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Hepatocellular carcinoma (HCC) and renal cell cancer (RCC) are malignancies, which are chemotherapy resistant and fatal at the advanced stages. Previously developed tyrosine kinase inhibitors are used in the treatment of advanced stage disease. In the present case study, a patient using sunitinib for stage IV RCC presented with HCC following 2 years of treatment. A patient who exhibited Child-Pugh class C cirrhosis initially, exhibited a marked improvement of hepatocellular parenchyma findings following treatment with sunitinib. Sunitinib is suggested to have preventive effects on the pathogenesis of liver fibrosis and cirrhosis in vitro , via an anti-vascular endothelial growth factor and anti-platelet-derived growth factor mechanism. However, no clinical supportive study has been performed until now. Improvement of liver functions may be explained in this manner. Therefore, investigations are required with different doses of sunitinib and other tyrosine kinase inhibitors in order to evaluate the efficacy on treatment of cirrhosis progression.

Attosecond electron dynamics in small- and medium-sized molecules, induced by an ultrashort strong optical pulse, is studied computationally for a frozen nuclear geometry. The importance of exchange and correlation effects on the nonequilibrium electron dynamics induced by the interaction of the molecule with the strong optical pulse is analyzed by comparing the solution of the time-dependent Schrödinger equation based on the correlated field-free stationary electronic states computed with the equationof-motion coupled cluster singles and doubles and the complete active space multi-configurational self-consistent field methodologies on one hand, and various functionals in real-time time-dependent density functional theory (TDDFT) on the other. We aim to evaluate the performance of the latter approach, which is very widely used for nonlinear absorption processes and whose computational cost has a more favorable scaling with the system size. We focus on LiH as a toy model for a nontrivial molecule and show that our conclusions carry over to larger molecules, exemplified by ABCU (C10H19N). The molecules are probed with IR and UV pulses whose intensities are not strong enough to significantly ionize the system. By comparing the evolution of the time-dependent field-free electronic dipole moment, as well as its Fourier power spectrum, we show that TD-DFT performs qualitatively well in most cases. Contrary to previous studies, we find almost no changes in the TD-DFT excitation energies when excited states are populated. Transitions between states of different symmetries are induced using pulses polarized in different directions. We observe that the performance of TD-DFT does not depend on the symmetry of the states involved in the transition.

Context: Cancer is a prothrombotic state and anticancer therapies are often complicated by vascular events. The risk of developing thromboembolic events is substantially increased in patients with pancreatic cancer. One possible presentation of vascular events in pancreatic cancer is disseminated intravascular coagulation (DIC)., Case Report: In our case a patient with a diagnosis of pancreatic cancer initially presented with thrombosis and received low molecular weight heparin (LMWH) in addition to standard chemotherapy regimen. He was thought to have DIC by assessment of clinical and laboratory findings., Conclusion: Clinically, thrombosis was first located in the left femoral vein and encountered at right femoral artery after three weeks. This pattern was an unusual presentation of DIC. Subclinical DIC is common in patients presenting with pancreatic cancer and is considered a 'poor' prognostic factor. Acute DIC, on the other hand is a potentially mortal condition.

Background: The resynchronization-defibrillation for ambulatory heart failure trial (RAFT) study demonstrated that adding cardiac resynchronization therapy (CRT) in selected patients requiring de novo implantable cardiac defibrillators (ICD) reduced mortality as compared with ICD therapy alone, despite an increase in procedure-related adverse events. Data are lacking regarding the management of patients with ICD therapy who develop an indication for CRT upgrade., Methods and Results: Participating RAFT centers provided data regarding de novo CRT-D (CRT with ICD) implant, upgrade to CRT-D during RAFT (study upgrade), and upgrade within 6 months after presentation of study results (substudy). Substudy centers enrolled 1346 (74.9%) patients in RAFT, including 644 de novo, 80 study upgrade, and 60 substudy CRT attempts. The success rate (initial plus repeat attempts) was 95.2% for de novo versus 96.3% for study upgrade and 90.0% for substudy CRT attempts (P=0.402). Acute complications occurred among 26.2% of de novo versus 18.8% of study upgrade and 3.4% of substudy CRT implantation attempts (P<0.001). The most common complication was left ventricular lead dislodgement. The principal reasons for not yet attempting upgrade in the substudy were patient preference (31.9%), New York Heart Association Class I (17.0%), and a QRS<150 ms (13.1%)., Conclusions: Among a broad group of implant physicians, CRT upgrades were performed in patients with an ICD in situ with no difference in implant success rate and a reduced acute complication rate as compared with a de novo CRT implant. Decisions to upgrade were influenced by predictors of benefit in subgroup analyses of the RAFT study and other trials., (© 2014 American Heart Association, Inc.)

Aims: Physical counter-pressure manoeuvres (PCM) are effective in young patients with vasovagal syncope and recognizable prodromal symptoms. The aim of this study was to investigate their effectiveness in patients ≥40 years with severe neurally mediated syncope (NMS) enroled in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3)., Methods and Results: In the ISSUE-3 study, 63 out of 162 patients had a diagnosis of hypotensive NMS (Types 2, 3, and 4A) documented by implantable loop recorder; of these, 40 were instructed to perform isometric leg and arm PCM therapy. Their mean age was 62 ± 13 years; 47% of patients had a history of some episodes without prodrome. A group of 45 untreated patients acted as controls. The primary endpoint was the time to first syncope recurrence. During follow-up, syncope recurred in 15 PCM patients (37%) and in 24 control patients (53%) (P = 0.14). At 21 months, the modelled syncope recurrence rates were 42% [95% confidence interval (CI): 27-61] and 64% (95% CI: 48-80), respectively (P = 0.27)., Conclusion: In conclusion, many ISSUE-3 patients affected by hypotensive NMS have syncopal recurrence despite PCM. Older age and the absence of sufficiently long recognizable prodromal symptoms in the ISSUE-3 population might have hampered the effectiveness of PC therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Epicardial high-density electrical mapping is a well-established experimental instrument to monitor in vivo the activity of the atria in response to modulations of the autonomic nervous system in sinus rhythm. In regions that are not accessible by epicardial mapping, noncontact endocardial mapping performed through a balloon catheter may provide a more comprehensive description of atrial activity. We developed a computer model of the canine right atrium to compare epicardial and noncontact endocardial mapping. The model was derived from an experiment in which electroanatomical reconstruction, epicardial mapping (103 electrodes), noncontact endocardial mapping (2048 virtual electrodes computed from a 64-channel balloon catheter), and direct-contact endocardial catheter recordings were simultaneously performed in a dog. The recording system was simulated in the computer model. For simulations and experiments (after atrio-ventricular node suppression), activation maps were computed during sinus rhythm. Repolarization was assessed by measuring the area under the atrial T wave (ATa), a marker of repolarization gradients. Results showed an epicardial-endocardial correlation coefficients of 0.80 and 0.63 (two dog experiments) and 0.96 (simulation) between activation times, and a correlation coefficients of 0.57 and 0.46 (two dog experiments) and 0.92 (simulation) between ATa values. Despite distance (balloon-atrial wall) and dimension reduction (64 electrodes), some information about atrial repolarization remained present in noncontact signals.

