Showing papers in "Journal of Cardiovascular Electrophysiology in 2003"

Heart rate variability: back to the beginning.

Abstract: Heart rate and blood pressure represent the integrated response to ongoing and dynamic changes in autonomic, cortical, environmental, and other inputs. The relatively “coarse” quantification of heart rate and blood pressure nevertheless is invaluable in predicting and treating cardiovascular disease and in understanding disease mechanisms. As part of an approach to better understanding cardiovascular physiology and possibly provide even earlier predictions of risk and progression of cardiovascular disease, a myriad of approaches have been taken to dissect out the finer points of blood pressure and heart rate regulation, and to understand the mechanisms and implications of the shortand long-term dynamics that regulate their change. Unprecedented software sophistication and computer processing power, and the availability of relatively simple measures for evaluating RR interval, have made analyses of changes in heart rate, or heart rate variability, widely accessible to physiologists and clinicians. For practical purposes, heart rate variability may be understood as the magnitude of “sway” or flexibility that is spontaneously inherent in cardiac rate control. Much as the sway inherent in a bridge or skyscraper will impart resilience to external stress, the magnitude of variability in the beat-to-beat changes of RR interval are generally a sign of sound cardiovascular health. This is demonstrated by visual inspection of the ECG of a young fit individual compared to that of someone with severe heart failure. The slower heart rate and marked sinus arrhythmia in a young athlete contrast markedly with the tachycardia and relatively fixed RR interval in a patient with heart failure in sinus rhythm. Approaches to study and quantify the variability of heart rate include measurements in the time and frequency domains, and application of these methods to short-term (several minutes) and long-term (24-hour Holter) measurements.1-7 Frequency-domain analysis seeks to quantify the magnitude of RR fluctuations at specific frequencies, whereas time-domain analysis quantifies the absolute variability of RR interval, measured, for example, as standard deviation, over a given period of time, varying from 5 minutes or up to 24 hours or longer. Other approaches include variations on these themes, such as wavelet transform analysis8 and fractal scaling.9,10 In patients with overt cardiovascular disease, abnormalities in heart rate variability, perhaps reflecting autonomic dysregulation or baroreflex impairment, may be linked to

Circadian profile of cardiac autonomic nervous modulation in healthy subjects: differing effects of aging and gender on heart rate variability.

Abstract: Introduction: Although heart rate variability (HRV) has been established as a tool to study cardiac autonomic activity, almost no data are available on the circadian patterns of HRV in healthy subjects aged 20 to 70 years. Methods and Results: We investigated 166 healthy volunteers (81 women and 85 men; age 42 ± 15 years, range 20–70) without evidence of cardiac disease. Time-domain HRV parameters were determined from 24-hour Holter monitoring and calculated as hourly mean values and mean 24-hour values. All volunteers were fully mobile, awoke around 7 A.M., and had 6 to 8 hours of sleep. Circadian profiles of vagus-associated HRV parameters revealed a marked day-night pattern, with a peak at nighttime and a plateau at daytime. The characteristic nocturnal peak and the day-night amplitude diminished with aging by decade. Estimates of overall HRV (geometric triangular index [TI], SD of NN intervals [SDNN]) and long-term components of HRV (SD of the averages of NN intervals for all 5-min segments [SDANN]) were low at nighttime and increased in the morning hours. There was a significant decline of 24-hour values of all HRV parameters (P < 0.001) and a strong negative correlation (P < 0.001) with increasing age. Mean 24-hour RR interval (P < 0.001), SDNN, mean SD of NN intervals for all 5-minute intervals (SDNNi), and SDANN (all P < 0.01) were significantly higher in men. Younger men also exhibited significantly higher values for vagus-associated parameters (root mean square successive difference [rMSSD], P < 0.05; SDNNi, P < 0.01); however, gender differences diminished with increasing age. Conclusion: Normal aging is associated with a constant decline of cardiac vagal modulation due to a significant decrease of nocturnal parasympathetic activity. The significant gender-related difference of HRV decreases with aging. These findings emphasize the need to determine age-, gender-, and nycthemeral-dependent normal ranges for HRV assessment. (J Cardiovasc Electrophysiol, Vol. 14, pp. 791-799, August 2003)

Rotors and spiral waves in atrial fibrillation.

Abstract: Despite many years of research, the mechanisms of atrial fibrillation (AF) are still poorly understood, and we currently are unable to adequately treat most patients with AF. Recently, the demonstration in both human and animal studies that the pulmonary veins (PVs) and the posterior left atrial (LA) wall play a substantial role in triggering and in driving the fibrillatory activity has opened new avenues for research into the mechanisms of initiation and maintenance AF at many levels of integration. This article focuses on recent studies at the whole-heart level that support the hypothesis that maintenance of AF, whether paroxysmal or persistent, may depend on the periodic activity of a small number of rotors in the posterior LA wall-PV region. These rotors activate the atria at exceedingly high frequencies and result in fibrillatory conduction. Recent clinical studies involving either segmental PV isolation or circumferential PV ablation support this view. Such encouraging results suggest that collaboration between basic and clinical electrophysiologists will lead to a more precise understanding of the manner in which rotors stabilize in the PV-LA junction, which should open new doors for the development of innovative approaches for the prevention, diagnosis, and treatment of AF.

Implantable cardioverter defibrillator in high-risk long QT syndrome patients.

