Transcoronary ablation of septal hypertrophy does not alter ICD intervention rates in high risk patients with hypertrophic obstructive cardiomyopathy

INTRODUCTION: Transcoronary ablation of septal hypertrophy (TASH) is safe and effectively reduces the intraventricular gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM). To analyze the potential of anti- and proarrhythmic effects of TASH, we studied the discharge rates of implanted cardioverter defibrillators (ICD) in patients with HOCM who are at a high risk for sudden cardiac death. METHODS: ICD and TASH were performed in 15 patients. Indications for ICD-implantation were secondary prevention in nine patients after resuscitation from cardiac arrest with documented ventricular fibrillation (n = 7) or sustained ventricular tachycardia (n = 2) and primary prevention in 6 patients with a family history of sudden deaths, nonsustained ventricular tachycardia, and/or syncope. All the patients had severe symptoms due to HOCM (NYHA functional class = 2.9). RESULTS: During a mean follow-up time of 41 +/- 22.7 months following the TASH procedure, 4 patients had episodes of appropriate discharges (8% per year). The discharge rate in the secondary prevention group was 10% per year and 5% in the group with primary prophylactic implants. Three patients died during follow-up (one each of pulmonary embolism, stroke, and sudden death). CONCLUSION: In conclusion, on the basis of ICD-discharge rates in HOCM-patients at high risk for sudden death, there is no evidence for an unfavorable arrhythmogenic effect of TASH. The efficacy of ICD treatment for the prevention of sudden cardiac death in HOCM could be confirmed, however, mortality is high in this cohort of hypertrophic cardiomyopathy patients.     

The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by ?-amyloid peptide

Background and purpose:

β-Amyloid peptide (Aβ) is implicated in the pathogenesis of Alzheimer''s disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress.

Experimental approach:

We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Aβ-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Aβ and on neurite outgrowth in PC12 cells were investigated.

Key results:

Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Aβ_1-42. Similar protective effects against Aβ_1-42 were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Aβ load was markedly diminished in the brain of those animals after treatment with piracetam. Aβ production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Aβ-induced mitochondrial dysfunction and Aβ-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam.

Conclusion and implications:

Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Aβ on brain function.This article is commented on by Moncada, pp. 217–219 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00706.x and to view related papers by Pravdic et al. and Puerta et al. visit http://dx.doi.org/10.1111/j.1476-5381.2010.00698.x and http://dx.doi.org/10.1111/j.1476-5381.2010.00663.x     

Ifosamide, epirubicin and granulocyte colony-stimulating factor: a regimen for successful mobilization of peripheral blood progenitor cells in patients with multiple myeloma.

In general, the mobilization of peripheral blood progenitor cells (PBPC) in multiple myeloma (MM) patients is poor and is achieved in most cases by combined cyclophosphamide and G-CSF. This study was performed to examine the efficacy of combined ifosfamide/epirubicine and G-CSF for PBPC mobilization and purging. Sixteen patients suffering from multiple myeloma in stage II/A and III/A according to Durie and Salmon underwent chemotherapy consisting of a total of three cycles of ifosfamide (3 g/m(2) on days 1 and 2 and epirubicine 80 mg/m(2) on day 1) and G-CSF (10 or 20 microg/kg body weight (BW) daily until harvesting). PBPC harvesting was performed after the first and third cycle of chemotherapy. The median number of PBPC after the first cycle of chemotherapy was 7.79 x 10(6) CD34+ cells/kg BW (ranging from 0.94-26.36 x 10(6)) and 6.38 x 10(6) CD34+ cells/kg BW (ranging from 0.79-29.31 x 10(6)) after the third cycle of chemotherapy. Clinical re-evaluation after three cycles of chemotherapy showed 13 (81 per cent) patients in partial remission (PR), two (12 per cent) in complete remission (CR) and one (6.25 per cent) in stable disease (SD). No major side-effects were observed, six patients developed hematological toxicity stage IV WHO for a median of 3.9 days but no serious infection episodes occurred. Combined ifosfamide/epirubicin and standard G-CSF is able to mobilize sufficient PBPC without serious side-effects for patients with MM and for purging procedures resulting in a high proportion of complete remissions after tandem high-dose melphalan chemotherapy.     

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