Pekka Raatikainen

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis.

David H. Birnie, MD (Chair), William H. Sauer, MD, FHRS, CCDS (Chair), Frank Bogun, MD, Joshua M. Cooper, MD, FHRS, Daniel A. Culver, DO,* Claire S. Duvernoy, MD, Marc A. Judson, MD, Jordana Kron, MD, Davendra Mehta, MD, PhD, FHRS, Jens Cosedis Nielsen, MD, Amit R. Patel, MD, Tohru Ohe, MD, FHRS, Pekka Raatikainen, MD, Kyoko Soejima, MD From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada, University of Colorado, Aurora, Colorado, University of Michigan, Ann Arbor, Michigan, Temple University Health System, Philadelphia, Pennsylvania, Cleveland Clinic, Cleveland, Ohio, VA Ann Arbor Healthcare System and University of Michigan, Ann Arbor, Michigan, Albany Medical College, Albany, New York, Virginia Commonwealth University, Richmond, Virginia, Mount Sinai School of Medicine, New York, New York, Aarhus University Hospital, Aarhus, Denmark, University of Chicago, Chicago, Illinois, Sakakibara Heart Institute of Okayama, Okayama, Japan, Heart Center, Tampere University Hospital, Tampere, Finland, and Kyorin University School of Medicine, Mitaka City, Japan.

Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era☆

OBJECTIVES This study assessed the predictive power of arrhythmia risk markers after an acute myocardial infarction (AMI). BACKGROUND Several risk variables have been suggested to predict the occurrence of sudden cardiac death (SCD), but the utility of these variables has not been well established among patients using medical therapy according to contemporary guidelines. METHODS A consecutive series of 700 patients with AMI was studied. The end points were total mortality, SCD, and nonsudden cardiac death (non-SCD). Nonsustained ventricular tachycardia (nsVT), ejection fraction (EF), heart rate variability, baroreflex sensitivity, signal-averaged electrocardiogram (SAECG), QT dispersion, and QRS duration were analyzed (n = 675). Beta-blocking therapy was used by 97% of the patients at discharge and by 95% at one and two years after AMI. RESULTS During a mean (+/-SD) follow-up of 43 +/- 15 months, 37 non-SCDs (5.5%) and 22 SCDs (3.2%) occurred. All arrhythmia risk variables differed between the survivors and those with non-SCD (e.g., the standard deviation of N-N intervals was 98 +/- 32 vs. 74 +/- 21 ms [p < 0.001] and the QRS duration was 103 +/- 22 vs.89 +/- 16 ms [p < 0.001]). Sudden cardiac death was weakly predicted only by reduced EF (<0.40; p < 0.05), nsVT (p < 0.05), and abnormal SAECG (p < 0.05), but not by autonomic markers or standard ECG variables. The positive predictive accuracy of EF, nsVT, and abnormal SAECG as predictors of SCD was relatively low (8%, 12%, and 13%, respectively). CONCLUSIONS The common arrhythmia risk variables, particularly the autonomic and standard ECG markers, have limited predictive power in identifying patients at risk of SCD after AMI in the beta-blocking era.

Mechanisms of Ischemic Preconditioning in Rat Myocardium

BACKGROUND Adenosine has been proposed as one mediator for the preconditioning effect in the myocardium of some animals, but recent investigations have shown that this may not be the mechanism in the rat heart, although the effect itself is clearly demonstrable. The cellular energy state has been shown to be better in preconditioned hearts, and the role of ATP consumption has been discussed. The role of inhibition of mitochondrial F1F0-ATPase as a mechanism for the preservation of ATP in preconditioned hearts remains controversial. METHODS AND RESULTS Three-minute global ischemia followed by 9 minutes of reperfusion was used to precondition Langendorff-perfused rat hearts, and control hearts were perfused under normoxic conditions for the same time. The duration of sustained ischemia in both groups of hearts was 21 minutes, after which the hearts were reperfused for 15 minutes to evaluate their mechanical and metabolic recovery. Separate experiments were performed for tissue metabolite determinations, mitochondrial ATPase activity measurements, and 31P nuclear magnetic resonance studies. The recovery of the rate-pressure product was better in the preconditioned group. Three-minute preconditioning ischemia caused inhibition of the mitochondrial ATPase that persisted throughout the 9-minute intervening reperfusion so that at the early stages of sustained ischemia the enzyme activity was still more inhibited in preconditioned hearts. ATP was better preserved in preconditioned hearts than in control hearts during sustained ischemia. The accumulation of adenosine and its degradation products during sustained ischemia was greater in the control group. More lactate and H+ ions accumulated in this group, indicating higher anaerobic glycolysis. Also, inhibition of mitochondrial ATPase by oligomycin slowed ATP depletion during ischemia. CONCLUSIONS The results indicate that preconditioning causes inhibition of rat heart mitochondrial ATPase that persists during reperfusion so that the enzyme is inhibited from the very beginning of the sustained ischemia. This inhibition leads to sparing of high-energy phosphates and improves the time-averaged energy state during ischemia. Although a causal relationship is difficult to prove, this reversible inhibition may contribute to postischemic recovery of the heart.

