Ambulatory high-dose methotrexate administration as central nervous system prophylaxis in patients with aggressive lymphoma.

High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.

Outcomes after radiofrequency catheter ablation of atrial tachycardia.

The purpose of this study was to evaluate the efficacy, safety, and clinical benefit of radiofrequency catheter ablation (RFCA) in a large series of patients with atrial tachycardia (AT). The determinants of success or failure of RFCA in AT remain unclear. We evaluated the results of radiofrequency ablation in 73 women and 32 men (mean age 48 +/- 19 years) with AT. Mapping techniques were based on identification of the earliest endocardial atrial electrogram recorded during AT. AT originated from the right atrium in 91 patients and from the left atrium in 14. The cardiac ventricles were dilated in 12 patients. AT ablation was successful in 80 patients (77%) regardless of the site of origin. Age, gender, rate of tachycardia, temperature achieved during application, or presence of tachycardiomyopathy were not significant determinants of acute success by univariate analysis. There was a significantly higher acute success rate of ablation in patients with paroxysmal (88%, 45 of 51) and permanent (71%, 30 of 42) forms than in patients with repetitive forms of AT (41%, 5 of 12) (p <0.005). The mean local endocardial electrogram time (relative-to-surface P-wave onset) was -47 +/- 17 ms at successful ablation sites and -29 +/- 21 ms at unsuccessful sites (p <0.03). Ablation was unsuccessful in 25 cases. Thus, RFCA of AT can be performed with a high acute success rate. Patients with repetitive forms and those with multifocal origin had a lower acute success rate. The highest incidence of recurrences was found in anterior right atrial foci.

Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction: effects on the electrophysiologic substrate and outcome.

OBJECTIVES: The objective of this study was to analyze the influence of coronary artery revascularization in patients with ventricular arrhythmias. BACKGROUND: Coronary artery revascularization is an effective treatment for myocardial ischemia; however, its effect on ventricular arrhythmias not related to an acute ischemic event has not been carefully studied. METHODS: Sixty-four patients (58 men, mean age 65 +/- 8 years old) with prior myocardial infarction, spontaneous ventricular arrhythmias not related to an acute ischemic event (55 ventricular tachycardia, 9 ventricular fibrillation) and coronary lesions requiring revascularization were studied prospectively. Electrophysiological study was performed before and after revascularization, and events during follow-up were analyzed. RESULTS: At initial study 61 patients were inducible into sustained ventricular arrhythmias. After revascularization, in 62 survivors, 52 out of 59 patients previously inducible were still inducible (group A), and 10 patients were noninducible (group B). No differences were found in clinical, hemodynamic, therapeutic and electrophysiological characteristics between both groups. During 32 +/- 26 months follow-up, 28/52 patients in group A (54%) and 4/10 patients in group B (40%) had arrhythmic events (p = 0.46). An ejection fraction <30% predicted recurrent arrhythmic events (p = 0.02), but not the presence of demonstrable ischemia before revascularization (p = 0.42), amiodarone (p = 0.69) or beta-adrenergic blocking agent therapy (p = 0.53). Total mortality was 10% in both groups. CONCLUSIONS: In patients with ventricular arrhythmias in the chronic phase of myocardial infarction, probability of recurrence is high despite coronary artery revascularization, but mortality is low if combined with appropriate antiarrhythmic therapy. Recurrences are related to the presence of a low ejection fraction but not to demonstrable ischemia before revascularization, amiodarone or beta-blocker therapy nor are they the results of electrophysiological testing after revascularization.

[Analysis of local electrograms and characteristics of the ablation procedure in left-sided accessory pathways that required five or more pulses of radiofrequency]. / Análisis de los electrogramas locales y de las características de la ablación en vías accesorias izquierdas que requirieron cinco o más applicaciones de radiofrecuencia.

