Background: The aim of this study was to investigate the cost-effectiveness of cardiac resynchronization therapy (CRT) in Denmark, Finland and Sweden. The analysis was based on the CARE-HF trial, a randomised clinical trial investigating the efficacy of adding CRT (n=409) to optimal pharmacological treatment (n=404) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony. The average follow-up time was 29.4 months.Methods: The health effects were measured in terms of quality-adjusted life years (QALYs) gained. Data on health care resource consumption from CARE-HF was combined with costs for CRT implantation and hospitalisation from university hospitals in Denmark, Finland and Sweden. Calculations were based on patients' expected life time. The expected device lifetime (6 years) was used for CRT, and no additional gains in clinical effects were assumed after the 6 years.Results: The cost-effectiveness ratio per QALY gained was (sic) 4800 in Denmark, (sic) 3600 in Finland and (sic) 6700 in Sweden. The 95% confidence intervals for the cost per QALY gained varied between a lower limit of (sic) 1169 in Finland to an upper limit of (sic) 17,482 in Sweden. These values were all below the threshold for being cost-effective in Denmark, Finland and Sweden.Conclusions: The study indicates that CRT is a cost-effective treatment in Scandinavian health care settings compared to traditional pharmacological therapy and can therefore be recommended for routine use in patients with moderate to severe heart failure and markers of dyssynchrony. (C) 2008 European Society of Cardiology. Published by Elesevier B.V All rights reserved.

BackgroundCardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. We evaluated its effects on morbidity and mortality.MethodsPatients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving standard pharmacologic therapy were randomly assigned to receive medical therapy alone or with cardiac resynchronization. The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event. The principal secondary end point was death from any cause.ResultsA total of 813 patients were enrolled and followed for a mean of 29.4 months. The primary end point was reached by 159 patients in the cardiac-resynchronization group, as compared with 224 patients in the medical-therapy group (39 percent vs. 55 percent; hazard ratio, 0.63; 95 percent confidence interval, 0.51 to 0.77; P<0.001). There were 82 deaths in the cardiac-resynchronization group, as compared with 120 in the medical-therapy group (20 percent vs. 30 percent; hazard ratio 0.64; 95 percent confidence interval, 0.48 to 0.85; P<0.002). As compared with medical therapy, cardiac resynchronization reduced the interventricular mechanical delay, the end-systolic volume index, and the area of the mitral regurgitant jet; increased the left ventricular ejection fraction; and improved symptoms and the quality of life (P<0.01 for all comparisons).ConclusionsIn patients with heart failure and cardiac dyssynchrony, cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death. These benefits are in addition to those afforded by standard pharmacologic therapy. The implantation of a cardiac-resynchronization device should routinely be considered in such patients.

The Maze III procedure is a surgical operation for curative treatment of AF. The procedure is extensive, however, with multiple incisions in both atria, and its effects on autonomic regulation of the heart rhythm are not known. This study comprises 17 patients, 10 with paroxysmal AF and 7 with chronic AF, who had no concurrent cardiac disease known to affect heart rate variability (HRV). A 24-hour Holter recording was performed preoperatively and 2 months (early) and 7 months (late) after surgery, for analysis of HRV in the time and frequency domains. Early after the Maze procedure all HRV components were markedly reduced compared to baseline (mean +/- 1 SD): SDNN 73 +/- 13 versus 148 +/- 50 (ms), total power 168 +/- 126 versus 560 +/- 1567 (ms2), low frequency (LF) power 47 +/- 67 versus 826 +/- 677 (ms2), high frequency (HF) power 47 +/- 40 versus 678 +/- 666 (ms2), and LF:HF 1.22 +/- 0.9 versus 2.55 +/- 1.4. Late after the Maze procedure all variables were still reduced. Only total power increased significantly between early and late follow-up (168 +/- 126 vs 496 +/- 435 ms2). Late after Maze surgery, values of the different HRV components did not differ between the patients with paroxysmal AF and chronic AF. Early after the Maze procedure there is a marked decrease of all HRV components, which is maintained 7 months after surgery, a pattern consistent with denervation of the heart.

