Dofetilide is a class III antiarrhythmic drug (potassium channel blocker) that has been approved by the regulatory agencies in the United States and throughout the world to convert atrial fibrillation and maintain sinus rhythm. Therapy is initiated in-hospital during heart rhythm monitoring. Doses are selected according to the QT interval and estimated creatinine clearance.
Cardiac resynchronization has proved a valuable adjunctive therapy in heart failure patients with ventricular conduction disturbances. It improves the patient's clinical status and quality of life, increases functional capacity and causes left ventricular reverse remodeling. The application of this new therapeutic method is expected to affect the pacemaker implantation rate, although the exact degree cannot yet be calculated. One of the main determining factors is the number of patients who are candidates for resynchronization therapy. Although this cannot be estimated precisely, it seems that it does not exceed 10–14% of heart failure patients. Additional factors that will influence the implantation rate, at least during the next few years, are the familiarization of cardiologists with the new implantation technique and follow-up, the availability of cardiac laboratory time and the cost of this new therapy.
It is remarkable that in patients with paroxysmal AF not sufficiently controlled by pharmacological therapy, ablation and pacemaker treatment is highly effective and superior to drug therapy in controlling symptoms and improving quality of life. The discontinuation of drug therapy exposes patients to further recurrences of paroxysmal AF and the risk of developing permanent AF. However, both pharmacological and electrical treatment can enhance quality of life in AF patients.
Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and various AF disease management strategies can be utilized.
Atrial overdrive pacing has been commonly practiced after cardiac surgery in hopes of suppressing atrial ectopy and postoperative atrial fibrillation. However, several studies show inefficacy with AAI pacing and some suggest a potential for proarrhythmia. In a study of AAI right atrial pacing after cardiac surgery, atrial ectopy was increased with no effect on atrial fibrillation suppression. Undersensing and loss of capture were observed not infrequently. Best efficacy for prevention of postoperative atrial fibrillation from other studies suggest that biatrial or Bachmann's bundle pacing, triggered mode pacing, atrial overdrive algorithms, or concomitant beta-blocker use might be more effective than single site right atrial pacing in the AAI mode. However, even with biatrial pacing, proarrhythmia has been reported, and this potential risk for increased atrial ectopy or atrial fibrillation should be recognized. Proarrhythmia may be precipitated by inappropriate sensing or loss of pacing associated with pacing through temporary wires.
The site of atrial pacing influences atrial activation patterns. It is believed that disparities in atrial activation and repolarization are contributors to the development and recurrence of atrial arrhythmias. We hypothesized that pacing from Bachmann's Bundle would improve clinical outcomes in patients with paroxysmal atrial fibrillation compared to right atrial appendage pacing. Pacing from Bachmann's Bundle results in a significant reduction in P wave duration and improvement in biatrial activation symmetry compared to right atrial appendage pacing. Compared to right atrial appendage pacing, Bachmann's bundle pacing improves sinus rhythm (75% vs. 47% at two years, p < 0.01) in patients with a history of paroxysmal atrial fibrillation. Recent studies have confirmed the benefits of Bachmann's Bundle pacing on atrial activation and rhythm regulation. Thus, Bachman's Bundle should be considered the preferred site for atrial pacing in patients with a history of paroxysmal atrial fibrillation.
Atrial fibrillation (AF) is present in a significant number of patients with heart failure (HF) caused by left ventricular systolic dysfunction and is associated with increased morbidity and mortality. The deleterious interaction of AF and HF is mediated through a number of mechanisms including hemodynamic alterations and activation of the sympathetic nervous system. Beta-blockers have been shown to improve symptoms and survival in patients with HF. In addition, beta-blockers have been used in patients with AF, primarily for rate control. A retrospective analysis of the U.S. Carvedilol Heart Failure Trial demonstrated that carvedilol improves outcomes in the high-risk subgroup of patients with HF and concomitant AF.
The optimal pacing mode for patients with paroxysmal atrial fibrillation (AF) following AV junction ablation remains the subject of some debate. Recent clinical trials have not demonstrated a superior advantage of maintenance of sinus rhythm over the rate control approach. However, clinical trials in pacemaker populations have demonstrated that physiologic pacing reduces the probability of paroxysmal and persistent AF compared to ventricular pacing. In the second phase of the PA3 study, patients were randomized to DDDR versus VDD pacing in a cross over study design. Of the 67 patients randomized, 42% developed permanent AF within one year following ablation. AF frequency and burden increases early following AV junction ablation suggesting that ventricular pacing even in an atrial synchronous mode promotes AF. Given the high probability of permanent AF developing early following ablation, VVIR pacing appears to be the appropriate pacing mode for symptomatic patients undergoing total AV junction ablation.
