bluuebunny/crossref_metadata_2025 huggingface dataset:
The Valve of Vieussens: An Important Cause of Difficulty in Advancing Catheters into the Cardiac Veins
Authors: CORCORAN SUSAN J. , LAWRENCE CHRISTOPHER , McGUIRE MARK A.
Published: April 2007

Catheterization of Cardiac Veins. Introduction: The coronary sinus and cardiac veins are useful conduits for the passage of electrode catheters for mapping the origin of cardiac arrhythmias. However, sometimes it is difficult to advance catheters an adequate distance into the cardiac veins. The aim of this study was to determine the reasons for this.

Methods and Results: In 50 cadaveric hearts, a deflectable 7‐French electrode catheter was passed from the right atrium into the coronary sinus and advanced to the anterior interventricular portion of the great cardiac vein (GCV). Causes of obstruction were determined. The catheter was obstructed by the valve of Vieussens in 23 of 50 hearts (46%). Once the valve was negotiated, obstruction was caused by an acute bend in the GCV in 28 of 50 hearts (56%). Clinical studies were undertaken in 10 patients in whom electrode catheters could not be advanced as far as required. Using contrast venography, the most frequent cause of obstruction was determined to be the valve of Vieussens in 8 of 10 cases (80%). An acute bend in the GCV caused obstruction in 2 cases (20%).

Conclusions: The valve of Vieussens is a frequent cause of obstruction to passage of a catheter in postmortem and in vivo studies. An acute bend in the vein, with or without lodgment in a tributary, is the other common cause. In adults, venous luminal diameter is not a cause of obstruction to the passage of a 7‐French catheter in the coronary sinus or proximal GCV.
Functional Effects of Mutations in KvLQT1 that Cause Long QT Syndrome
Authors: WANG Z. , TRISTANI‐FIROUZI M. , XU Q. , LIN M. , KEATING M.T. , SANGUINETTI M.C.
Published: April 2007

Mutations in KvLQT1. Introduction: The long QT syndrome (LQT) is caused by mutations in genes encoding ion channels that modulate the duration of ventricular action potentials. One of these genes, KVLQT1, encodes an α subunit that coassembles with another subunit, hminK, to form the cardiac slow delayed rectifier (IKs) K+ channel.

Methods and Results: The functional effects of seven mutations in KVLQT1 were assessed using two‐microelectrode voltage clamp and the Xenopus oocyte expression system. Most mutations in KVLQT1 caused loss of function when expressed alone. Oocytes were also injected with equal amounts of wild‐type (WT) KVLQT1 and mutant KVLQT1 cRNA (with or without coinjection of hminK) and the resulting currents compared to currents induced by WT KvLQT1 alone. A341V, RI90Q, or G189R KVLQT1 subunits did not affect expression of WT KvLQT1. The other mutations in KVLQT1 caused a variable degree of dominant‐negative suppression of IKs. The order of potency for this effect was G345E > G306R = V254M > A341E. Conclusions: LQTl‐associated mutations in KVLQT1 caused a spectrum of dysfunction in IKs and KvLQT1 channels. The degree of IKs dysfunction did not correlate with the QTc interval or the presence of symptoms in the respective gene carriers. In contrast to previous reports, we found that loss of function mutations are not exclusive to recessiveiy inherited LQT.
Gene Expression of the Natriuretic Peptide System in Atrial Tissue of Patients with Paroxysmal and Persistent Atrial Fibrillation
Authors: TUINENBURG ANTON E. , BRUNDEL BIANCA J.J.M. , Van GELDER ISABELLE C. , HENNING ROBERT H. , Van Den BERG MAARTEN P. , DRIESSEN CÉCILE , GRANDJEAN JAN G. , Van GILST WIEK H. , CRIJNS HARRY J.G.M.
Published: April 2007

Natriuretic Peptide System in AF. Introduction: Circulating cardiac natriuretic peptides play an important role in maintaining volume homeostasis, especially during conditions affecting hemodynamics. During atrial fibrillation (AF), levels of plasma atrial natriuretic peptide (ANP) becomes elevated. The aim of this study was to gather information about gene expression of the natriuretic peptide system on the atrial level in patients with AF.

Methods and Results: Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 case matched controls in sinus rhythm for mRNA expression of pro‐ atrial natriuretic peptide (pro‐ANP), pro‐brain natriuretic peptide (pro‐BNP), and their natriuretic peptide receptor type‐A (NPR‐A). We investigated patients without (n = 36) and with (n = 36) valvular disease. Persistent AF was associated with higher mRNA expression of pro‐BNP (+66%, P = 0.04, in patients without valvular disease, and +69%, P < 0.01, in patients with valvular disease) and lower mRNA expression of NPR‐A (‐58%, P = 0.02, in patients witbout valvular disease, and ‐62%, P < 0.01, in patients with valvular disease). The mRNA content of pro‐ANP was only increased in patients with valvular disease (+12%, P = 0.03). No changes were observed in patients with paroxysmal AF.

Conclusion: This study demonstrates that persistent, but not paroxysmal, AF induces alterations in gene expression of pro‐BNP and NPR‐A on the atrial level. Although AF generally is associated with an increase of plasma ANP level, a change in mRNA content of pro‐ANP is only observed in the presence of concomitant valvular disease and is of minor magnitude.
Ablation of Ventricular Tachycardia with a Saline‐Cooled Radiofrequency Catheter:
Authors: DELACRETAZ ETIENNE , STEVENSON WTLLIAM G. , WINTERS GAYLE L. , MITCHELL RICHARD N. , STEWART SARAH , LYNCH KRISTIN , ERIEDMAN PETER L.
Published: April 2007

Saline‐Irrigated RF Catheter Ablation. Introduction: In animal models, active cooling of the electrode during radiofrequency (RF) ablation allows creation of larger lesions, presumably by increasing the power that can be delivered without coagulum formation. These RF lesions have not been characterized in human myocardium in regions of infarction and scarring.