Ventricular tachyarrhythmia as a primary presentation of sarcoidosis

AIMS Sarcoidosis is a multisystem, granulomatous disease with occasional cardiac manifestations. The clinical course of patients with ventricular tachyarrhythmias as a primary presentation of sarcoidosis is mostly unknown. METHODS AND RESULTS We describe nine patients (four males and five females) in whom sarcoidosis manifested as ventricular tachycardia (VT). The age of the patients was 53 +/- 10 years (range 33-68). The disease was diagnosed by endomyocardial biopsy in eight patients and by lymph node biopsy in one patient. The presenting arrhythmia varied from non-sustained VT to incessant VT and ventricular fibrillation. All patients received implantable cardioverter defibrillator (ICD) and anti-arrhythmic medication. High-dose steroid treatment was used in eight cases. During the follow-up (50 +/- 34 months), five patients underwent appropriate ICD therapies and non-sustained VT episodes were detected in four patients. Two patients developed incessant VT, which was treated by catheter ablation. One patient was referred for heart transplantation. CONCLUSION Our data indicate that sarcoidosis can manifest as VT without any detectable systemic findings. This makes sarcoidosis an important diagnostic consideration in patients with VT of unknown origin. Arrhythmia control in cardiac sarcoidosis is difficult, and all modern treatments including high-dose steroids, anti-arrhythmic drugs, ICD, and catheter ablation are needed to suppress the arrhythmias.

Contemporary management of patients undergoing atrial fibrillation ablation: in-hospital and 1-year follow-up findings from the ESC-EHRA atrial fibrillation ablation long-term registry

Aims The ESC-EHRA Atrial Fibrillation Ablation Long-Term registry is a prospective, multinational study that aims at providing an accurate picture of contemporary real-world ablation for atrial fibrillation (AFib) and its outcome. Methods and results A total of 104 centres in 27 European countries participated and were asked to enrol 20–50 consecutive patients scheduled for first and re-do AFib ablation. Pre-procedural, procedural and 1-year follow-up data were captured on a web-based electronic case record form. Overall, 3630 patients were included, of which 3593 underwent an AFib ablation (98.9%). Median age was 59 years and 32.4% patients had lone atrial fibrillation. Pulmonary vein isolation was attempted in 98.8% of patients and achieved in 95–97%. AFib-related symptoms were present in 97%. In-hospital complications occurred in 7.8% and one patient died due to an atrioesophageal fistula. One-year follow-up was performed in 3180 (88.6%) at a median of 12.4 months (11.9–13.4) after ablation: 52.8% by clinical visit, 44.2% by telephone contact and 3.0% by contact with the general practitioner. At 12-months, the success rate with or without antiarrhythmic drugs (AADs) was 73.6%. A significant portion (46%) was still on AADs. Late complications included 14 additional deaths (4 cardiac, 4 vascular, 6 other causes) and 333 (10.7%) other complications. Conclusion AFib ablation in clinical practice is mostly performed in symptomatic, relatively young and otherwise healthy patients. Overall success rate is satisfactory, but complication rate remains considerable and a significant portion of patients remain on AADs. Monitoring after ablation shows wide variations. Antithrombotic treatment after ablation shows insufficient guideline-adherence.

Safety of pacemaker and implantable cardioverter–defibrillator implantation during uninterrupted warfarin treatment — The FinPAC study