The MADIT-II study (Moss et al., N Engl J Med 2002;346:877–883) demonstrated that implantation of a cardioverter/defibrillator (ICD) reduced mortality from 19.8% to 14.2% during 20 months of follow-up in patients with prior myocardial infarction and left ventricular ejection fraction ≤0.30. Concerns have been raised both about the cost and potential morbidity of implanting ICDs in a large group of patients when only a small fraction of the patients would be expected to benefit from the treatment. This concern has given rise to the hope that an effective means of risk stratifying the MADIT-II population might be developed so that ICD therapy can be directed to only those patients who are at significant risk and thus likely to benefit from treatment for purposes of primary prevention of arrhythmic death. Electrophysiology study (EPS) is probably not suitable for this purpose because of its established relatively high false negative rate and because it is itself an invasive procedure. QRS width has been proposed for this purpose but prospective data demonstrating its effectiveness in stratifying the MADIT-II population for risk of arrhythmic death are absent. Initial data suggest that microvolt T-wave alternans (MTWA) testing does appear to be a suitable candidate for risk stratifying the MADIT-II population. These data indicate that approximately 30% of the MADIT-II population test negative for MTWA and that these patients are at extremely low risk for sudden cardiac death and cardiac arrest. Furthermore, MTWA is an inexpensive non-invasive test which can be repeated over time to monitor whether a patient who initially tests negative develops arrhythmic risk with the progression of the underlying disease. As studies of MTWA testing in the MADIT-II population come to publication, a database will likely be formed which will establish MTWA as an effective means of stratifying the MADIT-II population. ICD therapy may not be indicated in patients who test MTWA negative, and conversely the remaining patients may enjoy a greater mortality benefit than that observed in the MADIT-II trial. Furthermore, widespread MTWA testing might have the further benefit in those patients who do not test negative of serving as a call to action to referring physicians to direct those patients to ICD therapy, thereby greatly increasing the number of appropriate patients who actually receive potentially life saving therapy.
The Chicago School of Arrhythmology (Katz, Langendorf and Pick) dominated the field of arrhythmias for at least 20 years until the advent of intracardiac electrophysiology in the late sixties. Thereafter they still played a fundamental role. Whereas other arrhythmologists also made contributions, they did not develop “schools” in the classical Platonic sense. The Chicago School's intuitive, deductive and inductive contributions to the understanding of multiple electrophysiological mechanisms were well appreciated, recognized and corroborated by basic and clinical electrophysiologists. Less known was their ability to propagate this knowledge in semi-tutorial courses which were so unique in explaining complex arrhythmic concepts that it is still used today by those who inherited their prominent position in the ever expanding world of invasive electrophysiology.
There are few data on the relationships between age and arrhythmias, except for the Wolff-Parkinson-White syndrome. In clinical practice, the most frequent arrhythmia is the atrial fibrillation (AF). It is well-known, that the prevalence of AF increases with age from 2 to 4% before 70 years up to 9 to 15% in patients older than 80 years. However, it is unknown if the increased prevalence of AF is related to the increase of the cardiac and extracardiac diseases, noted in the elderly, or to atrial electrophysiological changes. Probably, the incidence and mechanism of arrhythmia do not differ between adults and elderly patients when the other clinical data are similar.
Several randomized clinical trials have been designed to evaluate the usefulness of prophylactic implantable cardioverter defibrillator (ICD) therapy in patients with nonischemic cardiomyopathy. In 2 trials, CAT and AMIOVIRT, no survival benefit was reported for patients with dilated cardiomyopathy and prophylactic ICD therapy. The major limitation of both trials is the small sample size of 104 patients in CAT and 103 patients in AMIOVIRT. Another limitation of both trials is the lack of a run-in phase on optimized medical therapy. Since LV function may improve considerably on optimized medical therapy, LV function should be reevaluated 3 to 4 months after initiation of ACE inhibitors, ß-blockers and aldosterone antagonists before prophylactic ICD therapy is considered. Two additional trials, DEFINITE and SCD-HEFT, are still ongoing. Particularly SCD-HEFT will follow a sufficient number of patients with nonischemic cardiomyopathy to give a more definitive answer with regard to the clinical usefulness of prophylactic ICDs in patients with nonischemic cardiomyopathy. Recently, the Marburg Cardiomyopathy study (MACAS) was finished. The results of MACAS strongly suggest that reduced LV ejection fraction is the most important arrhythmia risk predictor in idiopathic dilated cardiomyopathy, whereas signal-averaged ECG, baroreflex sensitivity, heart rate variability and T wave alternans do not appear to be helpful for arrhythmia risk stratification. In addition, MACAS showed that total mortality in patients with idiopathic dilated cardiomyopathy and an ejection fraction <30% is only about 5% per year on optimized medical therapy after exclusion of patients with end stage heart failure and after exclusion of patients with sustained ventricular arrhythmias. Thus, any future study designed to demonstrate a mortality benefit by prophylactic ICD therapy with an 80% power in this patient population needs to enroll more than 1000 patients.
In MADIT-II, prophylactic ICD therapy was effective in improving survival in patients with prior myocardial infarction and an ejection fraction ≤0.30, and a host of prespecified secondary analyses indicate that life-saving effect of ICD therapy is consistent across all studied subgroups. We have not been able to identify any traditional risk factors that will permit selection of patients who will receive a significantly better effect from the ICD within any subgroup. The ICD provides appropriate therapy for life-threatening ventricular arrhythmias on at least one occasion in over a third of the patients during the first 4 years after device implantation. Computations from the MADIT-II database indicate that 9 patients need to be treated with an ICD to save one life during a 4-year period. The findings from MADIT-II have implications for patients, physicians, and society.
Although the use of amiodarone for the treatment of atrial fibrillation has increased, reports of its use for the restoration of sinus rhythm have been conflicting.
Azimilide dihydrochloride (or azimilide) is a class III antiarrhythmic drug currently under investigation that has been tested in atrial fibrillation in four randomized, placebo-controlled clinical trials to assess efficacy and dose range. These investigational trials showed that doses of azimilide 100 and 125 mg once daily prolonged the time to symptomatic arrhythmia recurrence in patients with a history of symptomatic atrial fibrillation, atrial flutter or both. Doses of 75 mg or less were not useful in this indication.
Atrial fibrillation after coronary artery bypass surgery occurs in 30 to 40% of patients. Prophylactic therapy with drugs is not always possible and not always efficient.
