Fibrillatory rate response to candesartan in persistent atrial fibrillation.

INTRODUCTION Angiotensin-receptor blockers may exert favourable anti-arrhythmic effects in atrial fibrillation (AF), but their mechanisms are not fully understood. In this study, we tested the hypotheses that (i) candesartan reduces atrial fibrillatory rate and (ii) fibrillatory rate and its response to candesartan are related with the outcome of cardioversion. For this purpose, a post hoc subanalysis of the randomized, placebo-controlled CAPRAF (Candesartan in the Prevention of Relapsing Atrial Fibrillation) trial was performed. METHODS AND RESULTS Patients with AF undergoing electrical cardioversion were randomized to receive candesartan 8 mg once daily (n = 58) or matching placebo (n = 66) and no additional class I or III anti-arrhythmic drugs. Fibrillatory rate was determined from ECG lead V1 at baseline and at the day of cardioversion using spatiotemporal QRST cancellation and time-frequency analysis. The median time on treatment was 29 days. Candesartan reduced fibrillatory rate [399 +/- 48 vs. 388 +/- 49 fibrillations/min (fpm), P = 0.04], but not placebo (402 +/- 58 vs. 402 +/- 61 fpm, P = 0.986). Candesartan effects were only observed if the baseline fibrillatory rate was high [>420 fpm: 445 +/- 21 vs. 415 +/- 49 fpm, P = 0.006 vs. intermediate (360-420 fpm): 397 +/- 19 vs. 391 +/- 37 fpm, P = 0.351 vs. low (<360 fpm): 326 +/- 26 vs. 338 +/- 29 fpm, P = 0.179]. Cardioversion success was 100% in patients with an on-treatment rate <360 fpm vs. 83% in patients with higher rates (P = 0.02). Risk for AF recurrence was similar in patients with low (64%), intermediate (75%), or high on-treatment rates (63%, P = 0.446) and was also independent of candesartan effects on the fibrillatory rate. CONCLUSION In patients with persistent AF, candesartan decreases the fibrillatory rate, but this effect is restricted to patients with high baseline fibrillatory rates and is not associated with improved cardioversion outcome. Fibrillatory rates <360 fpm are associated with successful cardioversion, but not with AF recurrence.

[1]  Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. , 2003 .

[2]  D. Haines,et al.  Electrical, Morphological, and Ultrastructural Remodeling and Reverse Remodeling in a Canine Model of Chronic Atrial Fibrillation , 2000, Circulation.

[3]  D. Haines,et al.  Assessment of Global Atrial Fibrillation Organization to Optimize Timing of Atrial Defibrillation , 2001, Circulation.

[4]  E. Bernal,et al.  Use of Irbesartan to Maintain Sinus Rhythm in Patients With Long-Lasting Persistent Atrial Fibrillation: A Prospective and Randomized Study , 2002, Circulation.

[5]  S. Mohiuddin,et al.  Meta-analysis: inhibition of renin-angiotensin system prevents new-onset atrial fibrillation. , 2006, American heart journal.

[6]  Leif Sörnmo,et al.  Atrial fibrillatory rate and sinus rhythm maintenance in patients undergoing cardioversion of persistent atrial fibrillation. , 2006, European heart journal.

[7]  G. Nollo,et al.  Dynamic electrophysiological behavior of human atria during paroxysmal atrial fibrillation. , 1995, Circulation.

[8]  Leif Sörnmo,et al.  Electrocardiographic characteristics of fibrillatory waves in new-onset atrial fibrillation. , 2007, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[9]  P. Langley,et al.  Analysis of surface electrocardiograms in atrial fibrillation: techniques, research, and clinical applications. , 2006, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[10]  Andreas Bollmann,et al.  Atrial Fibrillatory Frequency Predicts Atrial Defibrillation Threshold and Early Arrhythmia Recurrence in Patients Undergoing Internal Cardioversion of Persistent Atrial Fibrillation , 2002, Pacing and clinical electrophysiology : PACE.

[11]  Leif Sörnmo,et al.  Spatiotemporal QRST cancellation techniques for analysis of atrial fibrillation , 2001, IEEE Transactions on Biomedical Engineering.

[12]  M. Biehl,et al.  Spontaneous Reinitiation of Atrial Fibrillation Following Transvenous Atrial Defibrillation , 1998, Pacing and clinical electrophysiology : PACE.

[13]  Patients with Persistent Atrial Fibrillation Taking Oral Verapamil Exhibit a Lower Atrial Frequency on the ECG , 2002, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[14]  Leif Sörnmo,et al.  Characterization of atrial fibrillation using the surface ECG: time-dependent spectral properties , 2001, IEEE Transactions on Biomedical Engineering.

