Prevalence, risk factors, and type of sleep apnea in patients with paroxysmal atrial fibrillation.

BACKGROUND: Recent studies have suggested an association between sleep apnea (SA) and atrial fibrillation (AF). We aimed to study the prevalence, characteristics, risk factors and type of sleep apnea (SA) in ablation candidates with paroxysmal AF. METHODS/RESULTS: We prospectively studied 579 patients with paroxysmal AF, including 157 women (27.1%) and 422 men (72.9%). Mean age was 59.9 ± 9.6 years and mean body mass index (BMI) 28.5 ± 4.5 kg/m2. SA was diagnosed using polygraphy for two nights at home. The Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire, and Berlin Questionnaire (BQ) assessed the degree of SA symptoms. A total of 479 (82.7%) patients had an apnea-hypopnea index (AHI) ≥ 5, whereas moderate-severe SA (AHI ≥ 15) was diagnosed in 244 patients (42.1%). The type of SA was predominantly obstructive, with a median AHI of 12.1 (6.7-20.6) (range 0.4-85.8). The median central apnea index was 0.3 (0.1-0.7). AHI increased with age, BMI, waist and neck circumference, body and visceral fat. Using the Atrial Fibrillation Severity Scale and the SF-36, patients with more severe SA had a higher AF burden, severity and symptom score and a lower Physical-Component Summary score. Age, male gender, BMI, duration of AF, and habitual snoring were independent risk factors in multivariate analysis (AHI ≥ 15). We found no association between ESS and AHI (R2 = 0.003, p = 0.367). CONCLUSIONS: In our AF population, SA was highly prevalent and predominantly obstructive. The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. None of the screening questionnaires predicted SA reliably.

Temperature-controlled radiofrequency catheter ablation with a 10-mm tip electrode creates larger lesions without charring in the porcine heart.

BACKGROUND: Radiofrequency catheter ablation of atrial flutter, atrial fibrillation or ventricular tachycardia may be favoured by large lesions. We compared lesions created in unipolar mode using 10-mm/8 F electrodes with those of 4-mm/7 F catheters. METHODS: Ablations were first performed in porcine hearts in vitro (70 degrees C, 60 s, tangential catheter tip-tissue orientation). Anaesthetized pigs were thereafter ablated with 10- or 4-mm catheters in the right atrial free wall (RAFW), inferior vena cava-tricuspid valve (IVC-TV) isthmus and left ventricle (LV). RESULTS: In vitro, lesion length doubled and lesion volume tripled using the 10-mm catheter. Average power supply was 69 (SD12) (10-mm tip) versus 26 (SD7) W (4-mm tip). In vivo, lesion length increased by 50% and lesion volume fivefold. Charring at the lesion surface or sudden impedance rises were not observed in vivo. Histologically, coagulation necrosis and minor haemorrhages were found. One RAFW lesion (10-mm) showed a dissection approaching the epicardium. Fibrinous platelet clots or overt thromboses covered the endocardial surface in half of all lesions. Three 10-mm electrode isthmus lesions extended to the right descending posterior artery and one LV lesion to the left anterior descending artery, but there was no damage to the arterial walls. Following six ablations with the 10-mm electrode and two with the 4-mm tip, injury to the adjacent lung tissue of 0.5 to 6.0 mm depth was found (p = 0.22). CONCLUSION: RF ablation using 10-mm/8 F electrodes created significantly larger lesions. 10-mm electrodes appeared safe in the porcine IVC-TV isthmus and LV, but not in the RAFW.

Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified. Among patients with the most stringent clinical criteria of Romano Ward syndrome, a mutation was identified in 71%. Twelve of the 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome were provided with a molecular genetic diagnosis. Cascade genetic screening of 505 relatives of index patients with molecularly defined LQTS identified 251 mutation carriers. The observed penetrance was 41%. Although caution must be exerted, the prevalence of heterozygotes for mutations in the LQTS-associated genes in Norway could be in the range 1/100-1/300, based on the prevalence of patients with Jervell and Lange-Nielsen syndrome.

[Non-pharmacological treatment of arterial fibrillation]. / Ikke-farmakologisk behandling av atrieflimmer.

In selected patients with atrial fibrillation and severe symptoms, non-pharmacological treatment may be an alternative or supplement to medical therapy. Atrioventricular nodal radiofrequency ablation (requires pacemaker implantation), or atrial pacing for sick sinus syndrome, are established treatment modalities. All other non-pharmacological therapies for atrial fibrillation are still experimental. After the "Maze" operation, atrial depolarisation has to follow one specific path determined by surgical scars in the myocardium. This prevents new episodes of atrial fibrillation, but at the cost of perioperative morbidity and mortality. Catheter-based "Maze-like" radiofrequency ablation is technically difficult, and thromboembolic complications may occur. Paroxysmal atrial fibrillation is sometimes initiated by spontaneous depolarisations in a pulmonary vein inlet. Radiofrequency ablation against such focal activity has been reported with high therapeutic success, but the results must be confirmed by several centres. For ventricular rate control, most electrophysiologists presently prefer ablation to induce a complete atrioventricular conduction block (with pacemaker) rather than trying to modify conduction by incomplete block. Atrial or dual chamber pacing may prevent bradycardia-induced atrial fibrillation. It remains to be confirmed that biatrial or multisite right atrial pacing prevents atrial fibrillation more efficiently than ordinary right atrial pacing. An atrial defibrillator is able to diagnose and convert atrial fibrillation. The equipment is expensive, and therapy without sedation may be unpleasant beyond tolerability.

