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MEETING HIGHLIGHTS

Highlights of Heart Rhythm 2004, the Annual Scientific Sessions of the Heart Rhythm Society: May 19 to 22, 2004, in San Francisco, California

Anne B. Curtis, MD, FACC^*,*, William T. Abraham, MD, FACC, Peng-Sheng Chen, MD, Kenneth A. Ellenbogen, MD, FACC, Andrew E. Epstein, MD, FACC^||, Paul A. Friedman, MD, FACC^¶, Stefan H. Hohnloser, MD, FACC^#, Ronald J. Kanter, MD^** and William G. Stevenson, MD, FACC

^* Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida
Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio
Cedars-Sinai Medical Center, Los Angeles, California
Department of Medicine, Medical College of Virginia, Richmond, Virginia
^|| Division of Cardiovascular Diseases, The University of Alabama at Birmingham, Birmingham, Alabama
^¶ Division of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
^# Division of Cardiology, J.W. Goethe University, Frankfurt, Germany
^** Division of Pediatric Cardiology, Duke University Medical Center, Durham, North Carolina
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts

Manuscript received July 6, 2004; revised manuscript received July 13, 2004, accepted July 13, 2004.

^* Reprint requests and correspondence: Dr. Anne B. Curtis, University of Florida, 1600 S.W. Archer Road, Box 100277, Gainesville, Florida 32610 (Email: curtisa{at}medicine.ufl.edu).

	Abstract

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
Heart Rhythm 2004, the 25th Annual Scientific Sessions of the Heart Rhythm Society (formerly the North American Society of Pacing and Electrophysiology), met in San Francisco in May 2004. The meeting is the world's premier forum for the presentation of research and the exchange of state-of-the-art information in cardiac electrophysiology and pacing. Major new research findings were presented on the value of implantable cardioverter-defibrillator therapy, noninvasive methods for risk stratification, treatment of vasovagal syncope, radiofrequency ablation for atrial fibrillation, resynchronization therapy for heart failure, and new insights from basic science into the mechanisms of cardiac arrhythmias.

Abbreviations and Acronyms   AF = atrial fibrillation   AV = atrioventricular   Cai = intracellular calcium   CRT = cardiac resynchronization therapy   DCM = dilated cardiomyopathy   ECG = electrocardiographic   HCM = hypertrophic cardiomyopathy   ICD = implantable cardioverter-defibrillator   LV = left ventricular   LVEF = left ventricular ejection fraction   MI = myocardial infarction   NYHA = New York Heart Association   PV = pulmonary vein   QRSd = QRS duration   RF = radiofrequency   RV = right ventricular   TWA = T-wave alternans   VT = ventricular tachycardia

• The implantable cardioverter-defibrillator (ICD) was found to reduce all-cause mortality for patients with nonischemic dilated cardiomyopathy (DCM) in one trial but, in another, yielded little benefit if implanted early after a large myocardial infarction (MI).

• An antiarrhythmic agent that was used as an adjunct to the ICD may be more suited to this role than is the standard agent amiodarone.

• The presence or absence of T-wave alternans (TWA) may be as useful as QRS duration (QRSd) for refining risk stratification of patients at already known high risk of death due to ventricular arrhythmias.

• A beta-blocker has been judged the first proven agent for prevention of vasovagal syncope, although only for a specific age group.

• A verdict delivered by a randomized trial may do much to settle the debate over the optimal method of abolishing atrial fibrillation (AF) by catheter-based ablation of cardiac tissue.

• Biventricular pacing for cardiac resynchronization therapy (CRT) in patients with heart failure was the meeting's most prominent theme, and relevant preliminary reports pointed to a broadening of candidacy for the treatment.

The following is a brief summary of the meeting highlights.

