Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals.

Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine's effects may be subregion specific. In the context of a double-blind randomized placebo-controlled crossover trial investigating the clinical and resting-state fMRI effects of intravenous ketamine vs. placebo in patients with treatment resistant depression (TRD) vs. healthy volunteers (HV), we used seed-based resting-state functional connectivity (rsFC) analyses to determine differential changes in subgenual ACC (sgACC), perigenual ACC (pgACC) and dorsal ACC (dACC) rsFC two days post-infusion. Across cingulate subregions, ketamine differentially modulated rsFC to the right insula and anterior ventromedial prefrontal cortex, compared to placebo, in TRD vs. HV; changes to pgACC-insula connectivity correlated with improvements in depression scores. Post-hoc analysis of each cingulate subregion separately revealed differential modulation of sgACC-hippocampal, sgACC-vmPFC, pgACC-posterior cingulate, and dACC-supramarginal gyrus connectivity. By comparing rsFC changes following ketamine vs. placebo in the TRD group alone, we found that sgACC rsFC was most substantially modulated by ketamine vs. placebo. Changes to sgACC-pgACC, sgACC-ventral striatal, and sgACC-dACC connectivity correlated with improvements in anhedonia symptoms. This preliminary evidence suggests that accurate segmentation of the ACC is needed to understand the precise effects of ketamine's antidepressant and anti-anhedonic action.

Ketamine Modulates the Neural Correlates of Reward Processing in Unmedicated Patients in Remission From Depression.

BACKGROUND: Ketamine as an antidepressant improves anhedonia as early as 2 hours after infusion. These drug effects are thought to be exerted via actions on reward-related brain areas-yet these actions remain largely unknown. Our study investigates ketamine's effects during the anticipation and receipt of an expected reward, after the psychotomimetic effects of ketamine have passed, when early antidepressant effects are reported. METHODS: We examined ketamine's effects during the anticipation and receipt of expected rewards on predefined brain areas, namely, the dorsal and ventral striatum, ventral tegmental area, amygdala, and insula. We recruited 37 male and female participants with remitted depression who were free from symptoms and antidepressant treatments at the time of the scan. Participants were scanned 2 hours after drug administration in a double-blind crossover design (ketamine: 0.5 mg/kg and placebo) while performing a monetary reward task. RESULTS: A significant main effect of ketamine was observed across all regions of interest during the anticipation and feedback phases of win and no-win trials. The drug effects were particularly prominent in the nucleus accumbens and putamen, which showed increased activation on the receipt of smaller rewards compared with neutral. The levels of (2R,6R)-hydroxynorketamine 2 hours after infusion significantly correlated with the activation observed in the ventral tegmental area for that contrast. CONCLUSIONS: These findings demonstrate that ketamine can produce detectable changes in reward-related brain areas 2 hours after infusion, which occur without symptom changes and support the idea that ketamine might improve reward-related symptoms via modulation of response to feedback.

The effect of risperidone on reward-related brain activity is robust to drug-induced vascular changes.

Dopamine (DA) mediated brain activity is intimately linked to reward-driven cerebral responses, while aberrant reward processing has been implicated in several psychiatric disorders. fMRI has been a valuable tool in understanding the mechanism by which DA modulators alter reward-driven responses and how they may exert their therapeutic effect. However, the potential effects of a pharmacological compound on aspects of neurovascular coupling may cloud the interpretability of the BOLD contrast. Here, we assess the effects of risperidone on reward driven BOLD signals produced by reward anticipation and outcome, while attempting to control for potential drug effects on regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy male volunteers (n = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperidone or placebo in a double-blind, placebo-controlled, randomised, three-period cross-over study design. Participants underwent fMRI scanning while performing the widely used Monetary Incentive Delay (MID) task to assess drug impact on reward function. Measures of CBF (Arterial Spin Labelling) and breath-hold challenge induced BOLD signal changes (as a proxy for CVR) were also acquired and included as covariates. Risperidone produced divergent, dose-dependent effects on separate phases of reward processing, even after controlling for potential nonneuronal influences on the BOLD signal. These data suggest the D2 antagonist risperidone has a wide-ranging influence on DA-mediated reward function independent of nonneuronal factors. We also illustrate that assessment of potential vascular confounds on the BOLD signal may be advantageous when investigating CNS drug action and advocate for the inclusion of these additional measures into future study designs.

JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps.

Recent studies have shown that drug-induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross-modal correlation of MRI-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma-aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson's disease patients (PD) and risperidone-induced changes in rsfMRI and cerebral blood flow (CBF). Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD and dopaminergic (D2) and serotonergic systems (5-HT1b). Risperidone induced CBF alterations were correlated with its main targets in serotonergic and dopaminergic systems. JuSpace provides a biologically meaningful framework for linking neuroimaging to underlying neurotransmitter information.

Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles.

As a result of neuro-vascular coupling, the functional effects of antipsychotics in human brain have been investigated in both healthy and clinical populations using haemodynamic markers such as regional Cerebral Blood Flow (rCBF). However, the relationship between observed haemodynamic effects and the pharmacological action of these drugs has not been fully established. Here, we analysed Arterial Spin Labelling (ASL) rCBF data from a placebo-controlled study in healthy volunteers, who received a single dose of three different D2 receptor (D2R) antagonists and tested the association of the main effects of the drugs on rCBF against normative population maps of D2R protein density and gene-expression data. In particular, we correlated CBF changes after antipsychotic administration with non-displaceable binding potential (BPND) template maps of the high affinity D2-antagonist Positron Emission Tomography (PET) ligand [18F]Fallypride and with brain post-mortem microarray mRNA expression data for the DRD2 gene from the Allen Human Brain Atlas (ABA). For all antipsychotics, rCBF changes were directly proportional to brain D2R densities and DRD2 mRNA expression measures, although PET BPND spatial profiles explained more variance as compared with mRNA profiles (PET R2 range = 0.20-0.60, mRNA PET R2 range 0.04-0.20, pairwise-comparisons all pcorrected<0.05). In addition, the spatial coupling between ΔCBF and D2R profiles varied between the different antipsychotics tested, possibly reflecting differential affinities. Overall, these results indicate that the functional effects of antipsychotics as measured with rCBF are tightly correlated with the distribution of their target receptors in striatal and extra-striatal regions. Our results further demonstrate the link between neurotransmitter targets and haemodynamic changes reinforcing rCBF as a robust in-vivo marker of drug effects. This work is important in bridging the gap between pharmacokinetic and pharmacodynamics of novel and existing compounds.

Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes.

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained.

An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers.

Chronic administration of antipsychotic drugs has been linked to structural brain changes observed in patients with schizophrenia. Recent MRI studies have shown rapid changes in regional brain volume following just a single dose of these drugs. However, it is not clear if these changes represent real volume changes or are artefacts ("apparent" volume changes) due to drug-induced physiological changes, such as increased cerebral blood flow (CBF). To address this, we examined the effects of a single, clinical dose of three commonly prescribed antipsychotics on quantitative measures of T1 and regional blood flow of the healthy human brain. Males (n = 42) were randomly assigned to one of two parallel groups in a double-blind, placebo-controlled, randomized, three-period cross-over study design. One group received a single oral dose of either 0.5 or 2 mg of risperidone or placebo during each visit. The other received olanzapine (7.5 mg), haloperidol (3 mg), or placebo. MR measures of quantitative T1, CBF, and T1-weighted images were acquired at the estimated peak plasma concentration of the drug. All three drugs caused localized increases in striatal blood flow, although drug and region specific effects were also apparent. In contrast, all assessments of T1 and brain volume remained stable across sessions, even in those areas experiencing large changes in CBF. This illustrates that a single clinically relevant oral dose of an antipsychotic has no detectable acute effect on T1 in healthy volunteers. We further provide a methodology for applying quantitative imaging methods to assess the acute effects of other compounds on structural MRI metrics. Hum Brain Mapp 39:319-331, 2018. © 2017 Wiley Periodicals, Inc.

Predictors of reduction in mitral regurgitation in patients undergoing cardiac resynchronisation treatment.

