemia in children. Experience with this approach from Spanish Working Party for Bone Marrow Transplantation in Children in two sequential time periods (1982-1990 and 1991-2004) is reported. PATIENTS AND METHODS: Sixty two consecutive patients with a median age of 10 years were transplanted; 18 in the 1982-1990 period and 44 in the 1991-2004 period. Conditioning regimen consisted mainly of irradiation and cyclophosphamide in the first period (72 % of patients) and cyclophosphamide +/- anti-thymocyte globulin (62 %) in the second. Graft versus host disease prophylaxis consisted of cyclosporine in most patients (57/62). RESULTS: Fifty one patients are alive and disease-free at a median follow-up of 127 months. Five years probability of event-free survival is 82 %. The survival increased from 61 % to 91 % during the two time periods. Eleven patients died from graft failure or rejection (3), acute or chronic graft versus host disease and infection (4) or multi-organ failure (4). Univariate analysis identified two significant prognostic factors: interval diagnostic/transplant and time period of transplant (for both p = 0.03). CONCLUSIONS: This experience corroborates that allogeneic haematopoietic stem-cell transplantation is the best treatment for severe acquired aplastic anaemia, with a current disease-free survival of 90 % of patients.

Long-term outcome of patients with asystole induced by head-up tilt test.

AIMS: To analyse the long-term outcome of the largest reported cohort of patients presenting asystole during head-up tilt test. METHODS AND RESULTS: Since 1990, 1322 patients with syncope of unknown origin have undergone tilt-table testing. Of those, 330 patients (24 X 9%) presented an abnormal response (syncope or pre-syncope). Furthermore, 58 of those patients (17 X 5%) suffered a period of asystole (> or = 3000 ms) during the test. Asystole (median (interquartile range)) lasted 10 (4, 19 X 2) s (range 3-90). Two different protocols (angles) of tilting (Westminster (60 degrees) n=1124; isoproterenol (80 degrees) n=198)) influenced the time to the syncopal episode (13 (6 X 5, 20 X 5) vs 2 (1, 6 X 5) min, P=0,0005) but not the duration of the asystole. During this period, therapy for asystole featured three different stages: first patients were treated with pacemakers; later drug therapy (metoprolol and/or etilefrine) was recommended; lastly (from 1995), no specific treatment was given. In a cohort age- and gender-matched study, those patients without were compared to those with asystole in a 2:1 basis. During 40 X 7 months of follow-up (17 X 7, 66 X 8), 12 patients (20 X 6%) with asystole had syncopal recurrences. Furthermore, 34 patients (28 X 8%) without asystole presented syncopal episodes during a follow-up of 51 X 6 months (29 X 3, 73 X 1) (P=ns). The Kaplan-Meier analysis in patients with and without asystole showed a mean time free of recurrence of 92 X 6 +/- 6 months vs 82 X 6 +/- 4 X 7 months (P=ns). The previous number of syncopes had a significant relationship with recurrences (P=0 X 002), but not therapy. There were no cardiac related deaths. CONCLUSIONS: (1) Asystole during head-up tilt test does not imply a malignant outcome and syncope recurrence is low; (2) pacemaker or drug therapy do not significantly influence outcome which correlates to the previous number of syncopal episodes but not to gender, age, asystole occurrence, asystole duration and timing to asystole during head-up tilt test; (3) tilting protocol (angle) might influence time to and incidence of asystole during head-up tilt test.

Programmed ventricular stimulation: influence of early versus late introduction of a third extrastimulus, a randomized, prospective study.

OBJECTIVE: The aim of this prospective study was to analyze the yield of early vs late introduction of a third extra-stimulus during programmed ventricular stimulation. METHODS: Two randomized protocols of programmed ventricular stimulation were used in 94 consecutive patients with coronary artery disease who were studied because of non-sustained ventricular tachycardia (9.6%), sustained monomorphic ventricular tachycardia (46.8%), ventricular fibrillation (18.1) or syncope (25.5%). During protocol A, a third extrastimulus was introduced during a basic drive cycle length of 500 ms after completion of programmed ventricular stimulation with 1 and 2 extrastimuli during sinus rhythm and paced cycle lengths of 500, 430. 370 and 330 ms. During protocol B, the third extrastimulus was introduced early (after 1 and 2 extrastimuli during sinus rhythm and a paced cycle length of 500 ms). Both protocols began at the right ventricular apex. If sustained ventricular tachyarrhythmia had been induced, the same sequence of programmed ventricular stimulation was repeated at the right ventricular outflow tract. RESULTS: The overall incidence of induced arrhythmias did not differ between the two protocols. However, the use of the third extrastimulus (both protocols) increased the yield of ventricular fibrillation induction significantly (P < 0.04) compared with ventricular tachycardia induction. CONCLUSIONS: The introduction of the third extrastimulus should be considered only at the end of stimulation protocols (especially in those patients without previously documented sustained ventricular tachyarrhythmias) in order to prevent induction of polymorphic ventricular tachycardia or fibrillation.

D-Dimer is an early diagnostic marker of coronary ischemia in patients with chest pain.