Abstract: ICD in High-Risk LQTS Patients. Introduction: Implantable cardioverter defibrillators (ICDs) are increasingly being used in high-risk long QT syndrome (LQTS) patients, but there are limited data regarding clinical experience with this therapeutic modality. The aim of this study is to describe the clinical characteristics of 125 LQTS patients treated with ICDs compared with LQTS patients having similar risk indications who were not treated with ICDs. Methods and Results: Among 125 LQTS patients with ICDs, there were 54 cardiac arrest survivors, 19 patients who had ICDs implanted due to recurrent syncope despite beta-blocker therapy, and 52 patients with ICDs implanted due to other reasons, including syncope and LQTS-related sudden death in a close family member. Patients with cardiac arrest and those with recurrent syncope despite beta-blocker therapy (n = 73) were compared to 161 LQTS patients who had similar indications (89 cardiac arrest and 72 recurrent syncope despite beta-blocker therapy) but did not receive ICDs. Total mortality was the endpoint of the analysis. There was 1 (1.3%) death in 73 ICD patients followed an average of 3 years, whereas there were 26 deaths (16%) in non-ICD patients during mean 8-year follow-up (P = 0.07 from log rank test from Kaplan-Meier curves). Conclusion: ICDs provide an important therapeutic option to prevent sudden arrhythmic death in highrisk LQTS patients. A long-term prospective study is needed to determine the benefit of this therapeutic modality in LQTS patients. (J Cardiovasc Electrophysiol, Vol. 14, pp. 337-341, April 2003)

Development and Validation of an ECG Algorithm for Identifying the Optimal Ablation Site for Idiopathic Ventricular Outflow Tract Tachycardia

Abstract: Introduction: Idiopathic ventricular outflow tract tachycardia or premature ventricular contractions (OT-VTs) can originate from several different sites in the outflow tract, including the left ventricular (LV) endocardium and epicardium. The aims of this study were (1) to develop an ECG algorithm to predict the origin of OT-VT and (2) to test prospectively the accuracy of the algorithm. Methods and Results: An algorithm was developed by correlating the 12-lead ECG findings with the catheter ablation site in 80 patients with OT-VT. The ECG characteristics of the QRS complex during the arrhythmia were analyzed. The catheter sites were verified by multiplane fluoroscopy. The outflow tract was classified into six subdivisions: right ventricular (RV) septum, RV free wall, RV near the His-bundle region, LV endocardium, left sinus of Valsalva (LSV), and LV epicardium remote from the LSV. An OT-VT originating from the LV epicardium remote from the LSV was defined as an OT-VT in which the earliest ventricular activation was recorded at the LSV and radiofrequency ablation from the LSV failed. This algorithm subsequently was tested prospectively in 88 patients. Overall sensitivity was 88% and specificity was 95%. The positive and negative predictive values were 88% and 96%, respectively. Conclusion: We describe a new ECG algorithm having a high sensitivity and specificity to identify the optimal ablation site for idiopathic ventricular outflow tachycardia or premature ventricular contractions. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1280-1286, December 2003)

Electrocardiographic patterns of superior right ventricular outflow tract tachycardias: distinguishing septal and free-wall sites of origin.

Abstract: ECG Patterns of RVOT Tachycardias. Introduction: The superior right ventricular outflow tract (RVOT) septum and free wall are common locations of origin for outflow tract ventricular tachycardias (VT). We hypothesized that (1) unique ECG morphologies of pace maps from septal and free-wall sites in the superior RVOT could be identified using magnetic electroanatomic mapping for accurate anatomical localization; and (2) this ECG information could help facilitate pace mapping and accurate VT localization. Methods and Results: In 14 patients with structurally normal hearts who were undergoing ablation for outflow tract VT, a detailed magnetic electroanatomic map of RVOT was constructed in sinus rhythm, then pace mapping was performed from anterior, mid, and posterior sites along the septum and free wall of the superior RVOT. Pace maps were analyzed for ECG morphologies in limb leads and transition patterns in precordial leads. Monophasic R waves in inferior leads for septal sites were taller (1.7 ± 0.4 mVvs1.1 ± 0.3 mV; P < 0.01) and narrower (158 ± 21 msecvs168 ± 15 msec; P < 0.01) compared with free-wall sites; lacked “notching” (28.6% vs 95.2%;P < 0.05); and showed early precordial transition (by lead V4; 78.6% vs 4.8%;P < 0.05). A positive R wave in lead I also distinguished posterior from anterior septal and free-wall sites. Based on QRS morphology in limb leads and precordial transition pattern (early vs late), in a retrospective analysis, a blinded reviewer was able to accurately localize the site of origin of clinical arrhythmia (the successful ablation site on the magnetic electroanatomic map) in 25 of 28 patients (90%) with superior RVOT VT. Conclusion: Pace maps in the superior RVOT region manifest site-dependent ECG morphologies that can help in differentiating free-wall from septal locations and posterior from anterior locations. Despite overlap in QRS amplitude and duration, in the majority of patients a combination of ECG features can serve as a useful template in predicting accurately the site of origin of clinical arrhythmias arising from this region.

Anatomy of the pulmonary veins in patients with atrial fibrillation and effects of segmental ostial ablation analyzed by computed tomography.

Abstract: Pulmonary Vein Anatomy. Introduction: The anatomic arrangement of pulmonary veins (PVs) is variable. No prior studies have quantitatively analyzed the effects of segmental ostial ablation on the PVs. The aim of this study was to determine the effect of segmental ostial radiofrequency ablation on PV anatomy in patients with atrial fibrillation (AF). Methods and Results: Three-dimensional models of the PVs were constructed from computed tomographic (CT) scans in 58 patients with AF undergoing segmental ostial ablation to isolate the PVs and in 10 control subjects without a history of AF. CT scans were repeated approximately 4 months later. PV and left atrial dimensions were measured with digital calipers. Four separate PV ostia were present in 47 subjects; 3 ostia were present in 2 subjects; and 5 ostia were present in 9 subjects. The superior PVs had a larger ostium than the inferior PVs. Patients with AF had a larger left atrial area between the PV ostia and larger ostial diameters than the controls. Segmental ostial ablation resulted in a 1.5 ± 3.2 mm narrowing of the ostial diameter. A 28% to 61% focal stenosis was present 7.6 ± 2.2 mm from the ostium in 3% of 128 isolated PVs. There were no instances of symptomatic PV stenosis during a mean follow-up of 245 ± 105 days. Conclusion: CT of the PVs allows identification of anatomic variants prior to catheter ablation procedures. Segmental ostial ablation results in a significant but small reduction in ostial diameter. Focal stenosis occurs infrequently and is attributable to delivery of radiofrequency energy within the PV. (J Cardiovasc

Right ventricular outflow versus apical pacing in pacemaker patients with congestive heart failure and atrial fibrillation.