BACKGROUND: CRT causes reduction in MR due to left ventricular (LV) remodelling, but determinants of clinically meaningful MR reduction acutely after CRT have not been evaluated. OBJECTIVES: We evaluated echocardiographic predictors of significant reduction in functional mitral regurgitation (MR) by cardiac resynchronisation treatment (CRT). METHODS: 35 patients with >or= moderate to severe MR underwent CRT for presence of electrical and/or mechanical dyssynchrony. Significant reduction in MR post-CRT was defined as reduction to less than moderate MR (MR jet area/left atrial area <25%, group 1) on follow-up echocardiogram at 1.7 (SD 2.8) months post-CRT. RESULTS: Significant MR reduction of 62% (28%) from baseline MR occurred in 18 patients vs 22% (16%) in the remaining patients (group 2), p<0.01). Follow-up left ventricular ejection fraction (LVEF) was 0.43 (0.09) in group 1 patients vs 0.29% (0.1%) in group 2 patients (p<0.001). On multivariate analysis, time to peak strain in the mid inferior segment was the only significant predictor of MR reduction post-CRT (p = 0.008, OR = 1.023 (CI 1.006 to 1.041). The sensitivity and specificity of the combined variable of time to peak strain of >400 ms in the mid inferior segment and peak negative strain of >or=9% and 8% in the basal and mid posterior segments, respectively, to predict follow-up MR was 88% and 93% respectively and positive and negative predictive value was 94% and 87%. CONCLUSION: In patients with cardiomyopathy and significant MR, the presence of delayed longitudinal strain in the mid inferior LV segment along with preserved negative systolic strain in the basal and mid posterior segments predicts substantial reduction in MR post-CRT.

Plasma surface modification of poly vinyl chloride for improvement of antibacterial properties.

Plasma immersion ion implantation (PIII) was used to modify medical-grade PVC coated by triclosan and bronopol to enhance the antibacterial properties. The surface was first activated by O2 plasma to produce more hydrophilic groups so that triclosan and bronopol could be coated more effectively on the surface. Subsequently, an argon plasma treatment was conducted under optimal conditions to improve the antibacterial properties of the triclosan and bronopol-coated PVC samples. The modified surfaces were characterized by XPS, ATR-FTIR, SEM, and contact angle measurements. The antibacterial properties were evaluated utilizing the method of plate-counting of Staphylococcus aureus (gram positive) and Escherichia coli (gram negative). Our experimental results show that the plasma-modified PVC with bronopol exhibits good antibacterial properties while the favorable bulk properties of PVC are retained. The plasma-modified PVC with triclosan has better antibacterial performance against E. coli than bronopol. The change in the antibacterial effect on the modified PVC with time was also investigated and the antibacterial effect was observed to decrease with time.

Differential atrial stunning after electrical cardioversion: an echo tissue Doppler case study.

Left atrial stunning after cardioversion is a well-known phenomenon. It has been associated with higher risk of postcardioversion thromboemboli and increased risk of recurrence of atrial fibrillation. We present a case of differential atrial stunning after electrical cardioversion for atrial fibrillation. Diagnosis was made by pulsed wave Doppler of mitral, tricuspid, and pulmonary vein inflow and mitral and tricuspid annuli. Differential mechanical atrial stunning may be a common phenomenon after cardioversion and may suggest difference in right and left atrial transport function. Its prevalence needs to be determined by a large study. Doppler tissue imaging might be routinely used in patients after cardioversion for atrial fibrillation to detect atrial stunning.

Initial experience with an active-fixation defibrillation electrode and the presence of nonphysiological sensing.

Nonphysiological sensing by a pacing and defibrillation electrode may result in inappropriate defibrillator discharges and/or inhibition of pacing. Active-fixation electrodes may be more likely to sense diaphragmatic myopotentials because of the protrusion of the screw for fixation. In addition, the movement of the fixation screw in an integrated bipolar lead system could also result in inappropriate sensing. This may be increasingly important in patients who are pacemaker dependent because the dynamic range of the autogain feature of these devices is much more narrow. Five of 15 consecutive patients who received a CPI model 0154 or 0155 active-fixation defibrillation electrode with an ICD system (CPI Ventak A V3DR model 1831 or CPI Ventak VR model 1774 defibrillator) are described. In 2 of the 15 patients, nonphysiological sensing appearing to be diaphragmatic myopotentials resulted in inappropriate defibrillator discharges. Both patients were pacemaker dependent. Changes in the sensitivity from nominal to less sensitive prevented inappropriate discharges. In one patient, discreet nonphysiological sensed events with the electrogram suggestive of ventricular activation was noted at the time of implantation. This was completely eliminated by redeployment of the active-fixation lead in the interventricular septum. In two other patients, discreet nonphysiological sensed events resulted in intermittent inhibition of ventricular pacing after implantation. These were still seen in the least sensitive autogain mode for ventricular amplitude. These were not seen on subsequent interrogation 1 month after implantation. Increased awareness of nonphysiological sensing is recommended. The CPI 0154 and 0155 leads seem to be particularly prone to this abnormality. Particular attention should be made when deploying an active-fixation screw for an integrated bipolar lead. This increased awareness is more important when a given individual is pacemaker dependent, which may warrant DFT testing in a least or less sensitive mode in these patients.