Methods and Results: Cooled‐tip RF catheter ablation of ventricular tacbycardias (VTs) was performed in two patients who had severe congestive heart failure and subsequently underwent cardiac transplantation. The first patient bad four different monomorphic VTs. RF applications along the inferoseptal margin of a scarred region abolished all inducible VTs. The second patient had sarcoidosis involving the myocardium and four different inducible VTs. RF current applied at an inferobasal VT exit and at the right and left septa failed to abolish the VTs. The explanted hearts were examined at the time of cardiac transplantation 18 and 21 days later, respectively. Lesions extended to depths up to 7 mm, reaching clusters of myocardial cells deep to regions of fibrosis. Microscopically, the ablation sites contained coagulation necrosis with hemorrhage, surrounded by a rim of granulation tissue.

Conclusion: Saline‐irrigated RF catheter ablation produces relatively large lesions capable of penetrating deep into scarred myocardium.
Software Error Resulting in Malfunction of an Implantable Cardioverter Defibrillator
Authors: COPPESS MARK A. , MILLER JOHN M. , ZIPES DOUGLAS P. , GROH WILLIAM J.
Published: April 2007

ICD Software Error. Loss of ventricular output resulting from an unexpected software error in a dual chamber implantable cardioverter defibrillator (ICD) is reported. A 70‐year‐old man with a dual chamber ICD implanted for a history of cardiac arrest and infra‐Hisian block presented with acute onset of dizziness. He was found to have loss of ventricular output due to an internal software problem. The problem was corrected by software reprogramming via the programmer. This malfunction exemplifies the potential ability to correct current‐generation ICD software problems noninvasively, thus avoiding the need for replacement.
Value of Programmed Ventricular Stimulation in Patients with Congenital Heart Disease
Authors: ALEXANDER MARK E. , WALSH EDWARD P. , SAUL J. PHILIP , EPSTEIN MICHAEL R. , TRIEDMAN JOHN K.
Published: April 2007

Ventricular Stimulation in Congenital Heart Disease, introduction: The role of programmed ventricular stimulation (VSTIM) for risk stratification in congenital heart disease is unclear. We analyzed the results of VSTIM in selected congenital heart disease survivors at a single center lo determine whether it improved the ability to predict a serious outcome.

Methods and Results: Between July 1985 and September 1996. 140 primary VSTIM studies were performed on 130 patients (median age 18.1 years, range 0 to 51). Tetralogy of Fallot (33%), d‐transposition of the great arteries (25%), and left ventricular outflow tract obstruction (12%) accounted for the majority of patients. Indications included spontaneous ventricular tachycardia (VT) of ≥ 3 beats (72%) and/or symptoms (68%). Sustained VT was induced in 25% of the studies, and nonsustained VT in 12%. Atrial flutter or other supraventricular tachycardia was documented in 32% and bradyarrhythmias in 26%. By univariate analysis, mortality was increased in patients with positive VSTIM versus negative VSTIM (18% vs 7%, P = 0.04). Using multivariate analysis, positive VSTIM was associated with a sixfold increased risk of decreased survival and a threefold increased risk of serious arrhythmic events, allowing up to 87% sensitivity in predicting mortality. However, 7 (33%) of 21 patients with documented clinical VT had false‐negative studies.

Conclusion: VSTIM in a large, selected group of congenital heart disease patients identified a subgroup with significantly increased mortality and sudden arrhythmic events. Failure to induce VT was a favorable prognostic sign, but the frequency of false‐negative studies was high. Frequent supraventricular tachycardia further complicated risk stratification. Although VSTIM appears to be a reasonable tool for evaluation of this population, a larger, multicenter trial is recommended to clarify its utility.
Characterization of Sinoatrial Parasympathetic Innervation in Humans
Authors: QUAN KARA J. , LEE JAI H. , GEHA ALEXANDER S. , BIBLO LEE A. , VAN HARE GEORGE F. , MACKALL JUDITH A. , CARLSON MARK D.
Published: April 2007

Sinoatrial Parasympathetic Innervation. Introduction: The response to sinoatrial parasympathetic nerve stimulation (shortened atrial refractoriness) was used to determine the atrial distribution of these nerve fibers in humans. We hypothesized that, in humans, parasympathetic nerves that innervate the sinoatrial node also innervate the right atrium and that the greatest density of innervation is near the sinoatrial nodal fat pad.

Methods and Results: Temporary epicardial wire electrodes were sutured in pairs in the sinoatrial nodal fat pad, high right atrium, and right ventricle by direct visualization during coronary artery bypass surgery in nine patients. Appropriate electrode placement was confirmed by electrically stimulating the fat pad in the operating room to prolong sinus cycle length by 50%. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1‐cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness was determined in the presence and absence of sinoatrial parasympathetic nerve stimulation at each cutheter site. In 8 of 9 patients, parasympathetic nerve stimulation reproducibly prolonged sinus cycle length by 50%. There was no effect on AV nodal conduction (no prolongation of PR interval) and no change in AV nodal refractoriness. Atrial effective refractory periods reproducibly shortened in response to parasympathetic nerve stimulation in 1‐cm zones up to 3 cm surrounding the fat pad, by a mean (± SEM) of 26.6 ± 4.3 msec (zone 1), 11.4 ± 1.8 msec (zone 2), and 10.0 ± 2.5 msec (zone 3), respectively (P = 0.0001). At distances > 3 cm from the fat pad, the effective refractory period did not shorten.