Background: In the Third International Study on Syncope of Uncertain Etiology (ISSUE-3), cardiac pacing was effective in reducing recurrence of syncope in patients with presumed neurally mediated syncope (NMS) and documented asystole but syncope still recurred in 25% of them at 2 years. We have investigated the role of tilt testing (TT) in predicting recurrences., Methods and Results: In 136 patients enrolled in the ISSUE-3, TT was positive in 76 and negative in 60. An asystolic response predicted a similar asystolic form during implantable loop recorder monitoring, with a positive predictive value of 86%. The corresponding values were 48% in patients with non-asystolic TT and 58% in patients with negative TT (P=0.001 versus asystolic TT). Fifty-two patients (26 TT+ and 26 TT-) with asystolic neurally mediated syncope received a pacemaker. Syncope recurred in 8 TT+ and in 1 TT- patients. At 21 months, the estimated product-limit syncope recurrence rates were 55% and 5%, respectively (P=0.004). The TT+ recurrence rate was similar to that seen in 45 untreated patients (control group), which was 64% (P=0.75). The recurrence rate was similar between 14 patients with asystolic and 12 with non-asystolic responses during TT (P=0.53)., Conclusions: Cardiac pacing was effective in neurally mediated syncope patients with documented asystolic episodes in whom TT was negative; conversely, there was insufficient evidence of efficacy from this data set in patients with a positive TT even when spontaneous asystole was documented. Present observations are unexpected and need to be confirmed by other studies. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463358.

Purpose: Vasovagal syncope (VVS) is a chronic debilitating condition seen mostly in young women of reproductive age. There are anecdotal reports of increased syncope and presyncope around menstruation. This case-control study assessed the effects of the menstrual cycle on lightheadedness episodes and compared the gynecological and pregnancy history of VVS patients to healthy subjects., Methods: A custom-designed gynecological and menstrual cycle questionnaire was previously developed for patients with orthostatic intolerance. This questionnaire was administered to female patients with VVS (n = 128) as a part of the multicenter Second Prevention of Syncope Trial, and to gender-matched healthy subjects (n = 92)., Results: VVS patients and healthy subjects reported significant variability in self-reported lightheadedness throughout the menstrual cycle. Both cohorts experienced greatest lightheadedness during menses (53 ± 2 vs. 56 ± 4), which decreased during the follicular phase (44 ± 2 vs. 41 ± 4). VVS patients reported less severity in premenstrual symptoms (Fisher's method P = 2.7E-06) compared to healthy controls. There is no difference in the incidence of gynecological abnormalities (Fisher's exact P = 0.193) and pregnancy complications (P = 1.0) between the two cohorts. VVS patients have similar pregnancy rates compared to healthy subjects (P = 0.674)., Conclusion: The severity of lightheadedness varies during the menstrual cycle and is similar in both VVS patients and healthy controls. VVS patients have no greater risk of gynecological abnormalities and pregnancy complications than healthy subjects.

Background: Implantable cardioverter defibrillator (ICD) leads are subject to technical failures and the impact of the resulting public advisories on patient welfare is unclear. The psychological status of patients who received an advisory for their Medtronic Fidelis ICD lead (Medtronic Inc., Minneapolis, MN, USA) and followed either by self-surveillance for alarm or home monitoring with CareLink was evaluated prospectively and compared to patients with ICDs not under advisory., Methods: One hundred sixty consecutive consenting patients (90 alarms, 24 Carelinks, 46 controls) were recruited within 1.5 years of advisory notification. Advisory patients were seen immediately before being told that the automatic lead surveillance utilized since the advisory had been inadequate in warning of impending fracture, as well as 1 and 6 months after programming was optimized. Depression, anxiety, quality of life (QoL), and ICD-related concerns were assessed., Results: Symptoms of depression and state anxiety were experienced by 31% and 48% of patients, respectively. QoL was impaired on all subscales. No significant group differences in distress and ICD-related concerns emerged at baseline or at follow-up. At baseline, alarm patients reported greater limitations because of body pain compared to controls (P < 0.05). All patients showed a significant reduction in body pain-related QoL at the final versus first two evaluations (P < 0.001). Advisory patients were significantly less satisfied with surveillance at follow-up than at baseline (P < 0.05)., Conclusions: There was limited evidence for worse psychosocial functioning in those at risk for ICD lead fracture, irrespective of surveillance method. However, many control and advisory patients experienced chronic distress for which counseling may prove beneficial., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Background: To describe the association between body mass index (BMI) and a positive response during a head-up tilt test (HUT) in patients referred for an investigation of syncope., Methods: Observational study of patients referred for the diagnostic evaluation of syncope. Patients were divided into four groups according to their BMI: <18.5 kg/m(2), 18.5-24.9 kg/m(2), 25-29.9 kg/m(2), and > 30 kg/m(2)., Results: A total of 419 patients were evaluated. The mean age was 43 ± 22 years, and 62% were female. The prevalence of a positive tilt test was different between groups when stratified by BMI (P = 0.01), with a higher proportion of patients with positive tests among those with BMI <18.5 kg/m(2) compared with other groups (P = 0.05). Multivariate analysis also showed that underweight patients had a 3.9 times higher risk for a positive HUT response (P = 0.01); additionally, the use of contraceptive drugs was associated with a protective effect during HUT (odds ratio: 0.35, confidence interval: 0.19-0.45, P = 0.001)., Conclusion: In our sample, changes in BMI are associated with a positive response for HUT, and oral contraceptives seemed to protect against this response. Further studies are needed with larger numbers of patients to corroborate this finding., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Introduction: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT., Methods: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT., Results: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all-cause mortality occurred in 10% of patients in the no-DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21-1.31, P = 0.14)., Conclusions: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT., (© 2012 Wiley Periodicals, Inc.)

Aims: To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies., Methods: Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT-RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation., Results: Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p<0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p<0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia)., Conclusion: The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Following recent cases of nonphysiologic noise noted early after defibrillator implantation, the Canadian Heart Rhythm Society Device Committee decided to evaluate the implications of this problem., Objective: To determine the incidence and consequences of nonphysiologic noise early after defibrillator implantation., Methods: The Canadian Heart Rhythm Society Device Committee surveyed all Canadian defibrillator implanting centers regarding their implant volumes and number of cases where nonphysiologic noise had been noted early (< 24 hours) after implant over the preceding 2 years. For such cases, information regarding the manufacturer and occurrence of inappropriate shock or inhibition of pacing was reported., Results: Responses were obtained from 20 of 23 surveyed implanting centers, with a total implant volume of 4960 defibrillators per year. The occurrence of nonphysiologic noise early after implantation was noted in 25 cases over the preceding 2 years (0.25%). Noise was detected in devices of all 3 of the leading volume device manufacturers. There were 2 cases of inappropriate shocks and 2 cases of symptomatic pacing inhibition. In 4 cases, removal of the lead from the header and retesting with the analyzer confirmed normal lead function. In all cases, the noise resolved within 24 hours., Conclusion: Nonphysiologic noise early after defibrillator implantation was noted in 0.25% of procedures and was not limited to one specific manufacturer. This noise may result in an inappropriate shock or inhibition of pacing in a pacemaker-dependent patient. This transient phenomenon, possibly related to fluid and/or air in the header, appears to always resolve without surgical intervention., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

