YEAR IN CARDIOLOGY SERIES
The year in clinical electrophysiology
Melvin M. Scheinman, MD, FACC*,* and
Edmund Keung, MD
* Cardiac Electrophysiology, University of California San Francisco, San Francisco, California
Veterans Administration Medical Center, San Francisco, California
Manuscript received December 14, 2004;
accepted January 5, 2005.
* Reprint requests and correspondence: Dr. Melvin M. Scheinman, University of California San Francisco, 500 Parnassus Avenue, Box 1354, San Francisco, California 94143
(Email: scheinman{at}medicine.ucsf.edu).
Clinical electrophysiology has seen so many major advancements within the past year that we have decided to limit our review to four areas: catheter ablation of atrial fibrillation (AF), advances in drug therapy, genetics, and device therapy. Even with these limitations, it is not possible to cite all the worthwhile publications, and for this we offer our sincere apologies.
This paper is directed primarily to the clinical cardiologist in an effort to keep our brethren informed with regard to major advances in the understanding and treatment of cardiac rhythm disorders.
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Drug therapy for cardiac arrhythmias
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The search for newer, more effective antiarrhythmic agents continues. There is special interest in drugs that target ion channels found predominantly in the atrium in hopes that this will provide treatment of AF without the risk of torsades. Studies examined the effects of blockers that target Ikach (which may be important in the genesis of vagotonic AF) (1) or blockers of the Kv 1.5 or Kv 4.3 channels (2). The aim is to find atrial selective K+ channel blockers and, thus, obviate the risk for serious ventricular arrhythmias.
A concise review of current usage of drugs for both supraventricular as well as ventricular arrhythmias was authored by Singh et al. (3). A drug approach to the management of patients with ventricular arrhythmias due to Brugada syndrome was presented by Belhassen et al. (4). They felt that chronic oral quinidine therapy proved effective in the prevention of inducible ventricular fibrillation (in the laboratory) as well as in the prevention of spontaneous ventricular arrhythmias. Of note, the authors used a very demanding invasive electrophysiologic testing protocol, and 36% of patients could not tolerate long-term quinidine therapy. If confirmed, this therapy may prove to be an alternative to automatic implantable-cardioverter defibrillators (AICD) placement, especially in poorer countries where AICD therapy is not an option.
This past year showed the introduction of several new drugs that are still under investigation. Tedisimal is a new class III drug that blocks multiple K+ channels including Ito, Ikach, IKur, IKs, and IKr. It is felt to be more potent in blocking atrial K+ channels compared with ventricular K+ channels. Hohnloser et al. (5) described a multicenter double-blind, randomized placebo-control study sequential ascending-dose trial of intravenous tedisimal in 201 patients with AF or atrial flutter. They found a conversion to sinus rate in 41% in those receiving 0.4 mg/kg and 51% in the 0.6 mg/kg group but only 7% in the placebo group. There was one episode of monomorphic ventricular tachycardia and one of torsades, both in the 0.6 mg/kg group. This drug appears to be of comparable or greater efficacy compared to ibutilide, but still carries the risk for ventricular arrhythmias.
Another newer investigational drug is a new amiodarone analogue (dronedarone) (6). Dronedarone is a noniodinated amiodarone derivative. It has widespread blocking activity for Na+, K+, and Ca++ channels. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE), this drug appeared to be safe and effective in prevention of AF relapse. A drug trial using this agent in patients with moderate-to-severe congestive heart failure (HF) was prematurely terminated because of increased risk of death in the treated group.
There continues to be interest in the development of drugs or drug combinations for acute chemical conversion of AF or atrial flutter. Hongo et al. (7) demonstrated the efficacy and safety of combined agents (flecainide or propafenone) with ibutilide in acute conversion of AF. Similarly, Chiladakis et al. (8) showed that the use of ibutilide after oral propafenone proved safe and effective for AF conversion.