Abstract: Introduction: Prior studies suggest that right ventricular apical (RVA) pacing has deleterious effects. Whether the right ventricular outflow tract (RVOT) is a more optimal site for permanent pacing in patients with congestive heart failure (CHF) has not been established. Methods and Results: We conducted a randomized, cross-over trial to determine whether quality of life (QOL) is better after 3 months of RVOT than RVA pacing in 103 pacemaker recipients with CHF, left ventricular (LV) systolic dysfunction (LV ejection fraction ≤ 40%), and chronic atrial fibrillation (AF). An additional aim was to compare dual-site (RVOT + RVA, 31-ms delay) with single-site RVA and RVOT pacing. QRS duration was shorter during RVOT (167 ± 45 ms) and dual-site (149 ± 19 ms) than RVA pacing (180 ± 58 ms, P < 0.0001). At 6 months, the RVOT group had higher (P = 0.01) role-emotional QOL subscale scores than the RVA group. At 9 months, there were no significant differences in QOL scores between RVOT and RVA groups. Comparing RVOT to RVA pacing within the same patient, mental health subscale scores were better (P = 0.03) during RVOT pacing. After 9 months of follow-up, LVEF was higher (P = 0.04) in those assigned to RVA rather than RVOT pacing between months 6 and 9. After 3 months of dual-site RV pacing, physical functioning was worse (P = 0.04) than during RVA pacing, mental health was worse (P = 0.02) than during RVOT pacing, and New York Heart Association (NYHA) functional class was slightly better (P = 0.03) than during RVOT pacing. There were no other significant differences between RVA, RVOT and dual-site RV pacing in QOL scores, NYHA class, distance walked in 6 minutes, LV ejection fraction, or mitral regurgitation. Conclusion: In patients with CHF, LV dysfunction, and chronic AF, RVOT and dual-site RV pacing shorten QRS duration but after 3 months do not consistently improve QOL or other clinical outcomes compared with RVA pacing. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1180-1186, November 2003)

Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart

Abstract: Introduction: The prognostic value of electrophysiologic studies in individuals with the syndrome of right bundle branch block and ST segment elevation in precordial leads V1 to V3 (Brugada syndrome) remains controversial. Our previous data from 252 individuals with the syndrome suggested that programmed ventricular stimulation had a good overall accuracy to predict events. However, studies from independent investigators questioned our results. We report here the largest population with Brugada syndrome ever studied by programmed electrical stimulation of the heart. Methods and Results: Four hundred forty-three individuals with an ECG diagnostic of Brugada syndrome were studied by programmed electrical stimulation of the heart. The diagnosis was made because of the classic ECG showing a coved-type ST segment elevation in precordial leads V1 to V3. Of the 443 individuals, 180 had developed spontaneous symptoms (syncope or aborted sudden cardiac death) and 263 were asymptomatic at the time the diagnosis was made. The ventricular stimulation protocol included a minimum of two basic pacing cycle lengths with two ventricular premature beats from the right ventricular apex. A sustained ventricular arrhythmia was induced in 217 cases (49%). Symptomatic patients were more frequently inducible [126/180 (70%)] than asymptomatic individuals [91/263 (34%);P = 0.0001 ]. Males were more frequently inducible than females (54% vs 32%,P < 0.0001). Inducible individuals had a longer HV interval than noninducible patients (50 ± 12 msecvs46 ± 10 msec, P < 0.002). HV interval and number of premature beats needed to induce VF were not related to outcome. Inducibility was statistically a powerful predictor of arrhythmic events during follow-up. Sixty of 217 inducible patients (28%) had spontaneous ventricular fibrillation compared with 5 of 221 noninducible patients(2%; P = 0.0001). Conclusion: Inducibility of sustained ventricular arrhythmias during programmed ventricular stimulation of the heart is a good predictor of outcome in Brugada syndrome.(J Cardiovasc Electrophysiol, Vol. 14, pp. 455-457, May 2003)

Incidence and location of focal atrial fibrillation triggers in patients undergoing repeat pulmonary vein isolation: implications for ablation strategies.

Abstract: Introduction: The etiology of atrial fibrillation (AF) recurrences after pulmonary vein (PV) isolation is not well described. The aim of this study was to examine the reason for recurrent AF in patients undergoing a repeat attempt at AF trigger ablation. Methods and Results: Patients with recurrent AF more than 1 month after ablation returned for repeat mapping and ablation. A circular mapping catheter was advanced to each previously targeted PV ostium to determine if the PV was still electrically isolated. Ectopy then was provoked with isoproterenol (up to 20 μg/min), burst pacing, and pacing into AF followed by cardioversion. The location of ectopy triggering atrial premature depolarizations (APDs) or AF was noted. Of 226 patients who underwent ablation of AF triggers, 34 (8 women and 26 men; age 56 ± 10 years) with recurrent AF returned for a repeat procedure 207 ± 183 days after the first procedure. There were 84 previously completely isolated PVs in these 34 patients. Thirty-three (39%) of 84 previously isolated PVs were still completely isolated at the time of the second procedure. Fifty-one PVs (61%) had evidence of recovered PV potentials. Fifty triggers of APDs and AF (n = 30) or APDs only (n = 20) were identified in these 34 patients. The majority of triggers [27/50 (54%)] originated from previously targeted PVs. Sixteen triggers [16/50 (32%)] originated from previously nontargeted PVs. Conclusion: The majority of AF recurrences originate from previously isolated PVs. One third of recurrent triggers originated from PVs that were not targeted during the initial ablation session. Although empiric isolation of all PVs may reduce recurrences, strategies to ensure ostial PV isolation and to prevent recurrent PV conduction after ablation should have the greatest impact on reducing AF recurrence. (J Cardiovasc Electrophysiol, Vol. 14, pp. 685-690, July 2003)

Ambulatory electrocardiogram-based tracking of T wave alternans in postmyocardial infarction patients to assess risk of cardiac arrest or arrhythmic death.

