bluuebunny/crossref_metadata_2025 huggingface dataset:
Supraventricular Tachycardia‐Ventricular Tachycardia Discrimination Algorithms in Implantable Cardioverter Defibrillators: State‐of‐the‐Art Review
Authors: SWERDLOW CHARLES D.
Published: August 2003

SVT‐VT Discrimination Algorithms in ICDs. To reduce inappropriate therapy of supraventricular tachycardia (SVT), implantable cardioverter defibrillators (ICDs) include algorithms to discriminate ventricular tachycardia (VT) from SVT. Dual‐chamber algorithms analyze atrial and ventricular rates or AV relationship. They provide advantages over single‐chamber algorithms, but introduce new ways to detect SVT as VT inappropriately and to underdetect VT. Unlike pacemakers, dual‐chamber ICDs require accurate atrial sensing during high ventricular rates. A postventricular atrial blanking period prevents oversensing of far‐field R waves as atrial electrograms, but causes underdetection of atrial fibrillation during high ventricular rates. Tachycardias with 1:1 AV relationship and VT during atrial tachyarrhythmias present specific SVT‐VT discrimination problems. The first dual‐chamber algorithms performed comparably to single‐chamber algorithms. Present dual‐chamber algorithms correct some limitations of earlier versions.
Dissociation Between Coronary Sinus and Left Atrial Conduction in Patients with Atrial Fibrillation and Flutter
Authors: NDREPEPA GJIN , ZRENNER BERNHARD , SCHNEIDER MICHAEL A.E. , SCHREIECK JÜRGEN , KARCH MARTIN R. , SCHÖMIG ALBERT , SCHMITT CLAUS
Published: August 2003

Dissociation Between CS and LA Conduction.
Introduction: Coronary sinus (CS) recordings are routinely used during electrophysiologic studies for various supraventricular and ventricular arrhythmias with the understanding that they represent left atrial (LA) activity. However, the behavior of CS electrical activity during atrial arrhythmias has not drawn any special attention beyond standard considerations.

Methods and Results: The study population consisted of 9 patients (3 women; mean age 59 ± 11 years) with atrial fibrillation (AF) and atrial flutter (AFL) who developed dissociation of conduction between the CS and posterior LA during spontaneous AF and AFL. In all patients, the LA and the CS were mapped using a 64‐electrode basket catheter and a multipolar electrode catheter, respectively. The right atrium (RA) was mapped simultaneously using a 24‐polar electrode catheter (7 patients) or a 64‐electrode basket catheter (2 patients). Eight patients showed stable double potentials in CS recordings during AF (9 episodes) and AFL (3 episodes). During ongoing arrhythmias, the first row of potentials maintained a constant relationship with the RA activity, whereas the second row of potentials was discordant with the posterior wall of the LA in 7 patients and concordant in 2 patients. In 1 patient with counterclockwise AFL, CS activation was isolated from the posterior wall of the RA until it reached the distal portion of the CS, after which it entered the lateral region of the LA. In 1 patient, a macroreentrant LA tachycardia involving CS muscle was observed. Rapid atrial pacing from the proximal CS and extrastimuli produced longitudinal dissociation of CS activation in all patients.

Conclusion: Conduction between the CS and posterior LA can be dissociated during spontaneous atrial arrhythmias and provocative proximal CS pacing.
Possible Bradycardic Mode of Death and Successful Pacemaker Treatment in a Large Family with Features of Long QT Syndrome Type 3 and Brugada Syndrome
Authors: VAN DEN BERG MAARTEN P. , WILDE ARTHUR A.M. , VIERSMA JAN WILLEM , BROUWER JAN , HAAKSMA JAAP , VAN DER HOUT ANNEMIEKE H. , STOLTE‐DIJKSTRA IRENE , BEZZINA CONNIE R. , VAN LANGEN IRENE M. , BEAUFORT‐KROL GERTIE C.M. , CORNEL JAN HEIN , CRIJNS HARRY J.G.M.
Published: August 2003

Pacemaker Treatment in LQT3 and Brugada Syndrome.
Introduction: We recently identified a novel mutation of SCN5A (1795insD) in a large family with features of both long QT syndrome type 3 and the Brugada syndrome. The purpose of this study was to detail the clinical features and efficacy of pacemaker therapy in preventing sudden death in this family.

Methods and Results: The study group consisted of 116 adult family members: 60 carriers (29 males) and 56 noncarriers (28 males) of the mutant gene. Investigations included 24‐hour Holter monitoring, ergometry, and electrophysiologic studies. Mean, lowest, and highest heart rate were lower in the carriers, but heart rate variability was comparable. In carriers, disproportional QT prolongation was present during bradycardia. No complex ventricular ectopy was recorded, and there were fewer isolated premature beats (both ventricular and atrial) in carriers. All patients were asymptomatic, except for two individuals who experienced syncope; in one of these patients, asystolic episodes (up to 9 sec) were repeatedly recorded. Prolonged HV intervals were present in 5 of 6 patients. Thirty carriers received a prophylactic backup pacemaker. During median follow‐up of 4.5 years (range 0.0 to 22.6), their survival rate was 100%. There were five sudden deaths among the remaining 30 carriers without a pacemaker (P = 0.019).