	Noninvasive evaluation

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
A growing trend in the noninvasive evaluation of arrhythmic risk is further stratification of patients at known high risk of arrhythmic death, including those with impaired left ventricular (LV) function. One potential benefit is more cost-effective selection of candidates for the ICD. Several meeting reports pointed to a major role for TWA testing in such risk refinement, perhaps an even larger role than is accorded to analysis of the QRSd.

Currently, the Centers for Medicare and Medicaid use the QRSd in deciding whether to reimburse for ICD use in patients without traditional indications for implantation, such as documentation of inducible or spontaneous malignant ventricular arrhythmias. Reimbursement is reserved for patients with a QRSd >120 ms and additional risk factors that include a history of MI and a left ventricular ejection fraction (LVEF) 30%, based on the results of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II study. At the San Francisco meeting, Bloomfield et al. (1) reported that an abnormal (positive or indeterminate) TWA exercise test was a better predictor of all-cause mortality than was a QRSd >120 ms among 177 "MADIT II-like" patients in long-term follow-up. Similarly, Zabel et al. (2) found that a positive TWA test was a long-term predictor of a combined end point of cardiac death or major arrhythmic events (arrhythmogenic syncope or appropriate shock delivery in patients with ICDs) among patients with DCM.

Numerous papers testified to the seemingly inexhaustible potential of the venerable 12-lead surface electrocardiogram (ECG). In a study of 164 patients with ECG hallmarks of the Brugada syndrome, Nava et al. (3) found that sudden death or ventricular fibrillation during long-term follow-up was independently predicted by the degree of ST-segment elevation in lead VI, the amplitude of the S-wave in lead I, and the presence of an S-wave in lead II. A clinical study by Sanders et al. (4) was one of two that yielded ECG markers for differentiating various forms of atrial flutter. Those, for instance, that helped distinguish left atrial flutter included an isoelectric P-wave in lead I/aVL,no transition from negative to positive or vice versa in the chest leads, and a low P-wave amplitude in all leads except VI.

	Devices for tachycardias and bradycardias

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
There were important presentations on the use of the ICD for patients at risk of arrhythmic death but lacking traditional indications for implantation. Among previously reported randomized studies of such patients, the MADIT II found a statistically significant all-cause mortality advantage in supplementing conventional medical therapy with an ICD for patients with an LVEF 30% and a history of MI. Similarly, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) found that the ICD but not amiodarone therapy significantly reduces all cause five-year mortality in patients with ischemic or nonischemic New York Heart Association (NYHA) functional class II or III heart failure and an LVEF 35%. At the meeting, Jeanne E. Poole, MD (University of Washington, Seattle, Washington), reported that a new analysis of SCD-HeFT results could not identify any ECG markers for selecting patients most likely to benefit from ICD therapy. A QRSd >120 ms did not predict mortality benefit in this new, focused, SCD-HeFT analysis.

N. A. Mark Estes, MD (New England Medical Center, Boston, Massachusetts), reported on the Defibrillators in Non-Ischemic-cardiomyopathy Treatment Evaluation (DEFINITE) trial, which compared medical therapy alone with medical therapy plus an ICD for patients with nonischemic DCM and an LVEF 35%. The ICD was associated with: 1) a reduction in all-cause mortality that was statistically non-significant overall but significant for patients in NYHA functional class III (as opposed to I or II) heart failure, and 2) a significant reduction in the five-year rate of sudden cardiac death. Because of optimized medical therapy, the annual risk of death in the control group was only 7%.

In the Defibrillators in Acute Myocardial Infarction Trial (DINAMIT), patients with an LVEF 35% and reduced heart rate variability were randomized to receive or not receive an ICD 6 to 40 days after an acute MI. A previously reported DINAMIT analysis had found that the ICD significantly reduced arrhythmic but not all-cause death owing to an increase in nonarrhythmic death. A new DINAMIT analysis, reported by Paul Dorian, MD (University of Toronto, Toronto, Ontario, Canada), found that: 1) the increase in nonarrhythmic death among ICD recipients was confined to those receiving shocks, and 2) the majority of the nonarrhythmic deaths were cardiovascular. One potential explanation for the superior ICD results with post-MI patients in MADIT II is that the average patient was enrolled six years after the acute MI, allowing for greater infarct stability. The DINAMIT study indicates that patients with a heavy ischemic burden early after acute MI are questionable candidates for the ICD.