There has been great recent interest in the effects of cardiac nonarrhythmic drugs in the prevention of AF. Several laboratory studies have established the rationale for use of angiotensin-converting enzyme or angiotensin receptor blockers in prevention or possible treatment of patients with AF. Sakabe et al. (9) used an atrial-pacing-induced AF model in canines. They showed that enalapril prevented fibrosis and overexpression of connexin 43 in this model and suppressed atrial-pacing-induced AF. In addition, Li et al. (10) showed that losartan was more effective than diltiazem in preserving rate adaptation after rapid atrial pacing in rabbits, hence preventing the atrial electrical remodeling that contributes to AF maintenance. Several confirmatory clinical studies are now available. L'Allier et al. (11) reported a retrospective longitudinal cohort study of patients with hypertension treated with either an angiotensin-converting enzyme inhibitor or calcium channel blocker. They found that a reduced incidence of AF in the group treated with the angiotensin-converting enzyme inhibitor. Zaman et al. (12) found that long-term angiotensin-converting enzyme therapy facilitated electrical defibrillation in patients with persistent AF. Prospective studies using angiotensin-converting enzyme, angiotensin receptor blockers, and/or statins are clearly required.
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Genetic syndromes
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Important strides occurred over the past year in further elucidation of the short QT syndrome. This syndrome has been clinically categorized as consisting of a short QT interval ( 300 ms), tall peaked T waves, and a high incidence of sudden death (13). Invasive studies show a short refractory period and easily inducible ventricular fibrillation. Brugada et al. (14) were the first to describe two different missense mutations resulting in abnormalities in the S5-P loop region of the IKr channel (KCNH2). They found dramatic enhancement of the IKr current due to loss of rectification of the IKr channel. In addition, this abnormal channel was not responsive to IKr blockers. Gaita et al. (15) tested six affected individuals with the short QT syndrome with flecainide, sotalol, ibutilide, and quinidine. They found that only quinidine prolonged and normalized the QT interval. It was felt that quinidine, because of its broad spectrum block of outward K+ currents, would be a more effective drug therapy than the more selective IKr channel blockers. Bellocq et al. (16) found a 70-year-old man who presented with idiopathic ventricular fibrillation and was found to have the short QT syndrome due to a mutation in the KCNQ1 gene that encodes the IKs channel. A number of other candidate K+ or Ca++ mutants may be involved with this very interesting new syndrome.
Additionally, new potentially important findings have been described for patients with the long QT syndrome. In these patients the syndrome has usually been attributed to mutations in coding regions of the gene. Zhang et al. (17) described a novel intronic mutation that alters the KCNH2 (IKr channel) gene. They conclude that intronic mutations may be responsible for the syndrome in families with negative screening for the usual genes found in the long QT genes. This may account for some of the 30% to 50% of patients with long QT syndrome who have negative mutational screens. Other interesting reports involve patients with the long QT syndrome due to loss of function of the gene encoding IK1 channel (KCNJ2). This gene has previously been found to cause Andersen's syndrome. Fodstad et al. (18) showed two novel mutations in this gene producing the long QT syndrome without any other features of Andersen's syndrome. Westenskow et al. (19) described compound mutations in 20 of 252 long QT syndrome patients involving KVLQT1, HERG, KCNE1, KCNE2, and SCN5A genes. The compound mutation often resulted in a severe phenotypic pattern.
There were several manuscripts that provided further genotype-phenotype relationships that potentially impact patient care. Priori et al. (20) showed that there was a higher recurrence of cardiac events in patients with LQT2 and LQT3 treated with beta-blockers compared to those with LQT1. These data support prior observations on the relative resistance of LQT2 and LQT3 patients to beta-blocker therapy and raises the issue of use of a defibrillator for these patients. In addition, Shimizu et al. (21) found that patients with LQT1 due to mutations in the transmembrane domain carried a higher risk for cardiac events compared to those with a C-terminal mutation. The risk for cardiac events occurred at a younger age, and baseline and exercise QT parameters (i.e., QTc, Q-T peak, or QT end) were more pronounced for those with transmembrane mutations.