Conclusion: This family with a high incidence of nocturnal sudden death is characterized by bradycardia‐dependent QT prolongation, intrinsic sinus node dysfunction, and generalized conduction abnormalities. There is a striking absence of complex ventricular ectopy, and pacemaker implantation was effective in preventing sudden death. These findings raise the possibility of a bradycardic rather than tachycardic mode of death.
Simultaneous Analysis of Heart Rate Variability and Myocardial Contractility During Head‐Up Tilt in Patients with Vasovagal Syncope
Authors: MANGIN LAURENCE , KOBEISSI ADONIS , LELOUCHE DAVID , D' HÉROUVILLE YVES , MANSIER PASCALE , SWYNGHEDAUW BERNARD , MACQUIN‐MAVIER ISABELLE
Published: August 2003

Cardiac Autonomic and Inotropic Changes in Vasovagal Syncope.
Introduction: The aim of this study was to evaluate simultaneously cardiac autonomic activity, through heart rate variability (HRV) analysis, and cardiac inotropic changes during head‐up tilt (HUT) in patients with recurrent vasovagal syncope.

Methods and Results: Twelve subjects implanted with a permanent dual‐chamber pacemaker for recurrent vasovagal syncope characterized by marked bradycardia were studied. The tip of the right ventricular electrode was equipped with a sensor that measured peak endocardial acceleration (PEA) as an index of myocardial contractility. RR interval and PEA signals were acquired simultaneously and processed in the time and frequency (low frequencies [LF] and high frequencies [HF] of RR signal) domain during early HUT (T1), late HUT, or before syncope (T2). In the six subjects with positive HUT: (1) Abnormal heart rate oscillations were evidenced at T1 and discriminated this group from the negative group (LF/HF decreased by 46% from supine to T1, but increased by 55% in the negative group; P < 0.01 positive vs negative HUT). (2) Gradual diminution of the HF component was associated with an increase in PEA index during HUT with a correlation between PEA/RR interval (R =− 0.8, P < 0.001), PEA/HF components (R =− 0.6, P < 0.05). (3) Sympathetic stimulation responsible for changes in both HRV and PEA parameters occurred immediately before the faint (LF/LF+HF: 0.6 ± 0.2 to 0.8 ± 0.09; P < 0.05 T2 vs T1; PEA: 0.62 ± 0.10G to 0.83 ± 0.22G; P < 0.01 T2 vs T1).

Conclusion: Our findings showed that a homogeneous subgroup of patients with recurrent vasovagal syncope and positive HUT exhibited abnormal cardiac autonomic and inotropic responses to an orthostatic stimulus. Continuous changes over time of HRV and PEA parameters highlight the dynamic behavior of the mechanisms leading to syncope.
Prognostic Significance of Risk Stratifiers of Mortality, Including T Wave Alternans, After Acute Myocardial Infarction: Results of a Prospective Follow‐Up Study
Authors: TAPANAINEN JARI M. , STILL AINO‐MAIJA , AIRAKSINEN K.E. JUHANI , HUIKURI HEIKKI V.
Published: August 2003

Noninvasive Risk Assessment Including TWA After AMI.
Introduction: Occurrence of sustained microvolt‐level T wave alternans (TWA) at a specified heart rate has been suggested to predict life‐threatening arrhythmic events, but its prognostic value has not been well established in patients who survived an acute myocardial infarction (AMI). The purpose of this prospective study was to assess the predictive significance of various noninvasive risk indicators of mortality, including TWA, in consecutive post‐AMI patients with optimized medical therapy.

Methods and Results: In addition to a symptom‐limited predischarge exercise test with measurement of TWA, mortality risk was assessed using heart rate variability, 24‐hour ECG recordings, baroreflex sensitivity, signal‐averaged ECG, QTc interval, QT dispersion, and echocardiographic wall‐motion index in 379 consecutive patients. Twenty‐six patients (6.9%) died during a mean follow‐up of 14 ± 8 months. Sustained TWA was found in 56 patients (14.7%), none of whom died. Several risk variables, e.g., incomplete TWA test (inability to perform the exercise test or reach the required target heart rate of 105 beats/min), increased QRS duration on signal‐averaged ECG, increased QT dispersion, long QTc interval, nondiagnostic baroreflex sensitivity result, and low wall‐motion index, predicted all‐cause mortality in univariate analyses. In multivariate analysis, the incomplete TWA test was the most significant predictor of cardiac death (relative risk 11.1, 95% confidence interval 2.4 to 50.8; P < 0.01).

Conclusion: Sustained TWA during the predischarge exercise test after AMI does not indicate increased risk for mortality. An incomplete TWA test and several common risk variables provided prognostic information in this post‐AMI population.
Focal Atrial Tachycardia Arising from the Tricuspid Annulus: Electrophysiologic and Electrocardiographic Characteristics
Authors: MORTON JOSEPH B. , SANDERS PRASHANTHAN , DAS ARVIND , VOHRA JITENDRA K. , SPARKS PAUL B. , KALMAN JONATHAN M.
Published: August 2003

Tricuspid Annular Tachycardia.
Introduction: Focal right atrial tachycardia (RAT) arising from the crista terminalis, para‐Hisian, and coronary sinus os regions are well described. Less information exists regarding RAT arising from the nonseptal region of the tricuspid annulus (TA).

Methods and Results: From a consecutive series of 64 patients who had undergone successful radiofrequency ablation (RFA) of 67 RATs, the characteristics of 9 (13%) patients (6 men; mean age 50 ± 20 years) with a TA focus were reviewed. The annular focus was localized to the inferoanterior TA in 7 and the superior TA in 2. Mean tachycardia cycle length was 371 ± 66 msec. Mean activation time at the site of successful RFA in 9 of 9 patients was −43 ± 11 msec. At 9.3 ± 5.6 months of follow‐up, 1 of 9 patients had recurrent tachycardia successfully treated with repeat RFA. In 7 of 9 patients with RAT from the inferoanterior TA, the surface ECG P wave morphology was upright in aVL, inverted in III and V1, and either inverted or biphasic with an initial negative deflection from V2 to V6.