Presentations on antibradycardia devices highlighted efforts to achieve safe and effective function within magnetic resonance scanners; the emergence of remote monitoring and automaticity (e.g., automatic atrial capture); and progress in developing biologic pacemakers (e.g., by genetically engineered conversion of human ventricular myocytes to pacemaker cells with spontaneous and rhythmic action potentials). An assumption that suppression of premature atrial contractions will prevent AF has encouraged programming of pacemakers to high rates. One presentation described a relevant randomized comparison of two pacing algorithms: one providing high-rate antibradycardia pacing and preventive antitachycardia pacing, with the other employing antitachycardia pacing algorithms alone without high-rate background atrial pacing. The results showed fewer episodes of atrial arrhythmias without the use of high-rate back-up atrial pacing.

Daoud et al. (5) reported a new analysis from the Post AV Node Ablation Evaluation (PAVE) study, a randomized comparison of biventricular and right ventricular (RV) apical pacing in patients with chronic AF after atrioventricular (AV) node ablation to control rapid ventricular rates. An earlier PAVE analysis had linked biventricular pacing to significantly greater improvement in achieved distance on a six-minute walk test and in scores on a validated global health inventory. The new analysis found that the advantage on both assessments was confined to patients with an LVEF 35% before AV node ablation. A follow-up of only six months precluded exploration of whether long-term RV apical pacing might impair LV function. However, given previous favorable evidence on the long-term results of such pacing after AV node ablation, the investigators judged it acceptable in patients with baseline preservation of LV function.

	Cardiac resynchronization/ventricular function

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
Testifying to the explosion of interest in biventricular pacing, one-third to one-half of the device presentations concerned resynchronization therapy, an approximate fivefold increase over the past five years. Biventricular pacing currently is approved only for NYHA functional class III and IV heart failure patients with an LVEF 35% and a QRSd 120 ms. Many presentations at the meeting focused on CRT for subgroups of patients who were not well-represented in previous clinical trials. For example, does baseline AF predict lesser mortality benefit? Verdicts conflicted, one being that it does for heart failure patients who are in NYHA functional class III but not IV (6). Lead-placement failure was found to be more common among women than men, but, in its absence, gender did not predict mortality benefit (7). Patients with right bundle-branch block did as well as the majority with left bundle-branch block, but patients with non-specific intraventricular conduction delay did not (8). Virtually all the subpopulation findings, however, came from studies with small cohorts, retrospective designs, or other limitations that precluded definitive analysis (9).

There was preliminary support for extending CRT to wide-QRS patients with mild heart failure. In the previously reported Multicenter InSync Randomized Clinical Evaluation (MIRACLE) ICD II trial, randomization of such patients to CRT versus no CRT yielded better six-month outcomes in terms of LVEF and a combined clinical end point of death, hospitalization, and a patient self-assessment score. Similarly, in a comparison of NYHA functional class II patients and class III and IV counterparts for the three-month effects of CRT, no differences in six-min walk test performance were observed.

In a boost to the controversial concept of CRT by single-site pacing, a randomized comparison of CRT by biventricular or isolated LV pacing for standard candidates indicated that both yield similar long-term results in terms of LV function, mortality, and complications (10).

Heart failure aside, data were presented on the potential adverse effects of standard RV apical anti-bradycardia pacing. The latter is a known cause of mechanical interventricular dyssynchrony, a likely explanation for its association with deterioration of LV function. Further doubts about single-site RV pacing were raised by a crossover comparison of two six-month DDD regimens for patients with sinus bradycardia, preserved AV conduction, and a narrow QRS. Relative to pacing that capitalized on spontaneous AV conduction, pacing that mandated RV apical stimulation was associated with impaired LV contraction and a reduced quality of life (11).