BACKGROUND: Chest pain is a frequent symptom in the emergency department and often presents a diagnostic challenge. Because coronary thrombosis is a hallmark of acute ischemic syndromes, the substrates of the coagulation and fibrinolysis cascades may be markers of coronary ischemia. The objective of this study was to determine the diagnostic value of several hemostatic markers in patients presenting to the emergency department (ED) with chest pain syndromes. METHODS: Two hundred fifty-seven consecutive patients with acute chest pain were studied in this prospective study conducted in an urban ED. D-Dimer levels were measured at admission to the ED in all patients. We also measured thrombin-antithrombin complexes, prothrombin fragment 1+2, activated factor VII, and fibrinogen. We used regression analysis to estimate the likelihood of myocardial infarction and the diagnostic value of D-dimer. RESULTS: D-Dimer and fibrinogen levels were significantly higher in patients with acute ischemic events (myocardial infarction and unstable angina) than in nonischemic patients (P <.01 and P =.02, respectively). The other hemostatic markers were not significantly elevated in patients with ischemic events. D-Dimer level >500 microg/L had an independent diagnostic value for myocardial infarction and increased the diagnostic sensitivity of the electrocardiogram and history from 73% to 92%. CONCLUSION: D-Dimer, an expression of ongoing thrombus formation and lysis, is a marker of substantial incremental value for the early diagnosis of acute coronary syndromes presenting with chest pain. It adds independent information to the traditional assessment for myocardial infarction. D-Dimer can be incorporated into clinical decision models in the ED.

[Transplantation of umbilical cord blood hematopoietic progenitor cells in children]. / Trasplante de progenitores hematopoyéticos de sangre de cordón umbilical en niños.

AIM: Retrospective study of the outcome of cord blood transplantation (CBT) in children in Spain. METHODS: Twenty-eight patients (mean age 6.5 years; mean weight 25 kg) received a CBT between July 1994 and May 1998 in several centres of the Spanish Pediatric Bone Marrow Transplant Group. In 2 patients the donor was an identical human leukocyte antigen (HLA)-sibling and in two the donor was a mismatched family donor. In 24 patients the donor was unrelated, and 21 of these received an HLA-mismatched CBT. Twenty-one patients (75 %) received a CBT for leukemia mainly in advanced phase. Seven patients were transplanted for genetic disease. Of these, five had congenital immunodeficiency. The conditioning treatment included total body irradiation in ten patients and combined chemotherapy in the remaining patients. In all patients graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporine, and corticosteroids or methotrexate were added in patients with HLA-mismatched donors. The mean number of nucleated cells infused was 53.4 x 106/kg. RESULTS: Graft failure was observed in nine patients. Eighteen patients (64.3%) developed grade IIIV acute GVHD. Eight patients (28.6%) developed severe GVHD. Actuarial event free survival (EFS) of all the patients was 34.4 +/- 9% at 3 years, with a mean followup of 16.6 months. EFS was more favorable in patients with genetic disease (71>=6 17%) and in those with an HLA (A, B and DR) identical donor (6/6) (66>=6 19%). CONCLUSIONS: The most favorable results were obtained in patients with genetic diseases. We observed an inverse correlation between EFS and patients with HLA identical donors. The high incidence of severe acute GVHD could have been related to a lack of accuracy in the HLA typography of some patients.

Prediction of arrhythmia risk based on signal-averaged ECG in postinfarction patients.

In patients surviving acute MI, identification of those at high risk for life-threatening ventricular tachyarrhythmias and/or sudden death is of great importance. Numerous strategies based on indices such as the degree of left ventricular dysfunction, complex ventricular arrhythmias, or parameters of autonomic dysfunction have not yet led to an effective identification of the individual patient at risk. During the past decade, many investigators have recorded low amplitude, high frequency components in the terminal QRS complex (so-called late potentials) from patients prone to sustained ventricular tachycardia. The SAECG has been used to predict life-threatening tachyarrhythmias in patients after acute MI and to screen for inducible ventricular tachycardia in patients with unexplained syncope or sustained ventricular tachycardia. This review article describes the most frequently applied methodology and clinical applications of the SAECG in post-MI patients and discusses the usefulness of noninvasive recordings in various other clinical settings.

Efficacy and safety of d,l-sotalol in patients with ventricular tachycardia and in survivors of cardiac arrest.