Conclusion: The TA is an important site of origin of RAT. In the present study, the inferoanterior region of the TA was a preferential site of origin with resulting characteristic P wave morphology. Knowledge of this anatomic distribution and P wave morphology allows targeted mapping and may facilitate successful RFA.
Pace Mapping of Postinfarction Scar to Detect Ventricular Tachycardia Exit Sites and Zones of Slow Conduction
Authors: VAN DESSEL PASCAL F.H.M. , DE BAKKER JACQUES M. , VAN HEMEL NORBERT M. , LINNENBANK ANDRÉ C. , JESSURUN EMILE R. , DEFAUW JO A.
Published: August 2003

SR Characterization of Postinfarction Arrhythmias.
Introduction: The exit site and central common pathway of slow conduction are preferred sites to guide radiofrequency ablation of postinfarction ventricular tachycardia (VT). Both require inducibility of VT. In addition, their low amplitude hampers direct recording of potentials generated by activation in pathways of slow conduction. We hypothesized that pace mapping during sinus rhythm would help to detect the VT exit site and potentials generated by activation in pathways of slow activation.

Methods and Results: In 13 patients suffering from VT late after anterior (n = 10) or inferior (n = 3) myocardial infarction, stimulation was performed in scarred endocardium at 23.5 (range 13 to 36) sites per patient during arrhythmia surgery. Multielectrode recordings (64 sites) during stimulation at a fixed cycle length of 500 msec were obtained. Endocardial breakthrough sites distant (> 2 cm) from the pacing site were found at 4.3 (range 3 to 19) pacing sites per patient. Low‐amplitude discrete potentials (LADPs) could be detected between the pacing site and the breakthrough site in 2.3 (range 0 to 13) of 4.3 stimulation sequences. In these patients, 19 VTs were induced and the exit site determined. In 6 patients, the distant pacing breakthrough site was identical to the VT exit site; in 7 patients, no similar exit sites were found. LADPs during VT were found at a median 2.0 (range 0 to 14) sites per patient.

Conclusion: Pace mapping of the postinfarction endocardial scar during sinus rhythm revealed 50% of the endocardial exit sites of VT and the same number of LADPs observed during VT.
Atrioventricular Reciprocating Tachycardia Involving Twin Atrioventricular Nodes in Patients with Complex Congenital Heart Disease
Authors: EPSTEIN MICHAEL R. , SAUL J. PHILIP , WEINDLING STEVEN N. , TRIEDMAN JOHN K. , WALSH EDWARD P.
Published: August 2003

Twin AV Nodes in Complex Congenital Heart Disease.
Introduction: Histologic studies of autopsy specimens described the coexistence of two distinct AV nodes (so‐called “Mönckeberg sling” or “twin AV nodes”) in specific congenital heart defects; however, the clinical electrophysiologic (EP) characteristics of twin AV nodes have not been characterized in detail.

Methods and Results: Since April 1993, a total of seven patients with complex congenital heart disease presented with AV reciprocating tachycardia suspected to be mediated by twin AV nodes. A common anatomic finding was AV discordance ({S,L,L} or {I,D,D}) with a malaligned complete AV canal defect in 5 of 7 patients. Intracardiac EP study was performed in five cases, and ablation was attempted in three patients with successful elimination of tachycardia inducibility by interruption or modification of 1 of the 2 AV nodes. Important EP characteristics included (1) the existence of two discrete nonpreexcited QRS morphologies, each with an associated His‐bundle electrogram; (2) decremental as well as adenosine‐sensitive anterograde and retrograde conduction; and (3) inducible AV reciprocating tachycardia with anterograde conduction over one AV nodal pathway and retrograde conduction over the alternate AV nodal pathway. The existence of two AV nodes was further supported in the group treated with radiofrequency ablation by the development of transient accelerated junctional rhythm during energy delivery with an identical QRS morphology to that generated by anterograde conduction over the targeted AV node.

Conclusion: Reciprocating tachycardia mediated by twin AV nodes can be a source of recurrent supraventricular tachycardia in patients with specific forms of complex congenital heart disease. Successful treatment with catheter ablation is possible.
Brugada Syndrome and Supraventricular Tachyarrhythmias: A Novel Association?
Authors: ECKARDT LARS , KIRCHHOF PAULUS , LOH PETER , SCHULZE‐BAHR ERIC , JOHNA ROBERT , WICHTER THOMAS , BREITHARDT GÜNTER , HAVERKAMP WILHELM , BORGGREFE MARTIN
Published: August 2003

Brugada Syndrome and Supraventricular Tachyarrhythmias.
Introduction: The Brugada syndrome is a distinct form of idiopathic ventricular fibrillation characterized by a unique ECG pattern consisting of a right bundle branch block‐like aspect and ST segment elevation in leads V1 to V3. As a high induction rate of ventricular tachyarrhythmias has been reported in Brugada syndrome, we hypothesized that this also may be true for supraventricular tachycardias in these patients.

Methods and Results: Between January 1995 and December 2000, we identified 35 consecutive patients with Brugada syndrome; 26 had a history of cardiac arrest or syncope and 9 were asymptomatic. All patients underwent electrophysiologic study, including an atrial and ventricular stimulation protocol. Ten patients (29%) were found to have supraventricular tachyarrhythmias (SVT) in addition to the Brugada syndrome. These 10 patients presented with aborted sudden cardiac death (n = 3) and/or a family history of sudden cardiac death (n = 4), syncope (n = 4), or primarily with a Brugada typical ECG, a positive family history, and palpitations (n = 2). Eight of them underwent genetic testing, but only 1 had a mutation in the SCN5A gene. In 6 patients, an AV nodal reentrant tachycardia was easily and reproducibly inducible. Two patients had clinical documented and inducible episodes of an atrial tachycardia (1 in addition to an AV nodal reentrant tachycardia). One patient had paroxysmal atrial fibrillation alternating with sinus rhythm, and 2 patients with accessory pathways were identified.

