Lipid topology and physical properties of the outer mitochondrial membrane of the yeast, Saccharomyces cerevisiae.

The outer membrane of yeast mitochondria was studied with respect to its lipid composition, phospholipid topology and membrane fluidity. This membrane is characterized by a high phospholipid to protein ratio (1.20). Like other yeast cellular membranes the outer mitochondrial membrane contains predominantly phosphatidylcholine (44% of total phospholipids), phosphatidylethanolamine (34%) and phosphatidylinositol (14%). Cardiolipin, the characteristic phospholipid of the inner mitochondrial membrane (13% of total phospholipids) is present in the outer membrane only to a moderate extent (5%). The ergosterol to phospholipid ratio is higher in the inner (7.0 wt%) as compared to the outer membrane (2.1 wt.%). Attempts to study phospholipid asymmetry by selective degradation of phospholipids of the outer leaflet of the outer mitochondrial membrane failed, because isolated right-side-out vesicles of this membrane became leaky upon treatment with phospholipases. Selective removal of phospholipids of the outer leaflet with the aid of phospholipid transfer proteins and chemical modification with trinitrobenzenesulfonic acid on the other hand, gave satisfactory results. Phosphatidylcholine and phosphatidylinositol are more or less evenly distributed between the two sides of the outer mitochondrial membrane, whereas the majority of phosphatidylethanolamine is oriented towards the intermembrane space. The fluidity of mitochondrial membranes was determined by measuring fluorescence anisotropy using diphenylhexatriene (DPH) as a probe. The lower anisotropy of DPH in the outer as compared to the inner membrane, which is an indication for an increased lipid mobility in the outer membrane, was attributed to the higher phospholipid to protein and the lower ergosterol to phospholipid ratio. The data presented here show, that the outer mitochondrial membrane, in spite of its close contact to the inner membrane, is distinct not only with respect to its protein pattern, but also with respect to its lipid composition and physical membrane properties.

Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy.

BACKGROUND: Conventional activation mapping is difficult without inducible, stable ventricular tachycardia (VT). METHODS AND RESULTS: We evaluated 16 patients with drug refractory, unimorphic, unmappable VT. Nine patients had ischemic and 7 had nonischemic cardiomyopathy. All patients had implantable defibrillators and had experienced 6 to 55 VT episodes during the month before treatment. Patients underwent bipolar catheter mapping during baseline rhythm. The amount of endocardium with an abnormal electrogram amplitude was estimated using fluoroscopy in 3 patients and a magnetic mapping system (CARTO) in 13 patients. For the magnetic mapping, normal endocardium was defined by an amplitude >1.5 mV; this measurement was based on sinus rhythm maps in 6 patients who did not have structural heart disease. Radiofrequency point lesions extended linearly from the "dense scar," which had a voltage amplitude <0.5 mV, to anatomic boundaries or normal endocardium. To limit radiofrequency applications, 12-lead ECG during VT and pacemapping guided placement of linear lesions. No new antiarrhythmic drug therapy was added. The amount of endocardium demonstrating an abnormal electrogram amplitude ranged from 25 to 127 cm(2). A total of 8 to 87 radiofrequency lesions (mean, 55) produced a median of 4 linear lesions that had an average length of 3.9 cm (range, 1.4 to 9. 4 cm). Twelve patients (75%) have been free of VT during 3 to 36 months of follow-up (median, 8 months); 4 patients had VT episodes at 1, 3, 9, and 13 months, respectively. Only one of these patient had frequent VT. CONCLUSIONS: Radiofrequency linear endocardial lesions extending from the dense scar to the normal myocardium or anatomic boundary seem effective in controlling unmappable VT.

The variable contribution of functional and anatomic barriers in human ventricular tachycardia: an analysis with resetting from two sites.

