Alcohol-induced right bundle branch block is associated with a benign outcome in HOCM after alcohol septum ablation (ASA).

INTRODUCTION: Alcohol septum ablation (ASA) is a treatment option for hypertrophic obstructive cardiomyopathy (HOCM). We examined the impact of ASA-induced bundle branch block (BBB) on clinical and hemodynamic features. METHODS AND RESULTS: We retrospectively analysed 98 HOCM patients with regard to ASA-induced BBB. Clinical examination was performed at baseline, early after ASA and at chronic follow-up (FU). ASA reduced left ventricular outflow tract gradient (LVOTG) during chronic FU (69.2 ± 41.6 pre vs. 31.8 ± 30.3 mmHg post ASA; p < 0.05) and interventricular septal diameter (21.7 ± 3.4 pre vs. 18.7 ± 5.0 mm post ASA; p < 0.05). ASA-induced early right BBB (RBBB) until discharge was observed in 44.9% and chronic RBBB at FU in 32.7%. Left BBB (LBBB) occurred in 13.3% early after ASA and in only 4.1% at chronic FU. Chronic RBBB was associated with more pronounced exercise-induced LVOTG reduction (102.1 ± 55.2 with vs. 73.6 ± 60.0 mmHg without; p < 0.05). 6-min-walk-test (6-MWT) and NYHA class were not affected by RBBB. LBBB had no influence on LVOTG, 6-MWT and symptoms. More ethanol was injected in patients with early RBBB (1.1 ± 0.4 vs. 0.8 ± 0.3 ml without; p < 0.05), who also showed higher mean CK release (827 ± 341 vs. 583 ± 279 U/l without; p < 0.05). Pacemaker implantation during FU was necessary in 11.5% of patients with early RBBB, 3.1% with chronic RBBB, 7.7% with early LBBB and 0% with chronic LBBB (p = n.s. for BBB vs. no BBB). CONCLUSION: ASA-induced RBBB is associated with a higher volume of infused ethanol and higher maximum CK release. RBBB does not adversely affect the clinical outcome or need for pacemaker implantation but was associated with higher exercise-induced LVOTG reduction during chronic FU.

Enrichment of cardiac pacemaker-like cells: neuregulin-1 and cyclic AMP increase I(f)-current density and connexin 40 mRNA levels in fetal cardiomyocytes.

Generation of a large number of cells belonging to the cardiac pacemaker system would constitute an important step towards their utilization as a biological cardiac pacemaker system. The aim of the present study was to identify factors, which might induce transformation of a heterogenous population of fetal cardiomyocytes into cells with a pacemaker-like phenotype. Neuregulin-1 (alpha- and beta-isoform) or the cAMP was added to fresh cell cultures of murine embryonic cardiomyocytes. Quantitative northern blot analysis and flowcytometry were performed to detect the expression of connexins 40, 43 and 45. Patch clamp recordings in the whole cell configuration were performed to determine current density of I (f), a characteristic ion current of pacemaker cells. Fetal cardiomyocytes without supplement of neuregulin or cAMP served as control group. Neuregulin and cAMP significantly increased mRNA levels of connexin 40 (Cx-40), a marker of the early differentiating conduction system in mice. On the protein level, flowcytometry revealed no significant differences between treated and untreated groups with regard to the expression of connexins 40, 43 and 45. Treatment with cAMP (11.2 +/- 2.24 pA/pF; P < 0.001) and neuregulin-1-beta (6.23 +/- 1.07 pA/pF; P < 0.001) significantly increased the pacemaker current density compared to control cardiomyocytes (1.76 +/- 0.49 pA/pF). Our results indicate that neuregulin-1 and cAMP possess the capacity to cause significant transformation of a mixed population of fetal cardiomyocytes into cardiac pacemaker-like cells as shown by electrophysiology and increase of Cx-40 mRNA. This method may allow the development of a biological cardiac pacemaker system when applied to adult or embryonic stem cells.