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Device therapy
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A number of studies have shown that cardiac resynchronization therapy (CRT) resulted in improved symptoms and exercise tolerance, as well as in enhanced left ventricular performance, and reduction in hospitalization for HF patients. These studies have not been adequately powered to assess the effects of CRT on mortality (22–25). The Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure Trial (COMPANION) asked the question of whether resynchronization pacing with or without an implantable cardioverter-defibrillator (ICD) reduced the risk of death and hospitalization in patients with New York Heart Association functional class III to IV congestive HF and a wide QRS complex (26). In this multicenter trial, 1,520 patients were randomized to receive optimal medical therapy (308 patients), a CRT pacemaker (617 patients), or a CRT + ICD (595 patients). There were no significant differences in left ventricular ejection fraction (LVEF), 20% vs. 22%; incidence of ischemic heart disease, 54% versus 59%; or QRS duration between the CRT versus CRT-defibrillator groups. The primary end point included death from and/or hospitalization for any cause. Death from any cause alone was a secondary end point. When compared with the medical therapy group, both the CRT (hazard ratio = 0.81) and the CRT + ICD (hazard ratio = 0.80) groups significantly decreased the risk of the primary composite end point by 20%. Only the CRT + ICD group significantly reduced death from any cause (36%) (hazard ratio = 0.64). The results strongly suggest that the optimal device therapy for patients with severe HF and widened QRS duration consists of a CRT + ICD because of the added survival benefit. This study was not powered to determine whether an ICD without CRT would achieve a survival benefit.
The mortality benefit of ICD in patients with impaired LVEF due to ischemic cardiomyopathy has been well documented. The value of primary prevention of death in patients with nonischemic dilated cardiomyopathy was addressed by the Defibrillators in Non-ischemic Cardiomyopathy Treatment Evaluation trial (DEFINITE) (27). A total of 458 patients with nonischemic dilated cardiomyopathy and reduced LVEF (mean value = 0.21) were randomized in equal numbers to standard medical therapy and standard medical therapy plus a single-chamber ICD. Eight-five percent of the patients received an angiotensin-converting enzyme inhibitor and beta-blockers, while 5% were taking amiodarone. The ICD group showed a significantly reduced incidence of sudden death (80%) (hazard ratio = 0.20), and mortality rates at two years were 14.1% in the standard therapy group and 7.9% in the ICD group (not significant). These results were attributed to the relatively small size of this trial and the lower-than-expected annual mortality rate in the standard therapy group. A recently completed ICD trial, Sudden Cardiac Death in Heart Failure trial (SCD-HeFT), was presented at the American College of Cardiology Annual Scientific Session in 2004 (28). This trial examined whether amiodarone or ICD reduced all-cause mortality compared to placebo in patients with either HF due to ischemic or nonischemic dilated cardiomyopathy and reduced LVEF (0.35 or less). A total of 2,521 patients were enrolled, and approximately equal number of patients had ischemic (52%) or nonischemic cardiomyopathy (48%). When compared to placebo treatment, ICD reduced mortality by 23%. The reduction was observed in both ischemic (hazard ratio = 0.79) and nonischemic groups (hazard ratio = 0.73), regardless of QRS duration. The amiodarone group did not show improved survival. The results of the DEFINITE and SCD-HeFT studies support implantation of an ICD in patients with nonischemic dilated cardiomyopathy with reduced LVEF and moderate HF (New York Heart Association functional class II and III).
