Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Novel mutation in the KCNJ2 gene is associated with a malignant arrhythmic phenotype of Andersen-Tawil syndrome.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited multisystem disorder associated with mutations in KCNJ2 and low prevalence of life-threatening ventricular arrhythmias. Our aim was to describe the clinical course of ATS in a family, in which the proband survived aborted cardiac arrest (ACA) and genetic screening revealed a previously unknown mutation (c.271_282del12[p.Ala91_Leu94del]) in the KCNJ2 gene. METHODS: A cascade family screening was performed in a 5-generation family after identification of the KCNJ2 mutation in the proband. Subsequently, 10 of 21 screened individuals appeared to be mutation carriers (median age 38 [range 10-75] years, 3 female). Mutation carriers underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, and exercise stress test. RESULTS: (1) At baseline, 2 patients had survived ACA, 3 had syncope or presyncopal attacks, and 2 reported palpitations. Exercise-induced nonsustained bidirectional ventricular tachycardia was documented in 4 patients, 2 received implantable cardioverter-defibrillators (ICD) for primary prevention and 2 for secondary prevention. (2) During follow-up, 1 primary prevention and 1 secondary prevention patient received in total 4 adequate ICD shocks. Life-threatening ventricular arrhythmias were documented during childhood in 5 of 10 mutation carriers. (3) All mutation carriers presented with characteristic mild dysmorphic features. Only 1 patient suffered from periodic paralysis. All had normal serum potassium level at repeated assessments and none had any other extracardiac disease manifestation. CONCLUSION: Our findings suggest that the novel KCNJ2 mutation is associated with a predominantly cardiac phenotype of Andersen-Tawil syndrome with high propensity to life-threatening ventricular arrhythmias presenting from childhood and young adulthood.

Global repolarization sequence of the ventricular endocardium: monophasic action potential mapping in swine and humans.

The aim of this study was to evaluate the global sequence of repolarization over the ventricular endocardium. Disturbances in myocardial repolarization are associated with the genesis of arrhythmias. However, little is known about the global sequence of repolarization. Monophasic action potentials (MAPs) were recordedfrom 61 +/- 18 LV and/or RV sites in ten healthy pigs and from 43 +/- 15 LV or RV sites in eight patients using the CARTO system. Local activation time (AT), end-of-repolarization (EOR) time, and MAP duration were calculated and three-dimensional global maps of AT, EOR, and MAP duration constructed. LV maps were obtained from all ten pigs and RV maps from three pigs. Five RV maps and five LV maps were obtained from the eight patients. (1) EOR sequence was recognizable in 12 of 13 pig maps and in all the patient maps. (2) EOR followed the sequence of activation in 12 of 13 pig maps and 8 of 10 patient maps. (3) The longest MAPs were recorded in or near the earliest activation area, and the shortest ones in or near the latest activation area in all the pig maps and in nine often and eight often patient maps, respectively. (4) In all maps, MAP duration and AT were negatively correlated, and EOR and AT positively correlated. In conclusion, repolarization gradients exist over the pig and the human ventricular endocardium. The activation sequence is a determinant for the repolarization sequence. The magnitude of the progressive MAP shortening with progressively later activation, relative to local AT, is a critical factor governing the direction and pattern of the EOR.

Gender and atrioventricular conduction properties of patients with symptomatic atrioventricular nodal reentrant tachycardia and Wolff-Parkinson-White syndrome.

The objective of this study was to delineate the sex distribution and atrioventricular conduction properties in patients with manifest or concealed Wolff-Parkinson-White syndrome (WPW) and atrioventricular nodal reentrant tachycardia (AVNRT). The study comprised 328 patients with AVNRT, 347 with manifest, and 220 with concealed WPW who underwent radiofrequency ablation. A male preponderance was observed in patients with manifest WPW (69%), but not in those with concealed WPW (52%) and female preponderance in AVNRT patients (67%). The PR (166 +/- 25 ms) and AH (88 +/- 20 ms) intervals obtained 30 minutes after ablation in manifest WPW patients were significantly longer than in concealed WPW patients (149 +/- 20, 76 +/- 15 ms, P <.0001). The PR (146 +/- 20 ms) and AH intervals (75 +/- 15 ms) measured before ablation in AVNRT patients were shorter than those obtained before ablation in concealed WPW patients (154 +/- 21, 80 +/- 17 ms, P <.05) and after ablation in manifest WPW patients (P <.0001). The PR interval in AVNRT patients was also shorter than those measured during follow-up in concealed (153 +/- 21 ms, P <.05) and manifest WPW patients (165 +/- 23 ms, P <.0001). The ventriculoatrial block cycle length in AVNRT patients was significantly shorter than in manifest and concealed WPW patients. When age-matched patients were assigned to each group, significant differences in PR interval were observed between men and women (159 +/- 22 vs. 151 +/- 22 ms, P <.0001). Differences in sex distribution exist among patients with manifest and concealed WPW and AVNRT. The atrioventricular conduction properties required for the manifestation of pre-excitation and induction of AVNRT and gender differences in atrioventricular conduction may account for the differences in sex distribution.