In canines, excessive activation of select mediastinal nerve inputs to the intrinsic cardiac nervous system induces atrial fibrillation (AF). Since ablation of neural elements is proposed as an adjunct to circumferential pulmonary vein ablation for AF, we investigated the short and long-term effects of mediastinal nerve ablation on AF inducibility. Under general anesthesia, in 11 dogs several mediastinal nerve sites were identified on the superior vena cava that, when stimulated electrically during the atrial refractory period, reproducibly initiated AF. Cryoablation of one nerve site was then performed and inducibility retested early (1-2 months post Cryo; n=7) or late (4 months post Cryo; n=4). Four additional dogs that underwent a sham procedure were retested 1 to 2 months post-surgery. Stimulation induced AF at 91% of nerve sites tested in control versus 21% nerve sites early and 54% late post-ablation (both P<0.05). Fewer stimuli were required to induce AF in controls versus the Early Cryo group; this capacity returned to normal values in the Late Cryo group. AF episodes were longer in control versus the Early or Late Cryo groups. Heart rate responses to vagal or stellate ganglion stimulation, as well as to local nicotine infusion into the right coronary artery, were similar in all groups. In conclusion, focal damage to intrinsic cardiac neuronal inputs causes short-term stunning of neuronal inducibility of AF without major loss of overall adrenergic or cholinergic efferent neuronal control. That recovery of AF inducibility occurs rapidly post-surgery indicates the plasticity of intrathoracic neuronal elements to focal injury., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Analysis of T waves in the ECG is an essential clinical tool for diagnosis, monitoring, and follow-up of patients with heart dysfunction. During atrial flutter, this analysis has been so far limited by the perturbation of flutter waves superimposed over the T wave. This paper presents a method based on missing data interpolation for eliminating flutter waves from the ECG during atrial flutter. To cope with the correlation between atrial and ventricular electrical activations, the CLEAN deconvolution algorithm was applied to reconstruct the spectrum of the atrial component of the ECG from signal segments corresponding to TQ intervals. The locations of these TQ intervals, where the atrial contribution is presumably dominant, were identified iteratively. The algorithm yields the extracted atrial and ventricular contributions to the ECG. Standard T-wave morphology parameters (T-wave amplitude, T peak-T end duration, QT interval) were measured. This technique was validated using synthetic signals, compared to average beat subtraction in a patient with a pacemaker, and tested on pseudo-orthogonal ECGs from patients in atrial flutter. Results demonstrated improvements in accuracy and robustness of T-wave analysis as compared to current clinical practice.

Introduction: Radiofrequency(RF) ablation has become the first line of therapy for atrial flutter(AFL). Advances in catheter and mapping technologies have led to better understanding and different approaches for treating this arrhythmia. We describe the results of different approaches to ablate this arrhythmia., Materials and Methods: A cohort of 198 patients with isthmus dependent AFL. The techniques used were: 10mm-tip catheter with power set to 100w, 8mm-tip catheter with power set to 60W and irrigated tip catheter., Results: 212 procedures, including redos were done in 198 consecutive patients. We used irrigated tip catheters in 14 procedures, 8mm-tip in 55 procedures, and 10mm-tip in 143 procedures. Bidirectional block was achieved in 97.6% of cases with all techniques, with no difference among them. Procedure time was shorter in the 10mm-tip versus 8mm-tip(69.6±30.6min vs.105±43min) or irrigated tip(180±90min) (P<0.05). Fluoroscopy time was also shorter in the 10mm-tip versus 8mm-tip (24±18min vs. 37±23min) or irrigated tip (110±25min)(P<0.05). The cumulative incidence of failure during follow-up was 1.2%/year in the 10mm, 10.1%year in the 8mm and 6.9%year in the irrigated tip. The survival free of a new procedure was significantly higher among 10mm patients., Conclusions: In our series we found a high rate of acute success with the use of different techniques for AFL ablation. Procedure and fluoroscopic times were shorter with the use of 10mm-tip as compared with the others techniques. The long-term risk of recurrence was lower when we used the 10mm-tip catheter and the survival free of a second procedure was higher among patients treated with this catheter.

Introduction: Vasovagal syncope is common, often recurrent, and reduces quality of life. No therapies have proven useful to improve quality of life in adequately designed randomized clinical trials. Beta-blockers have mixed evidence for effectiveness in preventing syncope., Methods: The Prevention of Syncope Trial was a randomized, placebo-controlled, double-blind, multinational, clinical trial that tested the hypothesis that metoprolol improves quality of life in adult patients with vasovagal syncope in a 1-year observation period. Randomization was stratified in strata of patients <42 and > or =42 years old. The quality of life questionnaires Short Form-36 (SF-36) and Euroqol EQ-5D were completed at baseline and after 6 and 12 months of treatment by 204, 132, and 121 patients, respectively., Results: There were 208 patients, mean age 42 +/- 18, of whom 134 (64%) were females. All had positive tilt tests. There was no improvement in quality of life during the trial in the entire group or in either treatment arm. Patients in the metoprolol treatment arm did not have improved quality of life compared to the patients in the placebo arm using either the SF-36 or EQ5D after either 6 or 12 months. Finally, there was no improvement in quality of life associated with metoprolol use in patients either <42 or > or =42 years of age., Conclusion: Metoprolol does not improve quality of life in patients with recurrent vasovagal syncope and a positive tilt test.

Unlabelled: Syncope is experienced by a third of the population, and in the absence of cardiac pathology is most commonly of vasovagal (VVS) or unexplained origin (US). Psychiatric morbidity has been observed in up to 81% of patients with US but findings with VVS are contradictory. Little is known regarding the chronicity of their psychiatric morbidity., Objective: To determine the psychological profile of patients with recurrent syncope prior to and following diagnostic head-up tilt testing (HUT), and whether it predicts syncope recurrence., Method: Seventy-three women and 43 men (mean age=48+/-16.6) were recruited from all consenting patients referred for HUT. Psychological status (Psychiatric Symptom Index, Anxiety Sensitivity Index (ASI), Fear of Blood Injury Subscale) and presence of mood/anxiety disorders (Primary Care Evaluation of Mental Disorders) were evaluated 1 month prior to and 6 months following HUT. Follow-up data were collected for 83 patients (mean age=48+/-17.34)., Results: At baseline, clinically significant levels of distress were observed in 60% of patients. Those with US (negative HUT) had a fivefold greater risk of suffering from a depressive or anxiety disorder compared to VVS (positive HUT) after controlling for significant covariates. There was no significant change in distress level over follow-up, although psychiatric morbidity dropped from 33% to 22% (P=.049). Syncope recurrence was predicted by elevations in baseline psychological distress (OR=1.544, P=.013) independently of lifetime number of syncopes., Conclusions: Patients exhibited high levels of psychological distress and psychiatric morbidity despite reassurance and education received after HUT. Improved screening for and treatment of psychological distress in these patients is critical.

