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.

Prophylactic cavotricuspid isthmus block during atrial fibrillation ablation in patients without atrial flutter: a randomised controlled trial.

OBJECTIVES: This randomised trial evaluated if patients with atrial fibrillation (AF) and no history of atrial flutter (AFL) had any benefit of prophylactic cavotricuspid isthmus block (CTIB) in addition to circumferential pulmonary vein ablation (CPVA). METHODS: 149 patients with AF (54% paroxysmal) were randomised to CPVA and CTIB (group CTIB+, n = 73) or CPVA alone (group CTIB-, n = 76). Patients were followed for 12 months with repetitive 7-day Holter monitoring after 3, 6 and 12 months. RESULTS: Six patients (4%) had cardiac tamponade, and one patient had a stroke. No difference was found in the cumulative AFL-free rate between the two treatment groups (CTIB+: 88% vs CTIB-: 84%, hazard ratio (HR) 0.80, 95% CI (0.34 to 1.90), p = 0.61). There was no difference in the cumulative AF-free rate between the groups (CTIB+: 34% vs CTIB-: 32%, HR 0.93, 95% CI (0.63 to 1.38), p = 0.71). Overall, 33% of the patients were free of AF after a single procedure. Including reprocedures, a complete or partial beneficial effect was noted in 62% of the patients at 12 months. At 12-month follow-up, 24 (50%) patients with documented AF or AFL in the Holter recordings were asymptomatic. CONCLUSIONS: It was not possible to demonstrate any beneficial effect of CTIB in addition to CPVA with regard to AFL or AF recurrences during follow-up. Repetitive long-term Holter monitoring demonstrated a 33% rate of freedom from AF during a 1-year follow-up. Including additional CPVA procedures, a clinical effect was noted in 62% of the patients at 12 months. Patients with AF or AFL recurrences were often asymptomatic.

Episodes of atrial fibrillation and atrial vulnerability after successful radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

UNLABELLED: Episodes of atrial fibrillation occur in patients with WPW syndrome but frequently disappear after successful radiofrequency ablation. AIMS: To analyze the incidence of atrial fibrillation before and after successful ablation and the presence of increased atrial vulnerability. METHODS AND RESULTS: Fifty-four of 183 WPW patients had at least one documented episode of atrial fibrillation before ablation. During a follow-up of 24 +/- 12 months 13/54 patients (24%) experienced atrial fibrillation. At baseline, the patients with atrial fibrillation were more often men (74%) vs 53%, P=0.007), were older (45 +/- 15 vs 34 +/- 16 years, P=0.0001), more often had pre-excitation during sinus rhythm (87% vs, 73%, P=0.04) and had increased atrial vulnerability (41%, vs 18%, P<0.001). Only patients with atrial fibrillation before, developed atrial fibrillation after ablation. The 13 (of 54) patients who relapsed were also older (53 +/- 13 vs 42 +/- 15 years, P= 0.03), had increased atrial vulnerability at baseline (77% vs 29%, P=0.002), and were more symptomatic, (13 +/- 21 vs 1 +/- 3 arrhythmia attacks/month, P=0001). No patient without atrial fibrillation before ablation developed atrial fibrillation after treatment. CONCLUSIONS: The accessory pathway was important for the development of atrial fibrillation. Frequent tachycardias seem to promote an electrical remodelling and an increased atrial vulnerability to atrial fibrillation, whereas after successful ablation the majority of patients remain free of atrial fibrillation.

Perception and documentation of arrhythmias after successful radiofrequency catheter ablation of accessory pathways.