OBJECTIVES: This study sought to investigate the influence of stimulation site on the properties of the circuit in ventricular tachycardia. BACKGROUND: A fully excitable gap can be demonstrated in most human ventricular tachycardias. This requires the presence of an arc of block so that the entire circuit can recover from refractoriness within the period of the cycle length. Resetting characterizes the conduction properties of the tissue within the ventricular tachycardia circuit. Previous studies have not investigated the possibility of site-dependent differences in the resetting response. METHODS: Resetting was performed from the right ventricular apex and outflow tract in 23 patients. Two characteristics of the resetting response were analyzed: 1) the total duration of the flat portion, and 2) the slope of the increasing portion. RESULTS: A flat portion of the resetting response was observed in 18 tachycardias; in 8 of the 18, there was a significant site-dependent difference (> or = 40 ms) in the duration of the flat portion. A significant site-dependent difference in the slope of the increasing portion of the resetting curve was seen in 6 of 22 tachycardias. In all, a stimulation site-dependent change in at least one characteristic of the resetting response was seen in 12 (52%) of the 23 tachycardias. CONCLUSIONS: A stimulation site-dependent change in the flat portion of the resetting response is compatible with an arc of block that is at least partially functional in nature. A change in the slope of the increasing portion is compatible with either partially functional circuit barriers or variation in properties of conduction and refractoriness at different locations within the circuit, or both. These observations suggest that a spectrum of circuit properties may exist in humans, with a variable contribution of anatomic and functional characteristics.

Postoperative lead-related complications in patients with nonthoracotomy defibrillation lead systems.

OBJECTIVES: This study sought to document postoperative complications attributable to nonthoracotomy defibrillation lead systems in a large cohort. BACKGROUND: The incidence of postoperative complications specifically associated with nonthoracotomy defibrillation lead systems is unknown. METHODS: Postoperative lead-related complications were evaluated in 170 patients with a nonthoracotomy defibrillation lead system who were followed up for a mean (+/- SD) of 17 +/- 12 months. Each system incorporated one or more intravascular leads. In 117 patients (69%), the system incorporated a subcutaneous defibrillation patch. All implantations were performed in an operating room by cardiothoracic surgeons. Defibrillation thresholds were measured at implantation, before hospital discharge (mean 3 +/- 2 days) and at 4 to 18 weeks after implantation. Patients were evaluated every 2 to 3 months after implantation or as indicated by clinical exigency. RESULTS: Twenty-seven patients (15.9%) were diagnosed with a lead-related complication that either extended the initial hospital period or led to a second hospital admission. Complications included endocardial lead or subcutaneous defibrillation patch dislodgment in eight patients (4.7%), which was diagnosed between 2 and 345 days after implantation; endocardial or subcutaneous patch lead fracture in six (3.5%), which was diagnosed between 53 and 600 days after implantation; subcutaneous patch mesh fracture in one, which was diagnosed at 150 days after implantation; subclavian vein thrombosis in three (1.8%), which was diagnosed at 2 to 50 days after implantation; and unacceptably elevated defibrillation threshold (within 5 J of maximal device output) in nine (5.3%), which was documented at one of the two postimplantation evaluations in eight patients or at the time of failure to terminate a spontaneous ventricular tachycardia in one. Seventeen of the 27 patients required reoperation for correction of their complication. In addition, system infection requiring complete explantation occurred in seven other patients (4.1%) at an interval from implantation ranging from 14 to 120 days. CONCLUSIONS: Postoperative complications related to a nonthoracotomy defibrillation lead system were common and frequently required reoperation for correction. The rate of system explantation due to infection was also significant. Postoperative defibrillation testing and vigilant outpatient follow-up evaluation are necessary to ensure normal lead function.

Conduction block in the inferior vena caval-tricuspid valve isthmus: association with outcome of radiofrequency ablation of type I atrial flutter.