OBJECTIVE: The aim of this study was to assess the antiarrhythmic efficacy and safety of d,l-sotalol in patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) and in survivors of cardiac arrest and to identify the factors that are associated with arrhythmia suppression and therefore might be helpful in predicting drug efficacy. BACKGROUND: Despite increasing use of the class III antiarrhythmic agent d,l-sotalol, data on its short- and long-term efficacy in a large patient cohort are lacking. Information on its long-term tolerability and safety is limited. METHODS: A total of 396 patients with inducible sustained VT or VF (VT/VF) underwent programmed stimulation before and after receiving oral d,l-sotalol (240 to 640 mg/day). Patients in whom VT/VF was rendered either noninducible or more difficult to induce (more extrastimuli or faster drive cycle length needed for VT/VF induction) were discharged on a regimen of oral d,l-sotalol. RESULTS: d,l-Sotalol suppressed VT/VF in 151 patients (38.1%) and rendered the arrhythmia more difficult to induce in 76 patients (19.2%). The extent of drug-induced prolongation of right ventricular refractoriness and a shorter VT cycle length at baseline were independent predictors of immediate drug efficacy. Torsade de pointes developed in seven patients (1.8%). Two hundred ten patients (53%) continued to receive d,l-sotalol and were followed up for 34 +/- 18 months (mean +/- SD). The actuarial rates for the absence of arrhythmic recurrence (either VT/VF or sudden death) at 1 and 3 years were 89% and 77%, respectively. Actuarial rates for overall survival at 1 and 3 years were 94% and 86%, respectively. VT/VF suppression by d,l-sotalol was an independent discriminant variable that separated patients with and without arrhythmia recurrence. However, noninducibility of VT/VF did not predict freedom from sudden death. CONCLUSION: Oral d,l-sotalol is effective and safe in patients with VT/VF. However, sudden cardiac death develops in a significant proportion of patients, and programmed stimulation seems to be of limited value for its prediction.

Patients with valvular heart disease presenting with sustained ventricular tachyarrhythmias or syncope: results of programmed ventricular stimulation and long-term follow-up.

BACKGROUND: Programmed ventricular stimulation is commonly used to guide therapy in post-myocardial infarction patients with sustained monomorphic ventricular tachycardia (VT) or ventricular fibrillation (VF). In patients with valvular heart disease presenting with spontaneous VT, VF, or syncope, the usefulness of this technique is still unclear. The aim of the study was to analyze whether programmed ventricular stimulation was helpful in guiding therapy and determining prognosis in 97 patients with valvular heart disease presenting with VT (60%), VF (18%), or syncope (22%). METHODS AND RESULTS: Patients were classified as having either predominant ventricular pressure or volume overload or no significant pressure or volume overload. Overall, sustained VT or VF was inducible in 38 (39%) and 19 (20%) patients, respectively. Forty-six (47%) patients were discharged on antiarrhythmic drugs, 29 (30%) received an implantable cardioverter-defibrillator, and 22 (23%) remained without therapy. With serial drug testing, inducibility was completely or partially suppressed in 18 (19%) and 9 (9%) patients, respectively. During a mean follow-up of 51 months (n=97), 17 patients (18%) died (sudden death, n=7; heart failure, n=4; noncardiac causes, n=6). One-, 2- and 3-year event-free survival for sudden death, sustained VT, or VF was 77%, 68%, and 61%, respectively. Only inducibility of VT during baseline study (P<.0003) and left ventricular volume overload (P<.008) were significant predictors of arrhythmic events. Recurrence of arrhythmic events occurred in 56% and 56% of patients with complete or partial suppression of inducibility during serial drug testing as well as in 10 of 19 (53%) patients without a change in inducibility. CONCLUSIONS: Although programmed ventricular stimulation seems to predict adverse outcome, serial drug testing is unreliable in guiding therapy. The type of workload imposed on the ventricles influences outcome, being worse in patients with left ventricular volume overload. Therefore, implantation of a cardioverter-defibrillator should be considered early for the management of these patients.

Noninvasive risk modeling after myocardial infarction.

The aim of this study was to extract and combine non-invasive risk parameters from the signal-averaged electrocardiogram (SAECG) and heart rate variability (HRV) based on 24-hour ambulatory electrocardiography to optimize the prognostic value for arrhythmic events after acute myocardial infarction. A prospective series of 553 men < 66 years of age enrolled in the Post-Infarction Late Potential study were analyzed. Within 2 to 4 weeks after acute myocardial infarction, all patients underwent SAECG and 24-hour ambulatory electrocardiography before hospital discharge. During 6 months of followup, 25 patients (4.5%) experienced arrhythmic events (sustained ventricular tachycardia, n = 11; ventricular fibrillation, n = 7; sudden cardiac death, n = 7). The predictive power of SAECG and HRV parameters was assessed using a Cox proportional-hazards model. In HRV analysis, the most significant differences between patients with and without arrhythmic events were observed for the beat-to-beat parameter root-meansquare of successive RR differences [RMSSD]): 25.7 +/- 16.9 ms in patients with arrhythmic events versus 34.1 +/- 18.6 ms in patients free of arrhythmic events (p = 0.004). Time domain analysis of the SAECG showed the QRS duration to be most significantly different in both patient groups: 106.4 +/- 18.7 ms (arrhythmic events) versus 95.3 +/- 18.7 ms (no arrhythmic events) (p = 0.001). Based on the Cox regression model, RMSSD and QRS duration were demonstrated to be independent significant risk factors (regression coefficient for QRS duration: cq = 0.014 +/- 0.006 ms(-1), p = 0.014; for RMSSD: cr = -0.041 +/- 0.016 ms(-1), p = 0.009). Based on the regression coefficients, an analytic risk model was developed describing the arrhythmic risk as a function of QRS duration, RMSSD, and time after infarction. We conclude that the combination of beat-to-beat changes of heart rate measured by RMSSD and QRS duration from the SAECG enhances noninvasive risk stratification after myocardial infarction.