BACKGROUND: Some patients continue to have palpitations in spite of successful ablation of Wolff-Parkinson-White (WPW) syndrome. Recurrence of accessory pathways as well as unrelated arrhythmias may explain the symptoms. METHODS: We followed 194 consecutive patients after successful radiofrequency catheter ablation of overt (147) or concealed (47) WPW syndrome. The mean duration of symptoms was 16 +/- 13 years. Atrial fibrillation was documented in 54 patients (24%) prior to ablation. 185 patients responded to a questionnaire 24 +/- 12 months after ablation. RESULTS: The physical well-being was improved in 94%, unchanged in 5%, and deteriorated in 1%. However, 76 patients (39%) reported arrhythmia symptoms, in 40 patients causing pharmacological treatment (14 patients) and/or continued contact with their doctor. The underlying arrhythmias were orthodromic tachycardia (10), atrial fibrillation (12), premature beats (12), atrial flutter (1), and ventricular tachycardia (1), while in four patients no explanation was found. Minor symptoms in the other 36 patients were explained by premature beats in 29, while unexplained in 7. All patients with atrial fibrillation after ablation had atrial fibrillation before ablation. Ten relapses of WPW syndrome occurred: eight were known before the time of the questionnaire, two were confirmed at transesophageal atrial stimulation. CONCLUSION: 94% patients with a long history of tachyarrhythmias due to the WPW syndrome reported improved physical well-being after ablation, but palpitations were common during a 2-year follow-up period; 8% continued to use pharmacological antiarrhythmic treatment. Five percent had symptomatic relapses and in 6% atrial fibrillation episodes reoccurred, i.e., in half of those who had atrial fibrillation before ablation.

Sensing of atrial fibrillation by a dual chamber pacemaker: how should atrial sensing be programmed to ensure adequate mode shifting?

Patients with atrial fibrillation and a DDDR pacemaker were studied to assess mode switching at different atrial sensitivity settings. Thirty-one patients were investigated 7 +/- 9 months after pacemaker implantation and 20 of those patients were reinvestigated 23 +/- 9 months after implant. Adequate mode switching was evaluated by stepwise programming the atrial sensitivity setting from maximal to minimal in the bipolar mode. Adequate mode switching was observed in all 31 patients during the first evaluation. The lowermost sensitivity average allowing for mode switching was 1.1 +/- 0.7 mV (range 0.3-4.0 mV). A total of 22 (71%) patients demonstrated intermittent mode shifting at sensitivity settings above the atrial sensing threshold. In six (19%) patients, the adequate sensitivity threshold ranged from 0.3 to 0.5 mV, which did not allow for a two-fold sensitivity safety margin. During the second evaluation, adequate mode switching was achieved in all 20 patients, the lowermost sensitivity average allowing for mode switching being 1.1 +/- 0.7 mV (range 0.3-2.0 mV). A total of 16 (80%) patients showed intermittent mode shifting at a sensitivity setting above the atrial sensing threshold. In five (25%) patients, the sensitivity threshold ranged from 0.3 to 0.5 mV, which did not allow for a two-fold sensitivity safety margin. Adequate mode switching was achieved in 31 of 31 patients in response to atrial fibrillation on one occasion and in all 20 patients on two occasions. It was necessary to program the atrial sensitivity to the highest possible level (0.3 mV) to ensured adequate mode switching in all cases.

Incidence of sudden death after radiofrequency ablation of the atrioventricular junction for atrial fibrillation.

This study assesses the incidence of sudden death and classifies the causes of death following radiofrequency ablation of the atrioventricular (AV) junction. We studied 220 patients with paroxysmal (n = 105) or chronic (n = 115) atrial fibrillation (AF) and a mean age of 64 +/- 12 years. These patients were followed 31 +/- 15 months after radiofrequency ablation of the AV junction and pacemaker implantation. In 86 patients, structural heart disease was identified before the procedure. All patients were traced via the Swedish National Civic Registry and Cause of Death Registry. The cause-of-death was classified according to data from death certificates, autopsy protocols, and medical records. Thirty-one patients (mean age 69 +/- 11 years, 16 men) died 15 +/- 15 months (range 0.2 to 60) after the procedure. There were 6 sudden unexplained deaths, 14 cardiovascular deaths, and 11 deaths from noncardiovascular causes. Eleven patients, all with structural heart disease, died suddenly out of hospital 16 +/- 16 months (range 0.2 to 42) after the procedure. In 6 of these there was no obvious cause of death. Three of these 6 patients underwent autopsy, which showed extensive coronary artery disease (n = 1), severe heart failure (n = 1) and cardiac hypertrophy and dilation (n = 1). The remaining 3 all had depressed left ventricular systolic function and a history of congestive heart failure. Five of the patients who died suddenly from cardiovascular causes had autopsies that revealed acute myocardial infarction (n = 4) and massive pulmonary embolism (n = 1).

The value of exercise test, Holter monitoring, and programmed electrical stimulation in detection of ventricular arrhythmias in patients with hypertrophic cardiomyopathy.