BACKGROUND Periprocedural management of oral anticoagulation (OAC) in patients undergoing cardiac rhythm management (CRM) device implantation is controversial. Prior studies demonstrate that uninterrupted OAC may be safe, but limited data from randomized trials exist. METHODS We conducted a multicenter, randomized trial to evaluate the safety of uninterrupted OAC during CRM device implantation. Patients on long-term warfarin (N=213) treatment with contemporary indication for CRM device implantation were randomized to uninterrupted versus interrupted (2 days) OAC therapy. The primary outcome included major bleeding events necessitating additional intervention and thromboembolic events during 4 weeks follow-up. RESULTS The randomized groups were well matched in terms of bleeding and thromboembolic risk. Only one (1%) patient in the uninterrupted OAC group (N=106) needed blood transfusion due to rupture of proximal cephalic vein. Large hematomas were detected in 6% of patients in both groups, but there was no need for pocket revision in either group. Any pocket hematoma was observed in 35 patients (33%) in the uninterrupted OAC group and in 43 patients (40%) with interrupted OAC and uninterrupted OAC strategy was non-inferior to interrupted OAC (HR 0.86, 95%, p=0.001 for non-inferiority). One patient with interrupted OAC had stroke 3 days after the procedure. Hospital stay was comparable in all patient groups. CONCLUSION Our randomized study demonstrates that CRM devices can be safely implanted without discontinuation of warfarin treatment.

The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) Trial: clinical rationale, study design, and implementation

AIMS No large randomized multicentre trial has evaluated the efficacy of radiofrequency ablation (RFA) vs. anti-arrhythmic drug (AAD) therapy as a first-line treatment of paroxysmal atrial fibrillation (AF). METHODS AND RESULTS The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation (MANTRA-PAF) trial is a randomized, controlled, parallel group, multicentre study designed to test whether catheter-based RFA is superior to optimized AAD therapy in suppressing relapse within 24 months of symptomatic and/or asymptomatic AF in patients with paroxysmal AF without prior AAD therapy. The primary endpoint is cumulative AF burden on repeated 7 days Holter monitoring. Secondary endpoints are: thromboembolic events, hospitalization due to arrhythmia, pro-arrhythmic events, procedure/treatment-related side effects, health economics, quality of life, and change in left ventricular function. Ten centres in Scandinavia and Germany are participating in the study. Enrolment was started in 2005 and as of November 2008, 260 patients have been enrolled into the study. It is expected that enrolment will end by March 2009, when 300 patients have been included. CONCLUSION The MANTRA-PAF trial will determine whether catheter-based RFA is superior to optimized AAD therapy as a first-line treatment in suppressing long-term relapse of symptomatic and/or asymptomatic AF.

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.

Adaptation to myocardial ischemia during repeated dynamic exercise in relation to findings at cardiac catheterization

It has been suggested that the myocardium is able to recruit endogenous protective mechanisms in response to repeated ischemia and reperfusion. We set out to study whether this is manifested in patients with coronary artery disease in the form of fewer signs of myocardial ischemia during the second of two successive exercise tests and whether any relations exist between ischemia adaptation and findings at cardiac catheterization. Twenty-one patients with typical angina pectoris symptoms underwent two repeated bicycle exercise tests with identical protocols, followed by cardiac catheterization and coronary angiography the next day. The first exercise test was discontinued whenever a 2 mm ST depression in the electrocardiogram (ECG) was achieved or further exercise was limited by symptoms. The second exercise test was performed after disappearance of the symptoms or ST depression or both. Kaplan-Meier survival analysis for the appearance of a 1 mm ST depression demonstrated improved ischemia tolerance during the second test, when the required time for its appearance was significantly longer (6.5 +/- 0.8 min vs 4.5 +/- 0.5 min; p = 0.005). The maximal intensity of anginal pain was lower during the second exercise (2.2 +/- 1.0 min vs 0.7 +/- 0.3 min in Borgs scale; p < 0.001), and the time required for disappearance of the ST depression was shorter after this exercise (3.0 +/- 0.8 min vs 6.2 +/- 0.9 min; p = 0.003), with a similar tendency in the disappearance of angina. The rate-pressure product on the appearance of a 1 mm ST depression was significantly higher during the second test (17,990 +/- 1210 mm Hg x min-1 vs 15,960 +/- 869 mm Hg x min-1; p = 0.009). Eighteen of the patients had three-vessel disease, as evidenced by coronary angiography, and the change in the time required for the appearance of a 1 mm ST depression in the repeated exercise tests was inversely correlated with the severity of the left anterior descending (LAD) coronary artery obstruction (r = -0.61; p = 0.006) and left ventricular end-diastolic pressure (r = -0.50; p = 0.03). No significant correlation with the degree of collateral vessels was found. We conclude that most patients with extensive coronary artery disease are able to increase their tolerance of ischemia during repeated dynamic exercise and that increased vasodilation and oxygen delivery are the major mechanisms for this warm-up phenomenon. On the other hand, collaterals visible in routine resting anglography do not predict the degree of adaptation to ischemia during repeated dynamic exercise.