OBJECTIVES: We sought to 1) correlate conduction block in the isthmus of the right atrium between the inferior vena cava and the tricuspid annulus with the efficacy of catheter ablation of type I atrial flutter, and 2) characterize the effects of ablative lesions on the properties of isthmus conduction. BACKGROUND: There are few data on the mechanism of persistent suppression of recurrence of atrial flutter by catheter ablation. METHODS: Thirty-five patients with type I atrial flutter underwent catheter mapping and ablation. Radiofrequency lesions were applied in the isthmus. Transisthmus conduction before and after the lesions was assessed during atrial pacing in sinus rhythm from the medial and lateral margins of the isthmus at cycle lengths of 600, 400 and 300 ms and the native flutter cycle length. Isthmus conduction block was defined using multipolar recording techniques. There were three treatment groups: group 1 = radiofrequency energy applied during flutter, until termination (n = 14); group 2 = radiofrequency energy applied during atrial pacing in sinus rhythm from the proximal coronary sinus at a cycle length of 600 ms, until isthmus conduction block was observed (n = 14); and group 3 = radiofrequency energy applied until an initial flutter termination, after which further energy was applied during atrial pacing in sinus rhythm until isthmus conduction block was observed (n = 7). RESULTS: In group 1, after the initial flutter termination, isthmus conduction block was observed in 9 of the 14 patients. In each of these nine patients, flutter could not be reinitiated. In each of the remaining five patients, after the initial flutter termination, isthmus conduction was intact and atrial flutter could be reinitiated. Ultimately, successful ablation in each of these patients was also associated with isthmus conduction block. In groups 2 and 3, isthmus conduction block was achieved during radiofrequency energy application, and flutter could not subsequently be reinitiated. Before achieving conduction block, marked conduction slowing or intermittent block, or both, was observed in some patients. In some patients, isthmus conduction block was pacing rate dependent. In addition, recovery from conduction block was common in the laboratory and had a variable time course. At a mean follow-up interval of 10 months (range 1 to 21), the actuarial incidence of freedom from type I flutter was 80% (recurrence in three patients at 7 to 15 months). CONCLUSIONS: Isthmus conduction block is associated with flutter ablation success. Conduction slowing or intermittent block, or both, in the isthmus can occur before achieving persistent block. Recovery of conduction after achieving block is common. Follow-up has revealed a low rate of flutter recurrence after achieving isthmus conduction block, whether the block was achieved in conjunction with termination of flutter.

Narrowing of the superior vena cava-right atrium junction during radiofrequency catheter ablation for inappropriate sinus tachycardia: analysis with intracardiac echocardiography.

OBJECTIVES: The study explored the potential for tissue swelling and venous occlusion during radiofrequency (RF) catheter ablation procedures using intracardiac echocardiography (ICE). BACKGROUND: Transient superior vena cava occlusion has been reported following catheter ablation procedures for inappropriate sinus tachycardia (IST). Presumably, venous occlusion could occur owing to thrombus formation or tissue swelling with resultant narrowing of the superior vena cava-right atrial (SVC-RA) junction. METHODS: Intracardiac echocardiography (9 MHz) was used to guide ablation catheter position and for continuous monitoring during RF application in 13 ablation procedures in 10 patients with IST. The SVC-RA junction was measured prior to and following ablation. Successful ablation was marked by abrupt reduction in the sinus rate and a change to a superiorly directed p-wave axis. RESULTS: Eleven of 13 procedures were successful, requiring 29 +/- 20 RF lesions. Prior to the delivery of RF lesions, the SVC-RA junction measured 16.4 +/- 2.9 mm. With RF delivery, local and circumferential swelling was observed, causing progressive reduction in the diameter of the SVC-RA junction to 12.6 +/- 3.3 mm (24% reduction, p = 0.0001). A reduction in SVC-RA orifice diameter of > or = 30% compared to baseline was observed in five patients. CONCLUSIONS: The delivery of multiple RF ablation lesions, often necessary for cure of IST, can cause considerable atrial swelling and resultant narrowing of the SVC-RA junction. Smaller venous structures, such as the coronary sinus and the pulmonary veins, would also be expected to be vulnerable to this complication. Thus, ICE imaging may be helpful in preventing excessive tissue swelling leading to venous occlusion during catheter ablation procedures.

Repetitive monomorphic tachycardia from the left ventricular outflow tract: electrocardiographic patterns consistent with a left ventricular site of origin.

