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Biomedical subjects

George J Klein

Publications and source records attributed to George J Klein.

At least 19 recordsLinked to original sources
PubMed2007

The expectation effect and cardiac pacing for refractory vasovagal syncope.

BACKGROUND: Clinical trials of pacing for vasovagal syncope have shown conflicting results. We performed a meta-analysis to determine whether permanent pacemaker therapy prevents refractory vasovagal syncope. METHODS: Randomized trials comparing pacemaker therapy with medical therapy, usual care, placebo, or different pacing algorithms in the prevention of recurrent vasovagal syncope were considered. The primary endpoint was first recurrence of syncope. RESULTS: Nine randomized trials (2 double blind, 7 open label or single blind) were included. There was significant heterogeneity when all 9 trials were pooled (P=.0009 and I(2)=69.6%), reflecting methodological diversity in blinding and the nature of the control therapy. When pooled by trial methodology, heterogeneity was no longer apparent. Permanent pacing reduced the risk of recurrent syncope in unblinded studies (odds ratio [OR] 0.09, 95% confidence interval [CI], 0.04 to 0.22) and in studies comparing pacemaker algorithms (OR 0.04, 95% CI, 0.0 to 0.23). No effect was seen in double-blinded trials (OR 0.83, 95% CI, 0.41 to 1.70). Awareness that a permanent pacemaker was implanted and functional was associated with a significant 'expectation' effect, which itself reduced the risk of recurrent syncope (OR 0.16, 95% CI, 0.06 to 0.40, P=.0001). Results were similar when restricted to patients with a marked cardioinhibitory response on baseline tilt table testing. CONCLUSION: The results of small, preliminary trials have overestimated the treatment effect of pacemakers due to a lack of blinding of physicians and patients. Blinded trials suggest that the apparent response is due to a strong expectation response to pacing.

Cardiac Pacing, Artificial↗
PubMed2006

Improving SVT discrimination in single-chamber ICDs: a new electrogram morphology-based algorithm.

INTRODUCTION: Wide-spread adoption of ICD therapy has focused efforts on improving the quality of life for patients by reducing "inappropriate" shock therapies. To this end, distinguishing supraventricular tachycardia from ventricular tachycardia remains a major challenge for ICDs. More sophisticated discrimination algorithms based on ventricular electrogram morphology have been made practicable by the increased computational ability of modern ICDs. METHODS AND RESULTS: We report results from a large prospective study (1,122 pts) of a new ventricular electrogram morphology tachycardia discrimination algorithm (Wavelet Dynamic Discrimination, Medtronic, Minneapolis, MN, USA) operating at minimal algorithm setting (RV coil-can electrogram, match threshold of 70%). This is a nonrandomized cohort study of ICD patients using the morphology discrimination of the Wavelet algorithm to distinguish SVT and VT/VF. The Wavelet criterion was required ON in all patients and all other supraventricular tachycardia discriminators were required to be OFF. Spontaneous episodes (N = 2,235) eligible for ICD therapy were adjudicated for detection algorithm performance. The generalized estimating equations method was used to remove bias introduced when an individual patient contributes multiple episodes. Inappropriate therapies for supraventricular tachycardia were reduced by 78% (90% CI: 72.8-82.9%) for episodes within the range of rates where Wavelet was programmed to discriminate. Sensitivity for sustained ventricular tachycardia was 98.6% (90% CI: 97-99.3%) without the use of high-rate time out. CONCLUSIONS: Results from this prospective study of the Wavelet electrogram morphology discrimination algorithm operating as the sole discriminator in the ON mode demonstrate that inappropriate therapy for supraventricular tachycardia in a single-chamber ICD can be dramatically reduced compared to rate detection alone.

Algorithms↗
PubMed2006

A novel pacing maneuver to localize focal atrial tachycardia.