Conclusion: Stimulation of parasympathetic nerves that innervate the sinoatrial node shortened atrial refractoriness in humans.
Parasympathetic Inhibition of Sympathetic Effects on Pacemaker Location and Rate in Hearts of Anesthetized Dogs
Authors: MIYASHITA YUSUKE , FURUKAWA YASUYUKI , NAKAJIMA KOICHI , HIROSE MASAMICHI , KUROGOUCHI FUMIO , CHIBA SHIGETOSHI
Published: April 2007

Autonomic Effect on Pacemaker Location. introduction: The site of impulse origin in the right atrium generally is considered to be a single static locus within the sinoatrial (SA) node. Previous investigators showed that the pacemaker site may shift due to changes in sympathetic or parasympathetic neural activity. We investigated the interactions between sympathetic and parasympathetic influences on the site of impulse initiation in the right atrium in anesthetized dogs.

Methods and Results: We determined the site of impulse initiation and the spread of excitation over the anterior and posterior regions of the right atrium by a matrix of 48 unipolar recording electrodes. We assessed the spread of excitation at 3‐nisec intervals by constructing isochronal activation sequence maps. Sympathetic stimulation increased the frequency of atrial excitation (i.e., the heart rate), but also shifted the earliest activation region (EAR) from a locus in the SA node to a locus in the superior vena cava (the superior pacemaker site). Vagus stimulation decreased the heart rate and shifted the EAR to a lower site in the SA node or a site in the interior right atrium along the sulcus terminalis (the inferior pacemaker site). A short period of vagus stimulation during a more prolonged sympathetic stimulation elicited a larger decrease in rate than did vagus stimulation alone and shifted the EAR from the superior site to the SA node or to the inferior site. After atropine, combined stimulation shifted the EAR to the superior site, but propranolol did not change EAR location.

Conclusion: Our results suggest that parasympathetic activity predominates over sympathetic activity not only on heart rate, but also on the location of the EAR in the anesthetized dog.
A Case of Catheter Ablation of Accessory Atrioventricular Connection Between the Right Atrial Appendage and Right Ventricle Guided by a Three‐Dimensional Electroanatomic Mapping System
Authors: GOYA MASAHIKO , TAKAHASHI ATSUSHI , NAKAGAWA HIROSHI , IESAKA YOSHITO
Published: April 2007

Accessory AV Connection Between RAA and RV. A 12‐year‐old girl was referred to our institution because of frequent episodes of AV reciprocating tachycardia. Ventriculoatrial and AV intervals were relatively long along the tricuspid annulus. Earliest retrograde atrial activation was recorded at the mid‐portion of the right atrial appendage. 7 mm from the tricuspid annulus. The CARTO electroanatomic mapping system was very useful for providing accurate spatial orientation of the accessory connection. Complete ablation of this connection required multiple radiofrequency energy applications over an extensive area because of the multicomponent structure of the connection.
Validation of a Noninvasive Measure of Local Myocardial Repolarization in a Conscious Human Model:
Authors: DOUGLAS LEE S. , DORIAN PAUL , GEIST MICHAEL , DAVIES EDWARD , BARR AIALA , DUNNE CATHERINE , PAQUETTE MINEY , NEWMAN DAVID
Published: April 2007

Rate Adaptation of Myocardial Repolarization. Introduction: A commercial pacemaker sensor measure of the unipolar endocardial stimulus to T wave interval may accurately reflect changes in the monophasic action potential duration at 90% repolarization (APD90). This sensor system was used to study the kinetics of adaptation of repolarization duration to changes in heart rate in humans.

Methods and Results: Patients were studied using an external pacemaker capable of displaying all stimulus to T wave intervals for each paced beat. Right ventricular stimulation was delivered via the pacemaker and compared simultaneously to APD90. Steady‐state pacing was simulated by 60 seconds of pacing at cycle lengths (CLs) 350 to 700 msec. Adaptation to a new ventricular rate was analyzed with a sudden 200‐msec decrease in CL. The relation between repolarization measure and steady‐state CL (n = 16) was linear with a slope of 0.16 and 0.19 for APD90 and stimulus to T wave interval, respectively (P = NS). The adaptation of both repolarization measures to a sudden change in rate were best modeled by a biexponential function. Stimulus to T wave interval exhibited a parallel course to APD90, and an analysis of normalized differences between APD90 and stimulus to T wave interval followed an approximately normal distribution, with 93.5% of the paired differences within 2 SD of the mean.

Conclusion: A pacemaker sensor measure of stimulus to T wave interval accurately parallels APD90, during both steady‐state and sudden changes in rate. Repolarization in human endocardium follows a linear relation to steady‐state CL and adapts to a new rate with a biexponential function. This model represents a novel method for studying human cardiac repolarization.
Differential Effects of Parasympathetic Blockade and Parasympathetic Withdrawal on Heart Rate Variability
Authors: CHALLAPALLI SRIDEVI , KADISH ALAN H. , HORVATH GEORGE , GOLDBERGER JEEFREY J.
Published: April 2007

Parasympathetic Withdrawal and Blockade Effects on HRV. introduction: Low heart rate variability (HRV) has been shown to have important prognostic significance in multiple settings. Although this is believed to reflect reduced parasympathetic tone, the physiology of reduced parasympathetic tone has not been elucidated.

