Left atrial radiofrequency ablation during mitral valve surgery: a prospective randomized multicentre study (SAFIR).

BACKGROUND: Randomized studies evaluating left atrial radiofrequency ablation (RFA) in patients with persistent atrial fibrillation undergoing mitral valve surgery are scarce and monocentric. AIM: To evaluate the efficacy of left atrial RFA concomitant with mitral valve surgery to restore and maintain sinus rhythm. METHODS: The SAFIR is a multicentre, double-blinded, centrally randomized study involving four university hospitals. Between December 2002 and September 2005, 43 patients with mitral valve disease and long-standing, persistent atrial fibrillation (duration>6 months) were included. We compared valvular surgery alone (n=22) or with left atrial RFA (n=21). The main endpoint was sinus rhythm at 12 months without recurrence of arrhythmia during follow-up. Secondary endpoints were surgical adverse events, atrial fibrillation relapses, stroke and echocardiographic measurements after three and 12 months' follow-up. Analyses of the efficacy criteria were performed on an intention-to-treat basis. RESULTS: The primary endpoint occurred significantly more often in the RFA group than in the control group (respectively, 12/21 patients [57%] vs 1/22 patients [4%]; p=0.004). There were more patients with sinus rhythm in the RFA group than in the control group at discharge (72.7% vs 4.8%; p<0.005), 3-month follow-up (85.7% vs 23.8%; p<0.01) and 12-month follow-up (95.2% vs 33.3%; p<0.005). The patients in the RFA group had similar rates of postoperative complications and stroke during follow-up as those in the control group. CONCLUSIONS: This multicentre study suggests that left atrial RFA is effective and safe in patients with chronic atrial fibrillation and mitral valve disease.

Beat-to-beat variations of the electrocardiogram in survivors of sudden death without structural heart disease.

AIM: We sought to determine whether survivors of sudden death without structural heart disease have beat-to-beat electrocardiographic (ECG) characteristics at the microvolt and at the millisecond level that differ from normal subjects. METHODS: We studied patients at our implantable cardioverter defibrillator clinic who had been resuscitated from ventricular fibrillation with no evidence of underlying structural heart disease. Continuous 10-minute high-resolution unfiltered digital surface ECGs at 1000-Hz sampling rate were acquired in these subjects and in a group of healthy volunteers. We then analyzed different parameters of beat-to-beat variations in duration, amplitudes and vectors of the QRS complex, and the T wave using a locally developed program (Comparative Analysis of ECGs, Vectocardiograms, and their Interpretation with Auto-Reference to the patient) and compared them between the 2 groups. RESULTS: Thirteen patients (7 men; age, 46 +/- 16 years) were studied. Standard ECGs were unremarkable in 7 patients and suggestive of Brugada syndrome in the 6 others. The control group consisted of 23 age- and sex-matched subjects (13 men; age, 41 +/- 10 years). Although the QRS parameters showed only few differences between the 2 groups, there were several differences in parameters evaluating repolarization. CONCLUSION: High-resolution ECGs show distinct beat-to-beat variations in parameters of repolarization in survivors of sudden death without structural heart disease, as compared with normal subjects. These findings may reflect increased electrical instability and should be evaluated for stratifying arrhythmic risk in asymptomatic individuals.

Wavelet transform for analysis of heart rate variability preceding ventricular arrhythmias in patients with ischemic heart disease.

INTRODUCTION: Studies evaluating changes in HRV preceding the onset of ventricular arrhythmias using conventional techniques have shown inconsistent results. Time-frequency analysis of HRV is traditionally performed using short-term Fourier transform (STFT). Wavelet transform (WT) may however be better suited for analyzing non-stationary signals such as heart rate recordings. METHODS AND RESULTS: We studied patients with a history of myocardial infarction implanted with a defibrillator with an extended memory. The RR intervals during the 51 min preceding ventricular events requiring electrical therapy were retrieved, and HRV studied by WT and STFT. 111 episodes of ventricular arrhythmia were retrieved from 41 patients (38 males, age 64 +/- 8 years). Heart rate increased significantly before arrhythmia. There was no significant variation in low frequency / high frequency components (LF/HF) observed for the group as a whole, probably due to a great degree of heterogeneity amongst individuals. A subset of 30 patients also had heart rate recordings performed during normal ICD follow-up. WT did not show any difference in HRV before arrhythmia onset and during control conditions. CONCLUSION: Variations in HRV before onset of ventricular arrhythmias were not apparent in this large dataset, despite use of optimal tools for studying time-frequency analysis.