	Catheter ablation

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
Research into radiofrequency (RF) catheter ablation for AF and ventricular tachycardia (VT) was highlighted at the meeting. For AF, an RF catheter is passed into the left atrium by transseptal puncture for ablation around the pulmonary veins (PVs), which are often the sources of triggering discharges. Debate continues as to the optimal approach and the importance of complete electrical isolation of the PVs. Of two rival methods, one involves segmental tissue ablation near the PV ostium under guidance from a recording catheter seeking to abolish PV potentials. The second method is an anatomically guided circumferential approach that widely encircles the PV ostium. Lemola et al. (12) reported that the latter approach usually fails to achieve electrical isolation of all PVs, but persistent PV conduction does not predict recurrence of AF. Another study randomized 100 patients to circumferential or segmental ablation for drug-refractory AF. As described at a late-breaking clinical trial session by Claus Schmitt, MD (German Heart Center, Munich, Germany), Holter monitoring at six months revealed a higher rate of freedom from AF and/or atrial flutter (considered a proarrhythmic treatment effect) in the segmental ablation group (71% vs. 47%; p = 0.45), challenging previous evidence of greater efficacy for circumferential ablation. Interestingly, the very intensive monitoring during follow-up convincingly demonstrated that recurrent arrhythmias are often asymptomatic, illustrating the limitations of using patient-reported symptoms to assess efficacy.

Schreieck et al. (13) explored RF ablation to prevent VT recurrences for patients receiving ICDs. Patients receiving ICDs for sustained monomorphic VT caused by previous MIwere randomized to undergo or not undergo ablation. Ablation did not significantly reduce the proportion of patients receiving ICD shocks for VT during follow-up but did reduce the number of VT episodes. Ventricular tachycardia recurrences after ablation occurred because ofan inducible VT that had been judged "non-clinical" and not targeted by ablation, or to a new VT from a region that had not been ablated, or to recurrence of the initial VT attributed to healing of the initially effective RF, arguing for more extensive ablation procedures for this type of VT (13).

Many VTs are hemodynamically unstable, such that precise mapping during VT is not possible. During stable sinus rhythm, however, the infarct substrate that causes many VTs can potentially be identified from maps that show the amplitude of the electrical signal. This substrate area is usually very large such that complete catheter ablation is not practical. Two reports explored approaches to guiding ablation of unmappable forms of VT. In post-MI patients, Wilber et al. (14) found that pace-mapping during sinus rhythm identified potential VT exit regions in the infarct border where lines of RF ablation often achieved ablation of unstable VT. In an alternative approach, also during stable sinus rhythm, Nakagawa et al. (15) assessed the electrograms recorded in the infarct region for the presence of isolated late potentials that can represent islands of surviving myocardium that support reentry. They observed that elimination of all detected isolated late potentials in a low-voltage area by RF ablation usually abolished unmappable VTs. The presence of a relatively small low-voltage area was a predictor of VT recurrence during follow-up, which occurred in about 25% of patients. These reports on RF ablation for post-infarct VT collectively support its use to reduce VT episodes as adjunctive therapy, but not as an alternative to the ICD (15).