Methods and Results: To evaluate whether parasympathetic withdrawal and partial parasympathetic blockade result in similar changes in HRV, 27 normal volunteers underwent complete β‐adrenergic blockade and then were given (1) graded doses of nitroprusside to achieve baroreflex‐mediated parasympathetic withdrawal and (2) low‐dose atropine (0.01 mg/kg) to achieve partial parasympathetic blockade. Five‐minute ECG recordings were obtained for HRV analysis. In 19 subjects, paired 5‐minute recordings from each condition were available with mean RR intervals that differed by < 50 msec (low‐dose atropine: 869 ± 96 msec and nitroprusside 875 ± 99 msec). The root mean square of the successive RR interval differences was lower following low‐dose atropine than following parasympathetic withdrawal with nitroprusside (16 ± 11 msec vs 22 ± 15 msec; P < 0.02). During parasympathetic withdrawal, the low‐frequency (LF) power was 0.917 ± 0.602 bpm2 and the high‐frequency (HF) power was 0.501 ± 0.521 bpm2. During partial parasympathetic blockade, the LF and HF powers were significantly lower (0.443 ± 0.474 bpm2, P < 0.005; and 0.198 ± 0.207 bpm2, P < 0.02).

Conclusion: These data confirm that HRV reflects the character of parasympathetic modulation of the heart rate rather than parasympathetic tone per se. Furthermore, this study identifies two distinct physiologic explanations for the finding of low HRV, namely, diminished vagal discharge and resistance of cardiac muscarinic receptors to vagal discharge. Further delineation of the relationships between parasympathetic tone and HRV will allow for better understanding of the pathophysiologic derangements associated with low HRV.
Effects of Mibefradil, a T‐Type Calcium Current Antagonist, on Electrophysiology of Purkinje Fibers that Survived in the Infarcted Canine Heart
Authors: PINTO JUDITH M.B. , SOSUNOV EUGENE A. , GAINULLIN RAVIL Z. , ROSEN MICHAEL R. , BOYDEN PENELOPE A.
Published: April 2007

Mibefradil's Effects on Canine Purkinje Myocytes.Introduction: We studied the effects of mibefradil (MIB), a nondihydropyridine T‐type Ca2+channel antagonist, on T‐ and L‐type Ca2+(ICaT, ICaL) currents in Purkinje myocytes dispersed from the subendocardium of the left ventricle of normal (NZPC) and 48‐hour infarcted (IZPC) hearts.

Methods and Results: Currents were recorded with Cs*‐ and EGTA‐rich pipettes and in Na+‐K+‐free external solutions to eliminate overlapping currents. In all cells, ICawas reduced by MIB (0.1 to 10 μM). No change in the time course of decay of peak ICawas noted. Average peak T/L ratio decreased in NZPCs hut not IZPCs with 1 μM MIB. Steady‐state availability of ICaLwas altered with I μM MIB in both cell types (mean ± SEM) (V0.5= ‐22 ± 4 mV for NZPC and ‐25 ± 5 mV for IZPC before drug; ‐63 ± 9 mV for NZPC and ‐67 ± 6 mV for IZPC after drug: P < 0.05). For ICaTV0.5(‐50 ± 3 mV for NZPC and ‐52 ± 1 mV for IZPC before drug) shifted 10 ‐60 ± 2 mV (NZPC) and ‐62 ± 3 mV (IZPC) (P < 0.05) after drug. We also determined the effects of MIB on spontaneously heating Purkinje normal fibers and on depolarized abnormally automatic fibers from the infarcted heart using standard microelectrode techniques. When NZPC and IZPC fibers were superfused with [K+]0= 2.7 mM, MIB 3 μM and 10 μM had no effect on rate or the maximum diastolic potential, but action potential plateau shifted to more negative values, the slope of repolarization phase 3 decreased, and action potential duration increased.

Conclusion: MIB blocks L‐ and T‐type Ca2+currents in Purkinje myocytes hut lacks an effect on either normal or abnormal automaticity in Purkinje fibers.
Sequential Change in Action Potential of Rabbit Epicardium During and Following Radiofrequency Ablation
Authors: WU CHAU‐CHUNG , FASCIANO ROBERT W. , CALKINS HUGH , TUNG LESLIE
Published: April 2007

Action Potential Change During RF Ablation. introduction: Although radiofrequency (RF) catheter ablation is used to treat certain cardiac arrhythmias, little is known regarding transient changes in cellular electrophysiology during and following RF delivery. Optical recordings of action potential (OAP) with voltage‐sensitive dyes allow immunity from electrical noise during RF delivery. The purpose of this study was to clarify the possible synergistic effects of both the thermal and electrotonic components of RF ablation.

Methods and Results: In this study, OAPs were recorded on the epicardium of 16 isolated Langendorff‐perfused rabbit hearts within or adjacent to lesions made by RF catheters. Hearts were perfused at room temperature with Tyrode's solution containing 2,3‐butanedione monoxime and stained by the voltage‐sensitive dye di‐4‐ANEPPS. OAPs were recorded before, during, and after RF pulses. Within the lesion, the action potential duration at 80% repolarization (APD80) of OAP decreased rapidly during the RF pulse, without recovery following the pulse. In the border zone surrounding the lesion, the RF energy resulted in a rapid decrease in APD80, which recovered promptly after the pulse (recovery time constant: 82 ± 37 sec). APD80 was nonlinearly related to temperature during the RF ablation and responded faster to RF ablation than to purely thermal injury.

