Metabolism-perfusion imaging to predict disease activity in cardiac sarcoidosis.

FDG-PET is a sensitive but not specific test for myocardial sarcoidosis and its ability to define prognosis remains unclear. Combination with perfusion scanning may improve accuracy by differentiating scar from inflammation. We conducted this retrospective chart review to ascertain the utility of a rubidium -FDG PET scan for assessment of disease activity in patients with cardiac sarcoidosis. The presence of any perfusion-metabolism mismatch or a mismatch of > 6% of the myocardium on the scan were compared with the clinical course. Among 18 subjects, mismatched segments were present in 11 scans, whereas 7 demonstrated mismatch > 6%. There was a suggestion of association between PET scan and active disease using the threshold of any mismatch (p=0.09), with sensitivity of 80% and specificity of 62.5%. The threshold of >6% mismatch improved the specificity to 100% with 70% sensitivity, and the association between PET findings and clinically active disease was highly significant (p=0.0002). Eight patients had follow-up Rb-FDG PET scans, all of which were concordant with the clinical course. The positive predictive value of Rb-FDG PET scan showing >6% mismatch for detecting clinically active cardiac sarcoidosis was 100%. However, the finding of any mismatch still portends a high chance of clinical activity. Further studies to define the utility of Rb-FDG PET scan for management of cardiac sarcoidosis are warranted.

Detecting cardiac involvement in sarcoidosis: a call for prospective studies of newer imaging techniques.

Diagnosis of cardiac involvement in sarcoidosis is challenging and usually relies on a combination of clinical findings and imaging abnormalities. The case of a 53-yr-old female is described who presented with ventricular tachycardia and suspected angiosarcoma involving the right atrium and superior vena cava. A combination of magnetic resonance imaging and (18)F-2-fluoro-2-deoxyglucose-positron emission tomography were essential to the diagnosis of cardiac sarcoidosis. Reversibility of the disease was predicted more clearly by (18)F-2-fluoro-2-deoxyglucose-positron emission tomography than by magnetic resonance imaging, and clinical activity was predicted by persistent hypermetabolism on serial (18)F-2-fluoro-2-deoxyglucose-positron emission tomography.

Preimplantation B-type natriuretic peptide concentration is an independent predictor of future appropriate implantable defibrillator therapies.

OBJECTIVE: To assess prospectively whether preimplantation B-type natriuretic peptide (BNP) and C reactive protein (CRP) concentrations predict future appropriate therapies from an implantable cardioverter-defibrillator (ICD). DESIGN AND SETTING: Prospective cohort study conducted in a tertiary cardiac care centre. METHODS: 345 consecutive patients undergoing first time ICD implantation were prospectively studied. Serum BNP and CRP concentrations were obtained the day before ICD implantation. Patients were followed up with device interrogation to assess for appropriate shocks or antitachycardia pacing. Inappropriate therapies were excluded. Mean (SD) follow up was 13 (5) months. RESULTS: Patients had ischaemic (71%), primary dilated (17%), and valvar or other cardiomyopathies (12%). About half (52%) had ICDs implanted for primary prevention. Sixty three (18%) received appropriate ICD therapies. Serum creatinine, beta blocker, statin, and angiotensin converting enzyme inhibitor usage did not differ between therapy and no therapy groups. By univariate comparison, ejection fraction (p = 0.048), not taking amiodarone (p = 0.033), and BNP concentration (p = 0.0003) were risk factors for ICD therapy. However, by Cox regression multivariate analysis, only BNP above the 50th centile was a significant predictor (hazard ratio 2.19, 95% confidence interval 1.07 to 4.71, p = 0.040). Median BNP was 573 ng/l versus 243 ng/l in therapy and no therapy patients, respectively (p = 0.0003). More patients with BNP above the 50th centile (27% v 10%, p = 0.006) received ICD therapies. CONCLUSIONS: A single preimplantation BNP concentration determination is independently predictive of ICD therapies in patients with cardiomyopathies undergoing first time ICD implantation. CRP was not independently predictive of ICD therapies when compared with BNP.

KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death.

Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies which cause syncope and sudden death. LQT1, due to mutations of KCNQ1 (KVLQT1), is the most common form. This study describes the genotype-phenotype characteristics in 10 families with mutations of KCNQ1, including 5 novel mutations. One hundred and two families with a history of lethal cardiac events, 55 LQTS, 9 Brugada syndrome, 18 idiopathic ventricular fibrillation (IVF), and 20 acquired LQTS, were studied by single-strand conformational polymorphism (SSCP) and DNA sequence analyzes. Families found to have KCNQ1 mutations were phenotyped using ECG parameters and cardiac event history, and genotype-phenotype correlation was performed. No mutations were found in Brugada syndrome, IVF, or acquired LQTS families. Ten out of 55 LQTS families had KCNQ1 mutations and 62 carriers were identified. Mutations included G269S in domain S5; W305X, G314C, Y315C, and D317N in the pore region; A341E and Q357R in domain S6; and 1338insC, G568A and T587M mutations in the C-terminus. W305X, G314C, Q357R, 1338insC, and G568A, appeared to be novel mutations. Gene carriers were 26 +/- 19 years (32 females). Baseline QTc was 0.47 +/- 0.03 s (range 0.40-0.57 s) and 40% had normal to borderline QTc (< or = 0.46 s). Typical LQT1 T wave patterns were present in at least one affected member of each family, and in 73% of all affected members. A history of cardiac events was present in 19/62 (31%), 18 with syncope, 2 with aborted cardiac arrest (ACA) and six with sudden death (SD). Two out of 6 SDs (33%) occurred as the first symptom. No difference in phenotype was evident in pore vs. non-pore mutations. KCNQ1 mutations were limited to LQTS families. All five novel mutations produced a typical LQT1 phenotype. Findings emphasize (1) reduced penetrance of QTc and symptoms, resulting in diagnostic challenges, (2) the problem of sudden death as the first symptom (33% of those who died), and (3) genetic testing is important for identification of gene carriers with reduced penetrance, in order to provide treatment and to prevent lethal cardiac arrhythmias and sudden death.

SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with cardiac arrhythmias and sudden death in a white family.

Cardiac arrhythmias cause 400 000 sudden deaths annually in the United States alone. Mutations in the cardiac sodium channel gene SCN5A on chromosome 3p21 cause cardiac arrhythmias and sudden death. In this study, we define an SCN5A mutation, S1103Y, in a white family associated with syncope, ventricular fibrillation, and sudden death. A very recent study reported the same mutation in 13.2% of African Americans, but not in the white population. Our study shows that mutation S1103Y does exist in the white population, and it is associated with a considerable risk of syncope, ventricular arrhythmia, ventricular fibrillation, and sudden death in this population.

Kinetics of defibrillation shock-induced response: design implications for the optimal defibrillation waveform.

INTRODUCTION: Implantable cardioverter defibrillator (ICD) therapy is a well-established therapy for treating patients at high risk for sudden cardiac death. Recently formulated virtual electrode polarization theory is a promising foundation for the theory of defibrillation. Yet, continuing optimization of defibrillation therapy is limited to primarily empirical methods due to difficulties in assessing kinetics of cellular response in whole heart models of defibrillation. The aim of this study was to evaluate the response of the myocardium in the context of virtual electrode polarization. METHODS AND RESULTS: We used a Langendorff-perfused rabbit heart model of ICD therapy and voltage-sensitive fluorescent dye imaging in order to map kinetics of trans membrane potential during both mono- and biphasic shocks applied at various phases of the QT-interval. Cellular response was fitted to a single exponential function using the Levenberg-Marquardt method. Time constants (tau) were measured in 45 288 optical records from 17 hearts. We found that cellular response depends upon both QT-phase of application, intensity, polarity, and phase of the biphasic waveform. Shocks of larger strengths produce a faster response. The tau of the first-phase negatively polarizing response was significantly larger compared with the positively polarizing response at intensities below 200 V, but smaller at 200 V and above. The tau of the second phase negatively polarizing response was always slower than the positively polarizing response, regardless of amplitude, and timing. Overall, tau ranged from 1.6 ms to 14.2 ms. CONCLUSIONS: The time constant of the membrane depends on the field, action potential phase and the shock polarity, but exceeds 1 msec. Therefore, we suggest using a slower shock leading edge, since the membrane cannot follow potentially damaging faster waveforms.