Abstract: Introduction: This is the first study to assess T wave alternans (TWA) analyzed from routine ambulatory electrocardiograms (AECGs) to identify postmyocardial infarction (post-MI) patients at increased risk for arrhythmic events. Methods and Results: The new method of modified moving average (MMA) analysis was used to measure TWA magnitude in 24-hour AECGs from ATRAMI, a prospective study of 1,284 post-MI patients. Using a nested case-control approach, we defined cases as patients who experienced cardiac arrest due to documented ventricular fibrillation or arrhythmic death during the follow-up period of 21 ± 8 months. We analyzed 15 cases and 29 controls matched for sex, age, site of MI, left ventricular ejection fraction, thrombolysis, and beta-blockade therapy. TWA was reported as the maximum 15-second value at three predetermined times associated with cardiovascular stress: maximum heart rate, 8:00 A.M., and maximum ST segment deviation. TWA increased significantly from baseline in both leads at each time point (P ≪ 0.01) in cases and controls. TWA in V5 increased more in cases than controls during peak heart rate (P = 0.005) and at 8:00 A.M. (P = 0.02). A 4- to 7-fold higher odds of life-threatening arrhythmias was predicted by TWA level above the 75th percentile during maximum heart rate in leads V1 (odds ratio [OR] 4.2, 95% confidence interval [CI]: 1.1–16.3, P = 0.04) and V5 (OR 7.9, 95% CI: 1.9–33.1, P = 0.005). TWA at 8:00 A.M. also predicted risk in leads V1 (OR = 5.0, 95% CI: 1.2–20.5, P = 0.02) and V5 (OR = 4.2, 95% CI: 1.1–16.3, P = 0.04). Conclusion: TWA measurement from routine 24-hour AECGs is a promising approach for risk stratification for cardiac arrest and arrhythmic death in relatively low-risk post-MI patients. (J Cardiovasc Electrophysiol, Vol. 14, pp. 705-711, July 2003)

Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation.

Abstract: Introduction: Depolarizations similar to those from the sinus node have been documented from the pulmonary veins after isolation procedures. We assessed the hypothesis that sinus node-like tissue is present in the pulmonary veins of humans. Methods and Results: Pulmonary vein tissue was obtained from five autopsies (four individuals with a history of atrial fibrillation and one without a history of atrial arrhythmias) and five transplant heart donors. Autopsy veins were fixed in formaldehyde and processed for light microscopy to identify areas having possible conductive-like tissue. Areas requiring additional study were extracted from paraffin blocks and reprocessed for electron microscopy. Donor specimens were fixed in formaldehyde for histologic sections and glutaraldehyde for electron microscopy. Myocardial cells with pale cytoplasm were identified by light microscopy in 4 of the 5 autopsy subjects. Electron microscopy confirmed the presence of P cells, transitional cells, and Purkinje cells in the pulmonary veins of these cases. Conclusion: Our report is the first to show the presence of P cells, transitional cells, and Purkinje cells in human pulmonary veins. Whether these cells are relevant in the genesis of atrial fibrillation requires further study. (J Cardiovasc Electrophysiol, Vol. 14, pp. 803-809, August 2003)

Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia.

Abstract: Introduction: The combined role of atrial septal lead location and atrial pacing algorithms in the prevention of atrial tachyarrhythmias (AT/AF), including both atrial fibrillation and flutter, is unknown. We tested the hypothesis that atrial prevention pacing algorithms could decrease AT/AF frequency in patients with atrial septal leads, bradycardia, and paroxysmal AT/AF. Methods and Results: A total of 298 patients (age 70 ± 10 years; 61% male) from 35 centers were implanted with a DDDRP pacing system including three AT/AF prevention pacing algorithms. Lead site was randomized at implant to right atrial septal or nonseptal. Patients were randomized 1 month postimplant to AT/AF prevention ON or OFF for 3 months and then crossed over for 3 months. Patients logged symptomatic AT/AF episodes via a manual activator. Prevention efficacy was evaluated based on intention-to-treat in 277 patients (138 septal) with complete follow-up. No changes in device-recorded AT/AF frequency or burden were observed with algorithms OFF versus ON or between patients randomized to septal versus nonseptal lead location. Analysis of other secondary outcomes revealed that AT/AF prevention pacing resulted in decreased atrial premature contractions in both the septal (1.9 [0.2–8.7] vs 3.3 [0.3–10.6]× 103/day; P < 0.01) and nonseptal groups (0.9 [0.2–3.3] vs 1.3 [0.3–5.5]× 103/day; P < 0.001). Patients with septal leads had fewer symptomatic AT/AF episodes ON versus OFF (1.4 ± 3.0 vs 2.5 ± 5.2/month, P = 0.01). Conclusion: The combination of three atrial prevention pacing algorithms did not decrease device classified atrial tachyarrhythmia frequency or burden during a 3-month cross-over period in bradycardic patients and septal or nonseptal atrial pacing leads. Prevention pacing was associated with decreased frequency of premature atrial contractions and with decreased symptomatic atrial tachyarrhythmia frequency in patients with atrial septal leads. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1189-1195, November 2003)

Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial

Abstract: Introduction: The implantable cardioverter defibrillator (ICD) is commonly used to treat patients with documented sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Arrhythmia recurrence rates in these patients are high, but which patients will receive a therapy and the forms of arrhythmia recurrence (VT or VF) are poorly understood. Methods and Results: The therapy delivered by the ICD was examined in 449 patients randomized to ICD therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. Events triggering ICD shocks or antitachycardia pacing (ATP) were reviewed for arrhythmia diagnosis, clinical symptoms, activity at the onset of the arrhythmia, and appropriateness and results of therapy. Both shock and ATP therapies were frequent by 2 years, with 68% of patients receiving some therapy or having an arrhythmic death. An appropriate shock was delivered in 53% of patients, and ATP was delivered in 68% of patients who had ATP activated. The first arrhythmia treated in follow-up was diagnosed as VT (63%), VF (13%), supraventricular tachycardia (18%), unknown arrhythmia (3%), or due to ICD malfunction or inappropriate sensing (3%). Acceleration of an arrhythmia by the ICD occurred in 8% of patients who received any therapy. No physical activity consistently preceded arrhythmias, nor did any single clinical factor predict the symptoms of the arrhythmia. Conclusion: Delivery of ICD therapy in AVID patients was common, primarily due to VT. Inappropriate ICD therapy occurred frequently. Use of ICD therapy as a surrogate endpoint for death in clinical trials should be avoided. (J Cardiovasc Electrophysiol, Vol. 14, pp. 940-948, September 2003)

Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery.