INTRODUCTION AND OBJECTIVES: Radiofrequency ablation of left sided accessory pathways requires multiple pulses in some patients due to different factors such as inadequate mapping, inappropriate tissue electrode contact and particular anatomic factors. However these characteristics have not been specifically analyzed. METHODS: We have studied a prospective ablative series of 65 consecutive patients with left-sided pathways submitted to radiofrequency ablation by a simplified technique. In every application point, we analyzed the electrogram features, application point, impedance, potency and temperature. RESULTS: 52 patients (80%) required less than 5 radiofrequency pulses (group A) and 13 (20%) required > or = than 5 pulses (group B). The presence of a suggestive potential accessory pathway in local electrogram was similar in both groups and there were no differences in the local A-V or V-A intervals. However, in patients with pre-excitation the Delta-V interval was shorter in group A than in group B (8 ms vs 15 ms; p < 0.001). Furthermore, the impedance observed from the ablation point in group A was lower (108 +/- 12 vs 121 +/- 22 ohms; p < 0.001), and the maximum watts required to reach the predetermined temperature was higher in group A (42 +/- 16 vs 31 +/- 18 watts; p < 0.001). Final success of the procedure was 100%. CONCLUSIONS: Patients requiring more than 5 radiofrequency pulses had electrograms and tissue contact equal or better than those requiring less than 5 pulses. This suggests that difficulties encountered in some procedures can be due to anatomical factors rather than inaccurate mapping or insufficient tissue contact.

Arrhythmia recurrence in patients with a healed myocardial infarction who received an implantable defibrillator: analysis according to the clinical presentation.

OBJECTIVES: The purpose of this study was to analyze the type of arrhythmia recurrence, based on stored electrograms, in patients with a healed myocardial infarction (MI) who received an implantable defibrillator. BACKGROUND: Previous studies suggest that patients presenting with cardiac arrest (CA) tend to recur as ventricular fibrillation (VF), whereas those suffering sustained monomorphic ventricular tachycardia (SMVT) tend to recur as SMVT. However, these data have not been confirmed in a homogeneous population of patients with MI. METHODS: A total of 88 patients was divided into three groups according to their clinical presentation: SMVT (n = 57), CA (n = 16) or syncope (n = 15). RESULTS: There were no significant differences in clinical characteristics among groups. In the electrophysiologic study SMVT was induced in 93%, 94% and 80% of patients, respectively (p = NS). During the follow-up period, 52% of patients presented a total of 671 episodes of ventricular arrhythmia treated by the defibrillator. All recurrences were as SMVT except for one VF. There were 610 episodes of SMVT treated with antitachycardia pacing, with an effectiveness of 96%. A total of 61 episodes was treated initially with cardioversion. No differences in the probability of recurrence were observed among groups, although the statistical power was low (50%). CONCLUSIONS: In patients with an old infarction and malignant ventricular arrhythmias, the majority of recurrences are due to SMVT independently of the clinical presentation (SMVT, CA or syncope) or the induced arrhythmia at the electrophysiologic study. The programming of an antitachycardia zone seems to be appropriate also for patients who present with CA or syncope.

Long-term follow-up in patients with the permanent form of junctional reciprocating tachycardia treated with radiofrequency ablation.

This study sought to determine the long-term follow-up, safety, and efficacy of radiofrequency catheter ablation of patients with the permanent form of junctional reciprocating tachycardia (PJRT). We assessed the reversibility of tachycardia induced LV dysfunction and we detailed the location and electrophysiological characteristics of these retrograde atrioventricular decremental pathways. PJRT is an infrequent form of reciprocating tachycardia, commonly incessant, and usually drug refractory. The ECG hallmarks include an RP interval > PR with inverted P waves in leads II, III, a VF, and V3-V6. During tachycardia, retrograde VA conduction occurs over an accessory pathway with slow and decremental conduction properties, located predominantly in the posteroseptal zone. It is known that long-lasting and incessant tachycardia may result in tachycardia induced severe ventricular dysfunction. We included 36 patients (13 men, 23 women, mean +/- SD, aged 44 +/- 22 years) with the diagnosis of PJRT. Seven patients had tachycardia induced left ventricular dysfunction. Radiofrequency energy was delivered at the site of earliest retrograde atrial activation during ventricular pacing or during reciprocating tachycardia. All patients were followed at the outpatient clinic and serial echocardiograms were performed in those who presented with depressed LV function. Radiofrequency ablation was performed in 36 decremental accessory pathways. Earliest retrograde atrial activation was right posteroseptal in 32 patients (88%), right mid-septal in 2 (6%), right posterolateral in 1 (3%), and left anterolateral in 1 (3%). Thirty-five accessory pathways were successfully ablated with a mean of 5 +/- 3 applications. A mid-septal accessory pathway could not be ablated. After a mean follow-up of 21 +/- 16 months (range 1-64) 34 patients are asymptomatic. There were recurrences in 8 patients after the initial successful ablation (mean of 1.2 months), 5 were ablated in a second ablation procedure, 2 patients required a third procedure, and 1 patient required four ablation sessions. All patients with LV dysfunction experienced a remarkable improvement after ablation. Mean preablation LV ejection fraction in patients with tachycardiomyopathy was 28% +/- 6% and rose to 51% +/- 16% after ablation (P < 0.02). Our study supports the concept that radiofrequency catheter ablation is a safe and effective treatment for patients with PJRT. Radiofrequency ablation should be the treatment of choice in these patients because this arrhythmia is usually drug refractory. The majority of accessory pathways are located in the posteroseptal zone. Cessation of the arrhythmia after successful ablation results in recovery of LV dysfunction.