C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) may persist due to structural changes in the atria that are promoted by inflammation. C-reactive protein (CRP), a marker of systemic inflammation, predicts cardiovascular events and stroke, a common sequela of AF. We hypothesized that CRP is elevated in patients with atrial arrhythmias. METHODS AND RESULTS: Using a case-control study design, CRP in 131 patients with atrial arrhythmias was compared with CRP in 71 control patients. Among arrhythmia patients, 6 had frequent atrial ectopy or tachycardia, 86 had paroxysmal AF, 39 had persistent AF lasting >30 days, and 70 had lone arrhythmias. CRP was higher in arrhythmia than in control patients (median, 0.21 versus 0.096 mg/dL; P<0.001). Arrhythmia patients in AF within 24 hours before sampling had higher CRP than those in sinus rhythm (0.30 versus 0.15 mg/dL; P<0.001). CRP in controls was not different than in patients with atrial ectopy or tachycardia. Lone arrhythmia patients had a CRP of 0.21 mg/dL, which was not significantly lower than arrhythmia patients with structural heart disease (CRP, 0.23 mg/dL) but higher than controls (P=0.002). Persistent AF patients had a higher CRP (0.34 mg/dL) than paroxysmal AF patients (0.18 mg/dL; P=0.008); both groups had higher CRP levels than controls (P

Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study.

INTRODUCTION: The efficacy of midodrine for the management of patients with neurocardiogenic syncope was assessed prospectively in a randomized control study. METHODS AND RESULTS: Patients who had at least monthly occurrences of syncope and a positive tilt-table test were included in the study. A total of 61 patients were randomly allocated to treatment either with midodrine or with fluid, salt tablets, and counseling. Midodrine was given at a starting dose of 5 mg three times a day and increased up to a dose of 15 mg three times a day when required. Midodrine was given during the daytime every 6 hours. Thirty-one patients were assigned to treatment with midodrine; the other 30 patients were advised to increase their fluid intake and were instructed to recognize their prodromes and abort the progression to syncope. Patients were followed-up for at least 6 months. A quality-of-life questionnaire was administered at the time of randomization and 6 months after. At the 6-month follow-up, 25 (81%) of 31 midodrine-treated patients and 4 (13%) of the 30 fluid-therapy patients had remained asymptomatic (P < 0.001). One patient had to discontinue taking midodrine due to severe side effects and another six patients experienced minor side effects that did not require drug discontinuation. CONCLUSION: Midodrine appeared to provide a significant benefit in patients with neurocardiogenic syncope. To prevent recurrence of symptoms, dose adjustments were required in about one third of patients.

His electrogram alternans reveal dual-wavefront inputs into and longitudinal dissociation within the bundle of His.