Introduction: Vasovagal syncope is common and distressing. One important symptom is presyncope, but there are no clinimetric measures of this. We developed the Calgary Presyncope Form (CPF) and used it to test whether metoprolol reduces presyncope in a randomized trial., Methods: The CPF captures the frequency, duration, and severity of presyncope. We administered it to participants in the Prevention of Syncope Trial (POST), a randomized clinical trial that tested the hypothesis that metoprolol reduces syncope and presyncope in adult patients with vasovagal syncope., Results: The CPF was completed by 44 patients on metoprolol and 39 patients on placebo, of a total of 208 subjects. Completion of the CPF for each of the threedimensions was 84-87% in the 83 respondents. Results were centrally distributed in duration and severity dimensions, but not in frequency. Patients had a median of 1.2 presyncopal spells per day, with a median moderate severity, lasting a median 10 minutes. The 3 scales were statistically independent of each other. These results were independent of subject age, and results in all 3 dimensions were stable over the observation period. There was no significant difference between patients on metoprolol and placebo in any dimension., Conclusion: The 3-dimensional CPF is simple, easy to use, stable over time, measures 3 independent variables, and documents that metoprolol does not reduce presyncope.

Background/objective: The Canadian Heart Rhythm Society (CHRS) Device Advisory Committee was commissioned in 2006 to develop a mechanism for responding to advisories regarding cardiac rhythm device and lead performance., Methods: In the event of an advisory, the Chair classifies the advisory as urgent, semi-urgent, or routine based on the nature of the threat to the patient and the number of patients affected. The Chair uses an e-mail network with the committee members to disseminate advisory information and to assemble a consensus recommendation. Committee membership is broadly representative of the Canadian device community, including both academic and nonacademic centers, adult and pediatric specialists, and includes balanced regional representation. Recommendations are approved by the CHRS executive and made available to all implant and follow-up centers on the CHRS website., Results: With the Medtronic Fidelis lead advisory of October 15, 2007, the Chair classified the advisory as semi-urgent and initiated an e-mail discussion and preliminary survey of all Canadian implantable cardioverter-defibrillator (ICD) centers within 3 hours of advisory announcement. A CHRS membership statement was issued within 48 hours. Within 5 working days, sample letters to physicians and patients were posted for local adaptation and distribution. Complete data collection was obtained from all Canadian defibrillator centers. Analyses at 20, 25, 30, and 32 months suggest an accelerating course of failures (3.91% at 32 months, P <.0001), with a reduced likelihood of presentation with inappropriate shocks (from 56% to 21%, P = .0003)., Conclusion: A collaborative approach using an e-mail network provides a mechanism for a rapid national response to device advisories. The network allows collection of focused data on implanted device system performance and facilitates timely reporting of clinically relevant data to patients and clinicians.

Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by alpha-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (alpha(1)-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (alpha(2)-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined alpha-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by alpha(1,2)-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal alpha-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that alpha-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system.

In anesthetized dogs both epi-and endocardial atrial activation maps and corresponding isointegral repolarization maps were created before and during right or left mediastinal nerve (RMN and LMN) and cervical vagus nerve (CVN) stimulation. Right mediastinal nerve stimulation typically caused sinus slowing, atrial tachycardia (AT), followed by atrial fibrillation (AF). Activation maps during AT showed epicardial breakthroughs from the right atrial free wall or Bachmann's bundle. Left mediastinal nerve stimulation (LMN) rarely caused sinus slowing and ATs originated mostly from Bachmann's bundle or from the pulmonary vein ostial region. Atrial repolarization changes induced by neural stimulation were measured by integrating the area subtended by 161 epicardial unipolar electrograms. Atrial tachycardia epicardial breakthrough sites were closely associated with the border zone where repolarization changes occurred. Both AT and AF were abolished by I.V. atropine, as were sinus bradycardia and atrial repolarization effects of nerve stimulation. Shortening of latency of onset and duration of AT by I.V. timolol suggest concurrent activation of adrenergic efferent neurons. In conclusion, juxta-cardiac mediastinal nerve stimulation can induce atrial fibrillation from multiple, discrete right and left atrial sites, which correspond to localized repolarization changes. Secondly, sinus bradycardia is not a necessary index of parasympathetic neurally induced atrial fibrillation.

We sought to determine the sites of origin of atrial tachyarrhythmias induced by activating mediastinal nerves, as well as the response of such arrhythmias to autonomic modulation. Under general anaesthesia, atrioventricular block was induced after thoracotomy in 19 canines. Brief trains of 5 electrical stimuli were delivered to right-sided mediastinal nerves during the atrial refractory period. Unipolar electrograms were recorded from 191 right and left atrial epicardial sites under several conditions, i.e. (i) with intact nervous systems and following (ii) acute decentralization of the intrathoracic nervous system or administration of (iii) atropine, (iv) timolol, (v) hexamethonium. Concomitant right atrial endocardial mapping was performed in 7 of these dogs. Mediastinal nerve stimulation consistently initiated bradycardia followed by atrial tachyarrhythmias. In the initial tachyarrhythmia beats, early epicardial breakthroughs were identified in the right atrial free wall (28/50 episodes) or Bachmann bundle region (22/50), which corresponded to endocardial sites of origin associated with the right atrial subsidiary pacemaker complex, i.e. the crista terminalis and dorsal locations including the right atrial aspect of the interatrial septum. Neuronally induced responses were eliminated by atropine, modified by timolol and unaffected by acute neuronal decentralization. After hexamethonium, responses to extra-pericardial but not intra-pericardial nerve stimulation were eliminated. It is concluded that concomitant activation of cholinergic and adrenergic efferent intrinsic cardiac neurons induced by right-sided efferent neuronal stimulation initiates atrial tachyarrhythmias that originate from foci anatomically related to the right atrial pacemaker complex and tissues underlying major atrial ganglionated plexuses.

Background and Objective: Recurrence of atrial flutter (AFl) on antiarrhythmic drugs is frequently observed. To determine the reasons for drug inefficacy, the electrophysiological parameters of AFl were studied in eight patients without drug, six patients on sotalol (Sot), eight patients on amiodarone (Amio) and four patients on propafenone (PPF) who presented to the electrophysiology laboratory for conversion of AFl by rapid atrial pacing., Methods: A quadripolar electrode catheter was positioned in the right atrium in the pathway of the AFl circuit. The duration and composition of the excitable gap (EG) were determined by premature stimuli during AFl., Results: The EG in AFl recurring on Sot (80 +/- 25 ms), Amio (78 +/- 13 ms) and PPF (83 +/- 26 ms) was not significantly different from that without drug (88 +/- 14 ms). Furthermore, a fully excitable portion of the EG was present whether with or without drug., Conclusions: AFl recurrence on Amio, PPF or Sot is associated with the continued presence of an EG and fully excitable portion. These findings explain the persistent viability of the AFl circuit despite drug therapy in these patients.

Objectives: Using data from the Multicenter UnSustained Tachycardia Trial (MUSTT), we examined the factors used to select antiarrhythmic drug therapy and their impact on outcomes., Background: The MUSTT examined the use of programmed ventricular stimulation (PVS) to guide antiarrhythmic therapy in patients with coronary arteriosclerosis, left ventricular dysfunction and asymptomatic, unsustained ventricular tachycardia (VT). Trial outcomes may reflect factors used to select antiarrhythmic drug therapy., Methods: We compared subgroups of patients with inducible sustained VT randomized to PVS-guided antiarrhythmic therapy (n = 351), in particular those receiving PVS-guided antiarrhythmic drug therapy (n = 142) versus no antiarrhythmic therapy (controls, n = 353)., Results: "Effective" antiarrhythmic drug therapy (i.e., the term "effective" was used to denote therapy that resulted in noninducible VT or hemodynamically stable induced VT) was found for 142 of the 351 patients (43%), most often at the first or second PVS session (125/142, 88%). Mortality among the 142 patients did not differ from that among control patients. Of these 142 patients, the PVS end point was noninducibility in 91 patients and stable VT in 51 patients. Mortality did not differ between these two groups either, but arrhythmia was numerically more frequent in the PVS-induced stable VT group. Mortality was greatest in the few patients receiving propafenone (unadjusted p = 0.07, adjusted p = 0.14 vs. controls), but mortality with all agents did not differ from that of controls, even after adjustment., Conclusions: Even when presenting the results as favorably as possible, we found no benefit with PVS-guided drug therapy in patients with clinical unsustained VT who had inducible sustained VT. These findings are unaltered by using different end points for PVS or considering the response to individual drugs.

