Remission of paroxysmal atrial fibrillation with iron reduction in haemophilia A.

SUMMARY: Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12-15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing.

Atypical right atrial flutter patterns.

BACKGROUND: The purpose of our study was to define the incidence and mechanisms of atypical right atrial flutter. METHODS AND RESULTS: A total of 28 (8%) of 372 consecutive patients with atrial flutter (AFL) had 36 episodes of sustained atypical right AFL. Among 24 (67%) of 36 episodes of lower loop reentry (LLR), 13 (54%) of 24 episodes had early breakthrough at the lower lateral tricuspid annulus, whereas 11 (46%) of 24 episodes had early breakthrough at the high lateral tricuspid annulus, and 9 (38%) of 24 episodes showed multiple annular breaks. Bidirectional isthmus block resulted in elimination of LLR. A pattern of posterior breakthrough from the eustachian ridge to the septum was observed in 4 (14%) of 28 patients. Upper loop reentry was observed in 8 (22%) of 36 episodes and was defined as showing a clockwise orientation with early annular break and wave-front collision over the isthmus. Two patients had atypical right AFL around low voltage areas ("scars") in the posterolateral right atrium. CONCLUSIONS: Atypical right AFL is most commonly associated with an isthmus-dependent mechanism (ie, LLR or subeustachian isthmus breaks). Non-isthmus-dependent circuits include upper loop reentry or scar-related circuits.

Body surface mapping of counterclockwise and clockwise typical atrial flutter: a comparative analysis with endocardial activation sequence mapping.

OBJECTIVES: This study was directed at developing spatial 62-lead electrocardiogram (ECG) criteria for classification of counterclockwise (CCW) and clockwise (CW) typical atrial flutter (Fl) in patients with and without structural heart disease. BACKGROUND: Electrocardiographic classification of CCW and CW typical atrial Fl is frequently hampered by inaccurate and inconclusive scalar waveform analysis of the 12-lead ECG. METHODS: Electrocardiogram signals from 62 torso sites and multisite endocardial recordings were obtained during CCW typical atrial Fl (12 patients), CW typical Fl (3 patients), both forms of typical Fl (4 patients) and CCW typical and atypical atrial Fl (1 patient). All the Fl wave episodes were divided into two or three successive time periods showing stable potential distributions from which integral maps were computed. RESULTS: The initial, intermediate and terminal CCW Fl wave map patterns coincided with: 1) caudocranial activation of the right atrial septum and proximal-to-distal coronary sinus activation, 2) craniocaudal activation of the right atrial free wall, and 3) activation of the lateral part of the subeustachian isthmus, respectively. The initial, intermediate and terminal CW Fl wave map patterns corresponded with : 1) craniocaudal right atrial septal activation, 2) activation of the subeustachian isthmus and proximal-to-distal coronary sinus activation, and 3) caudocranial right atrial free wall activation, respectively. A reference set of typical CCW and CW mean integral maps of the three successive Fl wave periods was computed after establishing a high degree of quantitative interpatient integral map pattern correspondence irrespective of the presence or absence of organic heart disease. CONCLUSIONS: The 62-lead ECG of CCW and CW typical atrial Fl in man is characterized by a stereotypical spatial voltage distribution that can be directly related to the underlying activation sequence and is highly specific to the direction of Fl wave rotation. The mean CCW and CW Fl wave integral maps present a unique reference set for improved clinical detection and classification of typical atrial Fl.

The spatial dispersion of atrial refractoriness and atrial fibrillation vulnerability.

The local dispersion of conduction and refractoriness has been considered essential for induction of atrial arrhythmias. This study sought to determine whether a difference of refractoriness and vulnerability for induction of atrial fibrillation between trabeculated and smooth as well as high and low right atrium may contribute to initiation of atrial fibrillation in dogs. In 14 healthy mongrel dogs weighing 22.4 +/- 1 kg, closed-chest endocardial programmed stimulation was performed from four distinct right atrial sites. Atrial refractory periods and vulnerability for induction of atrial fibrillation or premature atrial complexes were determined during a basic cycle length of 400 and 300 ms and an increasing pacing current strength. For a pacing cycle length of 300 ms, atrial refractory periods were longer on the smooth, as compared to the trabeculated right atrium (102 +/- 25 vs. 97 +/- 17 ms, p < 0.05), whereas for a pacing cycle length of 400 ms, there was no significant difference. The duration of the vulnerability zone for induction of atrial fibrillation was longer on the smooth right atrium, for a cycle length of both 400 ms (40 +/- 30 vs. 31 +/- 22 ms; p < 0.05) and 300 ms (33 +/- 25 vs. 23 +/- 21 ms; p < 0. 01). When comparing high and low right atrium, refractory periods were longer on the the low right atrium, for a cycle length of both 400 ms (111 +/- 23 vs. 94 +/- 24 ms; p < 0.01) and 300 ms (104 +/- 20 vs. 96 +/- 23 ms; p < 0.01). For a pacing cycle length of 300 ms, the duration of the atrial fibrillation vulnerability zone was longer for the high, as compared to the low right atrium (34 +/- 22 vs. 22 +/- 22, p < 0.01). Seven dogs with easily inducible episodes of atrial fibrillation demonstrated significantly shorter refractory periods as compared to 7 non-vulnerable dogs, regardless of pacing site and current strength. In conclusion, significant differences in refractoriness and vulnerability for induction of atrial fibrillation can be observed in the area of the crista terminalis in healthy dogs. Thus, local anatomic factors may play a role in the initiation of atrial fibrillation.