Conclusion: The application of RF energy results in significant changes in myocardial cellular electrophysiologic properties. The RF energy bas a combination of thermal and electrotonic effects on the myocardial tissue. The results of this in vitro study may illustrate the cellular basis for commonly observed phenomena in clinical practice.
Preventing Sudden Death after Repair of Tetralogy of Fallot:
Authors: SAUL J. PHILIP , ALEXANDER MARK E.
Published: April 2007

Arrhythmias in Tetralogy of Fallot. Sudden arrhythmic death in patients with repaired tetralogy of Fallot or its variants has a variety of causes. Consequently, it can serve as a paradigm for management of potentially malignant arrhythmias in all pediatric patients, particularly with regard to the use of nonpharmacologic therapy for management. Five cases are presented as touchpoints for discussion and demonstrate a number of important issues concerning the assessment and reduction of sudden cardiac death risk in these patients. First, there are no clinical parameters that can be used to accurately assess risk. Second, pharmacologic agents alone rarely are adequate therapy. Third, catheter ablation and antitachycardia devices continue to play an ever increasing role in management of these patients, and, finally, additional data are necessary to establish clear management guidelines in patients with congenital heart disease at risk for arrhythmic death.
Cardiac Parasympathetic Stimulation via QRS‐Synchronous Low‐Energy Shocks In Humans
Authors: FRIEDMAN PAUL A. , HILL MICHAEL R.S. , STANTON MARSHALL S.
Published: April 2007

Parasympathetic Stimulation via Intracardiac Shocks. Introduction: In patients receiving test shocks to verify lead connections at implantation, we anecdotally have observed postshock delay. The purpose of this study was to determine whether QRS‐synchronous low‐energy shocks delivered by implantable defibrillators result in postshock cycle length prolongation, and to determine the mechanism of this phenomenon.

Methods and Results: Twenty‐five patients undergoing defibrillator testing were studied, three with epicardial patches and 22 with transvenous leads. Each patient received QRSsynchronous shocks of 0.2, 0.4, 0.6, and 2.0 J in random order. Patients were further randomized to receive either saline or 2.0 mg atropine intravenously, and then given a second sequence of shocks. At baseline, the postshock cycle length (1, 035 ± 245 msec) was significantly longer than the preshock cycle length (968 ± 177 msec, P = 0.01). In patients with a coronary sinus (CS) or superior vena cava (SVC) lead, the mean prolongation was 91 ± 160 msec, compared with 12 ± 106 msec for patients without such a lead (P < 0.0001). All energy levels resulted in significant postshock prolongation compared with preshock cycle lengths (P < 0.05). Postshock prolongation before atropine was 76 ± 162 msec, compared with −13 ± 52 msec afterward (P < 0.00001). Biphasic shocks resulted in greater postshock prolongation than monophasic shocks of equal energy.

Conclusion: Low‐energy shocks delivered during the QRS complex cause postshock cycle length prolongation in man. This effect required the presence of a CS or SVC lead. Atropine inhibited this effect, suggesting the phenomenon was mediated by direct cardiac parasympathetic nerve stimulation by the intracardiac shock.
Catecholamine Facilitated Reentrant Ventricular Tachycardia: Uncoupling of Adenosine's Antiadrenergic Effects
Authors: LERMAN BRUCE B. , STEIN KENNETH M. , MARKOWITZ STEVEN M. , MITTAL SUNEET , SLOTWINER DAVID
Published: April 2007

Catecholamine Facilitated Reentry. Introduction: Adenosine has no direct electrophysiologic function in ventricular tissue, but in the presence of cyclic adenosine monophosphate (cAMP), stimulation exerts a potent antiadrenergic effect. This effect has been exploited in the recognition and treatment of ventricular tachycardia (VT) due to cAMP‐mediated triggered activity and automaticity, which are respectively terminated and suppressed by adenosine. However, the effects of adenosine on catecholamine‐facilitated reentrant VT are unknown. A pivotal issue is whether termination of VT with adenosine is mechanism specific, or whether it represents a nonspecific antiadrenergic effect. The purpose of this study, therefore, was to define the effects of adenosine in a well‐characterized group of patients with catecholamine‐facilitated reentrant VT.

Methods and Results: Fourteen patients with catecholamine‐facilitated reentry were studied. In the 12 patients with structural heart disease (including two with arrhythmogenic right ventricular dysplasia), adenosine (260 to 550 μ/kg) failed to slow or terminate VT. Two patients without structural heart disease had intrafascicular tachycardia confined to the left posterior fascicle, a calcium‐dependent, verapamil‐sensitive arrhythmia. In the absence of isoproterenol, verapamil terminated VT but adenosine did not. However, when isoproterenol was subsequently required for facilitation of tachycardia, adenosine terminated VT in both patients.

Conclusion: Adenosine has no antiadrenergic (antiarrhythmic) effect in patients with catecholamine‐ facilitated VT due to structural heart disease. Patients with verapamil‐sensitive, left posterior intrafascicular reentry have an unusual dual response to adenosine. In the unstimulated state, adenosine has no effect on basal inward calcium current and, therefore, no effect on VT. However, when induction of VT requires amplification of the inward calcium current through stimulation of cAMP, adenosine sensitivity of VT becomes manifest. These results indicate that with few exceptions, termination of VT with adenosine is strongly suggestive of a cAMP‐mediated triggered mechanism rather than reentry.
Bezold‐Jarisch‐Like Reflex During Radiofrequency Ablation of the Pulmonary Vein Tissues in Patients with Paroxysmal Focal Atrial Fibrillation
Authors: TSAI CHIN‐FENG , CHEN SHIH‐ANN , TAI CHING‐TAI , CHIOU CHUEN‐WANG , PRAKASH V.S. , YU WEN‐CHUNG , HSIEH MING‐HSIUNG , DING YU‐AN , CHANG MAU‐SONG
Published: April 2007

Pulmonary Vein Ablation‐Induced Bradycardia. Introduction: Information is lacking about the occurrence of radiation‐related proarrhythmic events during application of radiofrequency (RF) energy at (he pulmonary veins in patients with paroxysmal focal atrial fibrillation. The purpose of this study was to assess the theoretical risk of reflex bradycardia and hypotension response during RF ablation of these regions rich in endocardial nerve terminals.