	Clinical electrophysiology and pharmacology

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
In clinical electrophysiology, arrhythmia mechanisms and new antiarrhythmic medications were major topics of interest. The traditional view of the mechanism underlying AF is that the arrhythmia is initiated by rapidly discharging triggers originating predominately in the PVs, and is maintained by atrial tissue (substrate). Recent observations challenge this notion. Dr. Michel Haissaguerre presented evidence that as the PVs were isolated, the cycle length measured at sites removed from the veins in the left atrium (along the coronary sinus) prolonged. When all PVs were isolated, AF terminated and was not inducible in 56% of patients. This suggests that the PV foci not only initiate but perpetuate AF. Similarly, in a reported 30-year follow-up of Mayo Clinic (Rochester, Minnesota) patients with lone paroxysmal AF, only 25% developed chronic AF in long-term follow-up (16). This raises questions about whether "AF begets AF" in this population, as is commonly believed, or whether AF is dependent on ongoing trigger discharge for its maintenance. In further support of the latter concept, fewer than 5% of patients with ectopy or paroxysmal supraventricular tachycardia at initial diagnosis developed chronic AF.

A report on the Prevention of Syncope Trial by Robert Sheldon, MD (University of Calgary, Alberta, Canada), addressed the issue of whether beta-blockers are effective in preventing vasovagal syncope. As described, 208 patients with historical and tilt-test documentation of vasovagal syncope were randomized to receive metoprolol or placebo. The risk of syncope recurrence was not significantly reduced in the overall metoprolol group but was in a subgroup defined by an age 42 years. This finding prompted the investigators to recommend metoprolol for this age group, but they also cautioned that the results did not necessarily apply to beta-blockers as a class. Metoprolol was not associated with an excess of adverse events. Challenging previous evidence, benefit from metoprolol was not predicted by a need for an isoproterenol infusion to produce a positive baseline tilt test.

There was much interest in the novel antiarrhythmic drug dronedarone, a deiodinated congener of amiodarone that may offer antiarrhythmic effects of the latter without its full range of toxicity. Approximately 20% to 30% of patients with ICDs require concomitant antiarrhythmic medications to prevent frequent shocks. Although amiodarone may reduce ICD shock frequency, it is known to raise defibrillation and pacing thresholds. In a pilot study reported by Peter R. Kowey, MD (MainLine Heart Health Center, Wynnewood, Pennsylvania), 76 ICD recipients with coronary artery disease and/or DCM and an LV EF <40% were randomized to any of the four following treatments: placebo or dronedarone at doses of 600, 800, and 1,000 mg twice daily.

The results indicated that dronedarone does not increase the defibrillation threshold. Relative to placebo, no dose of dronedarone significantly increased the proportion of patients with a defibrillation safety margin of <10 J, the primary end point. This undesired safety margin was observed in only two patients in the entire population, both in the 1,600 mg/day group. Dronedarone was associated with a lower rate of appropriate ICD discharges (a secondary end point) that constituted a statistical trend over an initial 30 days and became significant in long-term follow-up. Dronedarone had no significant effect on pacing thresholds. The plasma concentrations of dronedarone and its dibutyl metabolite were expectedly dose-related, and increased over the initial 30 days, suggesting an accumulation of the drug during chronic dosing.

The most common adverse events with dronedarone were gastrointestinal. The 2,000-mg/day dose was associated with incidences of adverse events and early treatment discontinuations that were judged unacceptable. Lower doses were generally well-tolerated. Only one death in the trial was judged related (possibly) to dronedarone. No cases of torsade de pointes or ventricular proarrhythmia were reported. These promising preliminary results await confirmation from larger and longer-term trials.

	Congenital and pediatric heart disease

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
The presentations on pediatric and congenital heart disease at this year’s meeting differed from those of recent predecessors by a shift in emphasis away from ablation for supraventricular arrhythmias and towards CRT and topics related to sudden cardiac death.

In North America, hypertrophic cardiomyopathy (HCM) is the most commonly identified underlying cause of sudden cardiac death in young athletes. Recognition that HCM is caused by mutations of up to 10 genes that encode proteins of the myocardial sarcomere has fueled efforts to develop a reliable genetic test for the disease. A report by Ackerman et al. (17) described a promising candidate test that screens for a variety of these mutations. The yield of the test for patients with known HCM was highest for those with any of the following traits: receiving a diagnosis of HCM at an age <25 years, a history of cardiac arrest, a family history of HCM, and a very thick left ventricle (17).

