Response to Letter Regarding Article, “Repolarization Alternans Reveals Vulnerability to Human Atrial Fibrillation”
We appreciate the insightful and clinically relevant comments of Dr Madias on our recent study.1 Dr Madias hypothesizes that prolongation of the P wave on the surface ECG, which has been epidemiologically linked with atrial fibrillation (AF),2 may complement our report1 that oscillations of atrial repolarization indicate a spectrum of AF vulnerability from control subjects without AF, through patients with paroxysmal AF to those with persistent AF.
We have recently studied this issue3 by analyzing biatrial conduction in these patients to test the hypothesis that dynamic conduction slowing indicates vulnerability to AF, and may be most marked at the site of AF initiation. It is noteworthy that baseline ECG P-wave duration did not differ between control subjects and patients with paroxysmal or persistent AF (P=0.35). This result may be reconciled with the cited Framingham study in which, although patients with maximal P-wave duration >95th percentile had a significantly greater AF incidence (228 cases per 10 000 years), the majority of AF cases (>92%, calculated from the authors' data) still occurred in patients without “extreme values of P wave duration.”2
To address our hypothesis, we studied whether dynamic (rate-dependent) conduction slowing, which may explain dynamic AF initiation after triggers, may better indicate arrhythmia vulnerability than baseline conduction. We measured biatrial conduction times by the use of 64-pole basket catheters (Constellation, Boston Scientific, MA) placed in the left or both atria simultaneously during progressively faster pacing from the pulmonary veins to the point of AF initiation. It is noteworthy that baseline biatrial conduction times also did not differ between control subjects and patients with paroxysmal or persistent AF (129±49 versus 120±22 versus 131±36 ms, P=0.51). Conversely, dynamic slowing (conduction restitution) did indeed indicate a spectrum of vulnerability to AF, with persistent AF patients exhibiting gradual slowing over a wide range of rates, paroxysmal AF patients exhibiting abrupt slowing only at the fastest rates just before AF onset, and control subjects exhibiting no slowing (P<0.05). Moreover, dynamic slowing was observed at the actual sites of AF initiation (P<0.05) that lay at patient-specific left atrial locations but rarely at the pulmonary veins.3
The interaction between dynamic conduction slowing and repolarization oscillations is likely complex, and under certain conditions may enable functional conduction block, reentry, and AF initiation.1,3,4 In the future, these indices may offer more pathophysiologically specific and clinically accurate predictors of AF risk than baseline ECG measurements of P-wave duration or potentially of atrial repolarization (Ta waves).5
We fully agree with Dr Madias that there is an urgent need to translate pathophysiologic observations to clinical practice, and thank him for these important comments.
Sanjiv M. Narayan, MB, MD
Paul Clopton, MS
David E. Krummen, MD
University of California, San Diego
San Diego, CA
Michael R. Franz, MD, PhD
Veterans Affairs Medical Center
Etienne J. Pruvot, MD
Centre Hospitalier Universitaire Vaudois
Dr Narayan was supported by grants from the National Institutes of Health, HL70529 and HL83359, and the Doris Duke Charitable Foundation. Dr Narayan is coauthor of intellectual property owned by the University of California regents and licensed to Topera Inc. He is cofounder and equity holder in Topera. Topera has not sponsored any research, including that presented here. In addition, Dr Narayan has received honoraria from Medtronic, St. Jude Medical, Biotronik, and Biosense-Webster. His institution has received fellowship support from Medtronic, Boston Scientific, St. Jude Medical, and Biotronik. Dr Franz was the original inventor of the MAP catheter used in this study. Dr Krummen has received honoraria from Medtronic. His institution has received fellowship support from Medtronic, Boston Scientific, St. Jude Medical, and Biotronik. The other authors report no conflicts.
- © 2012 American Heart Association, Inc.
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