[Patients with structural heart disease, syncope of unknown etiology and inducible ventricular arrhythmias treated with implantable defibrillators]. / Pacientes con cardiopatía estructural, síncope de etiología desconocida y arritmias ventriculares inducibles tratados con desfibrilador implantable.

OBJECTIVES: This study evaluates the hypothesis that in patients with syncope of unknown origin and heart anomalies, inducible ventricular arrhythmias are specific arrhythmias and therefore should be treated as such. BACKGROUND: Although syncope is a frequent clinical entity, the evaluation and treatment of patients with syncope without a clear etiology still remains undefined. Many patients with syncope of undetermined origin undergo invasive electrophysiologic evaluation. Abnormalities of the sinus node, prolongation of conduction times or inducible arrhythmias found during these evaluations are usually assumed to be the cause of syncope, and are consequently treated. However, whether tachyarrhythmias are truly the cause of syncope, and whether treatment of these tachyarrhythmias can prevent recurrent syncope and arrhythmic death, is unknown. PATIENTS AND METHODS: An electrophysiological study was performed on 160 patients with structural heart disease and syncope of unknown origin. In 23 out of the 160 patients (16%), programmed electrical stimulation induced sustained ventricular arrhythmias. In 18 out of the 23 patients an automatic defibrillator was implanted and they form the study group. RESULTS: In these 18 patients, programmed ventricular stimulation induced sustained monomorphic ventricular tachycardia in 12, sustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. During a mean follow-up of 14 months, 9 patients received 81 appropriate therapies from the device (53 because of ventricular tachycardia and 23 because of ventricular fibrillation). The probability of appropriate therapy was 100% at 1 year follow-up. There were no episodes of sudden death and 1 patient died of congestive heart failure. CONCLUSIONS: In patients with syncope of undetermined origin, heart disease and inducible ventricular tachyarrhythmias treated with a implantable cardioverter defibrillator, there is a high incidence of appropriate therapies. Our results support the practice of using implantable cardioverter defibrillators in patients with syncope of unknown origin, heart disease and inducible ventricular arrhythmias.

[Radiofrequency ablation of multiple atrioventricular accessory pathways in a patient with syncope, atrial fibrillation and fasciculoventricular fibers]. / Ablación por radiofrecuencia de múltiples vías accesorias auriculoventriculares en un paciente con fibrilación auricular sincopal y presencia de fibras fascículo-ventriculares.

Multiple accessory pathways in patients with the Wolff-Parkinson-White syndrome are infrequent and are associated with a higher risk of ventricular fibrillation. We present an exceptional case of a patient with four accessory pathways with anterograde conduction and a fasciculo-ventricular fiber in whom we performed a radiofrequency ablation. A 20 year old healthy male patient was seen at the emergency room after suffering syncope. The electrocardiogram showed atrial fibrillation with wide QRS complex suggestive of preexcitation. The electrophysiologic study demonstrated the presence of four atrio-ventricular accessory pathways with antegrade conduction (left lateral, right posteroseptal, right midseptal and right posterolateral). After ablation of the fourth accessory pathway, the electrocardiogram showed a persistent delta wave with a short HV interval. Atrial stimulation demonstrated decremental conduction, progressive lengthening of the AH interval and no modification in the HV interval nor in the preexcitation pattern, suggestive of the presence of a fasciculo-ventricular fiber. This exceptional case report is demonstrative of the complexity of the Wolff-Parkinson-White syndrome, and the feasibility and efficacy of radiofrequency catheter ablation in a single procedure.