BACKGROUND: Although focal atrial tachycardias cannot be entrained, we hypothesized that atrial overdrive pacing (AOP) can be an effective adjunct to localize the focus of these tachycardias at the site where the post-pacing interval (PPI) is closest to the tachycardia cycle length (TCL). METHODS: Overdrive pacing was performed in nine patients during atrial tachycardia, and in a comparison group of 15 patients during sinus rhythm. Pacing at a rate slightly faster than atrial tachycardia in group 1 and sinus rhythm in group 2 was performed from five standardized sites in the right atrium and coronary sinus. The difference between the PPI and tachycardia or sinus cycle length (SCL) was recorded at each site. The tachycardia focus was then located and ablated in group 1, and the atrial site with earliest activation was mapped in group 2. RESULTS: In both groups the PPI-TCL at the five pacing sites reflected the distance from the AT focus or sinus node. In group 1, PPI-TCL at the successful ablation site was 11 +/- 8 msec. In group 2, PPI-SCL at the site of earliest atrial activation was 131 +/- 37 msec (P < 0.001 for comparison). In groups 1 and 2, calculated values at the five pacing sites were proportional to the distance from the AT focus or sinus node, respectively. CONCLUSIONS: The PPI-TCL after-AOP of focal atrial tachycardia has a direct relationship to proximity of the pacing site to the focus, and may be clinically useful in finding a successful ablation site.

Cardiac Pacing, Artificial↗
PubMed2006

Utility and cost effectiveness of temporary pacing using active fixation leads and an externally placed reusable permanent pacemaker.

Active-fixation leads and externally placed permanent pacemakers for temporary pacing may be beneficial because they allow for greater patient mobility and comfort and increased reliability of lead placement. The relative cost of this form of pacing may be prohibitive unless markedly prolonged pacing is required. Twenty patients (63 +/- 15 years of age, 15 men) underwent external "temporary permanent" pacing. Pacing duration and associated complications were recorded. Cost models were then constructed using data from the London Health Sciences Center business unit to compare the cost of traditional temporary pacing and this technique using a Medtronic KSR903 pacemaker and 5,076 leads. Direct costs were calculated based on the 2005 Ontario Health Insurance Plan fee schedule, combined with calculation of labor and materials. Pacing was undertaken for a median of 2 days (range 2 to 83). There were no complications during implantation or pacing or after system removal. Sensing was lost in only 1 instance, which was reprogrammed uneventfully. Cost comparison showed that, although active-fixation lead placement was initially more costly ($798.71 vs $471.91), the added reliability of the permanent system allowed ward telemetry instead of cardiac care unit monitoring. This resulted in cost equivalence after only 18 hours and conferred a cost savings of $456 per 24-hour period thereafter. As a result, a savings of $585.20 is projected for a modeled patient after 48 hours of temporary pacing. In conclusion, temporary pacing using this technique is a reliable and comfortable alternative to traditional temporary pacing and appears to be a cost-effective temporary pacing option after 18 hours.

Adult↗
PubMed2006

Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common type of cardiac arrhythmia and a leading cause of cardiovascular morbidity, particularly stroke. The cardiac gap-junction protein connexin 40 is expressed selectively in atrial myocytes and mediates the coordinated electrical activation of the atria. We hypothesized that idiopathic atrial fibrillation has a genetic basis and that tissue-specific mutations in GJA5, the gene encoding connexin 40, may predispose the atria to fibrillation. METHODS: We sequenced GJA5 from genomic DNA isolated from resected cardiac tissue and peripheral lymphocytes from 15 patients with idiopathic atrial fibrillation. Identified GJA5 mutations were transfected into a gap-junction-deficient cell line to assess their functional effects on protein transport and intercellular electrical coupling. RESULTS: Four novel heterozygous missense mutations were identified in 4 of the 15 patients. In three patients, the mutations were found in the cardiac-tissue specimens but not in the lymphocytes, indicating a somatic source of the genetic defects. In the fourth patient, the sequence variant was detected in both cardiac tissue and lymphocytes, suggesting a germ-line origin. Analysis of the expression of mutant proteins revealed impaired intracellular transport or reduced intercellular electrical coupling. CONCLUSIONS: Mutations in GJA5 may predispose patients to idiopathic atrial fibrillation by impairing gap-junction assembly or electrical coupling. Our data suggest that common diseases traditionally considered to be idiopathic may have a genetic basis, with mutations confined to the diseased tissue.

Adult↗
PubMed2006

AHA/ACCF Scientific Statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation: in collaboration with the Heart Rhythm Society: endorsed by the American Autonomic Society.

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Adult↗
PubMed2006

Effect of defibrillation testing on management during implantable cardioverter-defibrillator implantation.