Low-power radiofrequency application and intracardiac echocardiography for creation of continuous left atrial linear lesions.

INTRODUCTION: Continuity of radiofrequency (RF) lesions for a catheter-based cure of atrial fibrillation is essential in order to avoid reentrant tachycardias. In the present study, we assessed the value of intracardiac echocardiography and preablation electrode-tissue interface parameters for creation of left atrial linear lesions. METHODS AND RESULTS: In six healthy dogs, two left atrial linear lesions (lesion 1, along the inferior posterior left atrium; lesion 2, from the appendage to the left atrial roof) were attempted via a transseptal approach using a deflectable catheter with six 7-mm coil electrodes. In a randomized fashion, one lesion was performed under echocardiographic guidance and one with blinded echocardiographic monitoring. The following preablation parameters were assessed for every coil electrode: (1) mean atrial electrogram amplitude of six consecutive sinus beats; (2) diastolic pacing threshold; and (3) temperature response to application of 5 W for 10 seconds. After ablation (target temperature 70 degrees C, maximum power 50 W, duration 60 sec), the excised left atrium was examined macroscopically and histologically for lesion length, continuity, and presence or absence of lesions associated with each coil. Out of 12 attempted RF lesions, 7 were continuous (length, 47+/-5 mm, lesion 2, n = 6) and 5 were discontinuous (lesion 1, n = 5). Fifty-two of 70 coil electrodes (74%) had pathologic evidence of lesion creation. Intracardiac echocardiography was superior to fluoroscopy with respect to the actual number of coil electrodes creating lesions, and lesion continuity was correctly predicted in 9 of 12 lesions. Intracardiac echocardiography was 85% sensitive and 54% specific in predicting lesions created by individual coils. The correlation between the mean 60-second ablation temperature and the preablation parameters was 0.45 for the electrogram amplitude, -0.67 for the pacing threshold, and 0.81 for the temperature response to low-power application. Sensitivity and specificity for prediction of lesions created by individual coils, respectively, were 84% and 48% for the electrogram amplitude, 90% and 68% for the pacing threshold, and 96% and 76% for the low-power RF application. CONCLUSION: Long linear lesions can be safely and effectively performed in the canine left atrium, using a tip-deflectable multielectrode catheter. Intracardiac echocardiography may be helpful for positioning the ablation catheter in some parts of the left atrium, and preablation parameters, especially a nontraumatic low-power RF application, are able to predict ultimate lesion creation with high accuracy.

Electrophysiologic effects of selective right versus left atrial linear lesions in a canine model of chronic atrial fibrillation.

INTRODUCTION: Long linear lesions have been shown to eliminate atrial fibrillation in animal models, but little is known about the electrophysiologic response in one atrium to lesions in the contralateral atrium. METHODS AND RESULTS: Twelve dogs with chronic atrial fibrillation were randomized to either right atrial ablation (n = 4), left atrial ablation first (n = 4), or a sham procedure (n = 4). Simultaneous biatrial endocardial mapping was performed before and after three linear lesions were applied at specific points in either atrium, using an expandable ablation catheter. Atrial fibrillation was reinducible after single atrial ablation in each dog and no longer inducible after biatrial ablation in five dogs. At baseline, the mean atrial fibrillation cycle length was longer on the trabeculated (117+/-15 msec) compared with the smooth right (101+/-16 msec) or left atrium (88+/-10 msec; P < 0.01). Single right and left atrial ablation caused a significant cycle length increase in the ablated atrium. Left atrial ablation increased the cycle length on both the trabeculated (121+/-18 msec vs 137+/-11 msec; P < 0.05) and smooth right atrium (108+/-12 msec vs 124+/-9 msec; P < 0.05). Right atrial ablation, however, had no significant effect on left atrial fibrillation cycle length (82+/-8 msec vs 86+/-7 msec). CONCLUSION: Left atrial linear lesions affect right atrial endocardial activation, whereas right atrial lesions do not affect left atrial activation in a canine model of atrial fibrillation. These findings suggest that the left atrium is the driver during chronic atrial fibrillation in this animal model and may explain the limited success of right atrial ablation alone in human atrial fibrillation.

Organized activation during atrial fibrillation in man: endocardial and electrocardiographic manifestations.