Atrial arrhythmias are believed to be influenced by autonomic nervous system tone. We evaluated the effects of sympathetic and parasympathetic activation on atrial flutter (AF1) by determining the effects of norepinephrine (NE) and acetylcholine (ACh) on the composition of the excitable gap. A model of reentry around the tricuspid valve was produced in 17 chloralose anesthetized dogs using a Y-shaped lesion in the intercaval area that extended to the right atrial appendage. Excitable gap characteristics were determined during AF1 by scanning diastole with a single premature extrastimulus at progressively shorter coupling intervals to define the reset-response curve. Measurements were made during a constant infusion of NE (15 microg/min) into the right coronary artery and repeated during ACh infusion (2 microg/min) following a 15 min recovery period. The excitable gap (27 +/- 1 ms) was significantly (P < 0.001) increased by NE (34 +/- 1 ms) and ACh (50 +/- 2 ms). The fully excitable portion (7 +/- 1 ms) was also significantly (P < 0.001) increased by NE (17 +/- 1 ms) and ACh (43 +/- 2 ms). We conclude that both neurotransmitters increase the safety margin of full excitability ahead of the wavefront, demonstrating that parasympathetic and sympathetic activation can facilitate the persistence of this refractory atrial arrhythmia.

Previous studies on atrial flutter (AF) presumed that resetting was due to the prematurity effect (PE) in which the stimulated antegrade wavefront travels in the tail of the AF preexisting wavefront. We studied the collision effect (CE) between the AF and the stimulated retrograde wavefronts, its contribution to resetting, and its relationship to AF termination and how they are affected by the Class IC agent propafenone (PPF). A canine model of AF was created using a Y-shaped lesion in the right atrium in 14 dogs (33 +/- 3 kg). Five atrial bipolar electrodes were positioned around the tricuspid valve. In a subsequent set of 11 dogs, we used 16 bipolar electrodes for recording. AF was induced by burst pacing. Single and multiple stimuli were applied to measure conduction time and reset-response curves (RRCs). This was repeated after the administration of PPF (1 mg/kg loading dose for 10 minutes, followed by 1.8 mg/kg/per hour infusion). Three distinct mechanisms were found to contribute to the RRC: the PE, the CE, and heterogeneity. PPF stabilized the RRC, increased significantly the cycle length (CL), the duration of the effective refractory period, as well as the duration of the excitable gap. However, PPF did not alter the duration of the fully excitable portion. We studied 36 annihilations without and 48 with PPF. Transient fibrillation was found in 75% of the episodes without, compared to 22% with PPF. Other types of termination such as conduction block, CL oscillations, and reversal of activation were found for 25% of the episodes without and 78% with PPF. In many cases, conduction block and CL oscillations were associated with a failure of propagation of the stimulated antegrade wavefront in the region of collision. Termination by reversal of activation suggests that propagation was two dimensional and could not be represented by a one dimensional movement. The average coupling interval (in percent of CL), that induced fibrillation was not significantly different from that at which conduction block occurred. This suggests that transient fibrillation is associated with a weak CE rather than with rapid pacing. The CE is amplified by multiple stimuli and PPF. The incidence of transient fibrillation in AF annihilation diminishes with PPF as the CE becomes more important. This suggests that the evaluation of PE and CE in AF may be an indication of the risk of atrial fibrillation.

Background: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial., Methods: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation., Results: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06)., Conclusions: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.

The objectives of this study were: (1) to evaluate quantitatively the spatial resolution of pacemapping; and (2) to assess the predictive value and role of pacemapping for the catheter ablation of overt APs. Sixty-three unipolar leads were used instead of the standard 12-lead ECG to acquire more information and assess the intrinsic accuracy of pacemapping. Spatial resolution was evaluated in 19 patients for whom data were recorded during bipolar ventricular pacing near the AV ring using the three electrode pairs of a quadripolar ablation catheter with a 5-mm interelectrode spacing. The predictive value was assessed in 27 patients with overt APs who underwent RF ablation; their data were recorded during pacing at the site of successful ablation and at one or two sites where RF energy delivery was ineffective. Data from different beats were compared visually by using body surface potential maps and quantitatively by computing average correlation coefficients (r). Reproducibility was high for paced beats (r = 0.98 +/- 0.02). Displacements of 5 mm of the pacing site could be detected with a sensitivity of 90% and a specificity of 87%. Correlation between pacing at successful ablation sites and preexcited sinus rhythm was low (r = 0.79 +/- 0.11) and the ablation outcome could be predicted with a negative prediction accuracy of 87% and a positive prediction accuracy of 49%. Despite an excellent spatial resolution, pacemapping is of limited value for the identification of successful AP ablation sites, probably because APs can be interrupted at some distance from their ventricular insertion point.

Background: The aim of this study was to determine whether cycle length (CL) variations at the onset of monomorphic ventricular tachycardias follow distinctive patterns., Methods and Results: We retrospectively analyzed 59 monomorphic ventricular tachycardias induced in 40 patients in whom intraoperative mapping was performed with 63 epicardial and 64 endocardial electrograms recorded simultaneously. Activation times and CL were determined at each electrode site over several beats (36+/-10 beats, mean+/-SD) starting with the first after programmed stimulation. In the majority of the tachycardias, CL variations were accounted for by fitting to an exponential function: CL=CLs+Ae-b/tau, where CLs is the stable CL, b is beat number, tau is the time constant (in beat number), and A is the magnitude of CL relaxation. A decelerating trend (with reference to rate) (negative A) accounted for 21 tachycardias, an accelerating trend in rate (positive A) accounted for 12 tachycardias, and 4 others displayed a double dynamic behavior, with an initial acceleration followed by a decelerating trend in rate. Among the ventricular tachycardias that were not fitted to exponential models, 12 showed a constant trend and 10 others showed irregular CL fluctuations. The monomorphic character of the tachycardias was established by principal-component analysis, which also indicated that CL dynamics associated with the accelerating and decelerating trends may be related to shortening and prolongation of activation times, respectively, occurring in equal proportion at all recording sites. In canine preparations in which reentry circuits could be mapped with high resolution, CL showed an accelerating trend in rate when circus movement of excitation occurred around a transmural scar in muscle generating unipolar electrograms with relatively high -dV/dtmax, and a decelerating trend in rate occurred when functional reentry occurred in muscle generating unipolar electrograms with depressed -dV/dtmax., Conclusions: Beat-to-beat CL variations may occur at the onset of sustained monomorphic ventricular tachycardia as a result of uniform acceleration or deceleration of activation times while the overall activation pattern remains constant. The associated initial trends in the rate of sustained monomorphic ventricular tachycardia follow typical patterns that might provide "signatures" corresponding to reentry substrates with distinctive functional properties.

