Benefit of combined resynchronization and defibrillator therapy in heart failure patients with and without ventricular arrhythmias.

OBJECTIVES: We attempted to assess the efficacy of combined cardiac resynchronization therapy-implantable cardioverter-defibrillator (CRT-ICD) in heart failure patients with and without ventricular arrhythmias. BACKGROUND: Because CRT and ICDs both lower all-cause mortality in patients with advanced heart failure, combination of both therapies in a single device is challenging. METHODS: A total of 191 consecutive patients with advanced heart failure, left ventricular ejection fraction <35%, and a QRS duration >120 ms received CRT-ICD. Seventy-one patients had a history of ventricular arrhythmias (secondary prevention); 120 patients did not have prior ventricular arrhythmias (primary prevention). During follow-up, ICD therapy rate, clinical improvement after 6 months, and mortality rate were evaluated. RESULTS: During follow-up (18 +/- 4 months), primary prevention patients experienced less appropriate ICD therapies than secondary prevention patients (21% vs. 35%, p < 0.05). Multivariate analysis revealed, however, no predictors of ICD therapy. Furthermore, a similar, significant, improvement in clinical parameters was observed at 6 months in both groups. Also, the mortality rate in the primary prevention group was lower than in the secondary prevention group (3% vs. 18%, p < 0.05). CONCLUSIONS: As 21% of the primary prevention patients and 35% of the secondary prevention patients experienced appropriate ICD therapy within 2 years after implant, and no predictors of ICD therapy could be identified, implantation of a CRT-ICD device should be considered in all patients eligible for CRT.     

Effect of left ventricular remodeling after cardiac resynchronization therapy on frequency of ventricular arrhythmias

We evaluated whether cardiac resynchronization therapy affects the prevalence of ventricular tachycardia in relation to reverse remodeling in patients with end-stage heart failure. Clinical, echocardiographic, and implantable cardioverter-defibrillator (ICD) data of 17 patients with ICDs were obtained before and after they had received an upgrade to an ICD-cardiac resynchronization therapy device.     

Identification of successful catheter ablation sites in patients with ventricular tachycardia based on electrogram characteristics during sinus rhythm

BACKGROUND: Zones of slow conduction facilitate reentry, the major mechanism of ventricular tachycardia (VT) after myocardial infarction (MI). Identification of these zones during sinus rhythm (SR) is desirable for radiofrequency (RF) catheter ablation of VT. Local conduction velocity may correlate with electrogram duration. OBJECTIVES: The purpose of this study was to revise the definition of normal electrogram characteristics and to reevaluate the significance of low-amplitude, long-duration electrograms recorded during SR to select RF catheter ablation sites in patients with VT. METHODS: Electroanatomic mapping was performed during SR in 10 control patients with normal left ventricles (LVs) and in 10 patients with stable VT after MI. From the controls, reference values for electrogram amplitude, duration (first peak to last peak distance), and fragmentation (positive deflection) were derived. In patients after MI, areas with signals exceeding these values were annotated and related to successful ablation sites. RESULTS: Ninety-five percent of normal LV electrograms were > or =1.0 mV and < or =28 ms (range 5-39 ms) and all had < or =4 deflections. Based on these results, cutoff values were set at 1 mV, four deflections, and 40 ms. In infarcted hearts, 653 electrograms (44%) were <1.0 mV and of these, 303 were > or =40 ms with >4 deflections and restricted to circumscribed areas. Twenty-seven of 28 targeted VTs remained noninducible after RF catheter ablation within these areas, resulting in 86% sensitivity and 94% specificity for low-amplitude, long-duration electrograms predicting successful ablation sites. CONCLUSION: Identification of successful RF target areas during SR in patients with VT is feasible with high sensitivity and specificity using a mapping strategy based on voltage and duration criteria.     

A novel stereocilia defect in sensory hair cells of the deaf mouse mutant Tasmanian devil

Stereocilia are specialized actin-filled, finger-like processes arrayed in rows of graded heights to form a crescent or W-shape on the apical surface of sensory hair cells. The stereocilia are deflected by the vibration of sound, which opens transduction channels and allows an influx of ions to depolarize the hair cell, in turn triggering synaptic activity. The specialized morphology and organization of the stereocilia bundle is crucial in the process of sensory transduction in the inner ear. However, we know little about the development of stereocilia in the mouse and few molecules that are involved in stereocilia maturation are known. We describe here a new mouse mutant with abnormal stereocilia development. The Tasmanian devil (tde) mouse mutation arose by insertional mutagenesis and has been mapped to the middle of chromosome 5. Homozygotes show head-tossing and circling and have raised thresholds for cochlear nerve responses to sound. The gross morphology of the inner ear was normal, but the stereocilia of cochlear and vestibular hair cells are abnormally thin, and they become progressively disorganized with increasing age. Ultimately, the hair cells die. This is the first report of a mutant showing thin stereocilia. The association of thin stereocilia with cochlear dysfunction emphasizes the critical role of stereocilia in auditory transduction, and the discovery of the Tasmanian devil mutant provides a resource for the identification of an essential molecule in hair cell function.     

Arterial wall injury,arterial wall healing and restenosis

Substantial damage is inflicted on the arterial wall by conventional balloon angioplasty as well as by newer interventional devices. Restenosis seems to be due to an exaggerated, albeit normal healing response of the arterial wall to interventional injury. Since the relationship between arterial wall damage and restenosis is not entirely clear, experimental studies were performed in the normal rabbit to assess the effects of the nature and the extent of injury on the subsequent myointimal proliferation. The results suggest that the myointimal proliferation is an aspecific repair response to wall injury. The results further suggest an on-off character of myointimal proliferation after injury, which would imply that alternative, less damaging interventional methods may not reduce the problem of restenosis.