Faculty Bibliography

INTRODUCTION: The need to detect impending implantable cardiac defibrillator (ICD) lead failure has grown. Automated sensing diagnostics have been developed for this reason. The sensing integrity counter (SIC) is one such oversensing diagnostic, which forms an integral part of the Medtronic lead integrity alert (LIA) feature on implantable defibrillators. It records nonphysiologic short VV intervals (NPSVVIs). It is unclear whether SIC data derived from integrated bipolar (IBP) leads need to be interpreted differently when compared to true bipolar (TBP) leads. We hypothesized that IBP ICD leads by virtue of a larger "antennae" may generate more NPSVVIs on than TBP leads, leading to more false-positive SIC counts. METHODS: Equal durations of remote monitoring records of 44 patients (mean age of 65.9 +/- 2.2 years, 52 % female) with IBP ICD leads and Medtronic (MDT) generators (IBP group) were compared with those of 44 randomly selected patients (64.0 +/- 2.2 years, 24 % female) who had TBP ICD leads and MDT generators (TBP group). Mean surveillance time, defined as the time over which the cumulative SIC count was acquired, was 614 +/- 44 days (TBP group) vs. 620 +/- 49 days (IBP group, p = ns). The mean time of follow-up following the first documented short VV interval was 115.2 months in the integrated bipolar group and 66.9 months in the true bipolar group. Leads on advisory were excluded from the study. RESULTS: A total of 26/44 patients in the IBP group displayed NPSVVI compared to 11/44 patients in the TBP group (59 vs. 25 %; p = 0.002, Fisher exact test). When adjusted for gender and lead age, the difference was still significant (p = 0.008). When evaluating the clinical consequence of NPSVVI in this cohort, 3/11 TBP leads with NPSVVI of >0 were eventually extracted due to additional abnormalities vs. 0/26 IBP leads with NPSVVI (p = 0.02, Fisher exact test). None of the IBP group patients with NPSVVI have developed inappropriate therapy from lead noise or a need for abandonment or extraction. CONCLUSION: Integrated bipolar ICD leads are more likely to have elevated SIC counts than true bipolar leads despite revealing no other evidence of lead failure. There does not appear to be a need for heightened surveillance in IBP leads with observed elevated SIC counts that have no other findings to suggest lead malfunction.

BACKGROUND: In the absence of overt structural heart disease, most left ventricular outflow tract ventricular tachycardias (VTs) have a focal origin and are benign. We hypothesized that multiple morphologies (MMs) of inducible left ventricular outflow tract VT may indicate a scar-related VT that can mimic idiopathic VT. METHODS AND RESULTS: Of 54 consecutive patients referred for ablation of sustained outflow tract VT without overt structural heart disease, 24 had left ventricular outflow tract VT, 10 had MM VT, and 14 had a single VT (SM). The MM group were older (70.3+/-4.3 versus 53.9+/-15.9 years; P=0.004), had more hypertension (100% versus 29%; P=0.0006), and had longer PR intervals and QRS durations compared with the SM group. In contrast to the SM group, the MM group VTs had features consistent with reentry, including induction by programmed stimulation without isoproterenol, entrainment in some, and abnormal electrograms in the periaortic area. Periaortic region voltages suggested scar in the MM group, but not in the SM group. MRI in 2 MM patients was consistent with scar, but not in 10 SM patients. Longer radiofrequency applications were required in the MM group than in the SM group. At a median follow-up of 9.7 (3.0-32.0) months, recurrences tended to be more frequent in the MM group than in the SM group (70% versus 22%; P=0.07). CONCLUSIONS: VTs from small regions of periaortic scar can mimic idiopathic VT but are suggested by multiple VT morphologies and are more difficult to ablate. Whether these patients are at greater risk, as feared for other scar-related VTs, warrants further study.