BACKGROUND: His electrogram (HE) amplitude and morphology changes were observed in our previous studies during transition from "fast" to "slow" atrioventricular nodal (AVN) conduction. This phenomenon and its significance for the dual-AVN electrophysiology are not well recognized and have not been studied. METHODS AND RESULTS: Experiments were performed on 17 healthy rabbit atrial-AVN preparations during standard programmed electrical pacing. HEs were mapped along the His bundle with roving surface electrodes, along with recording of cellular action potentials (APs). HEs recorded from the superior margin of the His bundle were of greater amplitude during basic beats and decreased substantially, by 42+/-19% (P<0.01), when premature A(1)A(2) shortened to 178+/-20 ms. In contrast, the HEs from the inferior margin increased dramatically, 2.9+/-1.7 times (P<0.01), during short A(1)A(2) and remained high until AVN block occurred. In addition, during long A(1)A(2), the superior HEs consistently preceded the inferior by 1.9+/-0.7 ms. In contrast, at short A(1)A(2), the superior HEs occurred 2.7+/-0.8 ms after the inferior. Cellular AP recordings demonstrated clearly the presence of and the transition between early (fast) and late (slow) excitation wavefronts that accompanied HE alternans. CONCLUSIONS: The morphological-electrophysiological evidence from the AV junction suggests that fast and slow wavefronts reach the His bundle differently, producing functional longitudinal dissociation into 2 domains. The characteristic HE alternans recorded from these domains are a new sensitive tool to determine the presence of distinctly different wavefronts and their participation in the conduction during reentrant or other arrhythmias. These findings provide further understanding of the mechanisms of dual-AVN electrophysiology.

Ventricular tachycardias arising from the aortic sinus of valsalva: an under-recognized variant of left outflow tract ventricular tachycardia.

OBJECTIVES: To describe a normal heart left bundle branch block, inferior axis ventricular tachycardia (VT), that could not be ablated from the right or left ventricular outflow tracts. BACKGROUND: Whether these VTs are epicardial and can be identified by a specific electrocardiographic pattern is unclear. METHODS: Twelve patients with normal heart left bundle branch block, inferior axis VT and previously failed ablation were included in this study. Together with mapping in the right and left ventricular outflow tracts, we obtained percutaneous epicardial mapping in the first five patients and performed aortic sinus of Valsalva mapping in all patients. RESULTS: No adequate pace mapping was observed in the right and left ventricular outflow tracts. Earliest ventricular activation was noted in the epicardium and the aortic cusps. All patients were successfully ablated from the aortic sinuses of Valsalva (95% CI 0% to 18%). The electrocardiographic pattern associated with this VT was left bundle branch block, inferior axis and early precordial transition with Rs or R in V2 or V3. Ventricular tachycardia from the left sinus had rS pattern in lead I, and VT from the noncoronary sinus had a notched R wave in lead I. None of the patients had complications and all remained arrhythmia-free at a mean follow-up of 8 +/- 2.6 months. CONCLUSIONS: Normal heart VT with left bundle branch block, inferior axis and early precordial transition can be ablated in the majority of patients from either the left or the noncoronary aortic sinus of Valsalva.

A simple method of mapping atrial premature depolarizations triggering atrial fibrillation.

Atrial premature depolarizations (APDs) originating from focal sites, particularly the pulmonary veins (PV), may become triggers of atrial fibrillation (AF). Accurate mapping of APDs with conventional methods may be time consuming and expose the patient to unnecessary instrumentation of the left atrium. We hypothesized that the atrial activation sequence recorded using a simple system that includes an esophageal catheter and a custom-made 16-electrode catheter with two sets of floating electrodes eight in the coronary sinus and eight in the high right atrium) could be sufficient to localize the APDs. The study included 29 patients with frequent APDs and AF refractory to antiarrhythmic medications. The APD site of origin was confirmed with single-point sequential mapping techniques using the CARTO system ten patients) or by placement of multielectrode catheters in the right and left PV (19 patients). Of the 29 patients, 20 patients had a single APD focus; 8 patients had two different APD morphologies; and 1 patient had three APD foci. Mapping for ablation of the APD foci showed earliest activation in the left superior PV in 12 patients, right superior PV in 15 patients, right middle PV in 4 patients, right inferior PV in 1 patient, the lingular branch of the left superior PV in 2 patients, left inferior PV in 2 patients, and right atrium along the crista terminalis in 3 patients. The activation sequence and relative timing of the recordings obtained with our catheter configuration was highly predictive of right and left atrial origin and, more importantly, of right and left PV foci.