BACKGROUND: Verification of defibrillation efficacy by defibrillation threshold (DFT) testing during implantable cardioverter-defibrillator implantation is the current standard. Generally, defibrillation of ventricular fibrillation at 10 J below the maximum output of a device is felt to establish an adequate safety margin. Nonetheless, DFT testing adds to cost and carries some potential for morbidity, whereas its impact on outcomes in the modern era of defibrillator technology is unclear. We aimed to determine the frequency that DFT testing resulted in a change at device implant and to identify clinical and echocardiographic predictors of the need for DFT testing. METHODS: We reviewed all implantable cardioverter-defibrillators that were implanted at the London Health Sciences Centre (Ontario, Canada) from June 1999 to August 2003 and used multivariate analysis to determine variables associated with DFT test failures and elevated DFT values. When a defibrillation failure was not observed, a lowest energy to defibrillate (LED) was recorded. RESULTS: Among 168 implants, DFT testing was successful with a minimum 10-J safety margin in 152 (90%), whereas the remaining 16 required changes at device implant. In a multivariate analysis, use of amiodarone was independently associated with DFT failure (odds ratio, 4.6; 95% confidence interval, 1.2-17.0). Significantly higher mean DFT/LED values were observed among patients on amiodarone (1.36 J; P = .0041). Those with nonischemic cardiomyopathy had a higher mean DFT/LED compared with those with ischemic cardiomyopathy (1.44 J; P = .028). CONCLUSIONS: Use of amiodarone is associated with a 4-fold increase in risk of DFT failure and subsequent need for changes at implant to achieve a safe threshold. Defibrillation threshold testing appears to be most useful for patients taking amiodarone.

Amiodarone↗
PubMed2006

Differentiating arrhythmogenic right ventricular cardiomyopathy from right ventricular outflow tract ventricular tachycardia using multilead QRS duration and axis.

BACKGROUND: Ventricular tachycardia (VT) resulting from arrhythmogenic right ventricular cardiomyopathy (ARVC) may be difficult to differentiate from idiopathic right ventricular outflow tract (RVOT) VT. OBJECTIVES: The purpose of this study was to investigate the hypothesis that QRS characteristics would be different in ARVC because of altered conduction through abnormal myocardium. METHODS: In 24 RVOT VT patients (18 women and 6 men; age 42 +/- 10 years) and 20 ARVC patients (12 women and 8 men; age 38 +/- 14 years), mean QRS duration, frontal plane axis, and precordial R-wave transition were measured in 12-lead ECGs recorded during VT. RESULTS: Mean QRS duration was longer in all 12 leads in ARVC patients. A significant difference was noted in leads I, III, aVL, aVF, V(1), V(2), and V(3) (P <.05). Leads I and aVL had the largest mean difference between ARVC and RVOT VT patients of 17.6 +/- 4.7 ms and 15.8 +/- 7.5 ms, respectively (P <.0001). Lead I QRS duration > or =120 ms had a sensitivity of 100%, specificity 46%, positive predictive value 61%, and negative predictive value 100% for ARVC. The area under the receiver operating characteristic (ROC) curve was 0.89. The addition of mean QRS axis <30 degrees (R<S in lead III) to the above criterion increased specificity for ARVC to 100%. QRS duration remained sensitive and specific in the subgroup of nine ARVC ECGs with an inferior axis (ROC area 0.82). R-wave transition was not different between groups. CONCLUSION: QRS duration is longer in ARVC compared with RVOT VT. An algorithm combining lead I QRS duration for sensitivity and axis for specificity is useful for differentiating the two tachycardia substrates.

Adult↗
PubMed2006

Investigating syncope: a review.