Conclusion: This is the first description of an association of the Brugada syndrome with SVT. Thus, the arrhythmogenic substrate in Brugada syndrome may not be restricted to the ventricular level. Palpitations in this syndrome should raise the possibility of SVT. Conversely, in patients with SVT and aborted sudden cardiac death or syncope not related to SVT, the Brugada syndrome should be considered a possible additional electrophysiologic abnormality.
Mechanisms for Spontaneous Changes in QRS Morphology Sometimes Resembling Torsades de Pointes During Reentrant Ventricular Tachycardia in a Canine Infarct Model
Authors: SCHMITT HEIKO , CABO CANDIDO , COSTEAS CONSTANTINOS , COROMILAS JAMES , WIT ANDREW L.
Published: August 2003

Changing QRS During Ventricular Tachycardia.
Introduction: Spontaneous changes in QRS morphology during sustained reentrant ventricular tachycardia, occurring gradually or abruptly, causing the tachycardia to be polymorphic, have been described in clinical cases. The purpose of this study was to determine the mechanism for such changes in a canine infarct model.

Methods and Results: Reentrant circuits were mapped in the epicardial border zone during sustained ventricular tachycardia in the canine heart, 4 days after left anterior descending coronary occlusion. In 10 tachycardias, there was either an abrupt change in QRS morphology or a gradual change that took up to 25 cycles. When the latter occurred, the ECG resembled torsades de pointes. Maps showed that the predominant mechanism for the change in QRS was a shift in the exit route by which the impulse left the reentrant circuit to activate the ventricles (9/10 tachycardias). Such shifts resulted from small changes in conduction velocity in segments of the circuit, either speeding or slowing, which modified the length of the functional lines of block. Movement of the circuit to a different region was responsible for the change in QRS in only one of these experiments, in which the reentrant mechanism also changed from functional to anatomic.

Conclusion: Subtle changes in conduction in reentrant circuits can alter QRS morphology. Changes in the exit route from a stable reentrant circuit can cause the ECG characteristics to resemble torsades de pointes.
Role of Wavelength Adaptation in the Initiation, Maintenance, and Pharmacologic Suppression of Reentry
Authors: GIROUARD STEVEN D. , ROSENBAUM DAVID S.
Published: August 2003

Wavelength Adaptation and Reentry.
Introduction: The stability of reentry is thought to depend on a critical balance between the spatial extent of refractory tissue in a reentrant wave (i.e., wavelength λ) and the reentrant path length. Because considerable evidence suggests that λ changes continuously in space and time during abrupt rate changes associated with the onset of tachycardia, we hypothesized that beat‐by‐beat adaptation of λ to the dimensions of the reentrant path plays a central role in the mechanism of initiation of reentry.

Methods and Results: To investigate the dynamic relationship between λ and path length during initiation of reentry, optical mapping with voltage‐sensitive dyes was used in a guinea pig model of reentrant ventricular tachycardia (VT). In this model, a computer‐guided laser obstacle precisely controlled the position and dimensions of the reentrant path. Under control perfusion and after addition of 15 μ M d‐sotalol, λ was monitored during steady‐state pacing, premature stimulation, and the initiating beats leading to nonsustained and sustained VT. During control perfusion, reentrant VT was reproducibly induced in 8 of 8 hearts, whereas in the presence of d‐sotalol, reentry could only be initiated in 1 of 8 hearts due primarily to the failure of λ to adapt to the reentrant path length. During successful initiation of VT, a consistent sequence was observed. The sequence was characterized by antidromic and orthodromic propagation around both sides of the anatomic obstacle, followed by unidirectional block of the antidromic impulse and persistence of reentry only if the λ of the orthodromic impulse adapted to the reentrant path (λ < path length). d‐Sotalol prevented initiation of VT by altering λ adaptation of the orthodromic wave; however, it failed to terminate ongoing VT because reverse use‐dependence developed after several beats of tachycardia.

Conclusion: In an experimental model where λ, path length, and cellular action potentials were monitored during initiation of reentry, we found that, in contrast to termination, the initiation of reentry and the transition from nonsustained to sustained VT is strongly dependent on beat‐to‐beat adaptation of λ to the dimensions of the reentrant path.
Excitable Gap in Canine Fibrillating Ventricular Myocardium: Effect of Subacute and Chronic Myocardial Infarction
Authors: TANEJA TARESH , HORVATH GEORGE , RACKER DARLENE K. , GOLDBERGER JEFFREY , KADISH ALAN
Published: August 2003

Excitable Gap in Infarcted Canine Myocardium.
Introduction: The existence of an excitable gap during ventricular fibrillation (VF) has been suggested in several prior studies. However, the effects of myocardial infarction on the presence and duration of an excitable gap during VF have not been evaluated.

Methods and Results: Electrophysiologic study was performed in normal dogs and in dogs with subacute and chronic infarction. Experimental infarction was produced by left anterior descending coronary ligation. The excitable gap was determined indirectly using either evaluation of intrinsic wavefronts during VF or from the shortest activation interval at individual sites using recordings from a 112‐ electrode plaque sutured to the epicardial surface of the left ventricle. The excitable gap also was correlated to local electrophysiologic and anatomic properties. The excitable gap using the wavefront propagation method and shortest activation method was significantly longer in subacute infarction dogs (48 ± 17 msec and 37 ± 18 msec, respectively) and chronic infarction dogs (41 ± 14 msec and 35 ± 14 msec, respectively) than normal dogs (32 ± 13 msec and 30 ± 11 msec, respectively; P < 0.05 normal vs subacute and chronic infarction dogs in both methods). The excitable gap occupied approximately 30% and 27% of the VF cycle length in all three groups using the wavefront propagation and shortest activation method, respectively. The excitable gap correlated better with local ventricular refractoriness determined using the wavefront propagation method than with the shortest activation method, but not at all with refractoriness determined using extrastimulus testing. Tissue necrosis was noted in subacute infarction dogs and fibrosis in chronic infarction dogs, but the gap was not highly correlated with anatomic changes.