The mechanisms of the vulnerable window: the role of virtual electrodes and shock polarity.

Vulnerability and defibrillation are mechanistically dependent upon shock strength, polarity, and timing. We have recently demonstrated that shock-induced virtual electrode polarization (VEP) may induce reentry. However, it remains unclear how the VEP mechanism may explain the vulnerable window and polarity dependence of vulnerability. We used a potentiometric dye and optical mapping to assess the anterior epicardial electrical activity of Langendorff-perfused rabbit hearts (n = 7) during monophasic shocks (+/-100 V and +/-200 V, duration of 8 ms) applied from a transvenous defibrillation lead at various coupling intervals. Arrhythmias were induced in a coupling interval and shock polarity dependent manner: (i) anodal and cathodal shocks induced arrhythmias in 33.2 +/- 30.1% and 53.1 +/- 39.3% cases (P < 0.01), respectively, and (ii) the vulnerable window was located near the T-wave. Optical maps revealed that VEP was also modulated by the coupling interval and shock polarity. Recovery of excitability produced by negative polarization, known as de-excitation, and the resulting reentry was more readily achieved during the relative refractory period than the absolute refractory period. Furthermore, anodal shocks produced wavefronts propagating in an inward direction with respect to the electrode, whereas cathodal shocks propagated in an outward direction. Wavefronts produced by anodal shocks were more likely to collide and annihilate each other than those caused by cathodal shocks. The probability of degeneration of the VEP-induced phase singularity into a sustained arrhythmia depends upon the gradient of VEP and the direction of the VEP-induced wavefront. The VEP gradient depends upon the coupling interval, while the direction depends upon shock polarity; these factors explain the vulnerable window and polarity-dependence of vulnerability, respectively.

Multicenter study of principles-based waveforms for external defibrillation.

STUDY OBJECTIVE: The efficacy of a shock waveform for external defibrillation depends on the waveform characteristics. Recently, design principles based on cardiac electrophysiology have been developed to determine optimal waveform characteristics. The objective of this clinical trial was to evaluate the efficacy of principles-based monophasic and biphasic waveforms for external defibrillation. METHODS: A prospective, randomized, blinded, multicenter study of 118 patients undergoing electrophysiologic testing or receiving an implantable defibrillator was conducted. Ventricular fibrillation was induced, and defibrillation was attempted in each patient with a biphasic and a monophasic waveform. Patients were randomly placed into 2 groups: group 1 received shocks of escalating energy, and group 2 received only high-energy shocks. RESULTS: The biphasic waveform achieved a first-shock success rate of 100% in group 1 (95% confidence interval [CI] 95.1% to 100%) and group 2 (95% CI 94.6% to 100%), with average delivered energies of 201+/-17 J and 295+/-28 J, respectively. The monophasic waveform demonstrated a 96.7% (95% CI 89.1% to 100%) first-shock success rate and average delivered energy of 215+/-12 J for group 1 and a 98.2% (95% CI 91.7% to 100%) first-shock success rate and average delivered energy of 352+/-13 J for group 2. CONCLUSION: Using principles of electrophysiology, it is possible to design both biphasic and monophasic waveforms for external defibrillation that achieve a high first-shock efficacy.

Empirical pulmonary vein isolation in patients with chronic atrial fibrillation using a three-dimensional nonfluoroscopic mapping system: long-term follow-up.