Objective: To assess the impact of adverse drug reactions on antiarrhythmic drug substitution in ambulatory patients., Setting: Tertiary care dysrhythmia clinic., Patients and Methods: A total of 671 medical records were reviewed. Sex of the study population was equally distributed, with an average age of 53 years. Follow-up averaged 26 months for patients seen more than once. Suspected adverse drug reactions and substitution of antiarrhythmic agent were used to ascertain events in patients' charts. Patients were exposed to 1253 treatment courses. The number of successive antiarrhythmic agents per patient averaged 1.8 and varied from one to seven., Results: One hundred and thirty-nine (20%) patients experienced a total of 194 adverse events (15.5% of drug courses), of which only eight (4%) were serious. Ninety-four per cent of the mostly benign adverse drug reactions were followed by a therapeutic modification: discontinuation or replacement in 87% and dosage reduction in 7%. The influence of successive drug changes was evident: the risk of a reaction was 7% in patients exposed to one agent compared with 100% in patients exposed to a seventh agent., Conclusions: First, therapeutic substitution in response to adverse drug reactions appears to be determined more by the combined expected benefit, the product of arrhythmia severity and drug efficacy, than by the severity alone of the adverse reaction; and second, the probability of an adverse drug reaction is proportional to the number of agents tried consecutively, possibly as a result of patient selection, drug selection and increased patient and doctor awareness.

Objective: To compare the diagnostic yield of transtelephonic monitoring (TTM) with Holter monitoring in patients presenting possibly arrhythmogenic symptoms., Design: A prospective comparison of Holter monitoring with TTM performed sequentially in all subjects., Setting: Tertiary arrhythmia clinic at Hôpital du Sacré-Coeur de Montréal, Montréal, Québec., Patients: One hundred consecutive patients (34 men and 66 women, mean +/- SD age 55 +/- 16 years) presenting over a two-year period for diagnosis of intermittent palpitations and/or syncope/dizziness., Interventions: Subjects first underwent 24 h Holter monitoring and then were provided with TTM for 25 +/- 13 days, with instructions to record during symptomatic episodes and subsequently to transmit the recording at their convenience., Main Results: Holter monitoring documented arrhythmia in 30 patients whereas TTM identified arrhythmia in 21. TTM was most useful in excluding arrhythmia during symptoms (34 patients) versus Holter (two patients). Neither method was useful in diagnosing syncope. Frequency of occurrence of palpitations did not predict which method would most likely yield a diagnosis but palpitations lasting longer than 2 mins were likely to be diagnosed by TTM., Conclusions: Holter and TTM are complementary studies whose combined use increases the diagnostic yield of arrhythmia. Further, TTM is of greatest use in excluding arrhythmia during intermittent symptoms.

Background: The purpose of this report is to describe the body surface potential maps (BSPMs) during idiopathic ventricular tachycardia (VT) and to determine what differences exist between different idiopathic VT morphologies., Methods and Results: We performed BSPMs during VT on 12 consecutive patients (3 women and 9 men; mean age, 42 +/- 13 years) presenting symptomatic idiopathic VT referred to our institution for electrophysiological study. Basal ECG, chest radiograph, and echocardiogram were normal in all patients. Clinical tachycardia showed left bundle branch block pattern (LBBB) in 9 patients, with sustained VT in 5 and nonsustained VT in 4, and right bundle branch block pattern (RBBB) in 3 with sustained VT. We found a unique pattern of BSPMs in each of the 9 patients during idiopathic LBBB VT configuration, whether sustained or nonsustained VT. This pattern appeared at the onset of the QRS and remained stable during the whole QRS complex. The area of minimal potential located in the upper anterior part of the torso was compatible with an origin of VT in the right ventricular outflow tract, as confirmed in 5 patients by successful radiofrequency ablation. We found an evolving pattern with two phases in each of the three RBBB VTs. The electrical axis during the initial part of the QRS could correspond to an endocardial-epicardial vector. The second phase, with a high voltage and area of minimal potential located in the inferior and anterior part of the torso, was compatible with a left ventricular apical origin that was confirmed by epicardial and endocardial mapping during cryosurgery in 1 patient. For all the VTs, the QRS isoarea maps showed the same pattern as the second phase of the QRS., Conclusions: Two different BSPM patterns were found. All LBBB VTs had the same stable pattern corresponding to an infundibular origin. All RBBB VTs had an evolving pattern that stabilized in the second part of the QRS complex corresponding to an apical origin.

Background: Comprehensive data based on single-beat analysis of the ventricular activation sequence during sinus rhythm in infarcted hearts are currently not available. It was the aim of our study (1) to measure and analyze these activation sequences on the epicardial surface of the right and left ventricles and on the left ventricular endocardial surface, and (2) to correlate specific activation patterns with the surface ECG., Methods and Results: Isochronal maps were computed from 127 endocardial and epicardial unipolar electrograms recorded simultaneously during sinus rhythm in 45 post-myocardial infarction patients operated on for recurrent ventricular tachycardia (age, 57 +/- 10 years [mean +/- SD], left ventricular ejection fraction, 29 +/- 9%). Patients with bundle-branch block, but not with intraventricular conduction defects, were excluded. Data such as the timing of initial and terminal activation, the number of breakthroughs, the total activation time, and the number of ventricular segments without activation were measured and analyzed according to location of the myocardial infarction. The global epicardial activation was characterized in all patients by a widespread initial breakthrough on the anterior right ventricle (16 +/- 8 milliseconds after QRS onset), which was followed by one or two other breakthroughs in 65% of patients. Subsequently, three characteristic epicardial patterns of the activation spread were found: (1) radial, from the right to the left ventricle, found in all patients with inferoposterior myocardial infarction; (2) counterclockwise rotation, in which posteroseptal crossing preceded the anteroseptal crossing, found in 38% of patients with anterior myocardial infarction; and (3) pincerlike encirclement, in which both septal crossings and/or breakthroughs occurred nearly simultaneously and merged at the left ventricular free wall (typical for apical involvement in anterior and combined myocardial infarction). The simultaneous presence of multiple major activation wave fronts typically found in patients with the pincerlike activation pattern was reflected on the surface ECG by multiphasic, notched QRS complexes. Activation delay was observed in 89% of patients, and terminal activation was topographically related to myocardial infarction in 94% of patients. Delayed activation exceeding the surface QRS was observed in 11% and 31% of cases on the endocardium and epicardium, respectively., Conclusions: These results offer a solid basis for a more precise interpretation of a wide range of electrophysiological data and provide a framework for future investigations of surface ECG reflections of endocardial and epicardial activation patterns recorded in patients with chronic myocardial infarction.

The cardiovascular oscillations during orthostasis were analyzed by time-frequency mapping in 23 patients with history of vasodepressor (VD) syncope and in 10 control subjects. Syncope was induced by head-up tilt (80 degrees, 25 min) alone in 11 patients (VD-1). Twelve patients remained asymptomatic (VD-2) during this tilt, but presented VD syncope or presyncope during tilt with an isoproterenol infusion. Data from the first tilt without isoproterenol infusion are presented here. Amplitude of sympathetically-mediated nonrespiratory fluctuations [0.01 Hz-respiratory frequency (Rf)] in blood pressure was greater at the beginning of the tilt in both (VD-1 and VD-2) groups compared to controls. Nonrespiratory oscillations were present throughout the tilt and their amplitude increased toward its end (p < 0.001) in VD-2 and control groups. In contrast, in the VD-1 group, the amplitude of 0.01-0.05 Hz rhythm in blood pressure diminished shortly after the beginning of tilt and continued to decline toward the syncope. Nonrespiratory fluctuations in R-R intervals were greatest in VD-1 group. The slow blood pressure rhythms reflect an integrity of feedback loops, and their disappearance is an early sign of an impending syncope.