Effect of local hemostatics on platelet aggregation.

The platelets play an important role in the normal hemostasis, and it is known that both natural and synthetic macromolecules may induce platelet activation and aggregation. Thus, the purpose of the present study was to investigate the platelet aggregating effect of five different local hemostatics. Platelet aggregation was assessed by aggregometry. Unwoven fleece of bovine collagen polymer in fibrillar form induced aggregation in combination with small amounts of platelet agonists; ADP and adrenaline. Ordinary, nonabsorbable bone wax also induced aggregation in combination with the agonists, but larger concentrations of agonists were needed. Bioerodible polyorthoester with physical properties such as bone wax, oxidized cellulose and gelatin sponge did not promote platelet aggregation.

[Heart rate variability. Parameters for risk stratification after myocardial infarction]. / Hjertefrekvensvariabilitet. Parameter for risikostratifisering etter hjerteinfarkt.

Reduced heart rate variability (HRV) is an independent risk factor after myocardial infarction, indicating higher risk of fatal and nonfatal arrhythmias and of cardiac death in general. Analysis of HRV is also a valuable tool in clinical research, providing a non-invasive measurement of fluctuations in sympathetic and parasympathetic activation. We expect increased use of these methods, since new 24-hour: ECG-monitoring equipment is to be delivered with software for HRV as an option. Statistical time domain analysis of the whole 24-hour system of recording is very suitable for stratifying risk after myocardial infarction. Frequency domain analysis requires manual as well as automatic editing, but is the method of choice in clinical research involving short-term recordings and standardized conditions.

Complications secondary to the use of standard bone wax in seven patients.

Ordinary bone wax, manufactured from beeswax, was used to stop bleeding from cancellous bone in elective surgery among seven women. Five of them had a resection of a calcaneal exostosis and bursa at the insertion of the calcaneous tendon, one underwent a resection of a medial exostosis of the first metatarsal head, and one had an acromial resection. Postoperatively, all patients had disabling local pain and tenderness. Three of them developed firm visible swellings where bone wax had been used, which was easily palpable under the intact skin. At reoperation, 4 to 52 months later, masses of brown, soft granulation tissue were excised in all patients. Five of seven were relieved from pain. Microscopically, a bone wax granuloma with marked foreign body reaction was seen in all patients.

Radiofrequency current ablation of porcine right atrium: increased lesion size with bipolar two catheter technique compared to unipolar application in vitro and in vivo.

Interruption of atrial flutter and fibrillation by RF catheter ablation may be favored by large, elongated lesions. We administered RF current in unipolar and bipolar mode in porcine right atrium. Bipolar ablation was performed between the tip electrodes of two serially coupled catheters. With 4-mm tip electrodes in vitro, lesion length increased from a mean (SD) of 7.9 (1.2) mm at 3 mm-interelectrode distance (i.e.d.) to 13.3 (3.3) mm at 9-mm IED, but decreased at 12-mm IED due to nonconfluent lesions (P < 0.0001). With 4 mm distal electrodes and 8 mm IED, bipolar lesions were 65% longer than corresponding unipolar ablations. Switching to bipolar mode increased the lesion length more than increasing electrode tip length to 6 mm in unipolar mode. Power and temperature controlled ablation created equally sized lesions. Twelve anesthetized pigs were randomized to unipolar or two catheter bipolar temperature controlled ablation of the right atrial free wall. Bipolar ablation created confluent lesions with endocardial length x width of 13.5 (5.8) x 7.3 (3.7) mm, unipolar ablation 6.4 (2.8) x 4.6 (1.4) mm (P < 0.001 when comparing length and P = 0.013 for lesion width). The atrial lesions in both groups were transmural and extended into hilar lung lesions with maximal depth of 3.0 (1.1) and 2.6 (1.0) mm, respectively (P = 0.44). Five bipolarly and four unipolarly ablated pigs developed right diaphragmal paresis. We conclude that bipolar ablation may be preferable in situations where large, elongated lesions are favorable. The two catheter technique is feasible in porcine right atrium. Both bipolar and unipolar ablation of the porcine right atrial free wall may frequently be complicated by injury to the phrenic nerve and adjacent lung tissue.

Bipolar radiofrequency catheter ablation creates confluent lesions at larger interelectrode spacing than does unipolar ablation from two electrodes in the porcine heart.