The purpose of this study was to assess the feasibility and long-term results of empirical isolation of both superior pulmonary veins in patients with chronic AF. Although localizing and ablating the focal triggers of AF has been proven an effective approach, this strategy is time consuming, often requires multiple procedures, and carries the risk of pulmonary vein stenosis. Whether ostial electrical isolation of the superior pulmonary veins, without initial detailed mapping, is a more efficient approach is not known. The study included 71 consecutive patients who had chronic AF. Using a nonfluoroscopic electroanatomic mapping system, the left and right superior pulmonary veins were ablated circumferentially at the venoatrial junction, with the aim of achieving electrical isolation of the veins. Following ablation, if frequent atrial ectopies were present, mapping and ablation were considered. The patients were periodically followed with 48-hour Holter and loop recorder monitoring. After the ablation of the right and left superior pulmonary veins 59 (83%) of 71 patients maintained sinus rhythm without premature atrial beats. The remaining 12 patients underwent further mapping and ablation including 5 patients who required isolation of the left inferior pulmonary veins. True electrical isolation could be achieved only in 45 (31%) of the 147 targeted veins. At the latest follow-up (mean 29 +/- 8 months), 80% of the patients with upper vein isolation remained in sinus rhythm off medications, 62% of the patients maintained sinus rhythm on previously ineffective medications, and 17% continued to be in AF. Fourteen (20%) patients developed intermittent episodes of left atrial flutter, and mapping in these patients revealed large electrically silent areas in the left atrium. Empirical isolation of pulmonary veins appeared to be an effective approach to help maintain sinus rhythm in patients with chronic AF. True electrical isolation of the pulmonary veins was associated with a higher likelihood of long-term success. Left atrial flutter was seen in a significant number of patients at long-term follow-up.

First human experience with pulmonary vein isolation using a through-the-balloon circumferential ultrasound ablation system for recurrent atrial fibrillation.

BACKGROUND: Standard mapping and ablation of focal sources of atrial fibrillation are associated with very long procedure times and low efficacy. An anatomic approach to complete pulmonary vein isolation could overcome these limitations. METHODS AND RESULTS: Fifteen patients with atrial fibrillation refractory to medication underwent circumferential isolation of the pulmonary veins by using a novel catheter, with an ultrasound transducer (8-MHz) mounted near the tip, in a saline-filled balloon. Twelve atrial foci and/or atrial fibrillation triggers were identified in 9 patients (pulmonary vein locations: left upper, 3; right upper, 6; right middle, 1; right lower, 1; and left inferior, 1). In 5 patients, lesions were placed in the absence of any mapped triggers. Irrespective of trigger mapping, circumferential isolation of both upper pulmonary veins was attempted in all patients. The lower pulmonary veins were ablated when sinus rhythm activation mapping revealed evidence of a sleeve of atrial muscle in the vein. The median number of lesions per patient required to isolate 1 pulmonary vein was 4 (range, 1 to 29). After ablation, no evidence of narrowing was seen with repeat venography or follow-up computed tomography scan. After a mean follow-up of 35+/-6 weeks, 5 patients had recurrence of atrial fibrillation. Three responded to drugs that were previously ineffective, and 2 remained in atrial fibrillation. CONCLUSIONS: This novel ultrasound ablation system can successfully isolate multiple pulmonary veins. At early follow-up, this approach seems to be effective in preventing recurrent atrial fibrillation in a significant number of patients.

Direct evidence of the role of virtual electrode-induced phase singularity in success and failure of defibrillation.