Objective: To report a new case and review the literature of amiodarone-related epididymitis to improve knowledge of the clinical characteristics of this reaction., Design: Cohort study., Setting: Tertiary out-patient arrhythmia clinic., Patients: Males currently treated for arrhythmias with amiodarone for at least two months. Thirty-two patients were identified and all were contacted., Outcome Measures: Swelling and or/pain in the scrotum with confirmation of noninfectious epididymitis by a urologist., Data Sources: Bibliography (Medline and Embase) and databases (Manufacturer, Health Protection Branch, World Health Organisation)., Study Selection: Four articles with case reports. Databases searched for these key words: amiodarone and epididymitis., Results: A new case is reported. Twelve cases have been presented individually and six more described collectively. Times to onset range from four to 71 months, daily doses range from 200 to 800 mg. The reaction is self-limited, with or without amiodarone reduction, and does not require antimicrobial drugs, but a noninvasive urological examination may be warranted., Conclusion: Awareness by cardiologists will prevent unnecessary invasive urological investigations or antibiotic therapy.

Atrioventricular (AV) node ablation to control ventricular response was attempted in two patients with recurrent drug refractory atrial flutter. Standard radiofrequency (RF) procedure, which delivers energy through the 4-mm tip electrode of an ablation catheter positioned at the right AV junction and a large back plate (unipolar mode), failed in both patients. As an accepted second step, high energy direct current (DC) ablation under general anesthesia was then performed in patient one. After two shocks of 200 J, complete AV block occurred, but complete recovery was noted 3 hours later. In a third session for patient 1 and in the first session for patient 2 (after 15 unsuccessful unipolar right-sided RF applications), a second ablation catheter was introduced via the femoral artery on the left side of the His bundle area under the aortic valves. Energy was then delivered in a bipolar fashion between the tip electrodes of the right-sided and the left-sided catheter. Complete and permanent AV block (follow-up: 3 and 1 months) was created within 4 and 1.5 seconds, respectively, in each patient. No complication was encountered and echocardiograms and blood levels of cardiac enzymes were all normal after the procedures. This new approach, after further evaluation, may represent a useful additional step in the strategy of AV node ablation and could be applied before high energy DC shock when the standard RF procedure is unsuccessful.

The efficacy of oral sotalol in preventing sustained ventricular tachycardia induction by invasive electrophysiological testing was assessed in 22 patients (60 +/- 9 years) with prior myocardial infarction. Programmed stimulation consisted of two basic drives followed by up to three extrastimuli at two right ventricular sites. At baseline, sustained monomorphic ventricular tachycardia was inducible in all patients. With sotalol (360 +/- 172 mg/day), it was no longer inducible in 10 patients; in 12 others, it remained inducible and its cycle length was only minimally prolonged (322 +/- 42 to 345 +/- 44 msec, p less than 0.05). Sotalol markedly prolonged sinus cycle length, uncorrected QT interval, and right ventricular effective and functional refractory periods, but had little effect on ventricular conduction time either in sinus rhythm or with right ventricular pacing. There was no significant difference in drug dose or in electrophysiologic effect of drug that related to efficacy, nor was there any correlation between drug-induced prolongation of ventricular tachycardia cycle length and its effects. Six patients received oral sotalol over the long term without spontaneous recurrence of ventricular tachycardia (follow-up: 23 +/- 18 months). These results demonstrate that sotalol is effective (45%) against sustained ventricular tachycardia induction at moderate doses and is well tolerated over a long term in the setting of remote myocardial infarction. However, its electrophysiologic effects as measured at invasive testing are not predictive of efficacy against ventricular tachycardia induction.

Holter monitoring, electrocardiographic (ECG) signal-averaging, body surface potential mapping (BSPM) for PQRST isoarea maps, and electrophysiologic study (EPS) were performed in 100 patients with syncope. Coronary artery disease (CAD) was found in 46 patients and other heart disease was found in 19. EPS was diagnostic in 44 patients, while Holter monitoring suggested a diagnosis in only 21 patients. Abnormal BSPM was frequently seen (56%), especially in CAD (70%), or with inducible ventricular tachycardia (VT) (87%). Late potentials were recorded in 13 patients with CAD; five had inducible VT. In seven other patients with VT, they were either absent or bundle branch block (BBB) was found. Thirteen deaths (three sudden) occurred in our series. EPS-guided therapy resulted in a low rate of total cardiac death. In conclusion, EPS had a higher diagnostic yield than Holter monitoring regardless of cardiac pathology. ECG signal-averaging was useful in predicting VT only in patients with CAD without BBB. BSPM was abnormal in most patients with cardiac disease, but poorly predicted VT.

The effects of procainamide were studied in a model of atrial flutter around the tricuspid valve in seven open chest, chloralose-anesthetized dogs (31 +/- 3 kg). A Y-shaped incision in the intercaval area extending to the right atrial appendage was made and five bipolar electrodes were sutured on the atrial epicardium around the tricuspid valve. Reentry tachycardia was induced in the absence and presence of drug by burst pacing. Procainamide (15 mg/kg bolus followed by 0.075 mg/kg/min infusion) produced stable plasma levels (38 +/- 9 microM) during the study. At a pacing cycle length of 200 msec, mean (+/- SD) diastolic threshold at the five sites increased from 1.6 +/- 1.5 to 2.0 +/- 1.7 mA and mean atrial effective refractory period from 125 +/- 9 to 140 +/- 16 msec on drug (P less than 0.05). Procainamide prolonged the cycle length of atrial flutter from 144 +/- 10 to 160 +/- 13 msec and slowed conduction velocity during atrial flutter around the tricuspid valve from 73 +/- 6 to 66 +/- 6 cm/sec (P less than 0.05). A reset response curve was determined by introducing premature stimuli during atrial flutter. Procainamide prolonged effective refractory period during atrial flutter from 101 +/- 13 to 116 +/- 17 msec but did not change the duration of the excitable gap (38 +/- 9 vs 40 +/- 18 msec). Although the reset response curve was predominantly increasing, in six of seven experiments there was present a flat portion at long coupling intervals approaching the atrial flutter cycle length that comprised 23% +/- 10% of the excitable gap.(ABSTRACT TRUNCATED AT 250 WORDS)

An antitachycardia pulse generator, the Intermedics Intertach 262-12 was implanted in 16 patients (14 patients with supraventricular tachycardia of various origins and two patients with recurrent ventricular tachycardia), who were not responsive to various antiarrhythmic drug regimens. The follow-up was from 6-49 months (mean 30.9 +/- 13.8). Five patients had a follow-up of over 3 years. The device was used in all patients. One patient with ventricular tachycardia died from a nonarrhythmic cause. Loss of responsiveness to burst pacing was observed in 1/14 patients with supraventricular tachycardia and nontolerance of antitachycardia pacing in one patient. Overall clinical success of pacing was observed in 13/16 patients = 81%. The pacemaker proved to be a versatile system with reliable tachycardia detection and termination functions.