Methods and Results: Among the 40 consecutive patients (29 men, 11 women; mean age 65 ± 12 years) with clinically documented frequent attacks of paroxysmal atrial fibrillation who underwent superior pulmonary vein ablation for left local atrial fibrillation, 6 patients (15%) developed bradycardia‐hypotension syndrome during energy delivery. A single atrial fibrillation trigger focus in the left or right superior pulmonary vein was found in 3 and 1 patients, respectively. Two patients had two trigger foci originating from the orifice or proximal part of both superior pulmonary veins. After RF current was applied for a period of 14 ± 10 seconds, 2 patients developed functional rhythm and sinus bradycardia, another 2 patients had profound sinus bradycardia, I patient had two episodes of sudden onset of complete AV block with resultant 9.5‐second a systole, and I patient showed profound sinus bradycardia, transient AV block, and an K‐second asystole due to sinus arrest. Blood pressure fell when any substantial bradyarrhythmias occurred. All 6 patients were free of rhythm disturbances during The postablation follow‐up period (mean 8 ± 2 months).

Conclusion: RF catheter ablation of the pulmonary vein tissues could evoke a variety of profound bradycardia‐hypotension responses. The Bezold‐Jarisch‐like reflex might be the underlying mechanism.
Preexcitation Secondary to Fasciculoventricular Pathways in Children: A Report of Three Cases
Authors: SALLEE DENVER , Van HARE GEORGE F.
Published: April 2007

Fasciculoventricular Pathways in Children. Introduction: Fasciculoventricular connections are the rarest form of accessory pathways leading to preexcitation. Electrophysiologic characteristics of these pathways include ventricular preexcitation with normal PR and AH intervals and short HV intervals during sinus rhythm. In addition, atrial overdrive pacing prolongs the PR interval without affecting the HV interval or the degree of preexcitation.

Methods and Results: From March 1994 through February 1997, 3 of 59 pediatric patients referred for electrophysiologic study for preexcitation on surface ECGs were found to have iasciculoventricular pathways. Two patients had no inducible supraventricular tachycardia. One patient had successful ablation of both a left lateral pathway and a concealed antentlateral pathway that had facilitated antidromic and orthodromic supraventricuiar tachycardias, respectively.

Conclusion: Children often manifest minimal preexcitation via accessory AV pathways due to rapid AV conduction and/or left lateral pathway location. Fasciculoventricular pathways may masquerade as Wolff‐Parkinson‐White syndrome. Separation of the two diagnoses depends on the demonstration of specific electrophysiologic criteria.
Heterogeneous Loss of Connexin43 Protein in Ischemic Dog Hearts
Authors: HUANG XIAO‐DI , SANDUSKY GEORGE E. , ZIPES DOUGLES P.
Published: April 2007

Heterogeneous Loss of Connexin43 Protein in Ischemic Dog Hearts. Introduction: Ischemia causes cell decoupling in the myocardium. Prolonged ischemia activates proteases and causes degradation of structural proteins as well as gap junctions. There is little information about the degradation of gap junction protein during the early time period after acute ischemia. The purpose of the present study was to investigate connexin43 (Cx43) protein degradation and distribution patterns in (he canine left ventricular wall during 1 to 6 hours of ischemia.

Methods and Results: Ischemia of canine left ventricular myocardium was induced by ligation of the left anterior descending coronary artery. Following a period of in situ ischemia of up to 6 hours, samples were harvested, and standard paraffin slides were prepared for Cx43 and wheat germ agglutinin double labeling. Cx43 distribution was visualized by confocal microscopy. In controls, homogeneous distribution of Cx43 staining was determined. Ischemia caused a loss of Cx43 with a heterogeneous pattern by mixing foci of infarcted cells among normal cardiac myocytes. To determine if the changes were induced by heterogeneous reduction in the blood supply, an in vitro ischemic model was studied to induce more homogeneous ischemia. Western blot analysis of these in vitro ischemic tissue samples revealed a reduction of Cx43 protein concentration with a 50% decay time of 4.8 hours. Cx43 dephosphorylation was detected after 1 hour of in vitro ischemia. Heterogeneous loss of Cx43 was found in the in vitro ischemic tissue. There were no. significant changes in Cx43 staining density during the first hour of ischemia at a time when dephospharylation of the protein was observed. After 1 hour of ischemia, Cx43 was reduced at intercalated disk areas, and. after 6 hours, most Cx43 disappeared at intercalated disk areas, while small amounts of Cx43 remained at side‐to‐side junctions.

Conclusion: Cx43 undergoes both distribution and concentration changes following acute cardiac Ischemia. The loss of Cx43 protein is heterogeneous. Cx43 dephosphorylation occurred within 1 hour following ischemia.
Field Stimulation of Isolated Chick Heart Cells
Authors: STONE BRADLEY A. , LIEBERMAN MELVYN , KRASSOWSKA WANDA
Published: April 2007

Activation Thresholds for Chick Heart Cells. Introduction: This study examines the accuracy of using membrane models to predict activation thresholds for chick heart cells during field stimulation.

Methods and Results: Activation thresholds were measured experimentally in ten embryonic chick heart cells at 37°C for stimulus durations 0.2 to 40 msec. Activation was assessed by observing the mechanical twitch of the cell. The heart cells ranged in diameter from 15.0 to 26.7μm. Since the electric field required for activation depends on diameter, the thresholds were expressed as the maximum field‐induced transmembrane potential, Vth= 1.5 a Eth where a is the cell radius and Eth is the strength of the electric field at threshold. A cell model was created using a singular perturbation method and membrane models describing the ionic currents of a heart cell. The study used membrane models of Ebihara and Johnsim (1980), Luo and Rudy (1991), Shrier and Clay (1994), and their combinations. The results show that for stimuli longer than 1 msec, theoretical activation thresholds were within one standard deviation of experimental thresholds. For shorter stimuli, the models failed to predict thresholds because of a premature deactivation of the sodium current. The modification of the in gates dynamics, so that they closed with a time constant of 1.4 msec, allowed to predict thresholds for all durations. The root mean square error between experimental and theoretical thresholds was 6.14%.