Atrioventricular conduction: a determinant for the manifestation of ventricular preexcitation in patients with Wolff-Parkinson-White syndrome.

The relation between the atrioventricular conduction properties of the atrioventricular node and the anterograde conduction ability over the accessory pathway in the Wolff-Parkinson-White syndrome has never been studied. Atrioventricular nodal characteristics were studied in 285 patients with manifest and 204 with concealed accessory pathway who underwent radiofrequency ablation, and compared with 146 controls. First and second degree atrioventricular block was observed in 13 (5%) preexcitation patients after ablation, compared with none in concealed accessory pathway (P=0.001) and control patients (P=0.006). The atrial-His intervals in preexcitation patients (88 +/- 20 ms) was significantly longer than in concealed accessory pathway (76 +/- 15 ms, P<0.0001) and control patients (77 +/- 15 ms, P=0.0007), as was PR intervals (165 +/- 25 versus 149 +/- 20 and 150 +/- 21 ms, P<0.0001, respectively) even after excluding those with atrioventricular block. Significant differences in PR and atrial-His intervals were not observed between concealed accessory pathway and control patients. More preexcitation patients had ventriculoatrial dissociation than had patients in the other groups. The results indicate that atrioventricular block is not uncommon in preexcitation patients and a relatively long atrioventricular conduction time is an electrophysiological prerequisite for the manifestation of preexcitation in the Wolff-Parkinson-White syndrome.

Further evidence of localized posterior interatrial conduction delay in lone paroxysmal atrial fibrillation.

AIMS: Prolongation of interatrial conduction time has been reported in patients with paroxysmal atrial fibrillation (PAF). The study objective was to localize the region of the conduction delay in patients with lone PAF. METHODS AND RESULTS: Twenty-one patients with lone PAF and 23 patients with AV nodal re-entrant tachycardia ablation without history of PAF (control group) were recruited. Endocardial recordings were made during sinus rhythm and programmed atrial stimulation. The authors measured the interatrial conduction time, the 'right-sided' conduction time between the high lateral right atrium and the proximal coronary sinus (RA-CSp), and the 'left-sided' conduction time between the proximal and the distal coronary sinus (CSp-LA). During sinus rhythm, the interatrial conduction time was longer in the PAF group (103 +/- 19 vs 86 +/- 12 ms, P<0.01) due to delay of right-sided conduction (RA-CSp was 74 +/- 20 vs 56 +/- 10 ms, P<0.01). During programmed stimulation at the distal coronary sinus, the maximal RA-CSp time was also longer in the PAF group (110 +/- 47 vs 69 +/- 16 ms, P<0.05). No differences in CSp-LA time were observed. CONCLUSION: This study supports the role of posterior septal right atrial conduction disturbances in the genesis of lone PAF.

Gender differences in the electrophysiological characteristics of atrioventricular conduction system and their clinical implications.

OBJECTIVE: The underlying mechanisms of the differences in sex distribution of patients with atrioventricular (AV) nodal re-entrant tachycardia and Wolff-Parkinson-White syndrome are poorly understood. The objective of this study was to determine potential gender differences in the electrophysiological properties of the normal AV conduction system that may be attributable to differences in sex distribution. DESIGN: The AV conduction properties were studied in 96 patients (52 men and 44 women) who underwent electrophysiological testing, 32 patients with atrial tachycardia, 39 with idiopathic ventricular tachycardia and 25 with unexplained palpitations or syncope. RESULTS: The AH (83 +/- 15 ms) and His-ventricular intervals in men (42 +/- 6 ms) were significantly longer than in women (78 +/- 14, 38 +/- 6 ms, p < 0.05, respectively), as was the PR interval (160 +/- 17 vs 152 +/- 13 ms, p = 0.02). The effective refractory period of AV node in men (349 +/- 75 ms) was longer than in women (297 +/- 45 ms, p = 0.03). However, no significant difference was observed between men and women with respect to the incidence of AV nodal dual pathway and the maximum AH interval achieved during premature stimulation or incremental pacing. The AV block cycle length was significantly longer in men (371 +/- 76 ms) than in women (330 +/- 52 ms, p = 0.02). A longer ventriculoatrial block cycle length was also found in men than in women although not at a significant level (436 +/- 107 vs 384 +/- 90 ms. p = 0.08). In addition, men (23%) were twice as likely to have ventriculoatrial dissociation during ventricular pacing as women were (11%, p = 0.2). CONCLUSION: The data show that gender-related differences in AV conduction properties may be responsible for the differences in sex distribution observed in patients with AV nodal re-entrant tachycardia and those with ventricular pre-excitation.

