Antoni Martínez-Rubio

Análisis coste-efectividad de dabigatrán para la prevención de ictus y embolia sistémica en fibrilación auricular no valvular en España

INTRODUCTION AND OBJECTIVES Assessment of the cost-effectiveness of dabigatran for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in Spain, from the perspective of the National Health System. METHODS Adaptation of a Markov chain model that simulates the natural history of the disease over the lifetime of a cohort of 10,000 patients with non-valvular atrial fibrillation. Model comparators were warfarin in a first scenario, and a real world prescribing pattern in a second scenario, in which 60% of the patients were treated with vitamin K antagonists, 30% with acetylsalicylic acid, and 10% received no treatment. Deterministic and probabilistic sensitivity analyses were performed. RESULTS Dabigatran reduced the occurrence of clinical events in both scenarios, providing gains in quantity and quality of life. The incremental cost-effectiveness ratio for dabigatran compared to warfarin was 17,581 euros/quality-adjusted life year gained and 14,118 euros/quality-adjusted life year gained when compared to the real world prescribing pattern. Efficiency in subgroups was demonstrated. When the social costs were incorporated into the analysis, dabigatran was found to be a dominant strategy (ie, more effective and less costly). The model proved to be robust. CONCLUSIONS From the perspective of the Spanish National Health System, dabigatran is an efficient strategy for the prevention of stroke in patients with non-valvular atrial fibrillation compared to warfarin and to the real-world prescribing pattern; incremental cost-effectiveness ratios were below the 30,000 euros/quality-adjusted life year threshold in both scenarios. Dabigatran would also be a dominant strategy from the societal perspective, providing society with a more effective therapy at a lower cost compared to the other 2 alternatives. Full English text available from:www.revespcardiol.org.

Predictive Value of Wavelet Correlation Functions of Signal-Averaged Electrocardiogram in Patients After Anterior Versus Inferior Myocardial Infarction

OBJECTIVES This study sought to evaluate the prognostic value of wavelet correlation functions of the signal-averaged electrocardiogram (ECG) for arrhythmic events in patients after myocardial infarction. BACKGROUND Wavelet transform of the signal-averaged ECG has been shown to be a nonstationary analysis technique describing the time evolution of frequency spectra throughout the QRS complex. To quantify the wavelet transform, we introduced the new concept of the wavelet correlation function. METHODS The relation among wavelet correlation functions, ventricular late potentials and the site of infarction was investigated in 769 men < 66 years old who survived the acute phase of myocardial infarction (351 [46%] anterior, 418 [54%] inferior infarctions). Signal-averaged ECG recordings were obtained 2 to 3 weeks after infarction. During 6 months of follow-up, 33 patients (4.3%) experienced a malignant arrhythmic event. Wavelet correlation functions of the signal-averaged ECG were evaluated in a time-frequency plane ranging from 25 ms before QRS onset to 25 ms after QRS offset in the frequency range between 40 and 100 Hz. RESULTS Patients with an anterior infarction had lower mean wavelet correlation coefficients (p < 0.001) and a lower incidence of ventricular late potentials than patients with an inferior infarction (32.3% vs. 42.7%, p = 0.003). The combination of wavelet correlation functions and late potentials increased the total predictive accuracy from 52% to 72% for inferior and from 64% to 76% for anterior infarctions. CONCLUSIONS Spectral changes in the signal-averaged QRS complex are more prominent in anterior than inferior infarctions. Combination of late potential analysis and wavelet correlation functions increases the prognostic value for serious arrhythmic events after myocardial infarction.

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.

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.

Electrophysiologic variables characterizing the induction of ventricular tachycardia versus ventricular fibrillation after myocardial infarction : relation between ventricular late potentials and coupling intervals for the induction of sustained ventricular tachyarrhythmias

OBJECTIVES The aim of this study was to analyze the relations between the presence of ventricular conduction delay and the necessary coupling intervals for the induction of sustained ventricular tachyarrhythmias. METHODS The electrophysiologic and signal-averaged electrocardiographic (ECG) data from 83 patients with previous myocardial infarction and inducible sustained monomorphic ventricular tachycardia (n = 71) and ventricular fibrillation (n = 12) were analyzed. RESULTS The sum of the coupling intervals needed for inducing ventricular tachycardia and ventricular fibrillation was 485 +/- 59 ms and 387 +/- 36 ms, respectively (p < 0.001). The mean difference between the effective refractory period and the second coupling interval for the induction of ventricular tachycardia and ventricular fibrillation was -3 +/- 40 ms and 24 +/- 29 ms, respectively (p < 0.02). QRS duration and duration of terminal low amplitude signals of the QRS complex (p < 0.004) were longer in patients with inducible ventricular tachycardia than in patients with inducible ventricular fibrillation. The root mean square of the voltage during the last 40 ms of QRS complex was lower in patients with inducible ventricular tachycardia than in patients with inducible ventricular fibrillation (p < 0.007). Patients with inducible ventricular tachycardia presented with a greater prevalence of ventricular late potentials than that of patients with inducible ventricular fibrillation (p < 0.007). For arrhythmia induction, significantly shorter coupling intervals were necessary in patients without than in patients with ventricular late potentials. A positive correlation was found between the cycle length of the induced ventricular tachycardia and the filtered QRS duration as well as with the sum of the coupling intervals. CONCLUSIONS Induction of ventricular fibrillation requires shorter coupling intervals than does induction of ventricular tachycardia. The presence of ventricular conduction delay seems to be a marker of facilitated induction of sustained monomorphic ventricular tachycardia rather than of ventricular fibrillation. The coupling intervals required to induce ventricular tachycardia or fibrillation are longer in patients with than in those without an abnormal signal-averaged ECG.