Are implantable cardioverter- defibrillators cost-effective?

Sudden cardiac deaths account for a large number of cardiovascular deaths, and ventricular tachyarrhythmias are implicated in many of these. In survivors of sudden cardiac deaths and other selected groups of patients, implantable cardioverter-defibrillators (ICDs) have been shown to have significant survival benefits in randomized controlled trials. The incremental costs for each extra year of survival conferred by ICDs were compared to the cost of antiarrhythmic drug therapy in some of these trials. In patients with nonsustained ventricular tachycardia with low ejection fraction (< 35%) and inducible sustained ventricular tachycardia on programmed electrical stimulation (nonsuppressible by procainamide), the incremental costs of ICD therapy amounted to $27,000 per life-year saved, compared with drug therapy. These costs may be acceptable increments for adaptation of the new technology in view of the definite survival advantage conferred by ICDs. Evolving technology may further reduce these costs by development of better devices with longer battery life.

Exercise conditioning and heart rate variability: evidence of a threshold effect.

BACKGROUND: A protective effect of exercise in preventing sudden cardiac death is supported by studies in healthy populations as well as in patients with cardiac disease. The mechanisms involved in this protective effect are unknown. HYPOTHESIS: We hypothesized that exercise conditioning would beneficially alter autonomic nervous system tone, measured by heart rate variability. METHODS: We prospectively studied 20 cardiac patients enrolled in a Phase 2 12-week cardiac rehabilitation program following a recent cardiac event. The patients underwent 24 h Holter monitoring at program entry and 12 weeks later. Heart rate variability analysis was assessed for both time domain and spectral analysis. RESULTS: The group demonstrated a modest mean conditioning effect, indicated by an average reduction in resting heart rate from 81 +/- 16 to 75 +/- 12 beats/min (p = 0.03), and an increase in training METS from 2.1 +/- 0.4 to 3.3 +/- 1.1 (p < 0.0001). Overall, 15 of 20 (75%) patients demonstrated increased total and high-frequency power, and mean high-frequency power was significantly increased (3.9 +/- 1.4 vs. 4.4 +/- 1.0 ln, p = 0.05). When stratified according to the magnitude of exercise conditioning, patients achieving an increase of > 1.5 training METS demonstrated significant increases in SDNN, SDANN index, SDNN index, pNN50, total power, and high-frequency power (all p < 0.05) (see text for explanation of abbreviations). CONCLUSIONS: Exercise conditioning improves heart rate variability in cardiac patients, particularly in patients who achieve a threshold of > 1.5 training METS increase over a 12-week period. These study results are supportive of the concept that exercise training lowers the risk of sudden cardiac death via increased vagal tone, which likely beneficially alters ventricular fibrillatory and ischemic thresholds.

Vein of marshall cannulation for the analysis of electrical activity in patients with focal atrial fibrillation.

BACKGROUND: Whether or not the muscle bundle within the ligament of Marshall (LOM) can serve as the origin of focal atrial fibrillation (AF) is unknown. METHODS AND RESULTS: A total of 28 consecutive patients with paroxysmal AF underwent balloon-occlusion coronary sinus angiograms to identify the vein of Marshall (VOM). Attempts were then made to advance a 1.5-French electrophysiological catheter into the VOM via the coronary sinus orifice. In 17 of the 28 patients (10 of 17 were men aged 38+/-15 years), cannulation was successful. Double potentials were registered in 8 of these 17 patients. The first potential corresponded with local left atrial activation. The second potential was shorter and narrower than the first. The sequence of activation in the second potential in the VOM was proximal to distal. In 6 patients with direct VOM recordings, we documented that the origin of AF was in the muscle bundle within the LOM. Radiofrequency catheter ablation aimed at the insertion site of the VOM successfully terminated AF in 4 of these 6 patients. CONCLUSIONS: (1) It is possible to cannulate and to record electrical potentials from the VOM. (2) The characteristics of the double potentials within the VOM suggest that the second potential is from the muscle bundle (Marshall bundle) within the LOM. (3) The Marshall bundle may be the origin of focal AF in some patients.