Conclusion: During VF, an excitable gap exists in both normal and infarcted canine ventricular myocardium. It is significantly longer in the presence of infarction. These finding have implications for understanding the pathophysiology of VF and targeting antiarrhythmic therapies.
Experimental and Theoretical Analysis of Phase Singularity Dynamics in Cardiac Tissue
Authors: BRAY MARK‐ANTHONY , LIN SHIEN‐FONG , ALIEV RUBIN R. , ROTH BRADLEY J. , WIKSWO JOHN P.
Published: August 2003

Phase Singularity Dynamics.
Introduction: Quantitative analysis of complex self‐excitatory wave patterns, such as cardiac fibrillation and other high‐order reentry, requires the development of new tools for identifying and tracking the most important features of the activation, such as phase singularities.

Methods and Results: Image processing operations can be used to detect the phase singularity at the tip of a spiral wave. The phase space behavior of a spatiotemporal sequence of data may be reconstructed using time‐series analysis. The phase singularities then are localized efficiently by computing the topologic charge density as the curl of the spatial phase gradient. We analyzed the singularity interaction dynamics of both experimentally observed and numerically simulated instances of quatrefoil reentry and found that the singularity behavior in the experimental preparations can be classified into three categories on the basis of how their separation changes with time.

Conclusion: Topologic charge densities can be calculated easily and efficiently to reveal phase singularity behavior. However, the differences between theoretical and experimental observations of singularity separation distances indicate the need for more sophisticated numerical models.
Use of Tissue Plasminogen Activator in a Stroke After Radiofrequency Ablation of a Left‐Sided Accessory Pathway
Authors: CANNON BRYAN C. , KERTESZ NAOMI J. , FRIEDMAN RICHARD A. , FENRICH ARNOLD L.
Published: August 2003

Use of tPA in a Stroke After RF Ablation. We describe the case of a 12‐year‐old girl who had a thromboembolic stroke after radiofrequency ablation of a left posterior accessory pathway involving a transseptal procedure. Symptoms of a stroke occurred 7 hours 15 minutes after completion of the procedure. Tissue plasminogen activator (tPA) was given 2 hours 30 minutes after the onset of symptoms, with complete resolution of her neurologic symptoms. No adverse effects from the tPA were seen. Because of the late onset of symptoms in this case, overnight in‐hospital observation is warranted for patients who undergo radiofrequency ablation of a left‐sided accessory pathway or an accessory pathway in a patient with the ability to shunt right to left. In this case, tPA was an effective and safe drug to use following a cerebral thromboembolic event occurring after a cardiac catheterization procedure.
Myocardial Ischemia: What Factors Determine Arrhythmogenesis?
Authors: CASCIO WAYNE E.
Published: August 2003

Arrhythmia Formation in Ischemic Heart. In ischemic myocardium, cellular architecture and heterogeneous changes in metabolic and ionic conditions interact to cause spatial and temporal heterogeneity of electrical properties predisposing to lethal ventricular arrhythmias. Yet, the details of their interaction, vis‐à‐vis the initiation and maintenance of reentry, remain poorly understood. Future studies are needed to address the mechanisms of the initial premature beat, reentry, and formation of wavebreaks contributing to ventricular fibrillation. New experimental methods including mathematical and transgenic mouse models are promising techniques to study these phenomena and thereby provide new insights into the fundamental mechanisms of ischemia‐related arrhythmias.
Endothelin System in Human Persistent and Paroxysmal Atrial Fibrillation
Authors: BRUNDEL BIANCA J.J.M. , VAN GELDER ISABELLE C. , TUINENBURG ANTON E. , WIETSES MIRIAN , VAN VELDHUISEN DIRK J. , VAN GILST WIEK H. , CRIJNS HARRY J.G.M. , HENNING ROBERT H.
Published: August 2003

Endothelin System in Atrial Fibrillation.
Introduction: Activation of the endothelin system is an important compensatory mechanism that is activated during left ventricular dysfunction. Whether this system plays a role at the atrial level during atrial fibrillation (AF) has not been examined in detail. The purpose of this study was to investigate mRNA and protein expression levels of the endothelin system in AF patients with and without concomitant underlying valve disease.

Methods and Results: Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 controls in sinus rhythm. The mRNA amounts of pro‐endothelin‐1 (pro‐ET‐1), endothelin receptor A (ET‐A), and endothelin receptor B (ET‐B) were studied by semiquantitative polymerase chain reaction. Protein amounts of the receptors were investigated by slot‐blot analysis. mRNA amounts of pro‐ET‐1 were increased (+ 40%; P = 0.002) only in AF patients with underlying valve disease. ET‐A and ET‐B receptor protein amounts were significantly reduced in patients with paroxysmal AF (−39% and −47%, respectively) and persistent AF with underlying valve disease (− 28% and − 30%, respectively) and in persistent AF without valve disease (−20% and −40%, respectively). ET‐A mRNA expression was unaltered in paroxysmal and persistent AF, whereas ET‐B mRNA was reduced by 30% in persistent AF with (P < 0.001) or without (P = 0.04) valve disease, but unchanged in paroxysmal AF.