INTRODUCTION: We recently demonstrated that virtual electrode-induced phase singularity is responsible for arrhythmogenesis during T wave shocks and explains the upper and lower limits of vulnerability. Furthermore, we suggested that the same mechanism might be responsible for defibrillation failure. The aim of this study was to experimentally support this hypothesis. METHODS AND RESULTS: We used the voltage-sensitive dye di-4-ANEPPS and fast imaging to assess electrical activity in Langendorff-perfused rabbit hearts. Ventricular arrhythmias were induced by monophasic shocks applied during T wave. Three types of defibrillation shocks (n = 79) were delivered from an intravenous right ventricular electrode: monophasic (8 msec), optimal biphasic (8/8 msec, 2/1 leading-edge voltage ratio), and nonoptimal biphasic (8/8 msec, 1/1 leading-edge voltage ratio). We found that a monophasic shock extinguished arrhythmic pattern of electrical activity via a virtual electrode polarization effect. However, the virtual electrode polarization was likely to produce phase singularities, leading to another arrhythmia and defibrillation failure. Nonoptimal biphasic shocks produced similar effects. Optimal biphasic shocks were successful because the first phase of the shock erased the arrhythmia via the virtual electrodes effect, whereas the second phase canceled the virtual electrodes, eliminating the substrate for phase singularities and arrhythmia resulting from them. CONCLUSION: Our data provide the first experimental support of the hypothesis implicating virtual electrode-induced phase singularity in defibrillation failure in the Langendorff-perfused rabbit heart. Optimal biphasic shock has a higher defibrillation efficacy because it does not produce virtual electrode-induced phase singularities.

New approach to biphasic waveforms for internal defibrillation: fully discharging capacitors.

INTRODUCTION: The use of two independent, fully discharging capacitors for each phase of a biphasic defibrillation waveform may lead to the design of a simpler, smaller, internal defibrillator. The goal of this study was to determine the optimal combination of capacitor sizes for such a waveform. METHODS AND RESULTS: Eight full-discharge (95/95% tilt), biphasic waveforms produced by several combinations of phase-1 capacitors (30, 60, and 90 microF) and phase-2 capacitors (1/3, 2/3, and 1.0 times the phase-1 capacitor) were tested and compared to a single-capacitor waveform (120 microF, 65/65% tilt) in a pig ventricular fibrillation model (n = 12, 23+/-2 kg). In the full-discharge waveforms, phase-2 peak voltage was equal to phase-1 peak voltage. Shocks were delivered between a right ventricular lead and a left pectoral can electrode. E50s and V50s were determined using a ten-step Bayesian process. Full-discharge waveforms with phase-2 capacitors of < or =40 microF had the same E50 (6.7+/-1.7 J to 7.3+/-3.9 J) as the single-capacitor truncated waveform (7.3+/-3.7 J), whereas waveforms with phase-2 capacitors of > or =60 microF had an extremely high E50 (14.5+/-10.8 J or greater, P < 0.05). Moreover, of the former set of energy-efficient waveforms, those with phase-1 capacitors of > or =60 microF additionally exhibited V50s that were equivalent to the V50 of the single-capacitor waveform (344+/-65 V to 407+/-50 V vs 339+/-83 V). CONCLUSION: Defibrillation efficacy can be maintained in a full-discharge, two-capacitor waveform with the proper choice of capacitors.

Voltage dependence of ICD lead polarization and the effect of iridium oxide coating.

Nonthoracotomy leads (NTLs) with an iridium oxide (IROX) coating exhibit lower defibrillation thresholds (DFTs) than uncoated NTLs. We tested whether adding an IROX coating to an active pectoral can would influence defibrillation efficacy. However, the primary purpose of this study was to examine the impedance changes that occur at different voltages for uncoated titanium NTLs and identical NTLs with an IROX coating. We studied anesthetized pigs with an NTL placed in the right ventricle and coupled this to an active pectoral can. Biphasic waveform DFTs were obtained for the four NTLs and can combinations: uncoated NTL and uncoated can, uncoated NTL and IROX can, IROX NTL and uncoated can, and IROX NTL and IROX can. The respective energy DFTs were: 23.6 +/- 6.9, 24.1 +/- 6.7, 21.3 +/- 6.0, and 21.4 +/- 7.0 J. The IROX NTL DFTs were significantly lower (P < 0.05) than the uncoated NTL DFTs (either can), confirming our previous study. We then used a low tilt monophasic waveform to assess impedance changes. The impedance rise for each NTL/can combination was measured at 50, 100, 300, and 700 V. Comparisons of impedance changes between voltage levels showed that the impedance rise was inversely related to voltage and was greatest with uncoated NTLs. The IROX coating of the NTL reduced the impedance rise at all shock voltages, but was particularly beneficial at the lower voltages. No advantage was seen when the pectoral can was coated with IROX regardless of which NTL was used. Our results suggest that low voltage applications, such as atrial defibrillation, would benefit most from the IROX-coated NTL, and further studies are warranted in this area.