OBJECTIVES: This study sought to characterize the electrocardiographic patterns predictive of left ventricular sites of origin of repetitive monomorphic ventricular tachycardia (RMVT). BACKGROUND: RMVT typically arises from the right ventricular outflow tract (RVOT) in patients without structural heart disease. The incidence of left ventricular sites of origin in this syndrome is unknown. METHODS: Detailed endocardial mapping of the RVOT was performed in 33 consecutive patients with RMVT during attempted radiofrequency ablation. Left ventricular mapping was also performed if pace maps obtained from the RVOT did not reproduce the configuration of the induced tachycardia. RESULTS: Pace maps identical in configuration to the induced tachycardia were obtained from the RVOT in 29 of 33 patients. Application of radiofrequency energy at sites guided by pace mapping resulted in elimination of RMVT in 24 (83%) of 29 patients. In four patients (12%), pace maps obtained from the RVOT did not match the induced tachycardia. All four patients had a QRS configuration during RMVT with precordial R wave transitions at or before lead V2. In two patients, RMVT was mapped to the mediosuperior aspect of the mitral valve annulus, near the left fibrous trigone; catheter ablation at that site was successful in both. In two patients, RMVT was mapped to the basal aspect of the superior left ventricular septum. Catheter ablation was not attempted because His bundle deflections were recorded from this site during sinus rhythm. CONCLUSIONS: RMVT can arise from the outflow tract of both the right and left ventricles. RMVTs with a precordial R wave transition at or before lead V2 are consistent with a left ventricular origin.

Characterization of the excitable gap in human type I atrial flutter.

OBJECTIVES: We sought to characterize the excitable gap of the reentrant circuit in atrial flutter. BACKGROUND: The electrophysiologic substrate of typical atrial flutter has not been well characterized. Specifically, it is not known whether the properties of the tricuspid valve isthmus differ from those of the remainder of the circuit. METHODS: Resetting was performed from two sites within the circuit: proximal (site A) and distal (site B) to the isthmus in 14 patients with type I atrial flutter. Resetting response patterns and the location where interval-dependent conduction slowing occurred were assessed. RESULTS: Some duration of a flat resetting response (mean +/- SD 40.1 +/- 20.9 ms, 16 +/- 8% of the cycle length) was observed in 13 of 14 patients; 1 patient had a purely increasing response. During the increasing portion of the resetting curve, interval-dependent conduction delay most commonly occurred in the isthmus. In most cases, the resetting response was similar at both sites. In three patients, the resetting response differed significantly between the two sites; this finding suggests that paced beats may transiently change conduction within the circuit or the circuit path, or both. CONCLUSIONS: Some duration of a flat resetting response was observed in most cases of type I atrial flutter, signifying a fully excitable gap in all portions of the circuit. The isthmus represents the portion of the circuit most vulnerable to interval-dependent conduction delay at short coupling intervals.

Comparison of initial detection and redetection of ventricular fibrillation in a transvenous defibrillator system with automatic gain control.

OBJECTIVES: The purpose of this study was to prospectively evaluate postshock redetection of ventricular fibrillation by a system that coupled an implantable cardioverter-defibrillator with an automatic gain control sense amplifier and a transvenous lead system. BACKGROUND: Redetection of ventricular fibrillation after an unsuccessful first shock has not been systematically evaluated. Previous studies have suggested that sensing performance of some lead systems may be adversely affected by the delivery of subthreshold shocks. METHODS: The time required for both initial detection and redetection of ventricular fibrillation was compared in 22 patients. These times were estimated by subtracting the capacitor charge time from the total event time. RESULTS: A total of 113 successful and 57 unsuccessful initial shocks were delivered during induced ventricular fibrillation. The mean +/- SD initial time to detection of ventricular fibrillation was 5.5 +/- 1.7 s (range 2.4 to 10.8); the time to redetection ranged from 1.5 to 18.5 s (mean 4.5 +/- 2.8, p = NS vs. detection time). Abnormal redetection episodes, defined as a redetection time > 10.2 s (i.e., > 2 SD above the mean redetection time), were observed in 4 (18%) of 22 patients. CONCLUSIONS: Redetection of ventricular fibrillation after a subthreshold first shock may be delayed. Device testing with intentional delivery of subthreshold shocks to verify successful postshock redetection of ventricular fibrillation should be performed routinely in all patients.

Efficacy and safety of catheter ablation in octogenarians.