Since the introduction of dual-chamber pacemaker in the 1980s, DDD pacing mode had been promoted to preserve atrioventricular synchrony despite absence of large-scale, randomized prospective trials demonstrating benefits. In 1997, Andersen et al. (29) reported that in 225 patients with sinus node dysfunction, atrial pacing (AAI) resulted in significantly lower cardiovascular death than ventricular pacing (VVI) (29). Recently, two large randomized trials, the Canadian Trial Physiological Pacing (CTOPP) and the Mode Selection Trial in Sinus Node Dysfunction (MOST) failed to demonstrate a difference in survival between VVI and dual-chamber pacing (30,31). In 2000, after three years of follow-up, the CTOPP study reported no significant benefits of physiological (DDD or AAI) pacing over VVI in reducing cardiovascular death or stroke, overall mortality, or hospitalization for HF. There was a moderate and statistically significant increase in the incidences of AF for those treated with VVI. To ascertain the presence of delayed beneficial effects of physiologic pacing mode, the follow-up was extended for another three years. In 2004, the CTOPP investigators reexamined the results after a mean follow-up of 6.4 years (32). There were no differences in cardiovascular death or stroke, or total mortality between patients implanted with ventricular versus physiologic pacemakers, and the incidence of AF remained higher in patients with VVI pacing. However, there was no difference in the composite end point of cardiovascular death or stroke. This large randomized trial with long-term follow-up failed to provide clear support for dual-chamber pacemakers that are general preferred by implanting physicians for bradytherapy in this country.
Curative catheter ablation of AF continues to excite the interventionalists. It is now recognized that sustained AF reflects interaction between triggers (largely in the pulmonary veins [PV]) (33) and substrate (largely the left atrium) (34). This has led to the introduction of techniques for pulmonary vein isolation (PVI) (35), to address the issue of triggers from these sources, and circumferential left atrial ablation (LACA) (36), which involves wide lesions encompassing the PVs together with additional lesions that are meant to join the superior veins and a so-called mitral isthmus lesion that joins the left inferior PV to the mitral annulus.
An entirely new approach solely directed at the substrate was introduced by Nademanee et al. (37). This group directed ablative lesions to areas showing complex fractionated electrograms in 110 patients with paroxysmal or chronic AF. They found that these electrograms tended to occur over the atrial septum but were also found in PVs left atrial roof, posterior mitral annulus, and coronary sinus os. Ablation of these targets resulted in a 95% spontaneous conversion to sinus rhythm, and 91% of patients were arrhythmia free after one year. Seven patients required drug therapy and 18 required a second ablation. The authors suggest that the complex electrograms represent continuous re-entry of fibrillatory waves or overlap of wavelets entering this area. Regardless of the mechanism, they have nicely demonstrated that a totally new approach to substrate modification may play an important therapeutic role.
In an important follow-up study, Oral et al. (38) reported a randomized study using a variant of the left atrial catheter ablation (LACA) technique. They performed the typical LACA technique (as previously described) in 100 patients. After completion of the procedure, there was spontaneous termination of AF in 40 patients. The remaining patients were randomly assigned to no further ablation (group 2 = 30 patients) or to further ablation of fractioned electrograms over the left atrial septum, roof, or anterior walls (group 3 = 30 patients). Of interest AF was rendered noninducible in 27 of 30 patients in group 3. After a six-month follow-up, 86% of the group 3 patients and 67% of group 2 were free of AF without drug therapy. This study complements the observations of Nademanee et al. (5) with respect to techniques directed at substrate alteration.
Haïssaguerre et al. (39) showed that sequential PVI resulted in an increase in AF cycle length parri passu with delivery of peripulmonary venous lesions as well as with additional linear left atrial lesions. They noted a decrease in fragmentation of the electrograms before conversion to sinus or atrial flutter. This study tends to support the prior studies relating to substrate modifications, although the authors attributed this finding to "extinguishing perpetuating activations" from the PVs.
The vagal effects on initiation and perpetuation of AF are well recognized (40). Pappone et al. (41) presented new findings relating to purposeful denervation of vagal efferents to the left atrium. They found that vagal responses were frequently elicited in the course of LACA, manifest by sinus bradycardia, atrioventricular block, and hypotension. They found that vagal reflexes could be elicited and abolished (with continued radiofrequency application) in about one-third of patients. They found persistent loss of vagal activity as manifest by sinus tachycardia and/or abnormal heart rate variability. Freedom from recurrent AF after 12 months ranged from 99% in those without vagal reflexes, compared with 85% in those with intact vagal tone (p = 0.0002). The authors concluded that parasympathetic attenuation during PV ablation confers added benefit to the LACA procedure. These studies will likely fuel a wide variety of studies to evaluate the role of autonomic influences for patients with AF treated by catheter ablation.
