Search

The genetic causes of atrial fibrillation (AF) with slow conduction are unknown. Eight kindreds with familial AF and slow conduction, including a family affected by early onset AF, heart block and incompletely penetrant non-ischemic dilated cardiomyopathy (DCM) underwent whole exome sequencing. A known pathogenic mutation in the desmin (DES) gene resulting in p.S13F substitution (NM_001927.3:c.38C>T) at a PKC phosphorylation site was identified in all four members of the kindred with early-onset AF and heart block, while only two developed DCM. Higher penetrance for AF and heart block prompted a genetic screening for DES modifier(s). A deleterious mutation in the phosphodiesterase-4D-interacting-protein (PDE4DIP) gene resulting in p.A123T substitution (NM_001002811:c.367G>A) was identified that segregated with early onset AF, heart block and the DES mutation. Three additional novel deleterious PDE4DIP mutations were identified in four other unrelated kindreds. Characterization of PDE4DIP(A123T) in vitro suggested impaired compartmentalization of PKA and PDE4D characterized by reduced colocalization with PDE4D, increased cAMP activation leading to higher PKA phosphorylation of the β2-adrenergic-receptor, and decreased PKA phosphorylation of desmin after isoproterenol stimulation. Our findings identify PDE4DIP as a novel gene for slow AF and unravel its epistatic interaction with DES mutations in development of conduction disease and arrhythmia.

Background: The genetic causes of atrial fibrillation (AF) with slow conduction are unknown. Methods: Eight kindreds with familial AF and slow conduction, including a family affected by early onset AF, heart block and incompletely penetrant non-ischemic cardiomyopathy (NICM) underwent whole exome sequencing. Results: A known pathogenic mutation in the desmin (DES) gene resulting in S13F substitution at a PKC phosphorylation site was identified in all four members of the kindred with early-onset AF and heart block, while only two developed NICM. Higher penetrance of the mutation for AF and heart block prompted the screening for DES modifier(s). A second deleterious mutation in the phosphodiesterase 4D interacting-protein (PDE4DIP) gene resulting in A123T substitution segregated with early onset AF, heart block and the DES mutation. Three additional novel deleterious PDE4DIP mutations were identified in four other unrelated kindreds. Characterization of PDE4DIP in vitro suggested impaired compartmentalization of PKA and PDE4D characterized by reduced colocalization with PDE4D, increased cAMP activation leading to higher PKA phosphorylation of the β2-adrenergic-receptor, and decreased PKA phosphorylation of Desmin in response to isoproterenol stimulation compared to wildtype PDE4DIP. Conclusion: Our findings identify an epistatic interaction between DES and PDE4DIP variants, increasing the penetrance for conduction disease and arrhythmia.

We present a case of post herpetic neuralgia in a patient admitted with a prior herpetic infection complicated by recurrent episodes of asystole and cardiac arrest. We first tried medical therapy with the use of high doses of intravenous analgesics, opiates, carbamazepine and phenytoin. However, the high recurrence rate of the pain episodes with concomitant cardiac arrest and cardiopulmonary resuscitation warranted first the placement of a temporary pacing lead, and shortly after a permanent device as a rescue procedure. This case illustrates the treatment difficulties in such an uncommon and extreme situation.