[Patients' and physicians' perceptions on participation in a clinical trial: results on a survey in a French hospital]. / Perception des essais cliniques par les patients et les investigateurs : enquête à l'hôpital Neuro-Cardiologique de Lyon.

OBJECTIVES: We report the first survey on French physicians and patients participating to assess motivations prior enrolment and benefits and constraints perceived after participation. METHOD: Twenty physicians were interviewed and 37 patients completed a questionnaire during clinical study participation. RESULTS: If the main patient's motivation is altruistic, physician wish their own patient feel better. After participation, patient is satisfied with being part of a research effort and contributing to medical science. Effect of trial treatment on physical well-being seems less pronounced. Main constraint is the randomisation to placebo group. For physicians, the main benefit is getting research experience and training. Main constraints are logistical. Otherwise, perceptions on the same clinical trial depend on participant. In fact, physician usually overestimates constraints of clinical trial for patient. CONCLUSION: The knowledge of patients and physicians perceptions of clinical trials and its taking into account should probably reduce difficulties in the recruitment in France.

[Perceptions of patients and physicians involved in clinical trials: an overview of the literature]. / Perception des essais cliniques par les patients et les investigateurs: revue bibliographique (1re partie).

UNLABELLED: OBJECTIVE - METHOD: The purpose of this review is to explore the expectations of patients and physicians prior to participate to a clinical trial and their positive or negative experiences after participating. A systematic review of Medline database from 1966 to 2005 identified 79 papers reported patients and physicians perceptions of clinical trials (only 3 in French), whom 27 English surveys conducted on patients and physicians. RESULTS: If primary patients' motivation for enrolment was altruistic, physicians wish to help their patient. After enrolment, the most perceived positive benefit for patients and physicians are, respectively, the emotional improvement and the greater opportunity for personal benefit offered to enrolled patients. Most physicians' negative experience included logistical difficulties while patients are unease with randomisation and often uncomfortable with medical procedures. Unlike patients, all physicians' expectations seem to be fulfilled. CONCLUSION: The knowledge of patients' and physicians' perception of participation may improve recruitment in clinical trials.

Significance of serum troponin I elevation in patients with acute aortic dissection of the ascending aorta.

OBJECTIVE: This study evaluated the prevalence of increased cardiac troponin I (cTnI) in patients with acute aortic dissection of the ascending aorta (type A). METHODS AND RESULTS: In 119 consecutive patients with type A acute aortic dissection, serum cardiac troponin I was measured along with clinical, haemodynamic, electrocardiographic and echocardiographic variables obtained on admission. Cardiac troponin I was positive in 28 patients (23.5%; mean +/- SD: 6.1 +/- 14.7 ng/ml) and above the myocardial infarction threshold (1.5 ng/ml) in 12 (10%). Catecholamine infusion (17.9% vs. 4.4%; p = 0.03) and higher value of creatinine (35.7% vs. 15.4%; p = 0.03) were more frequent in patients with elevated troponin. Total mortality was 29.7% (n = 35) and surgical mortality was 16.8% (n = 17). An increased troponin was discriminatory with respect to mortality (OR: 4.1 (1.6-9.9); p = 0.002) in univariate analysis. However, this association was lost when other markers of death (age, stroke, ST-segment elevation, tamponade, catecholamine infusion, renal failure) were added in a multivariate model (OR: 2.2 (0.7-7.4); p = 0.19) indicating that the myocardial loss associated with troponin increase is not in itself a factor of mortality. CONCLUSIONS: Cardiac troponin I elevation is frequent in patients with type A aortic dissection. It might reflect a higher haemodynamic stress but does not necessarily reflect a negative prognosis.

Is primary angioplasty more effective than prehospital fibrinolysis in diabetics with acute myocardial infarction? Data from the CAPTIM randomized clinical trial.