Another study that addressed the role of autonomic influences for those undergoing AF ablation was reported by Oral et al. (42). They divided 188 consecutive AF patients into those with random (72%), adrenergic (16%), or vagally mediated AF (12%). The patients underwent isolation of three or four PVs. At one year of follow-up, 69% of those with random, 83% of those with adrenergic, and 50% of those with vagotonic AF were free of recurrent AF without antiarrhythmic drugs. It would appear that PV isolation is less effective for those with vagotonic AF. A natural study would be to assess the effects of vagal denervation as described by Pappone et al. (41) in patients with vagotonic AF.
A very important complication after AF ablation is the development of atrial flutter. Over the past year, a number of studies have focused on the mechanism of this arrhythmia. It is clear that rapid, organized left atrial rhythms may occur just after left atrial ablation. Many of these have no long-term clinical expression. However, some patients may develop clinically significant left atrial tachycardias. Gerstenfeld et al. (43) reported a 2.9% incidence (10 patients) of recurrent tachycardia after PVI. In 8 of the 10 patients, the tachycardia was shown to be focal, and in 6 it appeared to arise from reconnected areas from previously ablated regions. Other focal sites included the posterior left atrium (33) or superior septum (33). In their experience, recurrent flutter was uncommon and usually arose from (and was successfully ablated) from reconnected PV ostial sites.
In contrast, Mesas et al. (44) described 13 patients with a left atrial tachycardia after a LACA. In their experience only three were focal, and the rest were macroreentry with either single- or double-loop configurations. The reentrant circuits involved the posterior left atrial wall, mitral isthmus, or gaps in the previous ablation lines. It would appear that complex macro–re-entrant tachycardia circuits are much more common after LACA compared with PVI. Finally, Scharf et al. (45) also found both focal as well as macroreentrant rhythms after left atrial ablation.
There are several important reports relative to complications of AF ablation. The most frightening were reports of development of atrioesophageal fistula after left atrial ablation. Two patients developed endocarditis associated with gaseous and septic emboli, and documented atrioesophageal fistula were reported (46). Signs of endocarditis, hematemesis, or systemic emboli should bring this complication to mind. This complication requires urgent surgery. Operators are warned to avoid use of high-power energy application to the posterior wall of the left atrium. Others have suggested use of esophageal probes to monitor the temperature in the esophagus during left atrial ablation. Another important complication after PVI is the development of PV stenosis. A potentially important study from Australia (47) suggests that, although stenosis was initially found in 16% of patients, PV stenosis was either unchanged (eight patients), improved, or fully resolved in five patients, and deteriorated in one patient. They point out that absent PV stenosis after the first procedure does not ensure that this complication would not occur with repeat ablation.
Lickfett et al. (48) studied the possible hazard of radiation exposure during the often lengthy AF catheter procedure. The projected lifetime risk of excess malignancy was 0.07% for females and 0.1% for males. They felt that the relatively small amount of radiation exposure despite the length of the procedure was due to very-low-frame pulsed fluoroscopy. The projected lifetime risk of fatal malignancy was similar to that previously reported for other ablative procedures (i.e., atrioventricular nodal or atrioventricular reentrant tachycardia).
The Cleveland Clinic group found that the PVI procedure was nearly as effective for those with impaired systolic function compared to those with normal function (49). They, moreover, found that PVI proved safe and effective for all age groups with AF but did report a higher incidence of thromboembolic complications in the elderly. They found a 3% incidence of stroke in those over 60 years of age, compared with none in those younger than 60 years of age (50). This important finding must be integrated into our discussions of AF ablation in older patients.
Cardiovascular surgeons continue to be very active in devising new techniques and procedures for operative cure of AF. This is largely performed in patients requiring concomitant cardiac surgery (51). The newer techniques involve microwave application (52), and use of cryoablation (53,54), as well as endoscopic robotic-guided ablation procedures (55).
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Footnotes
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Dr. Scheinman is on the speaker's bureau for Guidant, is a consultant for Proctor & Gamble and AstraZeneca, and is a stockholder with Medtronic.
