Dofetilide reduces the frequency of ventricular arrhythmias and implantable cardioverter defibrillator therapies.

BACKGROUND: Patients with an implanted cardioverter defibrillator (ICD) and ventricular arrhythmias leading to ICD therapies have poor clinical outcomes and quality of life. Antiarrhythmic agents and catheter ablation are needed to control these arrhythmias. Dofetilide has only been approved for the treatment of atrial fibrillation. The role of dofetilide in the control of ventricular arrhythmias in patients with an ICD has not been established. OBJECTIVE: Evaluate the safety and efficacy of dofetilide in a consecutive group of patients with an ICD and recurrent ventricular tachycardia (VT) and/ or ventricular fibrillation (VF) after other antiarrhythmic drugs have failed to suppress these arrhythmias. METHODS: We studied 30 patients (age 59 ± 11; 5 women) with symptomatic VT or VF and ICDs for secondary prevention of sudden cardiac death. These patients had an average of 1.8 ± 4.5 episodes of VT/VF per month despite antiarrhymic therapy. Twenty-one patients (70%) had recurrent appropriate ICD therapies prior to initiation of dofetilide, and 9 (30%) VTs below the programmed detection rate of the ICD. Twenty-three patients (77%) had coronary artery disease. Mean ejection fraction was 30 ± 14% and 26/30 (87%) had congestive heart failure. All patients had previously failed 2 ± 1 antiarrhythmic drugs including amiodarone (n = 19) and sotalol (n = 10). RESULTS: During the first month of treatment, 25 patients (83%) had complete suppression of VT/VF and of the 21 patients with ICD therapies 16 (76%) had no therapies during the first month of treatment. During a follow-up period of 32 ± 32 months, dofetilide reduced the monthly episodes of VT/VF from 1.8 ± 4.5 to 1.0 ± 3.5 (P = 0.006). Monthly ICD therapies decreased from 0.9 ± 1.4 to 0.4 ± 1.7 (P = 0.037). In 9 patients that presented with slow VTs under the ICD detection zone, dofetilide reduced monthly VT/VF episodes from 0.7 ± 0.6 to 0.1 ± 0.1 (P = 0.01) and 6 (67%) had no further ICD therapies. Dofetilide was discontinued in 13 patients (43%) after 24 ± 30 months due to failure to control VT/VF (n = 7), placement of a left ventricular assist device (n = 3), catheter ablation (n = 1), heart transplantation (n = 1), and left ventricular restoration surgery (n = 1). There were 7 documented deaths (2 patients died suddenly; 3 patients of progressive heart failure; and 2 of non-cardiac causes). CONCLUSIONS: In patients with an ICD and ventricular arrhythmias, dofetilide decreases the frequency of VT/VF and ICD therapies even when other antiarrhythmic agents, including amiodarone, have previously been ineffective. Recurrences still occur in some patients requiring catheter ablation, mechanical support, or heart transplantation.

Cardiac resynchronization therapy: evaluation of ventricular dysynchrony and patient selection.

Cardiac resynchronization therapy (CRT) is an established treatment modality for systolic heart failure. Aimed to produce simultaneous biventricular stimulation and correct the lack of ventricular synchrony in selected patients with congestive heart failure, CRT has shown to improve mortality and reduce hospital admissions when compared to medical treatment. At present, the indication criteria for the implantation of a CRT device include an ejection fraction of less than 35%, heart failure symptoms consistent with NYHA functional class III-IV and a QRS complex duration equal or longer than 120 milliseconds. It has been reported that 30% of patients who meet those criteria still may not derive clinical benefit from CRT. Due to the existing diversity of imagin modalities and resources for their process and analysis, a great expectation in terms of more accurate diagnosis of ventricular dyssynchrony has been raised. Reilable identification of dyssynchrony could allow us to better predict the favorable response of an individual patient to CRT and therefore offer this procedure to those individuals most likely to benefit. We review the available techniques for the study of ventricular dyssynchrony for CRT patient selection and the results of its application in clinical trials. Despite tremendous progress in the imaging technology available for the assessment and diagnosis of ventricular dyssynchrony, an ideal method has not been identified and the duration of QRS complex in the surface ECG remains the accepted criteria of dyssynchrony in the selection of patients for CRT.

Cardiac resynchronization therapy: evaluation of ventricular dysynchrony and patient selection / Terapia de resincronización cardiaca: evaluación de la disincronía ventricular y selección de pacientes

Cardiac resynchronization therapy (CRT) is an established treatment modality for systolic heart failure. Aimed to produce simultaneous biventricular stimulation and correct the lack of ventricular synchrony in selected patients with congestive heart failure, CRT has shown to improve mortality and reduce hospital admissions when compared to medical treatment. At present, the indication criteria for the implantation of a CRT device include an ejection fraction of less than 35%, heart failure symptoms consistent with NYHA functional class III-IV and a QRS complex duration equal or longer than 120 milliseconds. It has been reported that 30% of patients who meet those criteria still may not derive clinical benefit from CRT. Due to the existing diversity of imaging modalities and resources for their process and analysis, a great expectation in terms of more accurate diagnosis of ventricular dyssynchrony has been raised. Reliable identification of dyssynchrony could allow us to better predict the favorable response of an individual patient to CRT and therefore offer this procedure to those individuals most likely to benefit. We review the available techniques for the study of ventricular dyssynchrony for CRT patient selection and the results of its application in clinical trials. Despite tremendous progress in the imaging technology available for the assessment and diagnosis of ventricular dyssynchrony, an ideal method has not been identified and the duration of the QRS complex in the surface ECG remains the accepted criteria of dyssynchrony in the selection of patients for CRT.