The aim of this study was to assess if right atrial overdrive pacing can suppress symptomatic episodes of paroxysmal atrial fibrillation (PAF) in patients without bradyarrhythmias. Forty-two patients with frequent and symptomatic PAF without other pacing indication had a pacemaker implanted after a 4-week run-in period, during which the frequency of symptomatic PAF episodes and the mean heart rate were objectively documented. Depending on the mean heart rate recorded during run-in, the pacemaker was programmed in random order to right atrial AAI pacing at 10-19 beats/min > mean heart rate (medium overdrive [MO]), at 20-29 beats/min > mean heart rate (high overdrive [HO]) and to no pacing (OAO mode)for 4-12 weeks each using a crossover design. In the 35 patients who completed the protocol, the number of symptomatic episodes of PAF (>30-second duration) per week was significantly lower during MO pacing (median 0.88, P = 0.001, n = 35) and during HO pacing (median 0.75, P = 0.002, n = 20) than during OAO (median 2.02 and 2.04, respectively). There was no difference between MO and HO pacing in the 20 patients paced at both rates (0,97 vs 0.75, P = 0.33). Seven patients did not complete the protocol due to persistent atrial fibrillation (n = 4), angina pectoris requiring surgery (n = 1), and unwillingness to continue the study due to improvement (n = 1) or worsening (n = 1) of symptoms during the study periods. Right atrial overdrive pacing can reduce the number of symptomatic PAF episodes in patients with frequent and drug refractory PAF but without bradyarrhythmias.

This study assesses the occurrence of and identifies clinical characteristics associated with the development of aberrant conduction during infusion of the I(kr)-blocker almokalant. Class III drugs may induce aberrant conduction by prolongation of cardiac repolarization, especially during atrial fibrillation (AF). Ninety-two patients with AF received a 6-hour almokalant infusion, aiming at conversion to sinus rhythm (SR). Fiftyfive of the patients received an identical infusion during SR. During almokalant infusion, the number of patients with intermittent QRS aberration during AF increased, from 21% to 80% at rest, and was further increased to 89% during exercise, with predominantly left, and sequential bilateral, bundle branch aberrancy. Patients with aberrant conduction showed signs of more advanced myocardial disease. Predictors of the development of QRS aberration were female gender, arrhythmia duration, and decreased left ventricular ejection fraction, while use of calcium antagonists decreased the probability. No patient showed aberration during regular SR. Twenty-one patients experienced aberrantly conducted supraventricular premature beats. In conclusion, aberrant conduction is common during infusion of the I(kr)-blocker almokalant during AF, and seems to be more frequent in females and in patients with more advanced myocardial disease.

BACKGROUND:The Maze procedure is a curative surgical therapy for atrial fibrillation, restoring sinus rhythm and improving quality of life. Because the procedure results in tissue scarring, the atrial transport function is most likely affected.METHODS:Seventeen patients with paroxysmal atrial fibrillation underwent the Maze III procedure without any concomitant valve operation. Atrial size and transport function were measured before and at 2, 6, and 24 months after operations with two-dimensional echocardiography and pulsed-wave Doppler.RESULTS:Fifteen patients (88%) had signs of left atrial contractions as shown by the presence of a transmitral atrial filling wave on Doppler echocardiography at 6 months follow-up. The transmitral early filling wave and atrial filling wave were measured to calculate the early filling/atrial filling wave ratio, which increased from 1.2 before to 1.9 at 2 months after the Maze procedure (nonsignificant), and further to 2.8 at 24 months (p = 0.02). A decrease in the right and left atrial size was seen at 2 months after an operation, but no further decrease occurred.CONCLUSIONS:In patients with paroxysmal atrial fibrillation, there is a progressive increase in the transmitral early filling/atrial filling wave ratio after the Maze procedure, consistent with a gradual decrease in the left atrial transport function.

Lönnerholm, S. 2002. Evaluation of new non-pharmacological therapies for symptomatic atrial fibrillation: with special emphasis on the Maze procedure. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1113. 68 pp. ISBN 91-554-5215-9. Atrial fibrillation is a common disease. With pharmacological therapy most patients with atrial fibrillation have moderate or light symptoms, but a number of patients have severely symptomatic disease. This study evaluates two new non-pharmacological therapies for atrial fibrillation, the Maze procedure and atrial overdrive pacing. In the patients planned for Maze surgery, the quality of life, assessed with the SF-36 questionnaire, was very low before the operation. The quality of life was markedly improved 6 and 12 months after the Maze operation, and was comparable to values of the general Swedish population. In the patients with sinus rhythm before surgery, the atrial size and transport function was assessed with echocardiography, and the autonomic balance was assessed with heart rate variability (HRV). The sizes of both atria were reduced and the transmitral early/atrial filling velocity (E/A) ratio was increased at 6 months after the operation compared to before. A gradual increase of the E/A ratio was seen during the 24 months follow-up period, indicating a progressive decline of the left atrial transport function. All components of HRV, including the parameters expressing sympathetic and parasympathetic modulation, had markedly decreased early after the Maze procedure compared to before. Late after the operation all components of HRV were still markedly depressed. This is interpreted as a partial autonomic denervation of the heart Single-site right atrial overdrive pacing with two different levels of overdriving was compared with no pacing in patients with paroxysmal atrial fibrillation in a cross-over study. Overdrive pacing reduced the median number of episodes of atrial fibrillation with 50% compared to no pacing. There was no difference in efficacy between medium rate overdrive pacing and high rate overdrive pacing.