To determine the best way to detect serious ventricular arrhythmia in patients with hypertrophic cardiomyopathy (HCM), 15 patients with HCM performed an exercise test, had Holter monitoring during 24 hours, and programmed electrical stimulation (PES) in a randomized order, and the presence and type of ventricular arrhythmia was noted. During exercise testing, only one patient demonstrated ventricular tachycardia (VT) just prior to the test. By Holter monitoring, four patients had short episodes of asymptomatic VT. PES, using up to three extrastimuli induced VT or ventricular fibrillation (VF) in ten patients including those with VT during exercise testing and Holter monitoring. There were no differences between patients with and without ventricular arrhythmia during PES regarding age, left ventricular outflow obstruction, thickness of interventricular septum, interventricular septum/posterior wall thickness ratio, corrected QT interval, or the amplitude of the R wave in lead aVR in electrocardiography. Our results indicate that inducible VT/VF during PES is a common finding in patients with HCM. Twenty-four hour Holter monitoring was superior to exercise testing in revealing serious ventricular arrhythmia in those patients.

Tissue oxygen pressure in normal myocardium and across the border zone during coronary artery occlusion in the pig. Effects of different arterial oxygen pressures.

Tissue oxygen pressure (ptO2) in the pig heart was measured with two different oxygen electrodes: We measured ptO2 in normal myocardium with the MDO electrode while oxygen gradients across the border zone, during acute coronary artery occlusion, were measured with an array-multiwire-electrode (AME). The aim of the study was to investigate the effects of increased arterial oxygen pressure (paO2) during repeated, short-lasting (5 min) coronary artery occlusions. During ventilation with an inspired oxygen fraction (FIO2) of 0.3 the ptO2 levels in normal myocardium increased significantly, while the distribution type of ptO2 values remained normal. During ventilation with FIO2 0.7 there was an uneven distribution of ptO2 values indicating microcirculatory disturbances, however, no ischemic values were seen. We found no indication for any influence on the ptO2 of the border zone.

Myocardial surface oxygen pressure across the border zone in the pig during acute coronary artery occlusion. A comparison of pretreatment with metoprolol or isoprenaline.

Tissue oxygen pressure was measured in the pig heart during repeated coronary artery occlusions. ptO2 was measured with an array-multiwire-electrode across the border zone, i.e. the transition zone between normal and ischaemic myocardium. The LAD was occluded three times, each lasting 5 min and with 55 min of reperfusion between the occlusions. Three groups of animals were studied: Group 1 served as controls; Group 2 were given metoprolol 0.3 mg/kg i.v. after the first LAD occlusion; Group 3 were given isoprenaline in a continuous infusion, started after the first LAD occlusion and continued throughout the rest of the experiment. Heart rate differed as expected between the two treated groups. The pattern of ptO2 values across the border zone repeated itself for each animal. No change in the pattern of ptO2 values was seen in either treatment group. In conclusion, there were no indications that it was possible to change the ptO2 of the border zone in the pig heart either with metoprolol or isoprenaline in the doses used.

Predictive importance of clinical findings and a predischarge exercise test in patients with suspected unstable coronary artery disease.

The prognostic information of clinical variables and a predischarge exercise test was studied in 400 patients (282 men, 118 women) admitted to the coronary care unit with suspected unstable coronary artery disease, that is, recurring chest pain of new onset, increasing anginal pain in formerly stable angina pectoris or suspected nontransmural acute myocardial infarction. Forty-nine coronary events occurred in the 276 men who performed the exercise test during the following year, whereas only 5 coronary events occurred among the 118 women. The only variable of prognostic importance in women was nontransmural myocardial infarction. In men, the clinical variables increasing age, duration of angina, ST- or T-segment changes on the rest electrocardiogram and increasing angina or nontransmural myocardial infarction as inclusion criteria were associated with increased occurrence of coronary artery bypass surgery, transmural myocardial infarction or cardiac death. Findings of ST-segment depression, limiting chest pain or low rate-pressure product during the exercise test were of greater value than any clinical variable in prediction of coronary artery bypass surgery, transmural myocardial infarction or cardiac death. Within all clinical subgroups of men, the results of the exercise test had an additive predictive value for future coronary events. Combinations of clinical data and exercise test results enabled the best identification of patients with high or low risk for coronary events.