Recording monophasic action potentials using a platinum-electrode ablation catheter.

AIMS: The monophasic action potential (MAP) is conventionally recorded using Ag-AgCl electrodes which are not suitable for delivering radiofrequency currents. To be able to use the sharp MAP upstroke for identifying the local activation, as a step towards the development of a MAP-guided catheter ablation technique, the possibility of recording MAP via platinum electrodes of an ordinary ablation catheter was explored. METHODS AND RESULTS: One hundred and forty-two MAP recordings from the endocardium were obtained via an ablation catheter in 40 patients undergoing electrophysiological study/catheter ablation. During sinus rhythm and pacing, 90% of the ventricular and 100% of the atrial MAPs had stable baselines. The amplitudes were 13 +/- 4.2 mV for ventricular and 2.4 +/- 0.8 mV for atrial MAPs. During mapping and ablation, MAPs and uni- and bipolar electrograms were recorded simultaneously using the same tip electrode in eight patients. The MAPs provided more distinct local activation than the electrograms. During 17 MAP recordings, additional MAPs were recorded simultaneously using an Ag-AgCl electrode catheter in the immediate vicinity of the ablation catheter. The MAPs taken with the ablation catheter had characteristics consistent with those taken with the Ag-AgCl catheter. CONCLUSIONS: (1) Platinum electrodes can be used for timely recording of MAPs in patients. (2) It is feasible to record MAPs and deliver radiofrequency currents via the same platinum-tip electrode. These findings suggest that MAP-guided catheter ablation is technically possible.

[Atrial fibrillation--new knowledge yields new therapeutic possibilities]. / Förmaksflimmer--ny kunskap ger nya behandlingsmöjligheter.

Atrial fibrillation (AF) is the most common cardiac arrhythmia prompting treatment. Advances in our knowledge of the pathophysiology of AF provide the basis for new and improved treatment modalities. Thus, focal excitation and localised impulse conduction defects are possible trigger factors which can be counteracted by focal ablation and pacing synchronisation, respectively. Perpetuation of AF, caused by continuous multisite re-entry, is promoted by successive shortening of repolarisation. Internal defibrillation and anatomical limitation of re-entry are treatments that counteract perpetuation of the arrhythmia. Current knowledge of AF and the application of new treatments are discussed by the Lund AF research group.

Assessment of left ventricular diastolic function from mitral annulus motion, a comparison with pulsed Doppler measurements in patients with heart failure.

Mitral and pulmonary venous flow velocity recordings are often used for the assessment of left ventricular diastolic function. These curves are, however, also influenced by other factors. To investigate whether mitral annulus motion carries additional information in this context, mitral annulus motion was compared to Doppler registrations of mitral and pulmonary flow velocities in 38 patients with heart failure (NYHA II-III) after myocardial infarction. Patients with an increased atrial contribution to mitral annulus motion (> 57%, n = 12) had a higher mitral late-to-early flow velocity ratio (A/E) and pulmonary systolic to diastolic filling ratio (< 0.01). Patients with atrial displacement above average for the group (> or = 5.1 mm, n = 19) had a higher mitral (A/E) ratio and pulmonary systolic to diastolic filling ratio than patients with a lower than average atrial component (P < 0.05). There was a significant correlation between a/T ratio and A/E ratio (r = 0.61, P < 0.001) and between pulmonary flow and transmitral flow (= 0.76, P < 0.001). We conclude that an increased atrial displacement of the mitral annulus is a frequent finding in patients with signs of left ventricular relaxation abnormality. There is a significant correlation between a/T ratio and A/E ratio but the information contained in the two indices are not identical.