La terapia de resincronización cardiaca es una modalidad de tratamiento bien establecida para la insuficiencia sistólica cardiaca. Dirigida a producir una estimulación biventricular simultánea y a corregir la falta de sincronía ventricular en pacientes seleccionados con insuficiencia cardiaca congestiva, la terapia de resincronización cardiaca ha mostrado ser capaz de mejorar los índices de mortalidad y reducir las admisiones hospitalarias cuando se compara con el tratamiento médico. Actualmente, los criterios para la implantación de un dispositivo de terapia de resincronización cardiaca incluyen una fracción de eyección menor a 35%, síntomas de insuficiencia cardiaca consistentes con la clase funcional NYHA III-IV, y una duración del complejo QRS igual o mayor de 120 milisegundos. Se ha reportado que 30% de los pacientes que cumplen con estos criterios pueden inclusive no obtener beneficio clínico de la terapia de resincronización cardiaca. Debido a la diversidad existente de los estudios de imagenología y de los recursos para su proceso y análisis, ha surgido una gran expectativa en términos de un diagnóstico más exacto de la asincronía ventricular. La identificación confiable de la asincronía nos podría permitir predecir mejor la respuesta favorable de un paciente en particular a la terapia de resincronización cardiaca y así ofrecer este procedimiento a aquellos pacientes con mayores probabilidades de beneficiarse de dicha terapia. Hacemos una revisión de las técnicas disponibles para el estudio de la asincronía ventricular para la selección de pacientes para esta terapia y los resultados de su aplicación en pruebas clínicas. A pesar de los grandes progresos alcanzados en la tecnología de imágenes disponibles para la evaluación y diagnóstico de la asincronía ventricular, no se ha identificado un método ideal y la duración del complejo QRS en el ECG de superficie sigue siendo el criterio aceptado de asincronía en la selección de pacientes para terapia de resincronización cardiaca.

Distal balloon occlusion allows epicardial lead placement in a tortuous branch of the great cardiac vein.

Cardiac resynchronization therapy (CRT) is a well established treatment modality in heart failure. Using standard techniques, placement of the left ventricular (LV) lead is usually successful; however LV lead placement failure remains a clinical problem. In the present report, the standard over-the-wire technique was not successful due to absence of the necessary support to place the lead into a tortuous vein. This was achieved using balloon occlusion of the great cardiac vein distal to the target vessel. An 81 year old female candidate for CRT presented for biventricular pacemaker implantation. After placement of the right ventricular lead, the CS was cannulated and an occlusive venogram was performed. A lateral branch was selected as the target vessel. Initial attempts at cannulating the vessel were unsuccessful due to the guidewire and telescoping delivery system prolapsing into the great cardiac vein. The acute angle prevented instrumentation of the branch with the tools available. A second parallel CS sheath was advanced to drive a balloon catheter used to occlude the great cardiac vein distal to the target vessel. This provided support for the guidewire and lead allowing their advancement through the tortuous vessel. Consecutive traction on the balloon during also helped to reflect the lead towards the vessel. The lead remained stable in its final position on the lateral wall of the LV with appropriate thresholds and no diaphragmatic stimulation. We report a case where balloon occlusion of the great cardiac vein distal to the target branch aided in advancing the LV lead into the desired position. This approach can be used in navigating lead placement to branches thought to be unreachable. Techniques such as this can decrease the failure rate of CRT implants.

Efficacy and safety of dofetilide in patients with atrial fibrillation and atrial flutter.

BACKGROUND: Dofetilide, an I(Kr) blocker has been demonstrated to be effective in terminating persistent atrial fibrillation and flutter (AF/AFL), and in maintaining sinus rhythm after direct current cardioversion (CV). It is not known, however, whether pharmacological conversion with dofetilide predicts maintenance of sinus rhythm. In addition, there is limited information comparing the efficacy of dofetilide in persistent versus paroxysmal AF/AFL. METHODS AND RESULTS: Eighty consecutive patients with AF/AFL (51 persistent, 29 paroxysmal) admitted for initiation of dofetilide were studied. Termination of persistent AF/AFL occurred in 61% of patients while 39% required CV. After 21 +/- 19 months of follow-up, 37% of patients with persistent AF/AFL were free of recurrence. Acute conversion with dofetilide did not predict long term efficacy. Dofetilide was more effective in maintaining sinus rhythm in patients with AFL (65%) than in those with AF (25%) (p < 0.05). Dofetilide was more likely to maintain sinus rhythm in patients with persistent than paroxysmal AF/AFL (37 vs. 14%; p < 0.05). Torsades de Pointes developed in two patients despite careful dosing and monitoring of QT changes. CONCLUSIONS: Dofetilide is more effective in patients with persistent than in those with paroxysmal AF/AFL. Importantly, short-term response does not necessarily predict long-term efficacy. Significant proarrhythmia can occur even with careful in-hospital monitoring.