Myocardial oxygen pressure across the border zone during acute coronary artery occlusion in the pig heart.

An experimental model for studies of local myocardial ischemia is described. During coronary artery occlusion of various durations, from two to sixty minutes, tissue oxygen pressure (ptO2) was measured across the "border zone" i.e., the tissue between normal and ischemic myocardium. PtO2 was measured with a surface oxygen electrode with eight measuring points arranged in an array. In fourteen pigs a total of forty coronary artery occlusions were studied. During occlusion one single pattern of ptO2 values was found; the measurements from the first point, closest to the core of ischemia, dropped rapidly to zero while the second, third and fourth measuring points showed a stepwise slower decrease in ptO2. In four animals we found a spontaneous increase in ptO2 during coronary artery occlusion. Upon reopening of the occluded artery there was a rapid rise in ptO2 as well as an "overshoot". Our findings support the hypothesis of a narrow "border zone" with a small residual blood flow thus subjectable to treatment aiming at reduction in the size of the infarct.

A multiwire surface oxygen pressure electrode for measurement across zones of normal and damaged tissue.

The standard MDO multiwire surface oxygen electrode was redesigned to enable measurements across transition zones between normal and, e.g., ischemic tissues. The eight measuring points were arranged in an array 2.2 mm long. This array multiwire electrode (AME) has been tested and showed the same electrochemical properties as the standard MDO electrode. The resolving power was tested and an individual measuring point was affected by a change in surrounding pO2 if it occurred within a distance of 20 microns. In experiments in the pig heart subjected to local ischemia it was found that both ischemic and normal tissue oxygen pressure were registered simultaneously by the AME.

Acute coronary occlusion: oxygen pressure in the border zone studied in the pig.

The area between ischemic and normal myocardium after acute coronary occlusion-the border zone-is of great interest. It has been proposed that this area contains reversibly damaged myocardium subjectable to myocardial salvage. Twenty Swedish land race pigs were studied, 13 after acute occlusion of the left anterior descending coronary artery (LAD), while seven served as controls. We measured tissue oxygen pressures (ptO2) subepicardially with the MDO electrode. This is a multiwire surface electrode measuring ptO2 with eight individual platinum wires. Hundred and twenty values were collected in each measuring situation. The electrode was positioned on the lateral border zone, measurements were performed before and 5, 30 and 120 min after LAD occlusion. In five cases successful measurements were performed across the border zone. A mixture of normal and ischemic ptO2 values was found 5 min after occlusion. After 30 min of occlusion the number of ischemic values decreased and this was particularly the case after two hours of occlusion. The results support the view that the border zone was very narrow. The reduced number of ischemic values after two hours of permanent LAD occlusion also indicated that the border zone may be narrow but not necessarily fixed but instead dynamic. In this case there was a spontaneous decrease of the ischemic area.

A multipoint micro antimony pH electrode for tissue surface measurements.

Based on monocrystalline antimony we have developed a multipoint tissue surface pH electrode. The six electrodes were produced by spark cutting from a large antimony single crystal. The electrodes were then cast in epoxy resin in a ring shaped structure which fitted around the MDO oxygen electrode. The antimony electrode was ground and polished to expose an undisturbed closely packed crystal plane of antimony to the measuring solution. Before and after monitoring periods standardization was performed in TRIS buffers of pH 6.72, 7.32 and 7.74 at 37 degrees C. Antimony electrode potential is influenced by oxygen. Therefore, mean tissue oxygen pressure was registered simultaneously with an MDO electrode. The oxygen sensitivity factor used in this study was 18mV/logpO2. The correction factor for the antimony electrode oxygen dependence, measured in vitro, seemed to be correct also for the in vivo state. This, however, needs further investigation. To illustrate the usefulness of the multipoint pH electrode seven normal state rabbits were studied, and thereafter four - one each in a hypoxic, hypocarbic, hypovolemic or hyperoxic situation. In the normal state tissue pH measured on a skeletal muscle surface varied from 7.0 to 7.4. In the case of tissue microcirculation shutdown (in the hypocarbic or the hypovolemic situations), the initial reaction was a scattering of the pH values, and then the development of tissue acidosis. Our conclusion is that the use of a multipoint pH sensor enables improved and more detailed monitoring of the tissue acid-base status.