OBJECTIVES: To determine whether catheter ablation is safe and effective in patients over the age of 80. BACKGROUND: There is a tendency to withhold invasive therapy in the elderly until it has been proven safe and effective. METHODS: Over a two-year period from February 1, 1996 to February 1, 1998, 695 consecutive patients underwent 744 catheter ablation procedures of supraventricular and ventricular arrhythmias. These patients were divided into three groups based on age: > or =80 years, 60 to 79 years and <60 years. Acute ablation success, using standard criteria and complication rates for these three groups were determined. RESULTS: There were 37 patients > or =80 years, 275 patients 60 to 79 years and 383 patients <60 years old. The overall acute ablation success rate for the entire group was 95% with no difference in rates among the three groups (97%, > or =80 years; 94%, 60-79 years; 95%, <60 years). The percentage of patients undergoing His bundle ablation was greatest in the > or =80-year-old group (43% vs. 19% vs. 2%, p < 0.01), and the percentage of patients undergoing accessory pathway ablation was greatest in the <60-year-old patients (0% vs. 4% vs. 25%, p < 0.01). The overall complication rate for the entire group was 2.6%, and there was only one major/life-threatening complication. There was no difference in complication rates among the groups (0%, > or =80 years; 2.2%, 60 to 79 years; 3.1%, <60 years). Based on the sample size, the 95% confidence interval is 0% to 7.8% for an adverse event in the octogenarian. CONCLUSIONS: Catheter ablative therapy for the arrhythmias attempted in the very elderly appears to be effective with low risk. Ablation results appear to be comparable with those noted in younger patients.

Usefulness of the delta HA interval to accurately distinguish atrioventricular nodal reentry from orthodromic septal bypass tract tachycardias.

Surface electrocardiographic criteria may be inadequate to distinguish some cases of atrioventricular (AV) nodal reentrant supraventricular tachycardia (SVT) from those with orthodromic SVT incorporating a posterior septal bypass tract (orthodromic SVT) because of similarities in P-wave morphology and timing during SVT. Invasive electrophysiologic studies may occasionally leave uncertainty in the correct diagnosis, using currently accepted criteria. A new criterion for distinguishing these 2 forms of SVT was therefore devised and tested based on differences in the sequence of activation of the His bundle and atrium during SVT and ventricular pacing. Eighty-four patients underwent invasive electrophysiologic studies (60 with proved AV nodal SVT, 24 with proved orthodromic SVT), during which His to atrial (HA) intervals were measured during SVT as well as ventricular pacing at the same rate. The newly devised criterion, the delta HA interval (HApace-HAsvt) was found to accurately distinguish AV nodal SVT (delta HA greater than 0 ms) from orthodromic SVT (delta HA less than -27 ms). An intermediate value of delta HA = -10 ms was chosen which had a 100% sensitivity, specificity and predictive accuracy in differentiating the 2 forms of SVT. A clear retrograde His potential during ventricular pacing, which is essential for application of this criterion, was present in 78 of 84 (93%) cases. In summary, patients with delta HA intervals greater than -10 ms separate AV nodal reentry from orthodromic SVT incorporating a septal bypass tract, and no overlap exists between the 2 groups. This criterion may be useful in differentiating the mechanism of SVT in cases in which distinction is not possible by other methods.

Coupling intervals of ventricular extrastimuli causing resetting of sustained ventricular tachycardia secondary to coronary artery disease: relation to subsequent termination.

Single and double ventricular extrastimuli (VE) delivered during sustained, uniform ventricular tachycardia (VT) are able to reset or terminate the tachycardia. The relation between the coupling intervals of single and double VE resetting VT and those terminating it was examined in 80 uniform, morphologically distinct VT occurring in 52 patients. Of the 80 tachycardias receiving single VE, 41 were reset and 8 terminated. The corrected coupling interval of single VE first causing resetting was 0.81 +/- 0.08 compared with 0.66 +/- 0.06 for termination (p less than 0.001). Forty-two tachycardias received double VE with 33 being reset and 13 terminating. The corrected coupling interval of double VE at which resetting was first seen was 0.86 +/- 0.08 compared with 0.73 +/- 0.05 for termination (p less than 0.001). If the longest corrected coupling interval causing resetting was greater than or equal to 0.75, then 7 of 34 tachycardias terminated with single VE and 13 of 31 terminated with double VE compared with only 1 of 46 terminating with single VE and 0 of 10 with double VE if resetting was not observed by a corrected coupling interval of 0.75 (p less than 0.01 and p less than 0.02, respectively). If the longest corrected coupling interval at which resetting occurred was greater than or equal to 0.75, the predictive value for VT termination was 21% with single VE and 42% with double VE compared with only 2% with single VE and none with double VE if resetting was not observed by this corrected coupling interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of the intraoperative defibrillation threshold to successful postoperative defibrillation with an automatic implantable cardioverter defibrillator.