Background. To evaluate whether thoracic epidural anesthesia (TEA) can reduce the incidence of atrial. fibrillation (AE) after coronary artery bypass grafting (CABG).Methods. Forty-one patients undergoing CABG were treated with TEA intraoperatively and postoperatively. Another 80 patients served as the control group. The sympathetic and parasympathetic activities were evaluated by analysis of neuropeptides, catecholamines and heart rate variability (HRV), preoperatively and postoperatively.Results. Postoperative AF occurred in 31.7% of the TEA-treated patients and in 36.3% of the untreated patients (p = 0.77). TEA significantly suppressed sympathetic activity, as indicated by a less pronounced increase of norepinephrine and epinephrine (p = 0.03, p = 0.02) and a significant decrease of neuropeptide Y (p = 0.01) postoperatively in TEA-treated patients compared to untreated patients. The HRV variable expressing sympathetic activity was significantly lower and the postoperative increase in heart rate was significantly less in the TEA group than in the control group after surgery (p = 0.01, p < 0.001). Among patients developing AF, the maximal number of supraventricular premature beats per minute increased significantly in untreated patients postoperatively but remained unchanged in TEA-treated patients (p = 0.004 versus p = 0.86).Conclusions. TEA has no effect on the incidence of postoperative sustained AF, despite a significant reduction in sympathetic activity. (C) 2001 by The Society of Thoracic Surgeons.

OBJECTIVETo evaluate the role of the autonomic nervous system for the development of atrial fibrillation (AF) after coronary artery bypass surgery.DESIGNEighty patients without a previous history of AF were included. The sympathetic and parasympathetic activity were evaluated by the analysis of heart rate variability (HRV) in the frequency domain from 24-h Holter recordings and by measuring neuropeptides (neuropeptide Y, chromogranin A, chromogranin B, and pancreatic polypeptide (PP)) and catecholamines, obtained pre- and postoperatively.RESULTSPreoperatively, patients (36.3%) developing AF postoperatively showed a statistically significant less circadian variation in the HRV variables, the high-frequency (HF) component (p = 0.013) and the low-frequency (LF)/HF ratio (p = 0.007), than patients remaining in sinus rhythm. The HF component and PP. both reflecting parasympathetic activity, and all other variables in the frequency domain, decreased significantly after surgery in both patient groups (p < 0.0001). Although catecholamines increased significantly postoperatively in both patient groups, neither catecholamines nor neuropeptides expressing sympathetic activity, differed between the two groups. PP was, however, significantly higher in patients with postoperative AF than in those with sinus rhythm postoperatively on day 1.CONCLUSIONThe diminished circadian variation in HRV before surgery and the indirect signs of a higher parasympathetic activity in patients developing postoperative AF compared with patients remaining in sinus rhythm, may indicate a propensity for AF.

Jidéus, L. 2001. Atrial Fibrillation after Coronary Artery Bypass Surgery. A Study of Causes and Risk Factors. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1093. 56 pp. Uppsala. ISBN 91-554-5151-9. The aim was to study pathophysiological mechanisms and risk factors for developing atrial fibrillation (AF) after coronary artery bypass grafting (CABG), and the effect of thoracic epidural anaesthesia (TEA). The study included 141 patients undergoing CABG, including 45 patients randomised for TEA intraand postoperatively. All patients underwent 24-hour Holter monitoring preand postoperatively for the analysis of arrhythmias and heart rate variability (HRV). Catecholamines and neuropeptides (reflecting sympathetic and parasympathetic activity), atrial peptides and echocardiographically assessed atrial arias were obtained preand postoperatively. Logistic regression analysis identified body mass index (BMI), maximum supraventricular beats (SPB) per minute, and total amount of cardioplegia as independent predictors of postoperative AF. Patients developing AF showed limited diurnal variation of HRV preoperatively. All HRV parameters decreased significantly in all patients postoperatively. The significant postoperative increase in atrial areas and atrial peptides did not differ between patients developing AF and those who did not. TEA had no effect on the incidence of postoperative AF, but resulted in lower heart rate, less increase in adrenaline levels, and decreased neuropeptide levels (reflecting sympathetic and parasympathetic activity). AF was initiated by an SPB in 72.4% non-TEA and 100% TEA treated patients, whereas changes in heart rate only were seen in 17.2% non-TEA patients. The observed risk factors, SPB and cardioplegia, may both induce electrophysiological changes known to increase the susceptibility to AF. The observed postoperative atrial dilatation and autonomic imbalance, indicated by HRV and neuropeptide levels, may further favour the development of AF. The observation that a majority of postoperative AF was initiated by a premature atrial contraction supports our hypothesis that latent atrial foci may be a major trigger mechanism of postoperative AF.