Coexistent HCM and Wolff-Parkinson-White syndrome is a manifestation of a glycogen storage disease that has been traced to a defect in the PRKAG2 gene in familial but not sporadic cases. However, Collins et al. (18) reported that a mutation of this gene was found in one of a few pediatric patients who had sporadic forms of the combined disease and had presented with a diversity of electrophysiologic disturbances (including supraventricular tachycardia and ventricular fibrillation). A very common trait in this group was the existence of multiple accessory pathways (five in the case of the patient with the PRKAG2 gene mutation). Treatments for the group included RF ablation of the pathways (successful in most of the cases) and implantation of an ICD (18).

In a didactic presentation, Michael A. Gatzoulis, MD (Royal Brompton Hospital, London, UK), discussed a prolonged QRSd (usually >170 ms) as a robust predictor of life-threatening arrhythmias in pediatric patients with right bundle-branch block after surgery for congenital heart disease. Rapid increase of the QRSd appears to be especially ominous. Recent data, he said, indicate that the two electrophysiologic markers improve after surgery for pulmonary valve insufficiency or other causes of underlying hemodynamic disturbances.

Robert M. Campbell, MD (Sibley Heart Center, Atlanta, Georgia) and Robert M. Gow, MD (The Children's Hospital of Eastern Ontario, Ottawa, Canada), served as protagonist and antagonist, respectively, in a structured debate on whether ECG and echocardiographic screening should be a routine prerequisite for participation in school-age organized athletics. They agreed that both techniques produce high false-positive and false-negative rates. The limitations of these and other methods of identifying sudden cardiac death risk in young athletes have contributed to a trend to place automatic external defibrillators in public schools and other school-age sport sites. In a didactic presentation, Stuart Berger, MD (Medical College of Wisconsin, Milwaukee, Wisconsin), described a systematic effort in Wisconsin to protect young athletes by combining automatic external defibrillator placement with ancillary public education and training of operators. The annual sudden death rate among young athletes in Wisconsin is 0.5 to 2.0 per 100,000, consistent with the national rate.

Clinical data on CRT come largely from its use in adults without congenital heart disease. Alexander et al. (19) reported that the traditional adult-derived indications for CRT were present in only approximately 10% of a cohort of 153 pediatric patients (mean age 5.4 years) with LV dysfunction. A combination of left bundle-branch block and a QRSd >150 ms was uncommon and remained so when the patients were subgrouped for the presence of congenital heart disease or ostensibly normal cardiac structure. Moreover, many of the CRT-eligible patients would have required epicardial leads for CRT because of body weights <10 kg or single-ventricle anatomy. The same study also found that CRT was not commonly indicated in a different cohort of pediatric patients who had an indication for ventricular pacing in the presence or absence of LV dysfunction. In this group (n = 160), the paced QRS tended to be narrow, particularly in patients <10 years of age (19). Dubin et al. (20) reported on the use of CRT at 13 centers for 52 patients with structural congenital heart disease, congenital heart block, or DCM. The indications for CRT and the type and placement of the lead system for biventricular pacing were not standardized. Therapy was accompanied by a mean QRSd reduction of 40 ms, an increase in mean LVEF from 28% to 39%, and a general improvement in NYHA functional class. Approximately one-half the patients required placement of epicardial lead systems. Non-response to CRT did not seem to correlate with type of underlying heart disease (20). In a didactic session, Frank J. Zimmerman, MD (University of Chicago Children's Hospital, Chicago, Illinois), showed how three-dimensional echocardiography in patients with single-ventricle anatomy could help identify suitable locations for multisite pacing and, thus, improve global function.