To determine the relation between the intraoperative defibrillation threshold and successful postoperative termination of induced ventricular fibrillation (VF) with the automatic implantable cardioverter defibrillator (AICD), 33 patients who underwent AICD implantation were studied. The defibrillation threshold, determined after at least 10 seconds of VF, was 5 J in 2, 10 J in 6, 15 J in 10, 20 J in 10 and 25 J in 5 patients. The AICD energy rating on the first discharge was 28 +/- 1.8 J. Defibrillation of induced VF was demonstrated postoperatively in 29 of 33 (88%) patients. The AICD terminated VF postoperatively in all 18 patients with a defibrillation threshold less than or equal to 15 J. Only 11 of the 15 (73%) patients with a defibrillation threshold greater than or equal to 20 J (p less than 0.04) had VF terminated postoperatively. In all 4 patients in whom the AICD failed to terminate induced VF, the energy difference between the AICD rating and the defibrillation threshold was less than or equal to 10 J. Among the 14 patients with a difference of less than or equal to 10 J between the AICD energy rating and the defibrillation threshold, there were no significant differences between the 4 patients with and the 10 without successful VF termination with respect to the duration of VF induced postoperatively or the AICD lead system. In summary, failure to terminate VF with the AICD is not uncommon (27%) when the defibrillation threshold approaches the energy delivering capacity of the AICD.(ABSTRACT TRUNCATED AT 250 WORDS)

Imaging technique and clinical utility for electrophysiologic procedures of lower frequency (9 MHz) intracardiac echocardiography.

Intracardiac echocardiography using a new 9-MHz ultrasound catheter was performed in 30 patients undergoing percutaneous catheter mapping and radiofrequency ablation of a tachyarrhythmia, because the imaging capabilities with this intracardiac echocardiographic catheter permit detailed identification of normal and abnormal cardiac anatomy with improved imaging depth. Intracardiac echocardiography is of significant clinical utility during ablation for guiding interatrial septal puncture, assessing placement and contact of mapping/ablation catheters, monitoring ablation lesion morphologic changes, and diagnosing procedure-related complications.

Efficacy of radiofrequency catheter ablation for ventricular tachycardia in healed myocardial infarction.

Radiofrequency catheter ablation has been useful in the treatment of ventricular tachycardia (VT) in selected patients with healed myocardial infarction. Previous studies have demonstrated success rates of 60% to 96% for targeted VT morphologies; however, these studies included patients only after they have had successful mapping procedures and have received radiofrequency lesions. All patients referred for VT ablation from July 1992 to November 1996 were included in this analysis on an intention-to-treat basis. Ninety-five procedures were performed in 66 patients for 77 distinct presentations with tolerated, sustained VT. Fifty-five procedures were successful (58%) and 40 procedures failed. Reasons for procedural failure included failed radiofrequency application despite adequate VT mapping (21 procedures), no tolerated VT induced (12), and aborted procedures due to complications or technical difficulties (7). Fifty-five patients (71%) eventually had a successful VT ablation, although 10 required > 1 procedure. This analysis revealed factors that contribute to failure of VT ablation procedures in addition to inadequate mapping and lesion formation. Procedural difficulties, particularly the inability to induce tolerated VT, frequently prevent successful catheter ablation in patients who present with tolerated, sustained VT.

Circadian variation of ventricular arrhythmia recurrences after cardioverter-defibrillator implantation in patients with healed myocardial infarcts.