AIMS:Drug-induced increase in QT dispersion has been associated with increased risk of ventricular proarrhythmia. The aim of the present study was to compare QT dispersion during atrial fibrillation and sinus rhythm in the same patients at normal and prolonged ventricular repolarization.METHODS AND RESULTS:Sixty-one patients who had had chronic atrial fibrillation for 8 +/- 14 months received a 6 h infusion of the Ikr-blocker almokalant, the first 90 min of which are used for this analysis. The following day, after conversion to sinus rhythm, by almokalant (n = 19) or direct current cardioversion (n=42), an identical 90 min infusion was administered. Prior to infusion, there was no difference in precordial QT dispersion between atrial fibrillation and sinus rhythm (29 +/- 12 vs 36 +/- 17 ms, P=ns). During infusion, at prolonged repolarization, the increase in QT dispersion was greater during sinus rhythm than during atrial fibrillation (58 +/- 49 vs 30 +/- 15 ms, P=0.0011, after 30 min infusion). No correlation was found between QT dispersion and the QT or RR interval.CONCLUSION:QT dispersion during atrial fibrillation does not differ from QT dispersion during sinus rhythm during normal repolarization. while measurement of QT dispersion during prolonged repolarization, induced by an Ikr-blocker, yielded larger values during sinus rhythm than during atrial fibrillation.

Background. We evaluated the role of supraventricular arrhythmias and assessed clinical predictors of atrial fibrillation (AF) that developed after coronary artery bypass operations.Methods. Eighty patients, with a mean age of 65.8 years, underwent 24-hour Holter monitoring preoperatively and for 4 consecutive days postoperatively, or until clinically documented AF, for analysis of the number of premature beats and tachyarrhythmias. Atrial areas and atrial peptides were measured preoperatively and postoperatively.Results. Twenty-nine of 80 (36.3%) patients had postoperative AF. Preoperatively, the maximal supraventricular premature beats per minute were higher in the AF group (p = 0.02). The body mass index and total amount of cardioplegia were lower (p = 0.02 and p = 0.006, respectively), and withdrawal of P-blockers postoperatively more frequent (p = 0.001) in the AF group, but atrial areas and atrial peptides did not differ.Conclusions. Frequent supraventricular premature beats preoperatively may indicate a propensity for AF. A larger amount of cardioplegia during the cross-clamp period may reduce the risk of postoperative AF. Further studies are mandatory to clarify why patients with lower body mass index were more prone to AF. (C) 2000 by The Society of Thoracic Surgeons.

Background —Maze surgery for atrial fibrillation (AF) is a curative therapy, but its effect on health-related quality of life has not been studied. Methods and Results —Maze operations were performed in 48 patients with drug-refractory AF. The majority of patients (80%) had lone AF, and the primary indication for surgery in all patients was AF. The SF-36 Health Survey was used to assess quality of life before operation and at 6 months and 1 year after surgery. Twenty-five patients were available for the 1-year follow-up and completed all questionnaires. Before maze surgery, the SF-36 scores were significantly lower than in the general Swedish population, reflecting significant impairment in well-being, physical and social functioning, and mental health. After maze surgery, the quality of life was significantly improved at 6 months and at 1 year on all scales except for bodily pain, which, however, was not significantly decreased before surgery. At both 6 months and 1 year after maze surgery, quality of life, measured by the SF-36, reached the levels of the general Swedish population. Conclusions —The maze operation can significantly improve the health-related quality of life in selected groups of patients with both paroxysmal and chronic AF refractory to antiarrhythmic therapy.

Transesophageal atrial pacing and recording performed in 128 patients for palpitations or tachycardia was retrospectively evaluated and compared to the same procedure in 77 routinely evaluated patients after a catheter ablation procedure. The sensitivity and specificity of the described protocol was 74 and 90% respectively. The procedure was well tolerated and a majority of patients could be completely evaluated according to the protocol. The outcome of the first time investigation influenced the subsequent choice of therapy in the studied population. The results suggest that transesophageal pacing is a valuable tool for evaluation of atrial tachycardias with specificity, sensitivity and tolerability comparable to other noninvasive methods used in cardiology.