Abstract: Introduction: A congenital short QT interval constitutes a new primary electrical abnormality associated with syncope and/or sudden cardiac death. We report on the initial use of implantable cardioverter defibrillator (ICD) therapy in patients with inherited short QT interval and discuss sensing abnormalities and detection issues. Methods and Results: In five consecutive patients from two unrelated European families who had structurally normal hearts, excessively shortened QT intervals, and a strong positive family history of sudden cardiac death, ICDs were placed for primary and secondary prevention. Mean QT intervals were 252 ± 13 ms (QTc 287 ± 13 ms). Despite normal sensing behavior during intraoperative and postoperative device testing, 3 of 5 patients experienced inappropriate shock therapies for T wave oversensing 30 ± 26 days after implantation. Programming lower sensitivities and decay delays prevented further inappropriate discharges. Conclusion: The congenital short QT syndrome constitutes a new clinical entity with an increased risk for sudden cardiac death. Currently, ICD treatment is the only therapeutic option. In patients with short QT interval and implanted ICD, increased risk for inappropriate therapy is inherent due to the detection of short-coupled and prominent T waves. Careful testing of ICD function and adaptation of sensing levels and decay delays without sacrificing correct arrhythmia detection are essential. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1273-1277, December 2003)

Variable patterns of septal activation in patients with left bundle branch block and heart failure.

Abstract: Septal Activation in Patients with LBBB and Heart Failure.Introduction: Little is known about the septal activation pattern in patients with heart failure and left bundle branch block (LBBB-HF). Methods and Results: The right ventricular (RV) and left ventricular (LV) activation patterns of 12 patients (mean age 67 ± 11 years) with LBBB-HF and 5 patients (mean age 45 ± 14) with normal hearts were studied during sinus rhythm using a three-dimensional mapping system. The etiology of HF was myocardial infarction (n = 4) or idiopathic dilated cardiomyopathy (n = 8). In patients with LBBB-HF, endocardial activation usually started before the onset of the surface QRS complex on the RV free wall. Latest RV activation occurred in the basal region, and total RV activation time was longer than in patients with normal hearts. In patients with LBBB-HF, the left septum was activated via slowly conducting LBB or via right-to-left transseptal conduction. In both patients with LBBB-HF and those with normal hearts, latest LV activation occurred either in the posterior or posterolateral-basal region. Conduction velocity was slower in the peri-scar region, in patients with previous myocardial infarct and globally slow, in patients with idiopathic dilated cardiomyopathy. Conclusion: The two types of left septal activation observed in patients with LBBB-HF may have consequences for biventricular hemodynamic performance. Conduction slowing along the LV, regionally or globally, suggests a contribution outside the specific conduction system in the ECG pattern of LBBB. (J Cardiovasc Electrophysiol, Vol. 14, pp. 135-141, February 2003)

Magnetic resonance imaging findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia.

Abstract: Introduction: Magnet resonance imaging (MRI) findings in patients meeting Task Force criteria for the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) have not been systematically described. We report qualitative and quantitative MRI findings in ARVD using state-of-the-art MRI. Methods and Results: MRI was performed on 12 patients with ARVD who were prospectively diagnosed using the Task Force criteria. The imaging protocol included breath-hold double inversion recovery spin-echo and gradient-echo images. Ventricular volumes and dimensions were compared to 10 age- and sex-matched normal volunteers. High intramyocardial T1 signal similar to fat signal was observed in 9 (75%) of the 12 patients and in none of the controls. Right ventricular (RV) hypertrophy was seen in 5 (42%) patients, trabecular disarray in 7 (59%), and wall thinning in 3 (25%). Both the RV end-diastolic diameter and the outflow tract area were significantly higher in ARVD patients compared to controls (51.2 vs 43.2 mm,P < 0.01; and 14.5 vs9.3 cm2, P < 0.01, respectively). ARVD patients had a higher RV end-diastolic volume index and lower RV ejection fraction compared with controls (127.4 vs87.5, P < 0.01; and 41.6% vs 57%,P < 0.01, respectively). Conclusion: High intramyocardial T1 signal indicative of fat is seen in a high percentage (75%) of patients who meet the Task Force criteria for ARVD. Trabecular disarray is seen more frequently than wall thinning and aneurysms. RV dimensions and volumes differ significantly in ARVD compared to controls, indicating a role for quantitative evaluation in the diagnosis of ARVD.(J Cardiovasc Electrophysiol, Vol. 14, pp. 476-482, May 2003)

Pulmonary vein stenosis after catheter ablation for atrial fibrillation.

Abstract: Tree randomized trials (PIAF, AFFIRM, and RACE) 1-3 recently showed that rate control was not inferior compared to rhythm control for treatment of patients with atrial fibrillation (AF). However, it should be noted that frequent recurrences of AF and adverse effects of drugs decrease the potential benefits of rhythm control, prompting discontinuation of failed drugs in up to 40% of patients. 2 In addition, the beneficial effects of rhythm control may be nullified by life-threatening cardiovascular events. Such events may be related not to the rhythm but rather to severe adverse effects of antiarrhythmic drugs, especially if they are used in the long term. In this case, these trials emphasize the need for safer and more effective methods for maintaining sinus rhythm. The quest for better drugs and techniques to achieve this goal will, and should, continue in the future. The relative ineffectiveness of pharmacologic approaches to AF, the risks of antiarrhythmic treatment, and the growing recognition of deleterious AF health effects 4 have helped catalyze the development of curative nonpharmacologic approaches to maintenance of sinus rhythm. The management of AF has become more aggressive, with a shift toward nonpharmacologic therapies, including controlled destruction of the substrate generating and maintaining arrhythmia, so-called ablation therapy. 5-8 The important new discovery that some episodes of AF are initiated by rapid repetitive firing of atrial myocytes in muscle sleeves located in the pulmonary veins (PVs) has led to the use of catheter-based approaches to isolate these structures electrically, in some cases curing AF. 9-11 Mapping and selective ablation of these rapidly firing arrhythmogenic foci have the potential to cure AF. Although theoretically intriguing, the focal ablation approach is extremely arduous and is associated with prolonged procedure and fluoroscopy times, frequent need for second ablation, insufficient atrial ectopy, and development of a major complication—PV stenosis. 9 The incidence of this complication is unclear. PV stenosis has been reported in 20% of PVs treated with ablation. The risk of PV stenosis during long-term follow-up is not known. 12 As a typical complication of techniques delivering radiofrequency (RF) energy within PV tissue, PV stenosis can be partly explained by the anatomic and histologic characteristics of the junction between the pulmonary venous vasculature and the left atrium (LA). Myocardial sleeves are always found in the outer layer of PVs, with myocardial cells embed

Blockade of the inward rectifying potassium current terminates ventricular fibrillation in the guinea pig heart.