Past studies using Holter monitoring and retrospective reviews of death certificates have documented peak occurrence of sudden death and nonsustained ventricular tachycardia (VT) in the morning hours. We used the Ventritex Cadence device (Ventritex, Sunnyvale, California) which documents the date and time of all stored arrhythmias leading to device therapy to evaluate the circadian pattern of sustained ventricular arrhythmia recurrence. Mean follow-up after defibrillator implantation was 628 +/- 285 days. All 390 patients had at least 1 episode (range 1 to 43) of sustained VT documented from analysis of the stored electrograms associated with an arrhythmia event. Stored electrograms were available for review and analysis in 3,041 device detections; 349 stored events were excluded because they did not fulfill the diagnostic criteria for VT or failed to document the onset of the ventricular arrhythmia at the beginning of the recorded event of the arrhythmia episode. Criteria for the diagnosis of VT or ventricular fibrillation were met in 2,692 arrhythmia episodes occurring in 390 patients. There was circadian variation for ventricular arrhythmia recurrence for the whole patient group with the data fit to the sinusoidal density function: f(t) = 126 - 51 x cos (-57 + 2 pi t/24) - 25 x sin (63 + 2 pi t/12) (p < 0.0001). Ventricular arrhythmia occurrence rate was lowest between 2:00 and 3:00 A.M., and highest between 10:00 and 11:00 A.M. In addition, the same circadian pattern was demonstrated regardless of patient age, gender, left ventricular ejection fraction (< 35% or > or = 35%), and VT cycle length (< 300 or > or = 300 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Procainamide-induced slowing of ventricular tachycardia with insights from analysis of resetting response patterns.

To investigate the mechanism of slowing of the rate of ventricular tachycardias (VTs) by procainamide, resetting response patterns were characterized in 24 VTs in 22 patients. All patients had coronary artery disease and inducible sustained VT during procainamide therapy. Only tachycardias with the same surface QRS morphology before and after procainamide were studied: all were slowed by procainamide. The mean cycle length was 292 +/- 61 ms before and 374 +/- 61 ms after procainamide (p less than 0.05). The mean effective refractory period, measured at the right ventricle, was 241 +/- 21 ms before and 261 +/- 24 ms after procainamide (p less than 0.05). During procainamide therapy, single and double extrastimuli were delivered during VT and resetting response patterns identified. Patterns were characterized as flat, increasing or flat plus increasing. Resetting was seen in 17 (71%) of these VTs and resetting response patterns were identified in 16 (94%) of these. The resetting response pattern was flat in 7, flat plus increasing in 5 and increasing in 4. The finding of some flat portion at the end of resetting response patterns in 12 VTs after procainamide indicates that the reentrant impulse conducts through fully recovered tissue within the circuit. It suggests that procainamide slowed these VTs by slowing conduction velocity in fully recovered tissue due to sodium channel blockade and not by prolongation of action potentials and refractory periods.

Late potentials in an ovine model of acute transmural myocardial infarction.

The development of slow conduction during the first hours of acute transmural myocardial infarction (ATMI) was studied by signal-averaged electrocardiograms (SAE) in 19 adult anesthetized sheep. SAEs were recorded before and after intravenous infusions of lidocaine and bretylium were begun and 10, 30, and 60 min after ATMI produced by ligation of the left anterior descending and second diagonal coronary arteries. Four sheep died promptly of ventricular tachyarrhythmias; two others developed sustained ventricular arrhythmias, which precluded additional data. Biphasic changes in QRS duration, root mean square voltage of the terminal 40 ms of the QRS complex, and duration of terminal low-amplitude (less than 30 microV) signal were observed. Peak changes in conduction occurred 30 min after infarction and regressed toward baseline thereafter. At 30 min, all animals developed late potentials, which were defined as signals that exceeded both after-drug QRS duration and duration of terminal low-amplitude signal less than 30 microV by more than two standard deviations. At 60 min, only 3 of 13 (23%) animals had late potentials. Conduction is slowest 30 min after ATMI in sheep but may not be related to development of ventricular arrhythmias. In five of six sheep (83%), ventricular arrhythmias occurred within 15 min of infarction before peak slowing was observed by SAE.

Intracardiac echocardiography (9 MHz) in humans: methods, imaging views and clinical utility.