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References
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1. Brandts B, Van Bracht M, Dirkmann D, et al. Perspectives and limitations in the treatment of vagus-induced atrial fibrillationInsights from cellular pharmacology. (in German) Med Klin (Munich) 2004;99:341-346.
2. Brendel J, Peukert S. Blockers of the Kv1.5 channel for the treatment of atrial arrhythmias Curr Med Chem Cardiovasc Hematol Agents 2003;1:273-287.[CrossRef][Medline]
3. Singh SN, Patrick J, Patrick J. Antiarrhythmic drugs Curr Treatment Options Cardiovasc Med 2004;6:357-364.
4. Belhassen B, Glick A, Viskin S. Efficacy of quinidine in high-risk patients with Brugada syndrome Circulation 2004;110:1731-1737.[Abstract/Free Full Text]
5. Hohnloser SH, Dorian P, Straub M, Beckmann K, Kowey P. Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter J Am Coll Cardiol 2004;44:99-104.[Abstract/Free Full Text]
6. Doggrell SA, Hancox JC. Dronedarone: an amiodarone analogue Expert Opin Invest Drugs 2004;13:415-426.
7. Hongo RH, Themistoclakis S, Raviele A, et al. Use of ibutilide in cardioversion of patients with atrial fibrillation or atrial flutter treated with class IC agents J Am Coll Cardiol 2004;44:864-868.[Abstract/Free Full Text]
8. Chiladakis JA, Kalogeropoulos A, Patsouras N, Manolis AS. Ibutilide added to propafenone for the conversion of atrial fibrillation and atrial flutter J Am Coll Cardiol 2004;44:859-863.[Abstract/Free Full Text]
9. Sakabe M, Fujiki A, Nishida K, et al. Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexin43 in a canine model of atrial pacing-induced left ventricular dysfunction J Cardiovasc Pharmacol 2004;43:851-859.[CrossRef][Web of Science][Medline]
10. Li Y, Li WM, Xue JY, Han W, Yang SS, Gu HY. Effects of losartan on acute atrial electrical remodeling Chin Med J (Engl) 2004;117:643-646.
11. L'Allier PL, Ducharme A, Keller PF, Yu H, Guertin MC, Tardif JC. Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation J Am Coll Cardiol 2004;44:159-164.[Abstract/Free Full Text]
12. Zaman AG, Kearney MT, Schecter C, Worthley SG, Nolan J. Angiotensin-converting enzyme inhibitors as adjunctive therapy in patients with persistent atrial fibrillation Am Heart J 2004;147:823-827.[CrossRef][Web of Science][Medline]
13. Gaita F, Giustetto C, Bianchi F, et al. Short QT syndrome: a familial cause of sudden death Circulation 2003;108:965-970.[Abstract/Free Full Text]
14. Brugada R, Hong K, Dumaine R, et al. Sudden death associated with short-QT syndrome linked to mutations in HERG Circulation 2004;109:30-35.[Abstract/Free Full Text]
15. Gaita F, Giustetto C, Bianchi F, et al. Short QT syndrome: pharmacological treatment J Am Coll Cardiol 2004;43:1494-1499.[Abstract/Free Full Text]
16. Bellocq C, van Ginneken AC, Bezzina CR, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome Circulation 2004;109:2394-2397.[Abstract/Free Full Text]
17. Zhang L, Vincent GM, Baralle M, et al. An intronic mutation causes long QT syndrome J Am Coll Cardiol 2004;44:1283-1291.[Abstract/Free Full Text]
18. Fodstad H, Swan H, Auberson M, et al. Loss-of-function mutations of the K(+) channel gene KCNJ2 constitutes a rare cause of long QT syndrome J Mol Cell Cardiol 2004;37:593-602.[CrossRef][Web of Science][Medline]
19. Westenskow P, Splawski I, Timothy KW, Keating MT, Sanguinetti MC. Compound mutations: a common cause of severe long-QT syndrome Circulation 2004;109:1834-1841.[Abstract/Free Full Text]
20. Priori SG, Napolitano C, Schwartz PJ, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers JAMA 2004;292:1341-1344.[Abstract/Free Full Text]
21. Shimizu W, Horie M, Ohno S, et al. Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: multicenter study in Japan J Am Coll Cardiol 2004;44:117-125.[Abstract/Free Full Text]