Abstract: Introduction: Stable high-frequency rotors sustain ventricular fibrillation (VF) in the guinea pig heart. We surmised that rotor stabilization in the left ventricle (LV) and fibrillatory conduction toward the right ventricle (RV) result from chamber-specific differences in functional expression of inward rectifier (Kir2.x) channels and unequal IK1 rectification in LV and RV myocytes. Accordingly, selective blockade of IK1 during VF should terminate VF. Methods and Results: Relative mRNA levels of Kir2.x channels were measured in LV and RV. In addition, LV(n = 21)and RV(n = 20)myocytes were superfused with BaCl2 (5–50 μmol/L) to study the effects on IK1. Potentiometric dye-fluorescence movies of VF were obtained in the presence of Ba2+(0–50 μmol/L)in 23 Langendorff-perfused hearts. Dominant frequencies (DFs) were determined by spectral analysis, and singularity points were counted in phase maps to assess VF organization. mRNA levels for Kir2.1 and Kir2.3 were significantly larger in LV than RV. Concurrently, outward IK1 was significantly larger in LV than RV myocytes. Ba2+ decreased IK1 in a dose-dependent manner (LV change > RV change). In baseline control VF, the fastest DF domain(28–40 Hz)was located on the anterior LV wall and a sharp LV-to-RV frequency gradient of21.2 ± 4.3 Hzwas present. Ba2+ significantly decreased both LV frequency and gradient, and it terminated VF in a dose-dependent manner. At 50 μmol/L, Ba2+ decreased the average number of wavebreaks (1.7 ± 0.9to0.8 ± 0.6 SP/sec · pixel, P < 0.05) and then terminated VF. Conclusion: The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics. (J Cardiovasc Electrophysiol, Vol. 14, pp. 621-631, June 2003)

The electrical restitution curve revisited: steep or flat slope--which is better?

Abstract: The electrical restitution curve (ERC) traditionally describes the recovery of action potential duration (APD) as a function of the interbeat interval or, more correctly, the diastolic interval (DI). Often overlooked in modeling studies, the normal ventricular ERC is triphasic, starting with a steep initial recovery at the shortest DIs, a transient decline, and a final asymptotic rise to a plateau phase reached at long DIs. Recent studies have proposed that it would be advantageous to lower the slope of the ERC by drug intervention, as this might reduce the potential for electrical alternans and ventricular fibrillation. This review discusses the pros and cons of a flat versus steep slope of the ERC and draws attention to mechanisms thatjustify the (physiologically) steep slope, rather than a flat slope, as a better design against arrhythmias. Five potential mechanisms are discussed, which allows for a different interpretation of the effect of the slope on arrhythmogenicity. The most important appears to be the physiologic rate adaptive shortening of APD that, by reciprocal lengthening of the DI, allows the subsequent APD to move more quickly from the steep initial ERC phase onto the flat phase. A less steep initial ERC phase would protract the transition toward more fully recovered APD and, in fact, may perpetuate electrical alternans. The triphasic ERC time course in normal myocardium cannot be explained by or fitted to single exponentials or single ion channel recovery kinetics. A simple tri-ionic model is suggested that may help explain the shape of the ERC at various repolarization levels and place APD recovery into perspective with intracellular calcium recycling and recovery of contractile force.

Safety and Efficacy of Cryoablation of Accessory Pathways Adjacent to the Normal Conduction System

Abstract: Introduction: Catheter ablation has become a routine treatment for patients with Wolff-Parkinson-White syndrome because of its low risk and high efficacy; however, radiofrequency ablation in the septum close to the AV node or His bundle still carries a definite risk for AV block Cryoenergy catheter ablation has recently become available This technique has specific features, such as the ability to create reversible loss of function to predict the effects of ablation (ice mapping) and the adherence of the catheter tip to the endocardium with freezing, which avoids the risk for dislodgment Both of these characteristics may minimize the risk of complications The aim of this study was to analyze the effectiveness and safety of catheter cryoablation in 20 patients with para-Hisian or midseptal accessory pathways (AP) Methods and Results: Eleven patients with para-Hisian and 9 patients with midseptal AP underwent catheter cryoablation Ice mapping at −30°C was performed to ascertain the disappearance of AP conduction and the absence of impairment of AV nodal conduction If the expected result was obtained, cryoablation was performed by lowering the temperature to −75°C for 4 minutes in order to create a permanent lesion Cryoablation was successful in all patients using a mean of 12 ± 04 applications Recurrences occurred in 4 patients (20%) who underwent a second successful cryoablation session No complications were observed Conclusion: Cryoablation appears to be a safe and effective technique for ablation of APs close to the AV node or His bundle because of the ability to predict the acute effects of ablation with ice mapping before creation of an irreversible lesion (J Cardiovasc Electrophysiol, Vol 14, pp 825-829, August 2003)

Study of unipolar electrogram morphology in a computer model of atrial fibrillation.

Abstract: Keywords: LTS1 Reference LTS-ARTICLE-2003-004doi:10.1046/j.1540.8167.90308.xView record in Web of Science Record created on 2006-06-14, modified on 2016-08-08

ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs.

Abstract: Introduction: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. Methods and Results: Voltage clamp experiments demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by69%± 20%in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in α-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline:1.0 ± 0.2 nM: 6/12 vs 0/12; 7.7 ± 0.6 nM: 7/13 vs 1/12; and69.2 ± 5.4 nM: 9/13 vs 1/13. The preventive effect of ZP123 on reentrant VT was closely correlated to reversal of functional, unidirectional conduction block. ZP123 did not affect effective refractory period, surface ECG parameters, mean arterial pressure, or infarct size. Conclusion: The stable AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT.(J Cardiovasc Electrophysiol, Vol. 14, pp. 510-520, May 2003)

Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a Swine model of myocardial infarction.