Conclusion: Substantial changes in gene expression of the endothelin system were observed in human atria during AF, especially in the presence of underlying valve disease. Alterations in endothelin expression associated with AF could play a role in the pathophysiology of AF and the progression of underlying heart disease.
Intra‐Atrial Conduction Block Along the Mitral Valve Annulus During Accessory Pathway Ablation: Evidence for a Left Atrial “Isthmus”
Authors: LURIA DAVID M. , NEMEC JAN , ETHERIDGE SUSAN P. , COMPTON STEVEN J. , KLEIN RICHARD C. , CHUGH SUMEET S. , MUNGER THOMAS M. , SHEN WIN K. , PACKER DOUGLAS L. , JAHANGIR ARSHAD , REA ROBERT F. , HAMMILL STEPHEN C. , FRIEDMAN PAUL A.
Published: August 2003

Left Atrial Isthmus.
Introduction: We observed a change in the atrial activation sequence during radiofrequency (RF) energy application in patients undergoing left accessory pathway (AP) ablation. This occurred without damage to the AP and in the absence of a second AP or alternative arrhythmia mechanism. We hypothesized that block in a left atrial “isthmus” of tissue between the mitral annulus and a left inferior pulmonary vein was responsible for these findings.

Methods and Results: Electrophysiologic studies of 159 patients who underwent RF ablation of a left free‐wall AP from 1995 to 1999 were reviewed. All studies with intra‐atrial conduction block resulting from RF energy delivery were identified. Fluoroscopic catheter positions were reviewed. Intra‐atrial conduction block was observed following RF delivery in 11 cases (6.9%). This was evidenced by a sudden change in retrograde left atrial activation sequence despite persistent and unaffected pathway conduction. In six patients, reversal of eccentric atrial excitation during orthodromic reciprocating tachycardia falsely suggested the presence of a second (septal) AP. A multipolar coronary sinus catheter in two patients directly demonstrated conduction block along the mitral annulus during tachycardia.

Conclusion: An isthmus of conductive tissue is present in the low lateral left atrium of some individuals. Awareness of this structure may avoid misinterpretation of the electrogram during left AP ablation and may be useful in future therapies of atypical atrial flutter and fibrillation.
Identification and Catheter Ablation of Extracardiac and Intracardiac Components of Ligament of Marshall Tissue for Treatment of Paroxysmal Atrial Fibrillation
Authors: KATRITSIS DEMOSTHENES , IOANNIDIS JOHN P.A. , ANAGNOSTOPOULOS CONSTANTINE E. , SARRIS GEORGE E. , GIAZITZOGLOU ELEFTHERIOS , KOROVESIS SOCRATES , CAMM A. JOHN
Published: August 2003

Catheter Ablation of Ligament of Marshall Tissue.
Introduction: The ligament of Marshall is a left atrial neuromuscular bundle with sympathetic innervation that may be a source of atrial fibrillation (AF)‐inducing automatic activity.

Methods and Results: Twenty‐four patients with paroxysmal AF (including 18 with adrenergic AF) and 25 with other arrhythmias underwent catheter mapping. In cases of adrenergic AF, radiofrequency ablation was attempted when Marshall potentials were recorded. Patients were followed for 2 months before and 11.2 ± 4.2 months after the procedure. Catheterization of the distal superoposterior coronary sinus was feasible in 14 patients with AF (10 with adrenergic AF) and 12 patients without AF. A discrete Marshall potential was recorded in 12 patients with AF versus 3 patients without AF (P = 0.004). In 10 patients with adrenergic AF, this potential followed the atrial electrogram during sinus rhythm by 26 ± 5 msec on left atrial recordings and 24 ± 4 msec on coronary sinus recordings, and preceded it during atrial ectopy by 29 ± 5 msec and 26 ± 5 msec, respectively. It was abolished by epicardial (n = 1), endocardial (n = 4), or combined epicardial and endocardial ablation (n = 5). Seven patients with ablation showed significant reductions in adrenergic AF, whereas no significant change was seen in 8 adrenergic AF patients not undergoing ablation (P = 0.004). No improvement was seen in 3 of 4 patients with only endocardial ablation, whereas all 6 patients with epicardial ablation improved (P = 0.033).

Conclusion: Recording of Marshall potential is feasible in patients with paroxysmal AF. Combined epicardial and endocardial catheter ablation of ligament of Marshall tissue may reduce the paroxysms of adrenergic AF.
Microvolt T Wave Alternans in Human Cardiac Hypertrophy: Electrical Instability and Abnormal Myocardial Arrangement
Authors: KON‐NO YUJI , WATANABE JUN , KOSEKI YOSHITO , KOYAMA JIRO , YAMADA AKI , TODA SUNAO , SHINOZAKI TSUYOSHI , FUKUCHI MITSUMASA , MIURA MASAHITO , KAGAYA YUTAKA , SHIRATO KUNIO
Published: August 2003

T Wave Alternans and Hypertrophy.
Introduction: Although T wave alternans (TWA) is a promising risk marker for myocardial electrical instability, it remains unclear how the presence of TWA is related to myocardial damage.

Methods and Results: TWA was measured in 28 patients with hypertrophic cardiomyopathy (HCM), 29 patients with hypertensive left ventricular hypertrophy (HLVH), and 15 normal volunteers using a CH2000 system. The amplitude of TWA (Valt) was measured at the lead with the maximum amplitude. Cardiac biopsy was performed in 12 HCM patients, who were divided into two groups (severe and mild) based on histologic findings of myocardial disarray and fibrosis. TWA was positive (Valt > 1.9 μ V) in 61% of HCM and 31% of HLVH, despite a nearly identical left ventricular mass index (176 ± 65 g/m2 vs 175 ± 39 g/m2). Valt at heart rate = 110 beats/min was significantly greater in HCM with severe disarray and fibrosis than in HCM with mild disarray and in HLVH.