AIMS: Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart. METHODS AND RESULTS: In vitro, confluent lesions were reliably created by a 'dielectrode' catheter (energy delivered simultaneously (in parallel) from two 4 mm electrodes spaced 1 mm apart, towards an indifferent electrode), and a 'bipolar' catheter (energy delivered (in series) between two 4 mm electrodes spaced 5 mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30 s duration (70 degrees C) were administered to the inferior vena cava-tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4 h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length x width x depth measured 7.4 (2.4) x 5.4 (2.2) x 2.8 (0.8) mm in the standard unipolar mode, 10.2 (1.4) x 6.3 (0.7) x 3.3 (1.1) mm in the dielectrode mode and 14.0 (3.6) x 6.0 (1.7) x 3.8 (1.2) mm in the bipolar mode. Thus lesion length increased significantly through the three groups (P < 0.001), while width and depth did not. CONCLUSION: Both dielectrode and bipolar ablation were feasible in porcine right atrial ablation, and created longer lesions than the standard unipolar mode. By allowing a larger interelectrode distance, bipolar ablation created the longest lesions and may be favourable when linear lesions are necessary.

When should heparin preferably be administered during radiofrequency catheter ablation?

RF catheter ablation is complicated by thromboembolism in about 1% of patients. Limited knowledge exists concerning when and how to use anticoagulation or antithrombotic treatment. We studied the activation of coagulation (prothrombin fragment 1 + 2 [PF1 + 2] and D-dimer), platelets (beta-thromboglobulin [beta-TG]) and fibrinolysis (plasmin-antiplasmin complexes [PAP]) during RF ablation of accessory pathways in 30 patients. They were randomized to receive heparin (100 IU/kg, intravenously) (1) immediately after introduction of the femoral venous sheaths (group I) or (2) after the initial electrophysiological study, prior to the delivery of RF current (groups II and III). Group II additionally received saline irrigation of all femoral sheaths. After the initial bolus, 1,000 IU of heparin was supplied hourly in all groups. Within groups II and III, median plasma values of PF1 + 2 and beta-TG more than tripled (P < or = 0.007) during the diagnostic study and gradually declined during heparin administration despite RF current delivery. Median D-dimer tripled (P = 0.005) and PAP doubled (NS) before heparin administration; then both remained around the upper reference values. In the early heparin group, however, PF1 + 2, D-dimer, and PAP did not rise at all, and beta-TG showed only a slight increase towards the end of the procedure. The differences between group I versus groups II and III were statistically significant prior to the first RF current delivery (PF1 + 2, D-dimer, and beta-TG) and by the end of the procedure (PF1 + 2, D-dimer, and PAP). In conclusion, "late" heparin administration allows hemostatic activation during the initial catheterization and diagnostic study. By administering intravenous heparin immediately after introduction of the venous sheaths, hemostatic activation is significantly decreased. Saline irrigation of the venous sheaths added nothing to late heparin administration.

Assessment in rats of a new bioerodible bone-wax-like polymer.

Holes drilled in rats' skull, iliac crest, and tibia were filled with beeswax or with a new, wax-like, bioerodible polyorthoester (Alzamer). Empty drill-holes served as controls. In addition, beeswax and polyorthoester were deposited between the left and the right oblique abdominal muscles, respectively. In muscle, both the beeswax and polyorthoester elicited a transient foreign body reaction. The beeswax was not resorbed in bone or muscle, whereas the polyorthoester was. Bone healing was inhibited in the iliac crest and the tibiae filled with beeswax, whereas holes filled with polyorthoester healed readily.

The activation of platelet function, coagulation, and fibrinolysis during radiofrequency catheter ablation in heparinized patients.

INTRODUCTION: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients. METHODS AND RESULTS: We studied the activation of coagulation (prothrombin fragment 1+2 [PF1+2]), platelets (beta-thromboglobulin [beta-TG])) and fibrinolysis (plasmin-antiplasmin complexes [PAP] and D-dimer) during radiofrequency (RF) ablation in 13 patients. They received heparin 100 U/kg intravenously after the initial electrophysiologic study, prior to the delivery of RF current; thereafter 1,000 U/hour throughout the procedure. PF1+2 increased fourfold (P < 0.001) during the diagnostic study, but gradually declined to upper reference value during heparin administration. There was a strong correlation between procedure duration prior to heparin bolus (range 39 to 173 min); and (a) the maximal rise of PF1+2 (r = 0.83, P < 0.001) and (b) the increase of PF1+2 from baseline to end of the procedure (r = 0.74, P = 0.004). There was no correlation between postheparin changes of PF1+2 and (a) postheparin procedure duration (range 40 to 317 min), (b) number of RF pulses (range 1 to 16), or (c) RF current duration (range 46 to 687 sec). Plasma beta-TG concentration showed similar trends. Fibrinolytic activity increased moderately from baseline until heparin administration; then remained around the upper reference values. PAP at the end of procedure and D-dimer at the time of heparin administration both correlated with preheparin procedure duration (r = 0.70, P = 0.007 and r = 0.69, P = 0.01, respectively). All parameters were normal the next morning. CONCLUSION: Procedure duration prior to heparin administration, and not the delivery of RF current per se, determines activation of hemostasis and fibrinolysis during RF ablation.