Two emerging indications for CRT among patients with pediatric or congenital heart disease are right bundle-branch block resulting from RV surgery and a history of RV apical pacing from childhood for congenital heart block. In a comparison of adults with the latter trait and healthy volunteers, Thambo et al. (21) found that long-term asynchronous electromechanical activation by RV apical pacing produces asymmetrical hypertrophy, LV dilation, and impairment of LV function. Such deterioration might be prevented or halted by substituting biventricular for single-site pacing, said Patricio A. Frias, MD (Sibley Heart Center, Atlanta, Georgia), in a didactic session. Frias and colleagues have found the biventricular approach hemodynamically superior in an animal model of congenital heart block.

	Basic/translational science

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
The San Francisco meeting bore witness to the fact that an important current theme in basic cardiac electrophysiology is the relationship between the dynamics of intracellular calcium (Ca_i) and the mechanisms of cardiac arrhythmias. For example, Rajawat et al. (22) developed a transgenic mouse model of Andersen syndrome (a rare inherited human disorder characterized by periodic paralysis and ventricular arrhythmias) by overexpressing a mutant gene that encodes the slow rectifying K channel (Kir2.1). The mouse developed bidirectional VT, suggesting abnormalities of Ca_i dynamics (22). Tian et al. (23) developed a transgenic mouse with selective cardiac expression of a mutated sodium channel gene (SCN5A, N1325S). The model was characterized by spontaneous VT/ventricular fibrillation (preceded by single or multiple ventricular extrasystoles), up-regulation of the cardiac ryanodine receptor (RyR2) (which mediates calcium release from the sarcoplasmic reticulum in cardiac myocytes, thereby contributing to systolic function), and down-regulation of the Na-Ca exchanger. The authors concluded that the arrhythmogenic effects of a gain-of-function mutation contribute to Ca_i imbalance, which in turn triggers lethal arrhythmias. In addition, the pattern of observed arrhythmias suggested that abnormal Ca_i dynamics may contribute to the triggering of lethal arrhythmias associated with the long QT syndrome in humans (23). The studies by Rajawat et al. (22) and Tian et al. (23) are particularly interesting because the mutations affect the K and Na channels, but the arrhythmogenesis is related to abnormal Ca_i dynamics.

Miyoshi et al. (24) conducted a computer simulation study of the Brugada syndrome. Their results showed that the dispersion of I_CaLdensity in the RV can simulate the ECG changes associated with the syndrome. The authors concluded that it is possible to develop Brugada syndrome without an SCN5A mutation, which is a known cause of the syndrome but is associated with abnormalities of the Na rather than Ca channel (24). This third study further highlights the possible importance of calcium dynamics in arrhythmogenesis.

Additional information on the role of Ca_i dynamics in cardiac arrhythmogenesis was presented at didactic sessions by invited speakers. One noted that a rapid heart rate can lead to Ca_i accumulation, which might in turn result in spontaneous (voltage-independent) calcium release and trigger ventricular arrhythmias. Others described significant heterogeneity in the transmural distribution of calcium-handling proteins. These changes may contribute to the electrical heterogeneity of the ventricles.

	Heart Rhythm 2005

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 
Next year's meeting will be held in New Orleans, Louisiana, on May 4 to 7, 2005. It will be interesting to see if CRT, the ICD, and other topics so dominant this year remain so in the next. Change occurs rapidly in cardiac electrophysiology. The challenge of understanding and taming the electrical components of cardiac disease is exceptional, but so is the pace at which it is being met.

	References

Top Abstract Noninvasive evaluation Devices for tachycardias and... Cardiac... Catheter ablation Clinical electrophysiology and... Congenital and pediatric heart... Basic/translational science Heart Rhythm 2005 References

 

