Spatial heterogeneity of protein expression induced by dyssynchronous right ventricular pacing in the left ventricle of dogs with preserved systolic function.

BACKGROUND: Right ventricular (RV) apical pacing may result in ventricular dyssynchrony, which is associated with functional and morphological changes in the left ventricle (LV). Our aim is to assess contraction and hypertrophy-related protein expression changes in the LV after RV apical pacing. METHODS AND RESULTS: Six dogs underwent dual chamber pacemaker (DDD) implantation and atrioventricular nodal catheter ablation. The pacing group received atria-sensed RV apical pacing for 12 weeks. LV dyssynchrony was assessed with speckle tracking technique. Subsequently, hearts were processed for Western blotting. Four sham-operated dogs were included for comparison. After 12 weeks of RV pacing, cardiac chamber size and LV ejection fraction remained unchanged. Both electrical and mechanical dyssynchrony were evident in RV-paced dogs compared with sham-operated dogs. The late-activated LV lateral wall of paced dogs displayed a 23% reduction in the amount of sarcoplasmic reticulum Ca(2+) ATPase, a 32% reduction in phospholamban levels, but a 3.6-fold increase in phospho-JNK expression, a 2.2-fold increase in phospho-p38, and 1.9-fold increase in phospho-ERK expression. There were no significant differences in the early-activated LV septum between paced and sham dogs. CONCLUSIONS: Temporal dispersion of mechanical activation by RV apical pacing induced spatial dispersion of protein expression in the LV.

Left ventricular extracellular matrix remodeling in dogs with right ventricular apical pacing.

INTRODUCTION: Right ventricle (RV) apical pacing is associated with increased incidence of heart failure due to left ventricle (LV) desynchronization. We aim to investigate extracellular matrix (ECM) remodeling of the LV in dogs with atria-sensed RV apical pacing. METHODS AND RESULTS: Dogs with pacemakers underwent AV nodal ablation. After 12 weeks of atria-sensed obligatory RV pacing, LVs were separated into septum and lateral wall for analysis. Zymographic activity, including matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-3, collagen transcript expression, and histology were examined in opposite portions of the LV to identify possible ECM remodeling changes by RV apical pacing. Compared with sham-operated dogs, increased interstitial fibrosis and fragmentation of myofibrils was found in the LV lateral wall in the pacing group. Collagen type II mRNA showed a significant 2-fold increase in the LV lateral wall in the pacing group. Although collagen type I mRNA was increased, the difference was not significant. Zymography demonstrated MMP-9 activity was enhanced in both the LV lateral wall and septum in the pacing group, but MMP-2 activity was enhanced in the LV lateral wall. Immunofluorescence stain confirmed the activation of MMP-2 and MMP-9 in the LV lateral wall in the pacing group. Protein expression of TIMP-1 and TIMP-3 showed regional differences in the pacing group and both proteins were increased in the LV lateral wall. CONCLUSION: LV dyssynchrony by RV apical pacing elicits heterogeneous ECM remodeling in the LV. These findings assist in the elucidation of the pathophysiology of LV desynchronization.

Interventricular mechanical dyssynchrony determines abnormal heightening of plasma N-terminal probrain natriuretic peptide level in symptomatic bradyarrhythmia patients with chronic dual-chamber vs. single-chamber atrial pacing.

OBJECTIVE: Debates about adverse effects of ventricular- vs. atrial-based pacing have never ended, especially regarding cardiovascular outcomes in common pacemaker populations. METHODS: To investigate the contribution of right ventricular apical pacing to the left ventricular negative remodeling, we measured the inter- and intraventricular mechanical dyssynchrony by echocardiography as well as plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level in 116 consecutive patients of symptomatic bradyarrhythmias including sinus node dysfunction (SND) in 80 and atrioventricular block in 36. Dual-chamber rate-modulated pacing (DDDR) pacemakers were implanted in 76 patients (SND, 40), and single-chamber ventricular rate-modulated pacing (AAIR) pacemakers in 40 (all SND). Clinical manifestations were retrospectively correlated. RESULTS: After 3.5 years of pacing, DDDR pacemaker patients demonstrated higher plasma NT-proBNP concentration (503 +/- 111 pg/ml) than AAIR patients (194 +/- 42 pg/ml, p = 0.002) despite similar cardiovascular function at baseline. Multivariate regression analysis revealed that the only predictor of the highest quartile of plasma NT-proBNP, i.e. >or=386 pg/ml, was the interventricular contraction time difference (p = 0.01). Reprogramming to minimize ventricular pacing percentage in 8 patients of SND caused parallel reduction of plasma NT-proBNP. CONCLUSION: Interventricular mechanical dyssynchrony, imposed mostly by right ventricular apical pacing, could lead to abnormal heightening of plasma NT-proBNP concentration after chronic DDDR pacing in common pacemaker patients with normal baseline left ventricular function.