22. Adamson PB, Kleckner KJ, VanHout WL, Srinivasan S, Abraham WT. Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure Circulation 2003;108:266-269.[Abstract/Free Full Text]
23. Young JB, Abraham WT, Smith AL, et al. Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators Combined cardiac resynchronization and implantable cardioverter defibrillation in advanced chronic heart failureThe MIRACLE ICD trial. JAMA 2003;289:2685-2694.[Abstract/Free Full Text]
24. Alonso C, Ritter P, Leclercq C, Mabo P, Bailleul C, Daubert JC, MUSTIC Study Group Effects of cardiac resynchronization therapy on heart rate variability in patients with chronic systolic heart failure and intraventricular conduction delay Am J Cardiol 2003;91:1144-1147.[CrossRef][Web of Science][Medline]
25. Higgins SL, Hummel JD, Niazi IK, et al. Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias J Am Coll Cardiol 2003;42:1454-1459.[Abstract/Free Full Text]
26. Bristow M, Saxon LA, Boehmer J, et al. Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) Investigators Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure N Engl J Med 2004;350:2140-2150.[Abstract/Free Full Text]
27. Kadish A, Dyer A, Daubert JP, et al. Defibrillator in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy N Engl J Med 2004;350:2151-2158.[Abstract/Free Full Text]
28. Bardy GH. SCD-HeFT: the Sudden Cardiac Death in Heart Failure Trial, American College of Cardiology, March 8, 2004. Available at: http://www.sicr.org/scdheft_results_acc_lbcc.pdf. Accessed November 5, 2004..
29. Andersen HR, Nielsen JC, Bagger JP, Westerlund T, Thomsen PE. Prospective randomized trial of atrial versus ventricular pacing in sick-sinus syndrome Lancet 1994;344:1523-1528.[CrossRef][Web of Science][Medline]
30. Connolly SJ, Kerr CR, Gent M, et al. Canadian Trial of Physiological Pacing (CTOPP) Investigators Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes N Engl J Med 2000;342:1385-1391.[Abstract/Free Full Text]
31. Lamas GA, Lee KL, Sweeney MO, et al. Mode Selection Trial in Sinus-Node Dysfunction Ventricular pacing or dual chamber pacing for sinus-node dysfunction N Engl J Med 2002;346:1854-1862.[Abstract/Free Full Text]
32. Kerr CR, Connolly SJ, Abdollah H, et al. Canadian Trial of Physiological Pacing (CTOPP) Investigators Effects of physiological pacing during long-term follow-up Circulation 2004;109:357-362.[Abstract/Free Full Text]
33. Haïssaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins N Engl J Med 1998;339:659-666.[Abstract/Free Full Text]
34. Moe GK, Abildskov JA. Atrial fibrillation as a self-sustaining arrhythmia independent of focal discharge Am Heart J 1959;58:59-70.[CrossRef][Web of Science][Medline]
35. Chen S-A, Hsieh M-H, Tai C-T, et al. Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation Circulation 1999;100:1879-1886.[Abstract/Free Full Text]
36. Pappone C, Oreto G, Lamberti F, et al. Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system Circulation 1999;100:1203-1208.[Abstract/Free Full Text]
37. Nademanee K, McKenzie J, Kosar E, et al. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate J Am Coll Cardiol 2004;43:2044-2053.[Abstract/Free Full Text]
38. Oral H, Chugh A, Lemola K, et al. Noninducibility of atrial fibrillation as an end point of left atrial circumferential ablation for paroxysmal atrial fibrillation: a randomized study Circulation 2004;110:2797-2801.[Abstract/Free Full Text]
39. Haïssaguerre M, Sanders P, Hocini M, et al. Changes in atrial fibrillation cycle length and inducibility during catheter ablation and their relation to outcome Circulation 2004;109:3007-3013.[Abstract/Free Full Text]
40. Coumel P. Role of the autonomic nervous system in paroxysmal atrial fibrillation. In: Touboul PC, Waldo AL, editorsAtrial Flutter. Armonk, NY: Futura Publishing Co; 1996248–61.