[Long-term follow up of patients with nodal reentry tachycardia who had undergone radiofrequency ablation]. / Seguimiento a largo plazo de pacientes con taquicardia por reentrada nodal a quienes se les realizó una ablación por radiofrecuencia.

INTRODUCTION: The aim of this study was to assess the long term results (minimum of 3 years) of radiofrequency catheter ablation in patients with common (slow-fast) atrioventricular nodal reentrant tachycardia. PATIENTS AND METHODS: Sixty consecutive patients (mean age 56 +/- 16 years, range 14 to 83, 16 men and 44 women) underwent slow pathway (n = 51, Group A) or fast pathway (n = 9, Group B) radiofrequency catheter ablation between January 1992 and March 1994. All patients were followed at 1, 3, 6 and 12 months after ablation with serial examinations and electrocardiograms and the last follow-up was made on April 1997. RESULTS: During a mean follow-up period of 48 +/- 7 months (range 38 to 63) all evaluated patients remained asymptomatic. Eight recurrences were observed at a mean of 1 +/- 2 months (range, 0.5 to 7) after a successful ablation procedure. A second procedure was effective in eliminating the dual atrioventricular nodal pathway in each of them. In Group A patients, the pre-ablation PR interval, at 12 months after ablation and at last follow-up were 122 +/- 11, 124 +/- 13 and 124 +/- 15 ms, respectively. In Group B patients, the pre-ablation PR interval, at 12 months after ablation and at last follow-up were 130 +/- 24, 200 +/- 12, 200 +/- 24 ms, respectively. No significant atrioventricular conduction disturbances in any patient were observed. One patient developed a new onset left bundle branch block and 4 patients died of noncardiac causes. CONCLUSIONS: In patients with atrioventricular nodal reentrant tachycardia, radiofrequency catheter ablation is a safe and effective therapy, with substantial good results that persist during long term follow-up, with a low recurrence rate and without complications during short and long term outcome.

[Hemodynamic deterioration in patients submitted to ablation of the atrioventricular node]. / Deterioro hemodinámico en pacientes sometidos a ablación del nodo auriculoventricular.

INTRODUCTION: Radiofrequency ablation of the atrioventricular conduction system has become an established therapy for patients with drug-refractory atrial fibrillation. We observed 14 patients with hemodynamic deterioration related to worsening of mitral regurgitation after the procedure. PATIENTS AND METHODS: We retrospectively evaluated 256 consecutive patients with drug-refractory atrial fibrillation referred for radiofrequency ablation of the AV node and implantation of a pacemaker. Because we found hemodynamic deterioration related to worsening mitral regurgitation, we compared the clinical history, electrophysiologic and echocardiographic data from the patients with hemodynamic deterioration and worsening mitral regurgitation (group A) with those without hemodynamic deterioration (group B). RESULTS: Fourteen out of 256 patients (group A) undergoing ablation of the atrioventricular conduction system deteriorated with acute pulmonary edema (3 patients) or congestive heart failure (11 patients) at a mean of 6 weeks after the ablation procedure. Four of these patients were referred for mitral valve surgery. The length of the procedure and the number of applications during ablation were similar in both groups. Compared with group B patients, group A patients had significantly higher left ventricular end-diastolic diameters (64 +/- 6 mm vs 56 +/- 9 mm; p < 0.05) at baseline despite similar left ventricular end-systolic diameters, fractional shortening and grade of mitral regurgitation (1.15 +/- 1.05 vs 1.11 +/- 0.97). Moreover, whereas no change was observed in left ventricular end-diastolic diameter, left ventricular end-systolic diameter, fractional shortening and grade of mitral regurgitation in group B patients after ablation, group A patients experienced a significant increase in left ventricular end-diastolic diameter (64 +/- 6 mm vs 72 +/- 9 mm; p < 0.01) and grade of mitral regurgitation (1.15 +/- 1.05 vs 2.90 +/- 1.15; p < 0.01). In patients operated on no ablation related structural damage to the mitral valve apparatus could be detected. The worsening of the mitral regurgitation was related to dilation of the mitral valve annulus. CONCLUSIONS: Hemodynamic deterioration together with progression of mitral regurgitation is a potential complication of ablation of the atrioventricular conduction system.