INTRODUCTION: Atrial fibrillation is not entirely random, but little is known about the spatiotemporal endocardial organization and its surface ECG manifestations. METHODS AND RESULTS: In 16 patients with atrial fibrillation (chronic, n = 14), endocardial mapping of the trabeculated, the posteroseptal smooth right atrium, and the coronary sinus was performed using multipolar catheters. The surface ECG was analyzed by determining "fibrillation wave" (F wave) amplitude, rate, and polarity. During 50 minutes of atrial fibrillation, an organized activation was present 72% +/- 32% of the analyzed time on the trabeculated, 19% +/- 15% on the smooth right atrium (P < 0.01), and 51% +/- 33% along the coronary sinus (P < 0.05). The direction of organized activation was craniocaudal in 72% +/- 16%, caudocranial in 10% +/- 9% (P < 0.01), and indeterminable in 18% +/- 11%. The mean surface F wave amplitude in lead V1 was 0.128 +/- 0.06 mV during 28 seconds of atrial fibrillation with a craniocaudal direction of activation and 0.065 +/- 0.02 mV during a disorganized activation (P < 0.01). A stable relation between surface F waves and organized trabeculated right atrial activation was observed, and the mean F wave cycle length (190 +/- 27 msec) was highly comparable to the simultaneously measured endocardial cycle length (191 +/- 27 msec, correlation coefficient 0.97). F wave polarity in V1 was positive in 12 of 14 patients during craniocaudal and negative in 11 of 14 patients during caudocranial right atrial free-wall activation. CONCLUSION: An organized activation during atrial fibrillation with a predominant craniocaudal direction on the trabeculated right atrium is frequently present and influences the appearance of "coarse" or "fine" atrial fibrillation as well as F wave polarity on the surface ECG.

Body surface mapping of atrial arrhythmias: atlas of paced P wave integral maps to localize the focal origin of right atrial tachycardia.

Successful curative treatment of right atrial tachycardia (AT) can be obtained provided detailed catheter activation mapping of the target site for radiofrequency energy application has been accomplished. However, right AT mapping may be difficult with a single roving catheter due to infrequent presence or noninducibility of the arrhythmia. The present report describes the preliminary clinical use of body surface mapping as an adjunctive noninvasive method to identify the region of AT origin prior to catheter ablation. This technique has been previously applied to develop a reference data base of 17 different paced P wave integral map patterns. The data base was designed by performing right atrial pace mapping in patients without structural heart disease. Each P wave integral map pattern in the data base is unique to ectopic activation onset in a circumscribed right atrial endocardial segment. Localization of the segment of AT origin is accomplished by matching the P wave integral map of a single AT beat with the data base of paced P wave integral maps. The use of body surface mapping as an integral part of the mapping protocol during radiofrequency catheter ablation of right AT offers the possibility to: (1) noninvasively determine the arrhythmogenic target area for ablation using a single beat analysis approach; (2) confine detailed catheter activation mapping to a limited area; and (3) accelerate the overall procedure and limit fluoroscopic exposure by reducing the time required for mapping.

Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion.

BACKGROUND: A transitional rhythm precedes the spontaneous onset of atrial flutter in an animal model, but few data are available in man. METHODS AND RESULTS: In 10 patients, 16 episodes of atrial fibrillation (166+/-236 seconds) converting into atrial flutter during electrophysiological evaluation were analyzed. A 20-pole catheter was used for mapping the right atrial free wall. Preceding the conversion was a characteristic sequence of events: (1) a gradual increase in atrial fibrillation cycle length (150+/-25 ms after onset, 166+/-28 ms before conversion, P<.01); (2) an electrically silent period (267+/-45 ms); (3) "organized atrial fibrillation" (cycle length, 184+/-24 ms) with the same right atrial free wall activation direction as during atrial flutter; (4) another delay on the lateral right atrium (283+/-52 ms); and (5) typical atrial flutter (cycle length, 245+/-38 ms). The coronary sinus generally had a different rate than the right atrial free wall until the beat that initiated flutter, when right atrium and coronary sinus were activated in sequence. During 1313 seconds of fibrillation, there were 171 episodes of "organized atrial fibrillation." An additional activation delay at least 30 ms longer than the mean organized atrial fibrillation cycle length was sensitive (100%) and specific (99%) for impending organization into atrial flutter. During organized atrial fibrillation, right atrial free wall activation was craniocaudal in 70% and caudocranial in 30%, which may explain why counterclockwise flutter is a more common clinical rhythm than clockwise flutter. Atrial flutter never degenerated into fibrillation, even after adenosine infusion. CONCLUSIONS: Anatomic barriers, along with statistical properties of conduction and refractoriness during atrial fibrillation, may explain the remarkably stereotypical pattern of endocardial activation during the initiation of atrial flutter via fibrillation and the rarity of degeneration of flutter to fibrillation once it stabilizes.