1. Bloomfield DM, Steinman RC, Namerow PB, et al. T wave alternans identifies low risk patients who may not benefit from ICD therapy Heart Rhythm 2004;1(Suppl 1):S37.[CrossRef]
2. Zabel M, Pieschel K, Sticherling N, et al. Predictive value of T wave alternans testing in patients with dilated cardiomyopathy Heart Rhythm 2004;1(Suppl 1):S38.
3. Nava S, Brugada J, Brugada R, et al. Electrocardiographic determinants of risk for sudden death and recurrence in Brugada syndrome patients Heart Rhythm 2004;1(Suppl 1):S1.[Medline]
4. Sanders P, Jaïs P, Hsu LF, et al. Electrocardiographic characterization of spontaneous left atrial flutter Heart Rhythm 2004;1(Suppl 1):S1.[Medline]
5. Daoud E, Doshi R, Fellow C, et al. Ablate and pace with cardiac resynchronization therapy for patients with reduced ejection fraction: sub-analysis of PAVE study Heart Rhythm 2004;1(Suppl 1):S59.[CrossRef]
6. Sutherland JA, Tierney SP, Burke MC, et al. Does chronic atrial fibrillation impact response rates to cardiac resynchronization therapy? Heart Rhythm 2004;1(Suppl 1):S15.
7. Tierney SP, Sutherland JA, Lin AC, et al. Women and cardiac resynchronization therapy: are there gender dependent differences in implantation success and clinical response with biventricular pacing Heart Rhythm 2004;1(Suppl 1):S217.
8. Burkhardt JD, Khaykin Y, Bhargava M, et al. Cardiac resynchronization is equally beneficial in patients with right and left bundle branch blocks Heart Rhythm 2004;1(Suppl 1):S279.
9. Braunschweig F, Gras D, Mortensen PT, et al. Do heart failure patients in New-York-Heart Association Class II improve by cardiac resynchronisation therapy? Heart Rhythm 2004;1(Suppl 1):S247.[CrossRef]
10. Gasparini M, Bocchiardo M, Lunati M, et al. Left ventricular stimulation alone (LEFT) significantly increased ejection fraction (EF) at 1 year follow-up: preliminary results from the BELIEVE multi-center randomized study. Heart Rhythm 2004; Suppl 1:S69..
11. Padeletti L, Santini M, Ravazzi A, et al. Left ventricular function evolution in patients with RV pacing: the "WHERE" study Heart Rhythm 2004;1(Suppl 1):S68.[CrossRef]
12. Lemola K, Oral H, Cheung P, et al. Is complete pulmonary vein isolation necessary during left atrial ablation for atrial fibrillation? Heart Rhythm 2004;1 Suppl 1:S11..
13. Schreieck J, Schneider MAE, Röhling M, et al. Preventive ablation of post infarction ventricular tachycardias: results of a prospective randomized study Heart Rhythm 2004;1(Suppl 1):S36.[CrossRef]
14. Wilber DJ, Joseph B, Morton JB, et al. Relationship of post infarction ventricular tachycardia exit sites to the scar border: implications for catheter ablation Heart Rhythm 2004;1(Suppl 1):S36.
15. Nakagawa H, Singh D, Beckman KJ, et al. Ablation of unmappable post-MI ventricular tachycardia using substrate mapping during sinus rhythm: predictors for a recurrence Heart Rhythm 2004;1(Suppl 1):S36.
16. Lee V, Friedman PA, Gersh BJ, et al. Progression of paroxysmal lone atrial fibrillation to chronic atrial fibrillation: long-term follow-up of the Mayo Clinic experience Heart Rhythm 2004;1(Suppl 1):S43.[CrossRef]
17. Ackerman MJ, Van Driest SL, Tajik AJ, et al. Yield of cardiac sarcomere genetic testing in hypertrophic cardiomyopathy Heart Rhythm 2004;1(Suppl 1):S122.
18. Collins K, Tomlinson A, Browne A, et al. A novel mutation in the AMP-activated protein kinase (PRKAG2) gene in sporadic Wolff-Parkinson White syndrome and hypertrophic cardiomyopathy: correlating phenotype to genotype in a pediatric series Heart Rhythm 2004;1(Suppl 1):S49.[CrossRef]
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