Conclusions: The existing membrane models can predict thresholds for field stimulation only for stimuli longer than 1 msec. For shorter stimuli, the models need a more accurate representation of the sodium tail current.
Clinical Profile of Commotio Cordis: An Under Appreciated Cause of Sudden Death in the Young During Sports and Other Activities
Authors: MARON BARRY J. , LINK MARK S. , WANG PAUL J. , MARK ESTES N.A.
Published: April 2007

Blunt Chest Impact Leading to Cardiac Arrest. Not particularly well recognized are athletic Held catastrophes in which virtually instantaneous cardiac arrest is produced by nonpenetrating chest blows in the absence of heart disease or identifiable morphologic injury to the chest wall or heart (commotio cordis). To better characterize the clinical profile of this syndrome, we have assembled 70 cases, including 34 occurring during organized competitive athletics and 36 others that occurred during informal recreational sports at home, school or the playground, or during nonsporting activities. Ages were 2 to 38 (mean age: 12) with 70% < 16 years old. Most common sports involved were youth baseball (n = 40), softball (n = 7), and ice hockey (n = 7). Seven (10%) of the 70 commotio cordis victims, including six with documented ventricular fibrillation, have survived the consequences of their chest blow. Eleven of the events (16%) occurred despite the presence of chest padding believed to be potentially protective. Four victims experienced modest chest blows while in circumstances completely unrelated to sports activities; three of the four individuals who delivered these blows were ultimately convicted of criminal acts within the justice system. An experimental model of low‐energy chest wall impact demonstrates that commotio cordis events are due largely to the exquisite timing of blows during a narrow window within the repolarization phase of the cardiac cycle, 15 to 30 msec prior to the peak of the T wave.
Heterogeneous Changes in Electrophysiologic Properties in the Paroxysmal and Chronically Fibrillating Human Atrium
Authors: TSE HUNG‐FAT , LAU CHU‐PAK , AYERS GREGORY M.
Published: April 2007

Heterogeneous Changes in Atrial Electrophysiologic Properties. Introduction: The regional changes in atrial elettrophysiologic properties related to atrial fibrillation (AF) in patients with paroxysmal AF (PAF) and chronic AF (CAF) remain unclear. The purpose of this study was to investigate the regional changes in atrial electrophysiology in patients with AF. Methods and Results: We evaluated the atrial electrophysiology at different sites (high right atrium, low right atrium [LRAJ, and distal coronary sinus [DCS]) in 11 patients with CAF, 8 patients with PAF, and 10 controls. Patients with CAF had significantly prolonged interatrial conduction and corrected sinus node recovery time, and shortened atrial effective refractory period (ERP) with loss of rate‐related adaptation in the DCS, hut had paradoxic prolongation of atrial ERP in the LRA, as compared with patients with PAF and the controls. As a result, the spatial distribution of atrial ERP that was observed in the controls and in patients with PAF was reversed in patients with CAF, without an increase in the dispersion of atrial refractoriness. Patients with PAF showed intermediate changes in atrial conduction times and atrial refractoriness as compared with patients with CAF and controls.

Conclusion: There was a regional heterogeneity on the changes of atrial electrophysiology in different parts of the atrium, and the “normal” spatial distribution of atrial refractoriness was reversed in patients with CAF. The electrophysiologic changes observed in patients with PAF appear to behave as if in transition from the control state to CAF, suggesting progressive changes in atrial electropbysiologic properties.
Double Multielectrode Mapping Catheters Facilitate Radiofrequency Catheter Ablation of Focal Atrial Fibrillation Originating from Pulmonary Veins
Authors: HSIEH MING‐HSIUNG , CHEN SHIH‐ANN , TAI CHING‐TAI , TSAI CHIN‐FENG , PRAKASH V.S. , YU WEN‐CHUNG , LIU CHUEN‐CHIA , DING YU‐AN , CHANG MAU‐SONG
Published: April 2007

Ablation of Focal AF. Introduction: Several reports have demonstrated that focal atrial fibrillation (AF) may arise from pulmonary veins (PVs). The purpose of this study was to investigate the safety and efficacy of using double multielectrode mapping catheters in ablation of focal AF.

Methods and Results: Forty‐two patients (30 men, 12 women, age 65 ± 14 years) with frequent attacks of paroxysmal AF were referred for catheter ablation. After atrial transseptal procedure, two long sheaths were put into the left atrium. Two decapolar catheters were put into the right superior PV (RSPV) and left superior PV (LSPV), or inferior PVs if necessary, guided by pulmonary venography. All the patients had spontaneous initiation of AF either during baseline (2 patients), after isoproterenol infusion (8 patients) or high‐dose adenosine (2 patients), after short duration burst pacing under isoproterenol (14 patients), or after cardioversion of pacinginduced AF (16 patients). The trigger points of AF were from the LSPV (12 patients), RSPV (8 patients), and both superior PVs (19 patients). The trigger points from PVs (total 61 points) were 18 (30%) in the ostium of PVs and 43 inside the PVs (9 to 40 mm). After 6 ± 3 applications of radiofrequency energy, 57 of 61 triggers were completely eliminated, and the other 4 triggers were partially eliminated. During a follow‐up period of 8 ± 2 months, 37 patients (88%) were free of symptomatic AF without any antiarrhythmic drugs. Twenty patients received a transesophageal echocardiogram, and 19 showed small atrial septal defects (2.8 ± 1.2 mm) with trivial shunt. Fifteen defects closed spontaneously 1 month later.