BACKGROUND: Cardiac resynchronization therapy (CRT) increases transmural dispersion of repolarization (TDR) and can be pro-arrhythmic. However, overall arrhythmia risk was not increased in large-scale CRT clinical trials. Increased TDR as measured by T(peak ) -T(end) (TpTe) was associated with arrhythmia risk in CRT in a single-center study. This study investigates whether QT interval, TpTe, and TpTe/QT ratio are associated with ventricular arrhythmias in patients with CRT-defibrillator (CRT-D). METHODS: Post-CRT-D implant electrocardiograms of 128 patients (age 71.3 years +/- 10.3) with at least 2 months of follow-up at our institution's device clinic (mean follow-up of 28.5 months +/- 17) were analyzed for QT interval, TpTe, and TpTe/QT ratio. Incidence of ventricular arrhythmias was determined based on routine and directed device interrogations. RESULTS: Appropriate implantable cardioverter-defibrillator therapy for sustained ventricular tachycardia or ventricular fibrillation was delivered in 18 patients (14%), and nonsustained ventricular tachycardia (NSVT) was detected but did not require therapy in 58 patients (45%). Patients who received appropriate defibrillator therapy had increased TpTe/QT ratio (0.24 +/- 0.03 ms vs 0.20 +/- 0.04, P = 0.0002) and increased TpTe (105.56 +/- 20.36 vs 87.82 +/- 22.32 ms, P = 0.002), and patients with NSVT had increased TpTe/QT ratio (0.22 +/- 0.04 vs 0.20 +/- 0.04, P = 0.016). Increased QT interval was not associated with risk of ventricular arrhythmia. The relative risk for appropriate defibrillator therapy of T(p) T(e) /QT ratio >/= 0.25 was 3.24 (P = 0.016). CONCLUSION: Increased TpTe and increased TpTe/QT ratio are associated with increased incidence of ventricular arrhythmias in CRT-D. The utility of TpTe interval and TpTe/QT ratio as potentially modifiable risk factors for ventricular arrhythmias in CRT requires further study.

OBJECTIVES/BACKGROUND: Studies from several laboratories have implicated intracellular Ca(2+) dynamics in the modulation of electrical activity. We have reported that abnormal Ca(2+) wave activity is the underlying cause of afterdepolarization-induced electrical activity in subendocardial Purkinje cells that survive in the 48-hour infarcted canine heart. These cells form the focus of arrhythmias at this time postcoronary artery occlusion. METHODS: We studied the effects of agonists and antagonists on the abnormal Ca(2+) release activity of Purkinje cell aggregates dispersed from the subendocardium 48 hours postcoronary artery occlusion (IZPCs). Studies were completed using epifluorescent microscopy of Fluo-3 loaded Purkinje cells. RESULTS: Similar to our previous report, highly frequent traveling micro Ca(2+) transients (muCaiTs) and cell-wide Ca(2+) waves were seen in IZPCs in the absence of any drug. Isoproterenol (ISO) increased muCaiTs and cell-wide Ca(2+) waves in Purkinje cells dispersed from the normal heart (NZPCs). In IZPCs, ISO increased cell-wide wave frequency but had no effect on the already highly frequent micro Ca(2+) wave transient activity, suggesting that ISO lowers the threshold of cell-wide generators responding to micro Ca(2+) transients. Drugs that block inward sodium or calcium currents (verapamil, tetrodotoxin) had no effect on Ca(2+) activity in Purkinje cells. Antagonists of intracellular Ca(2+) release channels [ryanodine, JTV519(K201)] greatly suppressed spontaneous Ca(2+) release events in IZPCs. 2APB, an agent that blocks IP(3) receptors, greatly reduced the frequency of Ca(2+) events in IZPCs. CONCLUSIONS: In arrhythmogenic Purkinje cells that survive in the infarcted heart, agents that block or inhibit intracellular Ca(2+) release channel activity reduced Ca(2+) waves and could be antiarrhythmic.

OBJECTIVE AND METHODS: In this study, we investigated whether Ca(2+) transients are altered in Purkinje cell aggregates dispersed from the subendocardium overlying the infarcted zone of the left ventricle (IZPCs) 48 h after coronary artery occlusion. To do so, we combined epifluorescent imaging with microelectrode recordings of IZPCs and normal canine Purkinje cell aggregates (NZPCs). RESULTS: NZPCs respond to an action potential (AP) by a small Ca(2+) transient at the cell surface immediately after the AP upstroke followed by a large [Ca(2+)] transient, which propagates to the cell core. In addition, focal Ca(2+) waves can originate spontaneously later during the AP or during the diastolic interval (Circ Res 2000;86:448-55) and then propagate throughout the aggregate as 'cell-wide Ca(2+) waves'. Electrically-evoked Ca(2+) transients in IZPCs arose significantly faster than those in NZPCs, and showed substantial spatiotemporal nonuniformity within an IZPC aggregate as well as between IZPC aggregates. IZPCs showed, hitherto undetected, low amplitude, micro Ca(2+) transients (extent

PMCID:4332527

PMID: 12618230

ISSN: 0008-6363

CID: 1570732