Evidence of time-dependent autonomic reinnervation after heart transplantation.

BACKGROUND: Confirming the clinical significance of reinnervation is important in understanding and anticipating how heart rate (HR) responses of transplant recipients to physiologic stress differs early and late after transplant from that of normal individuals. OBJECTIVES: To evaluate the functional significance of cardiac reinnervation early and late after heart transplantation. METHODS: Handgrip and deep breathing tests, passive 80 degrees head-up tilt, and heart rate (HR) responsiveness of 33 transplant recipients (n = 16 at < 5 months and n = 17 at > 1 year after transplant) were compared with those of 16 age- and sex-matched control participants. RESULTS: HR responses to handgrip and passive tilt were absent early after transplant. HR acceleration normalized but was blunted late after transplant. These findings are consistent with late (>1 year) sympathetic reinnervation in transplant recipients. CONCLUSIONS: When caring for transplant recipients, nurses should consider the time elapsed since transplant in evaluating HR responsiveness to common procedures and interventions.

Correlation of acute and chronic defibrillation threshold with upper limit of vulnerability determined in normal sinus rhythm.

BACKGROUND: The upper limit of vulnerability (ULV) is the stimulus strength above which ventricular fibrillation cannot be induced, even when the stimulus occurs during the vulnerable period of the cardiac cycle. Determination of ULV using T-wave shocks during ventricular pacing has been shown to closely correlate with the defibrillation threshold (DFT) at ICD implantation. However, there are no data correlating ULV determined in sinus rhythm at ICD implantation, with DFT determined at implantation or during long-term follow-up. This is of clinical importance since ULV may be used to estimate DFT during ICD implantation, both during ventricular pacing or sinus rhythm. METHODS AND RESULTS: Twenty-one patients receiving a transvenous ICD system were studied prospectively. There were 16 males and 5 females, mean age 68 +/- 15 years, with mean ejection fraction 37.4 +/- 17.4%. All had structural heart disease. The ULV was defined as the lowest energy that did not induce ventricular fibrillation with shocks at 0, 20 and 40ms before the peak of the T-wave, using a step-down protocol. The initial energy tested was 15J and the lowest energy 2J. DFT was determined following a similar step-down protocol. The DFT was defined as the lowest energy that successfully defibrillated the ventricles. The linear correlation coefficient between ULV and DFT was r = 0.73 (p < 0.001). At implant, mean ULV was 9.2 +/- 5J, not statistically different from mean DFT 9.4 +/- 4J. ULV plus 5J successfully defibrillated 19 of 21 patients. During long-term follow-up of 10.1 +/- 1.8 months in eight patients, DFT was 8.8 +/- 5.8J, not significantly different than the DFT of 7.5 +/- 4.1J or ULV of 8.0 +/- 5.3 at implant. CONCLUSION: 1) When determined during normal sinus rhythm the ULV significantly correlates with DFT. 2) ULV testing might be used in lieu of standard DFT testing to confirm adequate lead placement thus minimizing or eliminating VF inductions, particularly in hemodynamically unstable patients. 3) Since ULV + 5J has a high probability of successful defibrillation in most patients, programming ICD first shock energy for VF at ULV + 5J may result in lower first shock energies compared to the standard methods of programming first shock energy at twice DFT. CONDENSED ABSTRACT: The purpose of this study was to determine if the upper limit of vulnerability (ULV) determined during normal sinus rhythm correlates with the defibrillation threshold (DFT), as has been previously shown when determined during ventricular pacing. The linear correlation coefficient between the ULV and DFT was r = 0.73 (p < 0.001). Mean ULV at implant was 9.2 +/- 5J, not statistically different from mean DFT of 0.4 +/- 4J. During long-term follow-up of 10.1 +/- 1.8 months in 8 patients, DFT was 8.75 +/- 8J, not significantly different than the DFT of 7.5 +/- 4.1J or ULV of 8.0 +/- 5.3 at implant. Shocks energies of ULV + 5J successfully defibrillated 19 of 21 patients at implant and 8 of 8 at follow-up. This study indicates that the ULV determined in normal sinus rhythm closely correlates with the DFT, and that ULV + 5J defibrillated most patients. ULV testing could be used to predict DFT and reduce or eliminate the need for DFT testing and VF induction. Programming ICD first shock energy for VF to ULV + 5J will result in lower energy than that used with standard DFT testing.