PURPOSE OF REVIEW: This review focuses on recent literature on the cardiovascular investigation of syncope. RECENT FINDINGS: Syncope is a common and complex clinical entity with many varied etiologies, the diagnosis of which can often be elusive. Recent advances in the area of investigation in syncope include improvements in technologies for arrhythmia event monitoring and an increase in applicability and efficacy of traditional investigations. These advances have increased our ability to manage syncope. SUMMARY: A better understanding of the etiology of syncope in certain cohorts has allowed tailoring of investigations and management of syncope. This is evident when syncope occurs in the presence of structural heart disease, which is associated with a higher incidence of arrhythmias and an increased 1-year mortality. Patients with left-ventricular dysfunction should be considered candidates for an implantable cardioverter defibrillator based on heart function and syncopal presentation. In the absence of significant heart disease, investigations need to be tailored to diagnose neurally mediated causes for syncope and detection of intermittent bradycardia. The improved understanding of syncope has arisen from studies using improved investigational tools for syncope, in particular loop recorders, which are able to monitor cardiac rhythm over long periods. In those without structural heart disease and undifferentiated syncope, neurally mediated causes should be pursed initially. Tilt testing and loop recorders are employed most often in this cohort. Electrophysiological studies have largely been supplanted by implantable cardioverter defibrillator use in structural heart disease, with a low yield in patients with preserved heart function.

Cardiac Pacing, Artificial↗
PubMed2006

Excitation of the intrinsic conduction system through his and interventricular septal pacing.

BACKGROUND: Direct His bundle pacing results in rapid synchronous ventricular activation. However, clinical experiences with such pacing have been associated with long procedure times and compromised pacing and sensing performance. METHODS: We evaluated myocardial activation sequences (AS) for pacing of the His bundle and peri-His region and assessed acute pacing performance using custom-designed plunge electrodes. Unipolar pacing was performed in isolated swine hearts (n = 10) using four quadripolar stimulation/sensing electrodes implanted into the interventricular septum and equally spaced between the membranous septum and the coronary sinus ostium (zones 1-4, respectively; electrode depth (ED) 1 = most distal, ED 4 = most proximal). Optimal pacing sites were defined as: pacing thresholds < or = 1.5 V, a P-R ratio of < or = 0.5, and > or = 50% occurrence of an intrinsic midseptal left ventricular (LV) endocardial electrical breakout (BO) and activation pattern. RESULTS: Pacing thresholds improved with greater depth of electrode location within the septum (ED 1: 1.51 +/- 0.8 V vs ED 4: 5.2 +/- 3.8 V, P < 0.001), as did the P-R ratio (0.34 +/- 0.6 vs 0.78 +/- 1.0, P < 0.05). His potentials were only observed in zone 1 and 2 electrodes (0.12 and 0.02 mV, respectively). Only electrodes in zones 1 and 2 produced LV endocardial electrical BOs in the midseptal region that demonstrated an intrinsic-like endocardial AS. Depth 1 and 2 electrodes (11.75 and 8.75 mm, respectively) in zone 1 satisfied all three optimal pacing site requirements. CONCLUSIONS: This study has shown that LV activation patterns similar to sinus rhythm may be achieved without direct activation of the His bundle, while maintaining acceptable pacing and sensing performance. These data indicate that pacing systems designed to stimulate the tissues below the point at which the His bundle penetrates the central fibrous body may provide improved system efficiency and LV performance in comparison to both direct His bundle pacing and traditional pacing sites.

Action Potentials↗
PubMed2006

The garden path.

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Atrial Flutter↗
PubMed2006

Characteristics of slow pathway conduction after successful AVNRT ablation.

BACKGROUND: AV node slow pathway conduction can persist following successful ablation for AV node reentrant tachycardia (AVNRT). We hypothesized that careful examination of AV nodal conduction curves before and after effective AVNRT ablation in patients with persistent slow pathway conduction could shed light on this apparent paradox. METHODS AND RESULTS: Thirty patients (age 40.9 +/- 14.3; 8 male) were included. AV node function curves were created based on pre- and postablation atrial extrastimulus testing. Analysis of slow pathway function curves demonstrated significant decrease in AH for any given coupling interval after ablation (mean difference -68.1 [-94.5, -41.7] P < 0.001), graphically indicated by downward displacement of the curve. In addition, mean slow pathway effective refractory period (ERP) increased from 247.9 +/- 36.1 msec to 288.6 +/- 56.0 msec (P < 0.001); mean maximum AH interval decreased from 361.3 +/- 114.2 msec to 306.9 +/- 65.2 msec (P = 0.013); mean difference in minimum and maximum AH interval during slow pathway conduction decreased (from 94.5 +/- 75.8 msec to 59.6 +/- 46.2 msec (P = 0.016). Finally, mean difference between the fast and slow pathway effective refractory periods, the span of coupling intervals over which slow pathway conduction occurred, decreased (from 113.9 +/- 61.4 msec to 63.2 +/- 41.5 msec, P = 0.001). CONCLUSIONS: Ablation, which successfully eliminates inducible and spontaneous AVNRT in the presence of persistent slow pathway conduction, is associated with significantly altered slow pathway conduction characteristics, indicating the presence of a damaged or different slow pathway after ablation, incapable of sustaining tachycardia.