Background The full circuit of common atrial flutter using conventional methods of sequential or multielectrode activation mapping is not completely understood. Methods and Results We performed three-dimensional right atrial endocardial activation mapping during common counterclockwise atrial flutter in 17 patients (16 men, 1 woman; mean age, 53±11 years) by using the Cordis-Biosense EP Navigation system and assessed the distribution of estimated conduction velocities and double and fractionated potentials. ECG flutter wave morphologies were compared with activation patterns. Points (91±29) were sequentially acquired covering 88±11% of the flutter cycle length of 239±22 ms. A wide and variable posterior zone of double and fractionated potentials coincided with blocking and colliding wave fronts and formed the posterior limit of the circuit. A progressively widening septal (sep) wave front ascending from just beyond the coronary sinus ostium, passed cranially as a broad front anterior to the superior vena cava (SVC) in 14 patients, whereas fusion around the SVC formed the superior (sup) limb of the circuit in 3. Bounded anteriorly by the tricuspid valve, the wave front descended down the lateral (lat) aspect of the right atrium before completing the circuit in all cases through the inferior vena cava–tricuspid annulus isthmus. The estimated conduction velocity in the medial isthmus (0.6±0.3 m/s) was lower than in the other limbs of the circuit (sup=1±0.5 m/s, lat=1±0.5 m/s, sep=0.9±0.4 m/s, P =.05). Double and fractionated potentials were constant and more prevalent in the posterior right atrium. ECG flutter wave morphology did not correlate with three-dimensional activation maps. Conclusions Interindividual variations occur in the right atrial circuit of common atrial flutter, with constant activation through the cavotricuspid isthmus. A variable zone of block forms the posterior limit. Fusion around the SVC can occur, and ascending medial septal activation does not follow a consistent pattern.

UNLABELLED Previous experimental data suggest that atrial activity is homogeneously distributed during paroxysmal atrial fibrillation (AFib). Little is known about this in human paroxysmal AFib. METHODS Twenty-five men and two women (mean age 49 +/- 11 years; five with structural heart disease) with paroxysmal AFib for a mean 5 +/- 6.2 years despite the use of a mean of 3.6 +/- 1.7 antiarrhythmic drugs underwent atrial mapping. The right atrium was divided into four regions: posterior (intercaval), lateral, anterior, and septal. A 14-pole catheter was positioned to assess complex electrical activity defined as the duration of continuous electrical activity or electrograms with FF intervals < 100 ms for 60 seconds (expressed as percentage of time). In addition, the left atrium (divided into three regions: posterior, anterior, and septal) was explored in 12 patients with a multipolar catheter. RESULTS The complex electrical activity time between all the regions explored was significantly different. In the right atrium, the septal (74% +/- 32%; P = 0.02) and the posterior (63% +/- 32%; P = 0.04) areas were significantly more disorganized than the lateral (22% +/-23%) and anterior (21% +/- 26%) regions. In the left atrium, complex electrical activity was predominant and widely distributed (posterior: 87% +/- 11%; septal: 65% +/- 27%) except in the appendage area (anterior region: 18% +/- 14%). CONCLUSIONS Quantitative assessment of complex electrical activity in both atria in humans shows heterogeneous temporal and spatial distribution. This may have implications for guiding catheter ablation of AFib.

Breath-holding spells (BHS) are frequent and benign in children. Medical treatment is rarely needed but exceptionally severe forms require the implantation of a pacemaker. We describe here the case of an 18-month-old girl who presented to our department with severe episodes of BHS associated with loss of consciousness. This child necessitated the insertion of a pacemaker, which resolved her BHS.

Despite operator experience and improved catheter technology, acute vessel closure is inherently associated with percutaneous transluminal coronary angioplasty (PTCA) of complex lesions. This case study describes a patient who developed an occlusive dissection post PTCA at the bifurcation of the left anterior descending artery (LAD) and its diagonal branch. The “T”-shaped wiktor stent placement immediately re-establishes full flow, obviating the necessity for emergent surgery. © 1996 Wiley-Liss, Inc.