Usefulness of single-bolus adenosine test for confirming sinus node dysfunction and correlation with atrial overdrive suppression test.

We prospectively studied 42 consecutive patients who had symptomatic sinus node dysfunction and 17 age-matched controls by measuring maximal and corrected maximal sinus node recovery times with an atrial overdrive suppression test and single-bolus adenosine administration (0.15 mg/kg). We found a positive correlation between the 2 methods, with reasonably good sensitivity, specificity, and predictive accuracy.

Use of double-potential barrier to identify functional isthmus at the cavotricuspid isthmus for facilitating catheter ablation of isthmus-dependent atrial flutter.

INTRODUCTION: The aim of the study was to identify an alternative target for more effective radiofrequency catheter ablation (RFCA) of isthmus-dependent atrial flutter (AFL). METHODS AND RESULTS: We hypothesized that a functional isthmus formed by preexisting double potential barrier at the cavotricuspid isthmus (CTI) could serve as a new target site for facilitating RFCA of AFL. Forty-three consecutive patients with recurrent isthmus-dependent AFL were studied using three-dimensional navigated magnetic mapping and ablation technique. Twenty patients (47%, group A) were shown to have a narrower functional channel at the CTI (functional isthmus). The remaining 23 patients did not have this feature (53%, group B). In group A, double potentials were clustered near the border of the inferior vena cava (IVC) of the CTI and served as a functional channel along the tricuspid annulus (TA). The interspike interval of double potentials was 87 +/- 26 ms near the IVC border and 45 +/- 17 ms (P < 0.0001) near the TA border of CTI. RFCA targeting at the functional isthmus in group A resulted in interruption of bidirectional transisthmus conduction with fewer radiofrequency pulses (6.7 +/- 4.7 in group A vs 21.1 +/- 17.1 pulses in group B, P < 0.001), shorter ablation line (11.6 +/- 4.0 mm vs 37.8 +/- 7.2 mm, P < 0.0001) with no arrhythmia recurrence. These functional isthmuses were found to be located at the lateral third of CTI in 12 patients, middle third in 7, and medial third in 1. This finding is different from that obtained by the conventional method in group B (lateral in 5, middle in 16, medial in 2, P < 0.038). CONCLUSION: In our study, a functional, rather than anatomic, isthmus formed by preexisting double-potential barrier at the CTI was identified in 47% of patients with isthmus-dependent AFL. It is a useful guide to facilitate RFCA of isthmus-dependent AFL.

Predictors of clinical recurrence after successful electrical cardioversion of chronic persistent atrial fibrillation: clinical and electrophysiological observations.

Recurrence of atrial fibrillation (AF) after electrical cardioversion of chronic AF is not uncommon. However, it remains unclear which parameter(s) predict clinical recurrence. To assess the potential predictors of clinical recurrence after successful electrical cardioversion, we analyzed clinical, echocardiographic and electrophysiologic parameters in 36 patients (age 63 +/- 11 years; 26 males, 10 females) with chronic persistent AF lasting more than 3 months. The dimensions of the left atrium and left ventricular end diastole and end systole were measured by echocardiography. The P wave characteristics from the surface 12-lead electrocardiogram (ECG) were studied in sinus rhythm. Atrial local activations were studied by biatrial basket electrode mapping in AF. With a mean of 7 +/- 2 months of follow-up, 17 (47%) patients had AF recurrence despite multiple antiarrhythmic drug therapy. None of the clinical or echocardiographic parameters were relevant to the recurrence. However, among the surface ECG and intraatrial electrophysiological parameters, the mean P wave duration was the only independent predictor of the risk of clinical recurrence after successful electrical cardioversion. The sensitivity and predictive accuracy of recurrence were 82 and 70%, respectively, when the mean P wave duration was more than 125 ms.