Abstract: Introduction: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac nerve density and contribute to the improved cardiac function is unclear. Methods and Results: Anterior wall myocardial infarction was created in 16 swine. One month later, 6 swine were given MSC and fresh bone marrow (BM) into infarcted myocardium (MSC group). Four swine were given fresh BM only (BM group), and 6 swine were given culture media (MI-only group). The swine were sacrificed 95.8 ± 3.5 days after MI. Six normal swine were used as control. Immunocytochemical staining was performed using antibodies against growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and three subtypes of tenascin (R, C, and X). Five fields per slide were counted for nerve density. The results show the following. (1) There were more GAP43-positive nerves in the MSC group than in the BM, MI-only, or Control group (P < 0.0001). TH staining showed higher nerve densities in the MSC group than in the MI-only (P < 0.01) or Control group (P < 0.0001) in the atria. (2) There were more sympathetic (TH-positive) nerves in myocardium distant from infarct than in the peri-infarct area (P < 0.05). (3) Optical intensity and color analyses showed significantly higher tenascin R and tenascin C expression in the MSC and BM groups than in the MI-only or Control group (P < 0.01). Conclusion: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac nerve sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection. (J Cardiovasc Electrophysiol, Vol. 14, pp. 841-848, August 2003)

Transvenous defibrillation leads: high incidence of failure during long-term follow-up.

Abstract: Implantable Defibrillator Lead Failure. Introduction: Patients with implantable cardioverter defibrillators (ICD) critically depend on correct functioning of their system. The aim of this study was to determine the incidence and clinical presentation of transvenous ICD lead failures during long-term follow-up. Methods and Results: The study group consisted of 261 consecutive patients who received Medtronic right ventricular polyurethane transvenous leads (models 6884, 6966, 6936) between 1990 and 1998 as part of an abdominal(n = 70)or pectoral(n = 191)ICD system. During mean follow-up of4.0 ± 2.6 years, 31 patients (12%) developed a lead-related sensing failure with oversensing of artifacts. All failures except two were compatible with an insulation defect and occurred late after ICD placement (6.0 ± 1.8 yearsafter implant). Lead survival decreased from 98% at 4-year follow-up to only 62% at 8-year follow-up. Lead survival was not related to patient age, sex, venous lead implantation route, or device implantation site. In 26 (87%) of 31 patients, a sensing defect resulted in inappropriate detection of ventricular fibrillation and subsequent delivery of3 ± 3(range 1–11) inappropriate shocks in 19 (61%) of 31 patients. Device interrogation showed artifacts classified as nonsustained ventricular tachycardia in 21 patients,40 ± 43 daysbefore clinically relevant failure of the system. One patient with a subclavian crush syndrome required resuscitation because of undersensing of true ventricular fibrillation. Conclusion: Transvenous polyurethane ICD leads showed a high rate of lead insulation failure late after implantation with frequent inappropriate shock deliveries. Close follow-up is mandatory in patients with these leads. Automated device control features with patient alert function integrated into new devices may contribute to early detection of lead failure.

How really rare are rare diseases?: the intriguing case of independent compound mutations in the long QT syndrome.

Abstract: Despite the explosion of interest in the long QT syndrome (LQTS) over the past decade, its prevalence remains unknown. LQTS almost always is referred to as a “rare disease,” although sometimes it is described as simply “infrequent.” In terms of quantification, the prevalence indicated more frequently is 1/10,000,1 but the limits range widely between 1/5,0002 and 1/20,000.3 These numbers, however, are based only on crude estimates and not on proper large prospective population studies. As occurs in research, a key finding shedding new light on the question of how rare LQTS is came from a serendipitous observation followed by a properly designed study. In the early days of molecular screening, different laboratories noted individual LQTS patients who possessed not just one but two different mutations on the LQTS genes.4,5 Because these mutations were different, consanguinity was not involved. We wondered whether these observations represented anecdotal events based on chance alone or actually represented the tip of the iceberg and underlined a more significant pattern of distribution of mutations located on genes encoding ion channels contributing to the control of ventricular repolarization. Accordingly, we attempted to quantify the phenomenon. After identifying a mutation in 130 consecutively genotyped probands, we continued molecular screening for all known LQTS genes. Genetic analysis was performed by singlestranded conformational polymorphism (SSCP) and DNA sequencing. A panel of 300 healthy subjects was used as the control group. Six probands (4.6%) were identified as compound heterozygous carriers of independent mutations on LQTS genes. These compound mutations involved all known genes: two probands had two independent KCNQ1 mutations, two had KCNQ1 + SCN5A mutations, one had KCNQ1 + HERG mutations, and one had HERG + SCN5A mutations. There were

Pulmonary vein stenosis by ostial irrigated-tip ablation: incidence, time course, and prediction.

Abstract: Monitoring and Prediction of PV Stenosis.Introduction: The incidence of pulmonary vein (PV) stenosis and its time course for ostial trigger elimination in paroxysmal atrial fibrillation (PAF) is uncertain. In addition, the clinical value of serial computed tomographic (CT) scanning of the PV ostia and the predictive value of energy requirements for radiofrequency ablation have yet to be established. Methods and Results: We performed irrigated-tip ablation in 37 patients with drug-resistant PAF. Serial spiral CT scans were taken prospectively in 34 patients the day before the procedure, at prehospital discharge, and at 3- and 6-month follow-up. Using a clock model, energy requirements were analyzed for every segment of the PV circumference. One hundred fifteen PVs were targeted in 57 procedures. Compared to baseline, 7 (6.08%) of 115 PV showed minor ( 90%) PV stenoses (1.73%) were detected with a mean follow-up of 275 ± 100 days. Luminal narrowing occurred most frequently in the left inferior PV (6/9 stenosed PV). Minor stenosed PVs showed their maximal luminal regression within the 3-month follow-up. Two of two PVs with narrowing >50% at 3 months progressed to high-grade stenosis. Analysis of delivered energy showed no significant correlation with the degree of stenosis. However, for the left inferior PV, more energy was applied in the superior segment of a stenotic PV (6697 ± 930 J vs 3555 ± 380 J, P = 0.005). Conclusion: Assessment of PV diameter by serial spiral CT scanning shows a low incidence of severe stenosis. The left inferior PV is at higher risk. Minor stenosed PV showed no progression after 3 months. Occurrence of stenosis tended to be related to the amount of energy delivered. (J Cardiovasc Electrophysiol, Vol. 14, pp. 158-164, February 2003)

Effects of acute atrial dilation on heterogeneity in conduction in the isolated rabbit heart.