Background Atrial fibrillation is usually thought to be due to multiple circulating reentrant wavelets. From previous studies, a focal mechanism is considered to be very unlikely. In this report, focal atrial fibrillation is defined on an ECG pattern of atrial fibrillation and later demonstrated to be due to a focal source. Methods and Results Nine patients (five men and four women; age, 38±7 years) with paroxysmal focal atrial fibrillation are reported here. All were free of structural heart disease and had frequent episodes of atrial fibrillation despite the use of a mean of 4±2 antiarrhythmic drugs. Atrial fibrillation was associated with runs of irregular atrial tachycardia or monomorphic extrasystoles. The electrophysiological study demonstrated that all the atrial arrhythmias were due to the same focus firing irregularly and exhibiting a consistent and centrifugal pattern of activation. Three foci were found to be located in the right atrium, two near the sinus node and one in the ostium of the coronary sinus. Six others were located in the left atrium at the ostium of the right pulmonary veins (n=5) and at the ostium of the left superior pulmonary vein (n=1). All atrial arrhythmias were successfully treated by use of a mean of 4±4 radiofrequency pulses. Conclusions In some patients, the surface ECG pattern of atrial fibrillation is due to a focal rapidly firing source of activity that can be eliminated by discrete radiofrequency energy applications.

INTRODUCTION The purpose of this study was to evaluate the efficacy and safety of radiofrequency (RF) catheter ablation of common atrial flutter and to determine the optimum target sites in a large series of patients. Three different approaches were used to target the ablation site. The first used a combined anatomic and electrophysiologic approach, whereas the second and the third approaches relied primarily on anatomic guidelines to target the critical area in the atrial flutter reentrant circuit located in the low right atrium. BACKGROUND Recent studies report the efficacy of RF current application in the low right atrial region to interrupt and prevent recurrences of common atrial flutter using either anatomic or electrophysiologic targets. However, larger groups of patients are required to confirm the efficacy of this technique and to specify the target sites. METHODS AND RESULTS Two hundred consecutive patients with drug-resistant common atrial flutter were studied. In the first 50 patients, target sites were localized using both anatomic landmarks and electrophysiologic parameters. The anatomic landmarks were area 1 between the tricuspid valve and inferior vena cava orifice; area 2 between the tricuspid valve and coronary sinus ostium; and area 3 between the inferior vena and coronary sinus. The electrophysiologic criterion was to ablate when there was an atrial electrogram occurring during the plateau phase (preceding F wave). The first targeted area was that giving the more stable catheter position. In the following 30 patients, we assessed the effect of RF energy application in a single line to area 1 in the first 10 patients, area 2 in the next 10, and area 3 in the last 10 patients. In the last 120 patients, RF energy was applied only in area 1 using repeated applications. RF energy of 12 to 30 W, or that achieving a temperature of 70 degrees C, was applied for 60 to 90 seconds at each site. The endpoint of the ablation procedure was interruption and noninducibility of common atrial flutter in the first 110 patients and additional isthmal block in 48 of the last 90 patients. Overall, atrial flutter was interrupted and rendered noninducible after a single session in 191 (95%) patients and could not be interrupted in 9 (4.5%) patients. The mean number of RF applications was 12 +/- 8. After a mean follow-up of 24 +/- 9 months, recurrences occurred in 31 (15.5%) patients, 26 of whom underwent a successful second or third session without further recurrences of atrial flutter. Atrial fibrillation not documented before the ablation was detected in 11 patients. On a retrospective analysis of the final successful site in the first group of 50 patients, the location was in area 1 in 39% of patients; area 2 in 36% of patients, and area 3 in 25% of patients. Atrial electrograms recorded at these sites showed a single spike pattern in 46% of patients, and double spike pattern (28%) or fractioned electrogram in 26% patients. When lines of RF lesions were placed at several sites, they produced a success rate of 70%, 40%, and 10% at areas 1, 2, and 3 respectively. In the last series of 120 patients, the procedure was successful in 119 patients: 92% of whom were successfully treated only by a linear lesion between the tricuspid annulus isthmus and the inferior vena cava, and the other 8% by additional applications near the coronary sinus ostium. No complications were observed. CONCLUSIONS RF catheter ablation of atrial flutter can be done with a high success rate and is safe. The highest success rate is achieved with RF energy applied in the isthmus between the inferior vena cava orifice and the tricuspid valve. However, 15.5% of patients need multiple sessions to achieve success because of recurrence of flutter. Further follow-up is needed to evaluate the long-term effects of this procedure.