[Long term follow-up in patients with the permanent form of junctional reciprocating tachycardia treated with radiofrequency ablation]. / Seguimiento a largo plazo de pacientes con la forma permanente de taquicardia recíproca de la unión tipo Coumel tratados mediante ablación con radiofrecuencia.

OBJECTIVES: This study sought to determine the long-term follow-up, safety and efficacy of radiofrequency catheter ablation in patients with the permanent form of junctional reciprocating tachycardia. We assessed the reversibility of tachycardia-related left ventricular dysfunction and we detailed the location and electrophysiologic characteristics of these atrioventricular decremental pathways. BACKGROUND: Permanent junctional reciprocating tachycardia is an infrequent form on reciprocating tachycardia, commonly incessant and usually drug-refractory. The electrocardiographic hallmarks include an RP interval > PR with inverted P waves in leads II, III, aVF and V3-V6. During tachycardia, retrograde ventriculo-atrial conduction occurs over an accessory pathway with decremental conduction properties, located predominantly in the posteroseptal zone. It is known that long lasting and incessant tachycardia may result in tachycardia-related severe ventricular dysfunction, the so called tachycardiomyopathy. PATIENTS AND METHODS: We included 24 patients (9 males, 15 females; mean age 42 +/- 22 years) with the diagnosis of permanent junctional reciprocating tachycardia at electrophysiologic study. Six patients had tachycardia-related left ventricular dysfunction. Radiofrequency energy was delivered at the site of earliest retrograde atrial activation during reciprocating tachycardia (n = 22) or ventricular pacing (n = 2). All patients were followed at the outpatient clinic and serial echocardiograms were performed in those who presented depressed left ventricular function. RESULTS: Radiofrequency catheter ablation was performed in 24 decremental accessory pathways. Earliest retrograde atrial activation was right posteroseptal in 22 patients (92%), right midseptal in 1 (4%) and right posterolateral in 1 (4%). Twenty-three accessory pathways were successfully ablated with a mean of 5 +/- 3 (median, 4) radiofrequency applications of a mean duration of 48 +/- 13 s. Only the midseptal accessory pathway could not be ablated. After a mean follow-up of 21 +/- 16 months (median, 15; range 2 to 64) 22 patients remain asymptomatic. There were recurrences in 4 patients after the initial successful ablation (three during the first month and one during the second month after the procedure), two were ablated in a second ablation procedure, one patient required a third procedure and one required a fourth. All patients with left ventricular dysfunction experienced an improvement after ablation. Mean preablation left ventricular ejection fraction in patients with tachycardiomyopathy was 28 +/- 6% (median, 27) and raised to 51 +/- 16% (median, 47) after ablation (p < 0.02). CONCLUSIONS: Our study supports the concept that radiofrequency catheter ablation is a safe and useful treatment for patients with permanent junctional reciprocating tachycardia. Radiofrequency current should be the treatment of choice in these patients because this arrhythmia is usually drug-refractory. The majority of accessory pathways with decremental conduction properties are localized in the posteroseptal zone. Cessation of the arrhythmia after successful ablation results in recovery of left ventricular dysfunction.

[Differential mortality by sex in three regions of Ecuador]. / Mortalidad diferencial por sexos en tres regiones del Ecuador.

PIP: The authors present information on general and infant mortality by sex. They analyze the principal causes of death at the national, regional, and provincial level in an attempt to identify regional inequalities.^ieng

[Correction of underregistration of general mortality]. / Correccion del subregistro de mortalidad general.

PIP: The authors evaluate the underregistration of mortality in Latin America, using the example of Ecuador. Underregistration by province, age groups, sex, and cause of death is investigated.^ieng