Atypical atrioventricular node reciprocating tachycardia masquerading as tachycardia using a left-sided accessory pathway.

OBJECTIVES: The study was performed to document that atrioventricular node reciprocating tachycardia (AVNRT) can be associated with eccentric retrograde left-sided activation, masquerading as tachycardia using a left accessory pathway. BACKGROUND: The eccentric retrograde left-sided activation during tachycardia is thought to be diagnostic of the presence of a left free wall accessory pathway. However, it is not known whether AVNRT can occur with eccentric retrograde left-sided activation. METHODS: We studied 356 patients with AVNRT who underwent catheter ablation. Retrograde atrial activation during tachycardia and ventricular pacing were determined by intracardiac recordings, including the use of a decapolar coronary sinus catheter. RESULTS: The retrograde atrial activation was eccentric in 20 patients (6%). Eight of these patients had the earliest retrograde atrial activation recorded in the lateral coronary sinus leads, and 12 had the earliest retrograde atrial activation recorded in the posterior coronary sinus leads, with the most proximal coronary sinus electrode pair straddling the coronary sinus orifice. These tachycardias were either the fast-slow or the slow-slow form of AVNRT. The slow-fast form of AVNRT was also inducible in 17 of the 20 patients. Successful ablation of the slow pathway in the right atrial septum near the coronary sinus ostium prevented the induction and clinical recurrence of reciprocating tachycardia in all patients. CONCLUSIONS: Atypical AVNRT with eccentric retrograde left-sided activation was demonstrated in 6% of all patients with AVNRT masquerading as tachycardia using a left-sided accessory pathway. Ablation of the slow pathway at the posterior aspects of the right atrial septum resulted in a cure in these patients.

Upper limit of vulnerability predicts chronic defibrillation threshold for transvenous implantable defibrillators.

INTRODUCTION: The upper limit of vulnerability (ULV) is the shock strength at or above which ventricular fibrillation cannot be induced when delivered in the vulnerable period. It correlates acutely with the acute defibrillation threshold (DFT) and can be determined with a single episode of fibrillation. The goal of this prospective study was to determine the relationship between the ULV and the chronic DFT. METHODS AND RESULTS: We studied 40 patients at, and 3 months after, implantation of transvenous cardioverter defibrillators. The ULV was defined as the weakest biphasic shock that failed to induce fibrillation when delivered 0, 20, and 40 msec before the peak of the T wave. patients were classified as clinically stable or unstable based on prospectively defined criteria. There were no significant differences between the group means for the acute and chronic determinations of ULV (13.5 +/- 5.3 J vs 12.4 +/- 6.8 J, P = 0.25) and DFT (10.1 +/- 5.0 J vs 9.9 +/- 5.7 J, P = 0.74). Five patients (15%) were classified as unstable. The strength of the correlation between acute ULV and acute DFT (r = 0.74, P < 0.001) was similar to that between the chronic ULV and chronic DFT (r = 0.82, P < 0.001). There was a correlation between the change in ULV from acute to chronic and the corresponding change in DFT (r = 0.67, P < 0.001). The chronic DFT was less than the acute ULV +3 J in all 35 stable patients, but it was greater in 2 of 5 unstable patients (P = 0.04). CONCLUSIONS: The strength of the correlation between the chronic ULV and the chronic DFT is comparable to that between the acute ULV and the acute DFT. Temporal changes in the ULV predict temporal changes in the DFT. In clinically stable patients, a defibrillation safety margin of 3 J above the acute ULV proved an adequate chronic safety margin.