41. Pappone C, Santinelli V, Manguso F, et al. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation Circulation 2004;109:327-334.[Abstract/Free Full Text]
42. Oral H, Chugh A, Scharf C, et al. Pulmonary vein isolation for vagotonic, adrenergic, and random episodes of paroxysmal atrial fibrillation J Cardiovasc Electrophysiol 2004;15:402-406.[CrossRef][Web of Science][Medline]
43. Gerstenfeld EP, Callans DJ, Dixit S, et al. Mechanisms of organized left atrial tachycardias occurring after pulmonary vein isolation Circulation 2004;110:1351-1357.[Abstract/Free Full Text]
44. Mesas CE, Pappone C, Lang CCE, et al. Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation: electroanatomic characterization and treatment J Am Coll Cardiol 2004;44:1071-1079.[Abstract/Free Full Text]
45. Scharf C, Oral H, Chugh A, et al. Acute effects of left atrial radiofrequency ablation on atrial fibrillation J Cardiovasc Electrophysiol 2004;15:515-521.[Web of Science][Medline]
46. Pappone C, Oral H, Santinelli V, et al. Atrio-esophageal fistula as a complication of percutaneous transcatheter ablation of atrial fibrillation Circulation 2004;109:2724-2726.[Abstract/Free Full Text]
47. Jin Y, Ross DL, Thomas SP. Pulmonary vein stenosis and remodeling after electrical isolation for treatment of atrial fibrillation Pacing Clin Electrophysiol 2004;27:1362-1370.[CrossRef][Medline]
48. Lickfett L, Mahesh M, Vasamreddy C, et al. Radiation exposure during catheter ablation of atrial fibrillation Circulation 2004;110:3003-3010.[Abstract/Free Full Text]
49. Chen MS, Marrouche NF, Khaykin Y, et al. Pulmonary vein isolation for the treatment of atrial fibrillation in patients with impaired systolic function J Am Coll Cardiol 2004;43:1004-1009.[Abstract/Free Full Text]
50. Bhargava M, Marrouche NF, Martin DO, et al. Impact of age on the outcome of pulmonary vein isolation for atrial fibrillation using circular mapping technique and cooled-tip ablation catheter J Cardiovasc Electrophysiol 2004;15:8-13.[CrossRef][Web of Science][Medline]
51. Hornero Sos F, Montero Argudo JA, Rodriguez Albarran I, et al. Ablation of permanent atrial fibrillation in cardiac surgeryShort-term and mid-term results. Rev Esp Cardiol 2004;57:939-945.[Medline]
52. Knaut M, Tugtekin SM, Jung F, Matschke K. Microwave ablation for the surgical treatment of permanent atrial fibrillation—a single centre experience Eur J Cardiothorac Surg 2004;26:742-746.[Abstract/Free Full Text]
53. Rostock T, Weiss C, Ventura R, Willems S. Pulmonary vein isolation during atrial fibrillation using a circumferential cryoablation catheter Pacing Clin Electrophysiol 2004;27:1024-1025.[CrossRef][Medline]
54. Kubota H, Takamoto S, Ohtsuka T, et al. Epicardial pulmonary vein isolation with a hook-shaped cryoprobe to treat atrial fibrillation Ann Thorac Surg 2004;78:1056-1059.[Abstract/Free Full Text]
55. Gerosa G, Bianco R, Buja G, di Marco F. Totally endoscopic robotic-guided pulmonary veins ablation: an alternative method for the treatment of atrial fibrillation Eur J Cardiothorac Surg 2004;26:450-452.[Abstract/Free Full Text]
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Drug therapy for cardiac...
Genetic syndromes