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.

Safety and efficacy of alcohol septal ablation in adolescents and young adults with hypertrophic obstructive cardiomyopathy.

INTRODUCTION: Data regarding alcohol septal ablation (ASA) in young patients with hypertrophic obstructive cardiomyopathy (HOCM) are scarce. The purpose of our study is to evaluate the safety and efficacy of ASA in patients ≤ 25 years. METHODS AND RESULTS: All ASAs between 2002 and 2020 at our institution were assigned to a group of patients 14-25 years of age (group 1) and a reference group > 25 years (group 2). 1,264 procedures were analysed in group 2 (58.6 ± 13.5 years) and 41 procedures in group 1 (20.9 ± 3.3 years). The baseline interventricular septal diameter (IVSD) was higher in group 1 (26.0 ± 6.5 mm vs. 21.3 ± 4.4 mm; p < 0.0001). There was no difference in baseline left ventricular outflow tract gradient (LVOTG) (group 1: 54.4 ± 24.4 mmHg; group 2: 52.4 ± 36.6 mmHg; p = n.s.). A previous cardiac device was more often observed in group 1 (31.7% vs. 9.0%; p < 0.0001). Symptoms were improved after 6 months (group 1: mean NYHA class 2.5 at baseline and 1.3 at FU; p < 0.0001; group 2: mean NYHA class 2.7 at baseline and 1.4 at FU; p <0 .0001). IVSD (group 1: 20.3 ± 8.2 mm; group 2: 16.8 ± 5.7 mm; p < 0.0001 for each group compared to baseline) and LVOTG improved during FU (group 1: 25.5 ± 20.0 mmHg; group 2: 22.1 ± 21.7 mmHg; p < 0.0001 for each group). Intrahospital mortality was 0.0% in patients 14-25 years and 0.9% in the reference group. Persistent AV-block was observed in 12.2% of the group 1 and 15.9% of the group 2 patients (p = n.s.). CONCLUSION: ASA is safe and effective in HOCM patients 14-25 years of age in experienced centres.

Acute and chronic effects of endocardial radiofrequency ablation of septal hypertrophy in HOCM.

INTRODUCTION: Endocardial radiofrequency ablation of septal hypertrophy (ERASH) is an alternative to alcohol septal ablation (ASA) or surgical myectomy for hypertrophic obstructive cardiomyopathy (HOCM). Several studies have confirmed that septal radiofrequency ablation leads to a significant reduction in the left ventricular outflow tract gradient. OBJECTIVES: We aimed to report the outcomes of 41 patients who underwent ERASH with a focus on severe complications. METHODS: Since 2004, 41 patients with HOCM (age: 58.2 ± 13 years) underwent ERASH at our institution. ERASH was performed, since ASA was ineffective (26 patients) or not possible (15 patients). RESULTS: The left ventricular outflow tract and the right ventricular septum were ablated in 26 and 15 patients, respectively. ERASH resulted in a significant reduction in acute gradient during the session and the results persisted during the 6-month follow-up (67% gradient reduction at rest and 73% after provocation, p = .0002). Pacemaker dependency after ERASH was 29% and pericardial tamponade occurred in two patients. In four patients, ERASH induced a paradoxical increase in obstruction (PIO), beginning suddenly at 30 min after the procedure and leading to lethal shock in one patient. PIO was not observed after ERASH from the right ventricular aspect. CONCLUSION: Morbidity and mortality after ERASH were higher than those after ASA. PIO, a life-threatening complication, was observed in 9% of the patients. Our data indicate that ERASH might be considered in patients who are not candidates for surgical myectomy or ASA.

Acute and chronic effects of nano- and non-nano-scale TiO(2) and ZnO particles on mobility and reproduction of the freshwater invertebrate Daphnia magna.

Among the emerging literature addressing the biological effects of nanoparticles, very little information exists, particularly on aquatic organisms, that evaluates nanoparticles in comparison to non-nanocounterparts. Therefore, the potential effects of nano-scale and non-nano-scale TiO(2) and ZnO on the water flea, Daphnia magna, were examined in 48-h acute toxicity tests using three different test media, several pigment formulations--including coated nanoparticles--and a variety of preparation steps. In addition, a 21-d chronic Daphnia reproduction study was performed using coated TiO(2) nanoparticles. Analytical ultracentrifugation analyses provided evidence that the nanoparticles were present in a wide range of differently sized aggregates in the tested dispersions. While no pronounced effects on D. magna were observed for nano-scale and non-nano-scale TiO(2) pigments in 19 of 25 acute (48-h) toxicity tests (EC50>100 mg L(-1)), six acute tests with both nano- and non-nano-scale TiO(2) pigments showed slight effects (EC10, 0.5-91.2 mg L(-1)). For the nano-scale and non-nano-scale ZnO pigments, the acute 48-h EC50 values were close to the 1 mg L(-1) level, which is within the reported range of zinc toxicity to Daphnia. In general, the toxicity in the acute tests was independent of particle size (non-nano-scale or nano-scale), coating of particles, aggregation of particles, the type of medium or the applied pre-treatment of the test dispersions. The chronic Daphnia test with coated TiO(2) nanoparticles demonstrated that reproduction was a more sensitive endpoint than adult mortality. After 21d, the NOEC for adult mortality was 30 mg L(-1) and the NOEC for offspring production was 3 mg L(-1). The 21-d EC10 and EC50 values for reproductive effects were 5 and 26.6 mg L(-1), respectively. This study demonstrates the utility of evaluating nanoparticle effects relative to non-nano-scale counterparts and presents the first report of chronic exposure to TiO(2) nanoparticles in D. magna.

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.