Surface potentials from the region of the atrioventricular node and their relation to dual pathway electrophysiology.

BACKGROUND: Clinical applications of the principles of dual atrioventricular nodal (AVN) electrophysiology in the treatment of AVN reentrant tachycardias rely on empirical findings, such as discontinued conduction curves or the presence of specific catheter-recorded signals. However, neither the shape of the conduction curve nor the surface electrograms have been validated as functionally related to the presence of slow or fast wavefronts. METHODS AND RESULTS: We performed in vitro studies using 10 rabbit atrial-AVN preparations. A bipolar roving electrode was used to explore the endocardial surface of the triangle of Koch during programmed electrical stimulation. Microelectrodes were impaled in AVN cells to correlate surface and intracellular responses. In 7 preparations, a specific area near the compact cell region produced surface electrograms that were dissociated in 2 distinct components, with progressive shortening of prematurity. Similar dissociation was demonstrated during Wenckebach periodicity and increased vagal tone. Cellular recordings supported the presence of early ("fast") and late ("slow") wavefronts, with different refractory properties. Although the fast-slow transition was a basis for discontinued propagation, the AVN conduction curves were smooth in the majority of cases. CONCLUSIONS: Exploration of the triangle of Koch during programmed pacing reveals the presence of dual-wavefront surface potentials. Clinical confirmation of these AVN potentials could provide a new, sensitive tool in defining dual AVN electrophysiology.

Transthoracic cardioversion of atrial fibrillation: comparison of rectilinear biphasic versus damped sine wave monophasic shocks.

BACKGROUND: Clinical studies have shown that biphasic shocks are more effective than monophasic shocks for ventricular defibrillation. The purpose of this study was to compare the efficacy of a rectilinear biphasic waveform with a standard damped sine wave monophasic waveform for the transthoracic cardioversion of atrial fibrillation. METHODS AND RESULTS: In this prospective, randomized, multicenter trial, patients undergoing transthoracic cardioversion of atrial fibrillation were randomized to receive either damped sine wave monophasic or rectilinear biphasic shocks. Patients randomized to the monophasic protocol (n=77) received sequential shocks of 100, 200, 300, and 360 J. Patients randomized to the biphasic protocol (n=88) received sequential shocks of 70, 120, 150, and 170 J. First-shock efficacy with the 70-J biphasic waveform (60 of 88 patients, 68%) was significantly greater than that with the 100-J monophasic waveform (16 of 77 patients, 21%, P<0.0001), and it was achieved with 50% less delivered current (11+/-1 versus 22+/-4 A, P<0.0001). Similarly, the cumulative efficacy with the biphasic waveform (83 of 88 patients, 94%) was significantly greater than that with the monophasic waveform (61 of 77 patients, 79%; P=0.005). The following 3 variables were independently associated with successful cardioversion: use of a biphasic waveform (relative risk, 4.2; 95% confidence intervals, 1.3 to 13.9; P=0.02), transthoracic impedance (relative risk, 0.64 per 10-Omega increase in impedance; 95% confidence intervals, 0.46 to 0.90; P=0.005), and duration of atrial fibrillation (relative risk, 0.97 per 30 days of atrial fibrillation; 95% confidence intervals, 0.96 to 0.99; P=0.02). CONCLUSIONS: For transthoracic cardioversion of atrial fibrillation, rectilinear biphasic shocks have greater efficacy (and require less energy) than damped sine wave monophasic shocks.