[15]  Steven Swiryn,et al.  Relationship between pattern of occurrence of atrial fibrillation and surface electrocardiographic fibrillatory wave characteristics. , 2004, Heart rhythm.

[16]  Wen-Chung Yu,et al.  Effects of 17β‐Estradiol on Tachycardia‐Induced Changes of Atrial Refractoriness and Cisapride‐Induced Ventricular Arrhythmia , 1999, Journal of cardiovascular electrophysiology.

[17]  5.6 Echo- and electrocardiographic predictors for atrial fibrillation recurrence following cardioversion , 2003 .

[18]  K. Arakawa,et al.  Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. , 2003, Journal of the American College of Cardiology.

[19]  S. Nattel,et al.  Consequences of Atrial Tachycardia-Induced Remodeling Depend on the Preexisting Atrial Substrate , 2002, Circulation.

[20]  S. Nattel,et al.  Enalapril effects on atrial remodeling and atrial fibrillation in experimental congestive heart failure. , 2002, Cardiovascular research.

[21]  Wen-Chung Yu,et al.  Spectral Analysis of Chronic Atrial Fibrillation and Its Relation to Minimal Defibrillation Energy , 2002, Pacing and clinical electrophysiology : PACE.

[22]  M. Allessie,et al.  The Wavelength of the Cardiac Impulse and Reentrant Arrhythmias in Isolated Rabbit Atrium: The Role of Heart Rate, Autonomic Transmitters, Temperature, and Potassium , 1986, Circulation research.

[23]  M. Allessie,et al.  Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. , 1995, Circulation.

[24]  Nobuo Fukuda,et al.  Relation of Age and Sex to Atrial Electrophysiological Properties in Patients with No History of Atrial Fibrillation , 2003, Pacing and clinical electrophysiology : PACE.

[25]  A. Bollmann,et al.  Atrial fibrillatory rate and risk of left atrial thrombus in atrial fibrillation. , 2007, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[26]  S. Yusuf,et al.  Clinical ResearchHeart Rhythm DisorderPrevention of Atrial Fibrillation With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Meta-Analysis , 2005 .

[27]  M. Stridh,et al.  Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil. , 1999, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[28]  L. Sornmo,et al.  Detection and feature extraction of atrial tachyarrhythmias , 2006, IEEE Engineering in Medicine and Biology Magazine.

[29]  Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation. A prospective and randomized study ☆ , 2002 .

[30]  A. Tveit,et al.  Candesartan in the prevention of relapsing atrial fibrillation. , 2007, International journal of cardiology.

[31]  P. Sanders,et al.  Absence of acute effects of angiotensin II on atrial electrophysiology in humans. , 2005, Journal of the American College of Cardiology.

[32]  Leif Sörnmo,et al.  Validation and Clinical Application of Time‐Frequency Analysis of Atrial Fibrillation Electrocardiograms , 2007, Journal of cardiovascular electrophysiology.

[33]  H. Wellens,et al.  Immediate Reinitiation of Atrial Fibrillation Following Internal Atrial Defibrillation , 1998, Journal of cardiovascular electrophysiology.

[34]  A. Bollmann,et al.  A Genotype-Dependent Intermediate ECG Phenotype in Patients With Persistent Lone Atrial Fibrillation: Genotype ECG-Phenotype Correlation in Atrial Fibrillation , 2009, Circulation. Arrhythmia and electrophysiology.

[35]  J. Tamargo,et al.  Direct effects of candesartan and eprosartan on human cloned potassium channels involved in cardiac repolarization. , 2001, Molecular pharmacology.

[36]  S. Nattel,et al.  Effects of Angiotensin-Converting Enzyme Inhibition on the Development of the Atrial Fibrillation Substrate in Dogs With Ventricular Tachypacing–Induced Congestive Heart Failure , 2001, Circulation.

[37]  M. Horie,et al.  Angiotensin II Potentiates the Slow Component of Delayed Rectifier K+ Current via the AT1 Receptor in Guinea Pig Atrial Myocytes , 2006, Circulation.

[38]  Leif Sörnmo,et al.  Detection and feature extraction of atrial tachyarrhythmias. A three stage method of time-frequency analysis. , 2006, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[39]  Martin Stridh,et al.  Echocardiographic and Electrocardiographic Predictors for Atrial Fibrillation Recurrence Following Cardioversion , 2003, Journal of cardiovascular electrophysiology.