Abstract: Introduction: Atrial dilation plays an important role in the development and persistence of atrial fibrillation (AF). The mechanisms by which atrial dilation increases the vulnerability to AF are not fully understood. Methods and Results: In 11 isolated rabbit hearts, the right atrium was acutely dilated by increasing the intra-atrial pressure from 2 to 9 and 14 cm H2O. A rectangular mapping array of 240 electrodes (spatial resolution 0.5 mm) was positioned on the free wall of the right atrium. The atrium was paced from four different sites at intervals of 240 and 125 msec. At normal atrial pressure (2 cm H2O), conduction was uniform in all directions with an anisotropy ratio between 1.5 and 1.7. Increasing the pressure to 9 cm H2O decreased the normalized conduction velocity during rapid pacing by 18%. The incidence of areas of slow conduction and conduction block increased from 6.6% and 1.6% to 10.2% and 3.3%. At 14 cm H2O, conduction velocity decreased by 31% and the percentage of slow conduction and block further increased to 11.5% and 6.6%(P < 0.001).The appearance of lines of intra-atrial block was largely dependent on the pacing site. Whereas during pacing at the cranial part of the crista terminalis no increase in conduction delays occurred, pacing from the low right atrium unmasked several lines of block oriented parallel to the major trabeculae and the crista terminalis. In an additional series of six hearts the left atrium also was mapped. The effect of dilation of the left atrium was comparable to that of the right atrium. Increasing the atrial pressure to 14 cm H2O increased the amount of intra-atrial conduction block threefold to fourfold. Conclusion: Acute atrial dilation results in slowing of conduction and an increase of the amount of intra-atrial conduction block. The increase in spatial heterogeneity in conduction was related to the anisotropic properties of the atrial wall.(J Cardiovasc Electrophysiol, Vol. 14, pp. 269-278, March 2003)

Site‐Specific Arrhythmogenesis in Patients with Brugada Syndrome

Abstract: Introduction: It has been believed that electrophysiologic abnormality of the epicardial region of the right ventricular free wall may play an important role in arrhythmogenesis of phase 2 reentry in Brugada syndrome, but clinical evidence of the occurrence of ventricular arrhythmias at the right ventricular free wall has not been evaluated. In this study, we evaluated the site-specific inducibility of ventricular fibrillation (VF) and the origin of spontaneous premature ventricular contractions (PVCs) in patients with Brugada syndrome. Methods and Results. Forty-five patients with Brugada-type ECG were enrolled in this study. Spontaneous PVCs were recorded in 9 patients. Programmed electrical stimulation (PES) was performed at the right ventricular apex (RVA), the free wall and septal region of the right ventricular outflow tract (RVOT), and the left ventricle (LV). The inducibility of PVT/VF was evaluated at each ventricular site, and the origin of PVC was determined by pace mapping. Sustained VF was induced in 17 patients. VF was induced in all 17 patients by PES at RVOT. Although PES at the septal region of the RVOT induced VF in only 5 patients (29%), PES at the free-wall region of the RVOT induced PVT/VF in 13 patients (76%). PES at RVA induced VF in only 2 patients (12%), and PES at LV failed to induce any arrhythmic events. Ventricular pace mapping showed that 64% of PVCs occurred at the free-wall region of the RVOT, 18% at the septal region of the RVOT, 9% at RVA, and 9% at LV. Conclusion: VF in patients with Brugada syndrome frequently is induced at the free-wall region of the RVOT area. The origin of PVC appears to be related to the site of PVT/VF induction by PES.(J Cardiovasc Electrophysiol, Vol. 14, pp. 373-379, April 2003)

Characterization of sustained atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure.

Abstract: Introduction: Atrial arrhythmias often complicate congestive heart failure (CHF). We characterized inducible atrial tachyarrhythmias and electrophysiologic alterations in dogs with CHF and atrial enlargement produced by rapid ventricular pacing. Methods and Results: Endocardial pacing leads were implanted in the right ventricle, right atrium, and coronary sinus in 18 dogs. The right ventricular lead was connected to an implanted pacemaker capable of rapid ventricular pacing. The atrial leads were used to perform electrophysiologic studies in conscious animals at baseline in all dogs, during CHF induced by rapid ventricular pacing at 235 beats/min in 15 dogs, and during recovery from CHF in 6 dogs. After20 ± 7 daysof rapid ventricular pacing, inducibility of sustained atrial tachycardia (cycle length120 ± 12 msec) was enhanced in dogs with CHF. Atrial tachycardia required a critical decrease in atrial burst pacing cycle length (≤130 msec) for induction and often could be terminated by overdrive pacing. Calcium antagonists (verapamil, flunarizine, ryanodine) terminated atrial tachycardia and suppressed inducibility. Effective refractory periods at 400- and 300-msec cycle lengths in the right atrium and coronary sinus were prolonged in dogs with CHF. Atrial cells from dogs with CHF had prolonged action potential durations and reduced resting potentials and delayed afterdepolarizations (DADs). Mitochondria from atrial tissue from dogs with CHF were enlarged and had internal cristae disorganization. Conclusions: CHF promotes inducibility of sustained atrial tachycardia. Based on the mode of tachycardia induction, responses to pacing and calcium antagonists, and presence of DADs, atrial tachycardia in this CHF model has a mechanism most consistent with DAD-induced triggered activity resulting from intracellular calcium overload.(J Cardiovasc Electrophysiol, Vol. 14, pp. 499-507, May 2003)