Adult↗
PubMed2006

Cavotricuspid isthmus conduction is dependent on underlying anatomic bundle architecture: observations using a maximum voltage-guided ablation technique.

OBJECTIVES: We hypothesized an ablation strategy directly targeting muscle bundles might demonstrate functionally distinct "routes" of conduction, potentially shortening ablation times. BACKGROUND: Pathological study demonstrated that the cavotricuspid isthmus is composed of distinct anatomically defined bundles, many with intervening gaps of connective tissue. METHODS: A line was mapped in the "6 o'clock" region and bipolar electrogram amplitude measured during pullback. Zones of peak voltage were ablated first regardless of position. RF was delivered using either a 5-mm externally irrigated catheter, or an 8-mm nonirrigated catheter. The zone of largest remaining voltage was then sequentially targeted until conduction. RESULTS: Eighteen patients were recruited and followed for 7.9 +/- 1.9 months block occurred (mean age 64 +/- 11.6 years, male:female ratio 14:4). Bi-directional block was achieved in all patients with recurrence of atrial flutter in 1 patient. Mean total RF times was 4.7 +/- 2.8 minutes with a mean of 6.1 +/- 3.3 applications, procedure time was 127.3 +/- 37.7 minutes, and fluoroscopy time was 25.5 +/- 12.0 minutes. Two patterns of block were observed in the study group. Pattern A described no change in conduction times until block, observed in 6 (33%); pattern B described a stepwise block with discrete "jumps," observed in 12 (67%). CONCLUSIONS: An ablation strategy targeting high-voltage isthmus electrograms obviates the need for a complete anatomic line. This finding together with discrete "jumps" during ablation is consistent with the concept of conduction over discrete bundles rather than a diffuse sheet of muscle.

Adult↗
PubMed2005

Physiologic pacing in patients with obstructive sleep apnea: a prospective, randomized crossover trial.

OBJECTIVES: This study was designed to assess the impact of prevention of bradycardia with physiologic pacing on the severity of obstructive sleep apnea. BACKGROUND: Apneic episodes during sleep are associated with slowing of the heart rate during apnea and tachycardia with subsequent arousal. Patients with permanent pacemakers may have reduced episodes of sleep apnea when their pacemaker rate is set faster than their spontaneous nocturnal heart rate. METHODS: We conducted a prospective, randomized, single-blind crossover trial of temporary atrial pacing in obstructive sleep apnea to reduce the apnea hypopnea index (AHI). Fifteen patients (age 60 +/- 13 years, 12 men) with moderate to severe obstructive sleep apnea (AHI 34 +/- 14) underwent insertion of an externalized atrial permanent pacing system via the left subclavian vein. Patients underwent overnight respiratory sleep studies in hospital, during atrial pacing at 75 beats/min, and with pacing turned off. The order of pacing mode was randomized, with crossover the subsequent night to the other mode. Patients were blinded to pacing mode, and the analysis of sleep recordings was blind to pacing mode. RESULTS: Pacing was tolerated without complications in all patients. Overnight physiologic pacing did not affect the AHI (pacing 39 +/- 21/h vs. control 42 +/- 21/h, p = 0.23, 95% confidence interval -9.3 to 2.5 for difference), desaturation time (pacing 3.8 +/- 6.0% vs. control 3.5 +/- 4.3%, p = 0.70), or the minimum SaO(2) (pacing 75 +/- 10% vs. control 77 +/- 11%, p = 0.38). There was a borderline significant reduction in circulatory time with pacing (pacing 23.4 +/- 3.2 s vs. control 25.5 +/- 4.4 s, p = 0.09). CONCLUSIONS: Temporary atrial pacing does not appear to improve respiratory manifestations of obstructive sleep apnea. Permanent atrial pacing in this patient population does not appear to be justified.

Aged↗