Multiresolution decomposition of the signal-averaged ECG using the mallat approach for prediction of arrhythmic events after myocardial infarction

The aim of this study was to analyze the ability of the multiresolution decomposition of the signal-averaged electrocardiogram (ECG) to discriminate between patients who develop life-threatening ventricular arrhythmias after myocardial infarction and those who do not and to compare the predictive values of this approach with those obtained from the analysis of ventricular late potentials in the time domain. Signal-averaged ECGs of 769 prospectively included patients were analyzed. A total of 42 arrhythmic events occurred during the follow-up period. For numerical calculations of wavelet analysis, the total and relative energies of the QRS complex were obtained in seven frequency bands. The combination of the relative energy in the frequency bands 7.8-15.6 Hz and 62.5-125 Hz enhanced statistical performance as compared with the time-domain parameters (positive predictive accuracy, 11.3 vs 8.2%). Combining wavelet transform and time-domain parameters enhanced the predictive values even more (positive predictive accuracy, 14.3%) compared with applying each method alone.

Reduced Beat-to-Beat Changes of Heart Rate: An Important Risk Factor after Acute Myocardial Infarction

The prognostic significance of heart rate variability derived from 24-hour electrocardiographic recordings was investigated in 250 patients with acute myocardial infarction. During a follow-up of 6 months 15 patients experienced a serious arrhythmic event. These patients showed a significantly reduced beat to beat variability (p = 0.006), a slightly reduced 5-min variability (p = 0.04) and no significant differences in the 24-hour variability compared to the patients free of arrhythmic events. Based on Cox proportional hazard analysis, beat to beat variability remained an independent risk factor (p = 0.0036) in addition to the presence or absence of ventricular late potentials (p = 0.0004) and history of previous infarction (p = 0.04).

Advances for Treating In-Hospital Cardiac Arrest: Safety and Effectiveness of a New Automatic External Cardioverter-Defibrillator

OBJECTIVES The purpose of this study was to prospectively analyze the performance and safety of a new programmable, fully automatic external cardioverter-defibrillator (AECD) in a European multicenter trial. BACKGROUND Although, the response time to cardiac arrest (CA) is a major determinant of mortality and morbidity, in-hospital strategies have not significantly changed during the last 30 years. METHODS Patients (n = 117) at risk of CA in monitored wards (n = 51) and patients undergoing electrophysiologic testing or implantable cardioverter-defibrillator (ICD) implantation (n = 66) were enrolled. The accuracy of the automatic response of the device to any change of rhythm (lasting >1 s and >4 beats) was confirmed by reviewing the simultaneously recorded Holter data and the programmed parameters. RESULTS During 1,240 h, 1,988 episodes of rhythm changes were documented. A total of 115 episodes lasted > or =10 s or needed treatment (pacing, n = 32; ICD, n = 51; AECD, n = 35) for termination. The device detected ventricular tachyarrhythmias with a sensitivity of 100% and specificity of 97.6% (true negatives, n = 1,454; true positives, n = 499; false positives, n = 35; false negatives, n = 0). The false positives were all caused by T-wave oversensing during ventricular pacing. There were no complications or adverse events. The mean response time was 14.4 s for those episodes needing a full charge of the capacitor. CONCLUSIONS This new AECD is safe and effective in detecting, monitoring, and treating spontaneous arrhythmias. This fully automatic device shortens the response time to treatment, and it is likely that it will significantly improve the outcome of patients with in-hospital CA.

Evaluación de riesgo tromboembólico y hemorrágico de los pacientes con fibrilación auricular

Resumen La fibrilacion auricular es la arritmia cardiaca mas frecuente en la practica clinica diaria. Ademas de las alteraciones hemodinamicas que ocasiona —consecuencia de la perdida de la contraccion auricular y la frecuencia cardiaca habitualmente elevada, que pueden causar la aparicion de insuficiencia cardiaca—, el principal riesgo de la fibrilacion auricular es que la estasis circulatoria en la auricula cause una embolia arterial. Se sabe que la fibrilacion auricular se asocia a un marcado aumento del riesgo de accidentes tromboembolicos arteriales, asociados a elevadas mortalidad y morbilidad y alto riesgo de recurrencia. Esta demostrado que el tratamiento antitrombotico con anticoagulantes orales se asocia a un drastico descenso del riesgo de accidentes tromboembolicos. Sin embargo, los anticoagulantes orales incrementan significativamente el riesgo de hemorragias mayores, de las que es especialmente devastadora la hemorragia intracraneal. Por lo tanto, al iniciar el tratamiento anticoagulante de un paciente con fibrilacion auricular, resulta imprescindible valorar adecuadamente el beneficio/riesgo del tratamiento segun sus caracteristicas clinicas. Multiples estudios han mostrado una serie de variables que determinan los riesgos emboligeno y de sangrado asociados al tratamiento anticoagulante, y con base en ellas se han desarrollado diversos sistemas de estratificacion para calcular el riesgo de embolia secundaria a la fibrilacion auricular y el riesgo de hemorragia relacionado con el tratamiento antitrombotico. En la practica clinica diaria, la aplicacion de estas escalas de riesgo es de gran ayuda para elegir la mejor alternativa terapeutica para un paciente concreto.