The efficacy of propafenone in preventing induction of ventricular tachycardia was evaluated in 25 consecutive patients (mean age 62 +/- 8 years) with remote myocardial infarction who underwent programmed electrical stimulation for ventricular arrhythmia using up to three extra-stimuli after basic drive at the right ventricular apex. In nine patients (Group A), propafenone prevented induction of sustained ventricular tachycardia (noninducible in four, nonsustained [less than 30 s] in five). In the other 16 patients (Group B), sustained ventricular tachycardia was still inducible; in 11 of the 16, the tachycardia configuration was unchanged but the cycle length was significantly longer (431 +/- 99 versus 284 +/- 44 ms, p less than 0.001). Propafenone did not significantly affect either sinus cycle length or AH and HV intervals. However, it prolonged QRS duration during sinus rhythm equally in both groups of patients. With ventricular pacing, propafenone also prolonged right ventricular effective and functional refractory periods and surface QRS duration. There was greater lengthening of the paced surface QRS duration when drug therapy was ineffective (for example, +35 +/- 12 ms in Group A versus +69 +/- 23 ms in Group B at a basic drive of 400 ms, p less than 0.01). Drug-induced prolongation of a paced QRS complex greater than 40 ms had a 94% positive predictive value for drug failure to prevent induction of ventricular tachycardia. Drug-induced percent prolongation of ventricular tachycardia cycle length in Group B did not correlate well with percent QRS prolongation.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of class la antiarrhythmic drugs (procainamide, quinidine) on the right ventricular effective refractory period (VERP) and intraventricular conduction time were assessed during serial invasive electrophysiologic studies for sustained monomorphic ventricular tachycardia (VT). In 47 patients with remote myocardial infarction, sustained VT was inducible by up to two extrastimuli after the basic drive at one of two basic cycle lengths at the right ventricular apex. With oral drug administration, sustained VT was no longer inducible (group I) in 27 patients but remained inducible (group II) in 20 with the same protocol. Class la drugs prolonged the VERP in both groups, but there was greater lengthening when drugs were effective (e.g., +32 +/- 14 msec in group I vs +12 +/- 19 msec in group II; p less than 0.005, basic cycle length 600 to 700 msec). Prolongation of the VERP by greater than 30 msec had an 88% positive predictive value for prevention of sustained VT induction. In all except one patient in group I, drugs prolonged the VERP such that the coupling intervals that had resulted in sustained VT induction under control conditions were no longer attainable. In contrast, conduction time through the ventricle (surface QRS duration) in sinus rhythm and during right ventricular pacing was prolonged similarly regardless of efficacy (e.g., +33 +/- 21 msec vs +27 +/- 27 msec at a cycle length of 400 msec). The presence of similar plasma levels of drug did not imply equivalent prolongation of the VERP in the two groups. These results suggest that greater prolongation of the VERP by oral procainamide or quinidine correlates with drug efficacy against VT induction and is a better predictor of drug effect than achievement of a "therapeutic plasma level."

The Intermedics Intertach 262-12 tachycardia reversion pulse generator was implanted in 14 patients (six male, eight female, mean age at implantation 45 +/- 16 years) with recurrent symptomatic tachycardias. Six patients had atrioventricular (AV) nodal reentrant tachycardia, three patients had orthodromic tachycardia with Wolff-Parkinson-White syndrome, two had circus movement tachycardia via a concealed bypass tract, two had ventricular tachycardia, one patient had atrial flutter. Mean duration of symptoms before implantation was 8 +/- 4 years and mean number of antiarrhythmic drug trials was 3.5 +/- 1. The primary tachycardia response made consisted of autodecremental pacing in one patient, burst pacing in two patients, and adaptive scanning of the initial delay or burst cycle length in eleven patients. The secondary tachycardia response mode consisted of autodecremental pacing in four patients, burst pacing in three patients and burst scanning in four patients. Tachycardia response was automatic in all but one patient with ventricular tachycardia. During a follow-up period of 30.5 +/- 10.6 months, one patient with ventricular tachycardia died from a nonarrhythmic cause. Reinterventions were necessary due to electrode fracture in one patient and due to pacemaker software defect in another one. Two patients underwent surgical cure of their arrhythmia: one patient with atrial flutter and one patient with AV nodal reentry tachycardia, 24 months and 11 months postpacemaker implantation, respectively. Four patients required digitalis to prevent pacing induced atrial fibrillation. Other proarrhythmic effects were not encountered. The pacemaker proved to be a versatile system with reliable tachycardia detection and termination functions. It provided a valuable adjunctive therapy in these selected patients.

A case of vasovagal syncope in an otherwise healthy 74-year-old woman is described. Attempts to prevent symptoms with ventricular and atrioventricular sequential temporary pacing (documented by continuous monitoring of heart rate and intra-arterial recording of blood pressure during spontaneous episodes) proved inadequate. However, the addition of a beta-blocker to permanent DDD pacing was clinically successful in markedly diminishing symptoms. The mechanisms of action of this treatment modality is discussed.

We compared the effects of a therapeutic concentration of disopyramide with those of quinidine and lidocaine on the action potential characteristics and on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential in the same normal Purkinje fiber in which constant impalement was maintained for more than 7 h. All the drugs depressed the steady-state upstroke velocity in the following order of magnitude: quinidine greater than disopyramide greater than lidocaine. Both lidocaine and disopyramide shifted the normalized steady-state curve to more negative membrane potentials indicating a greater depression of upstroke velocity at lower membrane potentials. Quinidine did not shift this curve. Lidocaine abbreviated all phases of repolarization while both disopyramide and quinidine shortened the plateau phase and lengthened the terminal phase of the action potential. The results suggest that the actions of disopyramide on upstroke velocity resemble those of lidocaine, while its effects on action potential duration resemble those of quinidine. The actions of this drug are therefore more complex than previously assumed.

The electrophysiologic effects of intravenous propafenone were studied in 15 consecutive patients with accessory pathways. Thirteen patients had sustained orthodromic supraventricular tachycardia induced during baseline study, and two patients needed isoproterenol to render it sustained. In all except one patient, propafenone, 2 mg/kg given intravenously over a 10-minute period, was successful in converting the arrhythmia to sinus rhythm. Atrial fibrillation was inducible in 10 patients before propafenone, but was no longer inducible in seven of these patients after the drug. The HV interval (23 +/- 20 to 41 +/- 25 msec) and the anterograde (310 +/- 96 to 509 +/- 145 msec) and retrograde (256 +/- 30 to 334 +/- 105 msec) effective refractory periods of the bypass tract were all significantly prolonged after the drug. The pacing cycle length that produced conduction block over the bypass tract anterogradely (319 +/- 126 to 446 +/- 150 msec) and retrogradely (272 +/- 25 to 360 +/- 97 msec) was also increased. During orthodromic tachycardia, propafenone increased conduction time in both the anterograde and retrograde limbs of the tachycardia. Tachycardia terminated in the retrograde limb in 64% of the patients. We conclude that propafenone is very effective in terminating orthodromic tachycardia when given intravenously and that it should be considered in patients initially seen with atrial fibrillation and short refractory periods.