Conclusion: In HCM patients, a positive TWA test probably is related to abnormal myocardial arrangement (disarray) and/or fibrosis, and it may reflect electrical instability of the myocardium.
VERDICT: The Verapamil versus Digoxin Cardioversion Trial: A Randomized Study on the Role of Calcium Lowering for Maintenance of Sinus Rhythm after Cardioversion of Persistent Atrial Fibrillation
Authors: VAN NOORD TRUDEKE , VAN GELDER ISABELLE C. , TIELEMAN ROBERT G. , BOSKER HANS A. , TUINENBURG ANTON E. , VOLKERS CORINE , VEEGER NIC J.G.M. , CRIJNS HARRY J.G.M.
Published: August 2003

Verapamil and Atrial Fibrillation.
Introduction: Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV). The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing) for maintenance of sinus rhythm after ECV.

Methods and Results: Ninety‐seven patients with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for 1 month before and 1 month after ECV. The first month after ECV, patients recorded heart rhythm using daily transtelephonic monitoring. No additional antiarrhythmic drugs were given. Of the 97 patients, 43 patients (20 verapamil) underwent ECV per protocol. Median previous AF duration was 18 and 26 days for verapamil and digoxin, respectively. There were no differences in atrial dimensions and underlying heart disease between the two groups. The success rate of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had recurrence of AF. Median time to recurrence was 5 days (range 0 to 26) versus 8 days (range 2 to 28) (P = NS), respectively.

Conclusion: Stand‐alone intracellular calcium lowering by verapamil around ECV does not enhance cardioversion outcome.
Repolarization Abnormalities Detected by Magnetocardiography in Patients with Dilated Cardiomyopathy and Ventricular Arrhythmias
Authors: KORHONEN PETRI , VÄÄNÄNEN HEIKKI , MÄKIJÄRVI MARKKU , KATILA TOIVO , TOIVONEN LAURI
Published: August 2003

Repolarization Abnormalities by Magnetocardiography.
Introduction: Abnormal repolarization is one of the acknowledged mechanisms leading to malignant ventricular arrhythmias. We used a novel magnetocardiographic technique to investigate the role of inhomogeneous repolarization in patients with nonischemic dilated cardiomyopathy prone to sustained ventricular arrhythmias.

Methods and Results: Forty‐nine dilated cardiomyopathy patients were studied, 18 with a history of sustained ventricular tachycardia (n = 6) or ventricular fibrillation (n = 12) and 31 with no ventricular arrhythmias. The magnetocardiogram was registered and QT apex and QT end intervals were determined by a computer algorithm. Inhomogeneity of repolarization was characterized with indices describing QT apex and QT end dispersion, and T wave end duration. In addition, time‐domain late fields of the QRS complex in magnetocardiography and QT dispersion in 12‐lead ECG were determined. T wave end was longer in the arrhythmia group in patients with sinus rhythm (87 ± 15 msec vs 73 ± 12 msec; P = 0.005) and in those not having bundle branch block. Magnetocardiographic late fields of the QRS complex were not different between groups. QT apex and end dispersion on magnetocardiography or 12‐lead ECG showed no difference.

Conclusion: Prolongation of the end part of the T wave revealed by magnetocardiography is related to malignant ventricular arrhythmias in dilated cardiomyopathy. The results suggest that abnormal repolarization rather than delayed conduction underlies the arrhythmias in this disease.
Electrocardiographic Analysis of Ectopic Atrial Activity Obscured by Ventricular Repolarization: P Wave Isolation Using an Automatic 62‐Lead QRST Subtraction Algorithm
Authors: SIPPENSGROENEWEGEN ARNE , MLYNASH MICHAEL D. , ROITHINGER FRANZ X. , GOSEKI YOSHINARI , LESH MICHAEL D.
Published: August 2003

62‐Lead QRST Subtraction Algorithm.
Introduction: Atrial activity on the surface ECG during premature beats and supraventricular arrhythmias frequently is obscured by the superimposed QRST complex of the previous cardiac cycle. This study examines the performance of a newly developed automatic QRST subtraction algorithm to isolate ectopic P waves from the preceding T‐U wave.

Methods and Results: The 62‐lead ECG recordings were obtained during (1) sinus rhythm and programmed right atrial stimulation in 12 patients (group A); and (2) sinus rhythm and atrial premature beats, atrial tachycardia, or paroxysmal atrial fibrillation in 5 patients (group B). Pacing in group A patients was conducted at a slow drive cycle length to generate an ectopic P wave not obscured by the previous QRST complex and by delivering single premature extrastimuli at progressively shorter coupling intervals to produce an ectopic P wave obscured by the upsloping (early T‐U wave), peak (middle T‐U wave), and downsloping component of the T‐U wave (late T‐U wave). All ectopic P waves in group B patients were concealed by the preceding T‐U wave. Automatic QRST subtraction was attained using an adaptive template constructed from averaged QRST complexes (mean 83 ± 25 complexes) obtained during sinus rhythm (groups A and B) or atrial overdrive pacing (group A). P wave integral maps subsequently were computed, visually compared, and mathematically correlated. A high correspondence in spatial map pattern was observed between integral maps of “nonobscured” and previously “obscured” paced P waves obtained in group A patients (mean r = 0.88 ± 0.07) as well as between integral maps of two to three previously obscured P waves with the same atrial arrhythmia morphology obtained in group B patients (mean r = 0.94 ± 0.05). Improved morphologic P wave replication in group A patients was acquired when concealment occurred in the early (mean r = 0.90 ± 0.08) or late part of the T‐U wave (mean r = 0.90 ± 0.06) as opposed to the middle T‐U wave (mean r = 0.85 ± 0.07) (P = NS and P < 0.05 for early vs middle and late vs middle T‐U wave, respectively).