Conclusion: The technique using double multielectrode mapping catheters is a relatively safe and highly effective method for mapping and ablation of focal AF originating from PVs.
Efficacy and Safety of the Initial Use of Stability and Onset Criteria in Implantable Cardioverter Defibrillators
Authors: WEBER MAX , BÖCKER DIRK , BÁNSCH DIETMAR , BRUNN JÜRGEN , CASTRUCCI MARCO , GRADAUS RAINER , BREITHARDT GÜNTER , BLOCK MICHAEL
Published: April 2007

Primary Programming of Stability and Onset Criteria. Introduction: Inappropriate therapies are the most frequent adverse event in patients with implantable cardioverter defibrillators (ICDs). Most ICDs offer a stability criterion to discriminate ventricular tachycardia (VT) from atrial fibrillation and an onset criterion to discriminate VT from sinus tachycardia. The efficacy and safety of these criteria, if used immediately after implantation, is unknown.

Methods and Results: In a case control study, 87 patients in whom stability and onset criteria had been activated immediately after ICD implantation were matched to 87 patients in whom these criteria had not been activated. The groups were matched for known predictors of inappropriate therapies. With stability and onset criteria off, 24 patients (28%) received inappropriate therapies due to atrial fibrillation (n = 14) or sinus tachycardia (n = 11); with stability and onset on, only 11 patients (13%) were treated by the ICD due to atrial fibrillation (n = 5) or sinus tachycardia (n = 7) (log rank: P = 0.029). Five patients suffered inappropriate therapies despite the fact that onset (n = 4) or stability (n = 1) criteria were not fulfilled once tachycardias continued for a prespecified duration. Only one patient experienced a failure to detect VT due to the onset criterion; none because of stability.

Conclusion: The immediate use of stability and onset criteria after ICD implantation reduces inappropriate therapies due to atrial fibrillation and sinus tachycardia. Because of the potential for underdetection of VT, this approach should be limited to tachycardia rates hemodynamically tolerated by the patient.
Pharmacologic Cardioversion of Chronic Atrial Fibrillation in the Goat by Class IA, IC, and III Drugs
Authors: WIJFFELS MAURITS C.E.F. , DORLAND RICK , ALLESSIE MAURITS A.
Published: April 2007

Pharmacologic Cardioversion of Chronic AF. Introduction: Recently, we reported that repetitive induction of atrial fibrillation (AF) in the goat causes electrical remodeling of the atria leading to the development of sustained AF. The aim of the present study was to compare Class IA, IC, and III drugs in their ability to cardiovert chronic AF in remodeled atria.

Methods and Results: In 16 goats with sustained AF, hydroquinidine (HQ), cibenzoline (Ci), flecainide (FI), and d‐sotalol (dS) were infused. HQ, Ci, FI, and dS restored sinus rhythm (SR) in 83%, 91%, 67%, and 92% of the cases, while adverse drug effects occurred in 17%, 36%, 56%, and 8%. Prior to restoration of SR, AF cycle length prolonged by 68%, 103%, 53%, and 20%, respectively. The QRS width increased by 14%, 64%, and 58% (HQ, Ci, and FI), and remained unchanged by administration of dS. RR intervals were slightly prolonged by HQ, Ci, and FI, and markedly prolonged by dS (48%). The QT interval was moderately prolonged by HQ, Ci, and FI, and considerably by dS (34%). QTc was only slightly prolonged by each of the drugs. Directly after cardioversion of AF, the atrial refractory period was 87 ± 29 (HQ), 119 ± 32 (Ci), 66 ± 10 (FI), and 73 ± 18 msec (dS) (control: 146 ± 18 msec). Atrial conduction velocity was 85 ± 6, 71 ± 11, 86 ± 12, and 110 ± 11 cm/sec compared with a control value of 116 ± 10 cm/sec. Because directly after cardioversion the atrial wavelength was still very short (5.7 to 8.4 cm), the vulnerability for AF was still very high, and a single premature beat reinduced AF in 71% (Ci) to 100% (HQ, FI, and dS) of the cases.

Conclusion: In a goat model of sustained AF, Class IA, IC, and III drugs restored sinus rhythm in 67% to 92% of the cases. However, after cardioversion, the atrial wavelength was still abnormally short, and AF was readily inducible in 71% to 100% of the cases.
ST Segment Elevation in the Right Precordial Leads Induced with Class IC Antiarrhythmic Drugs
Authors: FUJIKI AKIRA , USUI MASAHIRO , NAGASAWA HIDEHIKO , MIZUMAKI KOICHI , HAYASHI HIDEKI , INOUE HIROSHI
Published: April 2007

ST Segment Elevation by Class IC Drugs. We evaluated two patients without previous episodes of syncope who showed characteristic ECG changes similar to Brugada syndrome following administration of Class IC drugs, flecainide and pilsicainide, but not following Class IA drugs. Patient 1 had frequent episodes of paroxysmal atrial fibrillation resistant to Class IA drugs. After treatment with flecainide, the ECG showed a marked ST elevation in leads V2, and V3, and the coved‐type configuration of ST segment in lead V2. A signal‐averaged ECG showed late potentials that became more prominent after flecainide. Pilsicainide, a Class IC drug, induced the same ST segment elevation as flecainide, but procainamide did not. Patient 2 also had frequent episodes of paroxysmal atrial fibrillation. Pilsicainide changed atrial flbrillation to atrial flutter with 2:1 ventricular response, and the ECG showed right bundle branch block and a marked coved‐type ST elevation in leads V1 and V2. After termination of atrial flutter, ST segment elevation in leads V1 and V2/ continued. In this patient, procainamide and quinidine did not induce this type of ECG change. In conclusion, strong Na channel blocking drugs induce ST segment elevation similar to Brugada syndrome even in patients without any history of syncope or ventricular fibrillation.