A new low-frequency (9 MHz, 9 Fr) catheter-based ultrasound (US) transducer has been designed that allows greater depth of cardiac imaging. To demonstrate the imaging capability and clinical utility, intracardiac echocardiography (ICE) using this lower frequency catheter was performed in 56 patients undergoing invasive electrophysiological procedures. Cardiac imaging and monitoring were performed with the catheter transducer placed in the superior vena cava (SVC), right atrium (RA) and/or right ventricle (RV). In all patients, ICE identified distinct endocardial structures with excellent resolution and detail, including the crista terminalis, RA appendage, caval and coronary sinus orifices, fossa ovalis, pulmonary vein orifices, ascending aorta and its root, pulmonary artery, RV and all cardiac valves. The left atrium and ventricle were imaged with the transducer at the limbus fossa ovalis of the interatrial septum and in the RV, respectively. ICE was important in identifying known or unanticipated aberrant anatomy in 11 patients (variant Eustachian valve, atrial septal aneurysm and defect, lipomatous hypertrophy, Ebstein's anomaly, ventricular septal defect, tetralogy of Fallot, transposition of the great arteries, disrupted chordae tendinae and pericardial effusion) or in detecting procedure-related abnormalities (narrowing of SVC-RA junction orifice or pulmonary venous lumen, atrial thrombus, interatrial communication). In patients with inappropriate sinus tachycardia, ICE was the primary ablation catheter-guidance technique for sinus node modification. With ICE monitoring, the evolution of lesion morphology with the three imaging features including swelling, dimpling and crater formation was observed. In all patients, ICE was contributory to the mapping and ablation process by guiding catheters to anatomically distinct sites and/or assessing stability of the electrode-endocardial contact. ICE was also used to successfully guide atrial septal puncture (n = 9) or RA basket catheter placement (n = 4). Thus, ICE with a new 9-MHz catheter-based transducer has better imaging capability with a greater depth. Normal and abnormal cardiac anatomy can be readily identified. ICE proved useful during electrophysiological mapping and ablation procedures for guiding interatrial septal puncture, assessing placement and contact of mapping and ablation catheters, monitoring ablation lesion morphological changes, and instantly diagnosing cardiac complications.

Accuracy of fluoroscopic localization of the Crista terminalis documented by intracardiac echocardiography.

The crista terminalis is an important anatomic target for ablation of atrial arrhythmias. We determined the accuracy of catheter placement guided by fluoroscopy alone when directed to 24 sites along the crista terminalis in 6 patients. The sites selected included the most medial superior, most lateral superior, mid lateral, and most inferolateral sites along the crista terminalis in each patient. These sites were selected because of their recognized importance in sinus node and/or atrial tachycardia ablation and the importance of avoiding caval structures when targeting the most superior and/or inferior right atrium. The position of the catheter tip was documented using a catheter based ultrasound transducer in the right atrium or vena cava. The operator was blinded to the intracardiac echocardiographic (ICE) results until reviewing the images after the procedure in each patient. The catheter tip, guided by fluoroscopy alone, was identified by ICE to be within the right atrium and within 1cm of the crista terminalis at only 10 of the 24 sites (42%). Importantly, when targeting the most superior and inferior sites along the crista terminalis, the catheter tip, guided by fluoroscopy, was noted to be adjacent to the venous junction with the right atrium but actually located in the superior or inferior vena cava at 5 of the 18 such sites. The catheter was positioned appropriately (within 1 cm of the crista and within the right atrium) guided by fluoroscopy alone when targeting 1 of the 12 sites in the first 3 patients versus 9 of 12 sites in the last 3 patients, p<0.05. In conclusion, it appears that using fluoroscopic guidance alone: 1) localization of the crista terminalis is frequently inaccurate and 2) catheter positioning in the superior/inferior vena cava is commonly noted when targeting very superior and inferior sites along the crista terminalis. A learning curve, assisted by review of ICE recordings after each procedure, appears to improve the accuracy of catheter placement by fluoroscopy alone but still does not result in uniform success. ICE appears to facilitate and ensure accurate targeting of specific anatomic sites along the crista terminalis and thus may serve as an important adjunctive imaging technique in electrophysiology.