Conclusion: This novel automatic 62‐lead QRST subtraction algorithm enables discrete isolation of T‐U wave obscured ectopic atrial activity on the surface ECG while retaining the intricate spatial detail in P wave morphology. Future clinical application of the algorithm may enable improved ECG localization of focal triggers of paroxysmal atrial fibrillation, atrial tachycardia, and the atrial insertion of accessory pathways.
Different Mechanisms of Isoproterenol‐Induced and Nitroglycerin‐Induced Syncope During Head‐Up Tilt in Patients with Unexplained Syncope: Important Role of Epinephrine in Nitroglycerin‐Induced Syncope
Authors: TAKASE BONPEI , UEHATA AKIMI , NISHIOKA TOSHIHIKO , ISOJIMA KAZUSIJE , SATOMURA KIMIO , OHSUZU FUMITAKA , KURITA AKIRA
Published: August 2003

Isoproterenol‐Induced vs Nitroglycerin‐Induced Syncope.
Introduction: A reduction in left ventricular volume and an increase in epinephrine levels have been reported in tilt‐induced neurally mediated syncope. To compare the mechanisms of isoproterenol‐induced and nitroglycerin‐induced syncope during head‐up tilt and to investigate the role of catecholamines, the temporal changes in plasma levels of norepinephrine and epinephrine and in left ventricular volume were measured.

Methods and Results: The first study population consisted of 90 patients with syncope of unknown etiology and 12 control subjects. The second study population consisted of 43 patients with unexplained syncope. In the first study, head‐up tilt (80° angle) was conducted for 40 minutes, and norepinephrine and epinephrine levels were measured. In the second study, all patients were randomly allocated to either isoproterenol test (20 patients) or nitroglycerin test (23 patients) for 20‐minute head‐up tilt. Isoproterenol infusion was given at a rate of 1 to 3 μ g/min. Intravenous infusion of nitroglycerin was started at 250 μ g/hour with increasing dosages up to 1,500 μ g/hour. Norepinephrine and epinephrine were measured in peripheral venous blood. Left ventricular volumes were measured by echocardiography with patients in the supine position and during head‐up tilt every 1 minute. End‐diastolic volume and end‐systolic volume were calculated. In the first study, 61 patients demonstrated a positive response and 29 patients demonstrated a negative response. Plasma norepinephrine changes during head‐up tilt were not significantly different, whereas epinephrine levels were significantly higher in the positive patients than in the negative and control subjects (148 ± 118 pg/mL vs 66 ± 31 pg/mL and 55 ± 27 pg/mL). Thirteen of the 20 patients given isoproterenol and 15 of the 23 patients given nitroglycerin showed a positive head‐up tilt (65.0% vs 65.2%; P = NS). During isoproterenol and nitroglycerin infusion head‐up tilt, epinephrine in the positive group determined by the nitroglycerin test was significantly higher than that in the other three groups (103 ± 38 pg/mL vs 60 ± 33 pg/mL, 31 ± 21 pg/mL, and 50 ± 52 pg/mL). In contrast, end‐systolic volume was significantly smaller in the positive group than in the other three groups based on findings of the isoproterenol test.

Conclusion: The findings suggest that nitroglycerin triggers head‐up tilt‐induced syncope by increasing epinephrine levels, whereas isoproterenol induces syncope by decreasing left ventricular volume.
Sinus Pacemaker Function after Cardioversion of Chronic Atrial Fibrillation: Is Sinus Node Remodeling Related with Recurrence?
Authors: MANIOS EMMANUEL G. , KANOUPAKIS EMMANUEL M. , MAVRAKIS HERCULES E. , KALLERGIS ELEFTHERIOS M. , DERMITZAKI DESPINA N. , VARDAS PANOS E.
Published: August 2003

Sinus Node Remodeling and Atrial Fibrillation.
Introduction: The objective of this study was to investigate the temporal changes in sinus node function in postcardioversion chronic atrial fibrillation (AF) patients and their possible relation with the recurrence rates of AF.

Methods and Results: In 37 chronic AF patients, internally cardioverted to sinus rhythm, corrected sinus node recovery time (CSNRT), and the pattern of corrected return cycle lengths were assessed 5 to 20 minutes and 24 hours after conversion. The last 20 consecutive patients also were evaluated after autonomic blockade. Twenty subjects with normal atrial structure and no history of AF served as the control group. Patients were followed‐up for 1 month for recurrence, and the density of supraventricular ectopic beats per hour was obtained during the first 24 hours after conversion. Fifteen patients (40.5%) relapsed during follow‐up. CSNRT values at 600 msec (371 ± 182 msec) and 500 ms (445 ± 338 msec) were significantly higher than those of control subjects (278 ± 157 msec, P = 0.050, and 279 ± 130 msec, P = 0.037, respectively). Significant temporal changes in CSNRT also were observed during the first 24 hours after conversion (600 msec: 308 ± 120 msec, P = 0.034; 500 msec: 340 ± 208 msec, P = 0.017). No significant interaction and temporal effects were observed with regard to corrected return cycle length pattern. Similar data regarding CSNRT and corrected return cycle length pattern were obtained after autonomic blockade. Patients with abnormal CSNRT after cardioversion had higher recurrence rates (50%) than those with normal function (37%; P = NS). Patients who relapsed had a higher density of supraventricular ectopic beats per hour (159 ± 120) compared with those who did not (35 ± 37; P = 0.001).

Conclusion: Depressed sinus node function is observed after conversion of chronic AF. Recovery from this abnormality and its independence from autonomic function suggest that AF remodels the sinus node. Our data do not support a causative role of sinus node function in AF recurrence, but they do indicate such a role for the density of atrial ectopic beats.