Letizia Bacchi

Cardiac Resynchronization Therapy: Variations in Echo‐Guided Optimized Atrioventricular and Interventricular Delays During Follow‐Up

Background: Relatively few data are available on long‐term echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay programming in cardiac resynchronization therapy (CRT). We assessed variations in optimized AV and VV delays during long‐term follow‐up. Methods: Thirty‐seven consecutive heart failure patients received Doppler echocardiographic optimization of AV and VV delay within 48 hours from CRT device implantation, at 6 months and at 12 months (the last for the first enrolled 14 patients). Results: After implantation, median optimized AV delay was 100 ms (range, 45 ms); VV optimization led to simultaneous biventricular activation in 4 patients, left ventricular preactivation in 17 patients and right ventricular preactivation in 16 patients. At 12 months median AV delay decreased to 85 ms (23 ms) (P < 0.05 vs. baseline). With respect to previous assessment, VV delay variations ≥40 ms were observed in 41% of the patients at 6 months and in 57% of the tested patients at 12 months. A nonconcordance (by Kappa test) of optimized VV delays was found between each new assessment and the previous one. VV delay optimization was associated with significant (P < 0.001) increases in aortic velocity time integral both at baseline and during follow‐up. Conclusions: Echocardiographic optimization of AV and VV delay is associated with broad intraindividual variability during follow‐up. A new assessment of optimized VV delays during long‐term follow‐up reveals a nonconcordance with previous values and provides increases in forward stroke volume.

Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response.

Despite interest in neurohormonal activation as a determinant of prognosis in chronic heart failure (CHF) and as a target for pharmacological treatments, data are lacking on the time-related effects of electrical cardiac resynchronization therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this study was to assess time-courses and extents of changes within the neurohormonal profile of CHF patients treated with CRT. We performed a prospective follow-up study in 32 patients with NYHA class III-IV CHF to investigate the effects of CRT on a broad panel of neurohormones proposed for characterization of CHF patients. Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine, norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3 months of CRT; when feasible, measurements were also performed at 1 week, 1 month and 12 months (clinical evaluation, echocardiography and ECG were also performed at each time-point). The results showed that at 3 months improvement in NYHA class and echographically assessed left ventricular (LV) reverse structural remodeling were accompanied by significant reductions versus baseline in ANP and BNP, but not in other neurohormones. Moreover a baseline ANP concentration < or = 150 pg/ml was a good predictor of response to CRT in terms of NYHA class reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly reduce natriuretic peptides concentrations, while values of other neurohormones and inflammatory cytokines are relatively unvaried. A baseline ANP concentration < or = 150 pg/ml might be a clinically useful predictor of medium-term response to CRT.

Predictors of Atrial Defibrillation Threshold in Internal Cardioversion

This study examined the clinical, echocardiographic, and electrophysiological factors influencing the atrial defibrillation threshold (ADFT) in patients with chronic, persistent AF undergoing transvenous, low energy, atrial cardioversion. Twenty‐two patients (age 57 ± 15 years) with a mean AF duration of 7.8 ± 7.1 months (range 2–32 months) underwent internal cardioversion with catheters placed in the right atrium and coronary sinus. Biphasic shocks (3/3 ms) were delivered in a step‐up protocol. ADFT was defined as the lowest energy shock that converted AF to sinus rhythm. All patients were successfully cardioverted at a mean ADFT of 5.62 ± 2.82 J (range 2.6–12.9 J). Fifteen variables, including clinical characteristics (age, body mass index, AF duration, etiology), echocardiographic measurements (atrial diameter and volumes, indexes of ventricular performance), hemodynamic measurements, and mean atrial cycle during AF were analyzed as possible predictors of ADFT. In univariate regression analysis, AF duration, mean RR interval, and cardiac index correlated with ADFT. In multivariate regression analysis, AF duration remained as the only significant predictor of ADFT (B coefficient 0.311, P < 0.001; 95% confidence interval [CI] 0.194‐0.427). AF duration was the most powerful predictor of ADFT. It should be considered when planning internal CV of AF to limit the number of shocks delivered. Furthermore, long intervals between AF onset and CV should be avoided.

Late Improvement in Ventricular Performance Following Internal Cardioversion for Persistent Atrial Fibrillation

The aim of the study was to evaluate the time course of atrial and ventricular function improvement following internal atrial cardioversion in patients with structural heart disease. Twenty‐nine patients with chronic persistent atrial fibrillation (AF) and underlying structural heart disease were followed by serial echocardiograms performed at 1 and 6 hours, 1 day, 1, 2, and 3 weeks, and 1, 2, 3, and 6 months after successful cardioversion. Sinus rhythm was maintained at 6 months in 24 patients. Following cardioversion the time course of left atrial mechanical function (peak A wave, percent A wave filling) differed from that of left ventricular ejection fraction: peak A wave values (cm/s) increased significantly at 1 week ( 51 ± 23 vs 35 ± 15 at 1 hour, P < 0.05 ), percent A wave filling (%) increased significantly at 2 weeks ( 34 ± 12 vs 22 ± 9 at 1 hour, P < 0.05 ), whereas left ventricular ejection fraction (%) increased later (at 1 month 60 ± 14 vs 55 ± 14 at baseline, P < 0.05 and at 2 months 60 ± 14 vs 56 ± 14 at 1 hour, P < 0.05 ). In conclusion, restoration of sinus rhythm results in an improvement in left ventricular ejection fraction during follow‐up, even in patients with structural heart disease without fast ventricular rates at baseline. The dissociation between the time course of atrial and ventricular function improvement suggests that the latter was partly due to regression of a concealed form of cardiomyopathy and/or of a ventricular dysfunction due to chronic AF. (PACE 2003; 26:1218–1226)

Repolarization changes in a double-blind crossover study of dofetilide versus sotalol in the treatment of ventricular tachycardia.

The aim of this study was to determine whether a therapeutic response to Class III antiarrhythmic drugs is related to predictable changes in repolarization on the electrocardiogram (ECG). A group of 57 patients with ischemic heart disease and inducible ventricular tachycardia (VT) at electrophysiological study (EPS) were selected from a population enrolled in a randomized double‐blind crossover study of dofetilide (500 μg bid) versus sotalol (160 mg bid). ECGs were analyzed blindly, and RR, QT (maximum value/12 leads), QTc (Bazetts formula), QT dispersion (QTmax ‐ QTmin over 12 leads) and QTc dispersion, were calculated at baseline and on the third day of treatment (4 hours after dosing), when patients underwent EPS to test the effects of study drugs on VT inducibility. Results: At EPS 21 patients were responders to dofetilide and 22 to sotalol. On day 3, a significant increase in QT and QTc and decrease in QT and QTc dispersion, compared to baseline, was measured in responders and nonresponders, with both dofetilide and sotalol. No significant difference in QTc or QT dispersion between responders and nonresponders was observed in either treatment group. In conclusion, treatment with dofetilide and sotalol was associated with an increase in QT and QTc, and a decrease in QT and QTc dispersion. In contrast with previous reports, a differential effect on QT or QTc dispersion was not observed in drug responders versus nonresponders.