AIMS: The CAPTIM study randomized patients managed within 6 h of acute ST-segment elevation myocardial infarction to primary angioplasty or prehospital fibrinolysis (rt-PA), with immediate transfer to a centre with interventional facilities. It found a similar incidence of the primary endpoint of death, recurrent MI, or stroke at 30 days with both strategies. We report here the outcome in the diabetic subgroup. METHODS AND RESULTS: The relationship of diabetic status (diabetics, n=103, non-diabetics, n=731) and treatment strategy with the occurrence of the primary endpoint and of death was analysed. Compared with non-diabetics, diabetics had a higher baseline risk profile, a higher rate of the primary endpoint (14.6 vs. 5.6%; P=0.002), and a high rate of mortality (8.7 vs. 3.1%; P=0.01) at 30 days. The incidence of the primary endpoint tended to be higher in diabetics randomized to prehospital fibrinolysis compared with those randomized to primary angioplasty [21.7 vs. 8.8% (10/46 vs. 5/57); RR: 2.47 (0.91-6.74); P=0.09]. This difference was driven by the higher mortality in the fibrinolysis group [13.0 vs. 5.3% (6/46 vs. 3/57); RR: 2.47 (0.7-9.4); P=0.29]. For non-diabetics, no such trend was observed. Compared with non-diabetics, diabetics had a much higher rate of rescue angioplasty (41.4 vs. 23.5%; P=0.01) and a higher mortality after rescue angioplasty [17.4 vs. 0% (4/23 vs. 0/90); P=0.001]. CONCLUSION: These results suggest that diabetic patients presenting within 6 h of an acute myocardial infarction may derive particular benefit from a strategy of primary angioplasty. However, the small number of diabetic patients in this subgroup analysis does not allow a final conclusion and a specifically designed study is warranted.

Primary angioplasty is cost-minimizing compared with pre-hospital thrombolysis for patients within 60 min of a percutaneous coronary intervention center: the Comparison of Angioplasty and Pre-hospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) cost-efficacy sub-study.

OBJECTIVES: This ancillary study of the Comparison of Angioplasty and Pre-hospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) trial sought to assess the cost-efficacy ratio of primary coronary angioplasty (PCA) and pre-hospital thrombolysis (PHT) in patients suffering from an acute myocardial infarction (AMI) (<6 h) close to (<60 min journey) a percutaneous coronary intervention (PCI) center. BACKGROUND: In the CAPTIM study, at 30 days follow-up PCA was as equally effective as PHT with rescue angioplasty if needed. The cost efficacy of these two strategies has not yet been compared. METHODS: Data were prospectively collected for 299 patients in three centers. The efficacy analysis was extended at one-year follow-up for those patients. Direct fixed and variable actual costs were assessed with a piggyback data collection. RESULTS: The one-year primary end point event-rate (death, non-fatal myocardial infarction, and stroke) was not different after PCA or PHT (14% vs. 16. 4%, p = NS). Costs were lower in the PCA group either during the in-hospital period (8,287 vs. 9,170 $, p = 0.0001) and after one-year follow-up, in relation to a higher rate of subsequent revascularizations in the PHT group (49% vs. 23%, p < 0. 01), leading to a longer hospital stay (10 vs. 9.1 days, p = 0. 03). CONCLUSIONS: After AMI in patients less than 1 h from a PCI center, PCA is as effective and less costly than a combined strategy of PHT followed by rescue angioplasty.

Perioperative outcome and long-term survival of surgery for acute post-infarction mitral regurgitation.

OBJECTIVE: To determine factors predictive of mortality in patients undergoing emergency mitral valve surgery in the setting of severe post-infarction regurgitation. METHODS: Patients admitted for an acute myocardial infarction who required urgent mitral valve surgery for severe regurgitation were studied. Factors predictive of outcome were analysed. RESULTS: Fifty-five consecutive patients (mean 65+/-10 years, 37 males) were included. The infarct was inferior in 31 patients, posterior in 10, anterior in 9 and lateral in 5. Thirty-four patients (62%) were in Killip class IV. Peroperative findings confirmed total papillary muscle rupture in 25 patients (posteromedial in 21, anterolateral in 4), and partial rupture in 12 patients (posteromedial in 10, anterolateral in 2). Papillary muscle dysfunction without rupture was responsible for regurgitation in 18 patients (posteromedial in 15, anterolateral in 3). The mitral valve was replaced by a prosthesis in all but 4 patients, who had valvuloplasty. Coronary angiography was done in 32 patients, of whom 18 underwent concomitant coronary artery bypass grafting and 2 balloon angioplasty. Surgery was performed on average 7 days after infarction. Thirteen patients (24%) died during the perioperative period. Absence of coronary revascularisation was significantly associated with increased perioperative mortality (34% vs. 9%, P = 0.02). Of the 42 surviving patients, there were 5 deaths during a mean follow-up of 4.0+/-3.7 years. CONCLUSION: In patients with acute post-infarction mitral regurgitation, perioperative mortality is high, but can be improved with concomitant CABG in addition to valve surgery. Long-term outcome of survivors is favourable.

Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial.

BACKGROUND: CAPTIM was a randomized trial comparing prehospital thrombolysis with transfer to an interventional facility (and, if needed, percutaneous intervention) with primary percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). Because the benefit of thrombolysis is maximal during the first 2 hours after symptom onset, and because prehospital thrombolysis can be implemented earlier than PCI, this analysis studied the relationship between the effect of assigned treatment and the time elapsed from symptom onset. METHODS AND RESULTS: Randomization within 2 hours (n=460) or > or =2 hours (n=374) after symptom onset had no impact on the effect of treatment on the 30-day combined primary end point of death, nonfatal reinfarction, and disabling stroke. However, patients randomized <2 hours after symptom onset had a strong trend toward lower 30-day mortality with prehospital thrombolysis compared with those randomized to primary PCI (2.2% versus 5.7%, P=0.058), whereas mortality was similar in patients randomized > or =2 hours (5.9% versus 3.7%, P=0.47). There was a significant interaction between treatment effect and delay with respect to 30-day mortality (hazard ratio 4.19, 95% CI 1.033 to 17.004, P=0.045). Among patients randomized in the first 2 hours, cardiogenic shock was less frequent with lytic therapy than with primary PCI (1.3% versus 5.3%, P=0.032), whereas rates were similar in patients randomized later. CONCLUSIONS: Time from symptom onset should be considered when one selects reperfusion therapy in STEMI. Prehospital thrombolysis may be preferable to primary PCI for patients treated within the first 2 hours after symptom onset.

Dronedarone for prevention of atrial fibrillation: a dose-ranging study.

AIMS: Dronedarone, a benzofurane derivative without iodine substituents, shares the electrophysiologic properties of amiodarone. This study was designed to determine the most appropriate dose of dronedarone for prevention of atrial fibrillation (AF) after cardioversion. METHODS AND RESULTS: Patients with persistent AF were randomly allocated to 800, 1200, 1600 mg daily doses of dronedarone or placebo. The main analysis was conducted on 199/270 patients, who entered the maintenance phase following pharmacological cardioversion or, if unsuccessful, DC cardioversion. Within 6-month follow-up, the time to AF relapse increased on dronedarone 800 mg, with a median of 60 days vs 5.3 days in the placebo group (relative risk reduction 55% [95% CI, 28 to 72%] P=0.001). No significant effect was seen at higher doses. Spontaneous conversion to sinus rhythm on dronedarone occurred in 5.8 to 14.8% of patients (P=0.026). There were no proarrhythmic reactions. Drug-induced QT prolongation was only noticed in the 1600 mg group. Premature drug discontinuations affected 22.6% of subjects given 1600 mg dronedarone versus 3.9% on 800 mg and were mainly due to gastrointestinal side effects. No evidence of thyroid, ocular or pulmonary toxicity was found. CONCLUSION: Dronedarone, at a 800 mg daily dose, appears to be effective and safe for the prevention of AF relapses after cardioversion. The absence of thyroid side effects and of proarrhythmia are important features of the drug. Further studies are needed to better delineate the antiarrhythmic profile of the drug.

QT dynamicity and sudden death after myocardial infarction: results of a long-term follow-up study.

INTRODUCTION: The aim of this study was to determine whether impaired adaptation of the QT interval to changes in heart rate predicts sudden death after an acute myocardial infarction. METHODS AND RESULTS: The Groupe d'Etude du Pronostic de l'Infarctus du Myocarde (GREPI) trial was a prospective multicenter study designed to evaluate the long-term outcome of myocardial infarction. QT dynamicity was evaluated in 265 patients by analyzing 24-hour Holter recordings obtained 9 to 14 days after myocardial infarction. The linear regression slope of QT intervals measured to the apex and to the end of the T wave (QTe) plotted against RR intervals was calculated using a dedicated Holter algorithm. The value of QT/RR in predicting sudden death and total mortality was compared with those of ejection fraction, heart rate variability, and late potentials. Mean follow-up was 81 +/- 27 months. There were 73 deaths, of which 23 were sudden. Of all the parameters, an increased diurnal QTe/RR slope (>0.18) was the strongest independent predictor of sudden death (relative risk 6.07, confidence interval 1.48-24.95, P = 0.01). CONCLUSION: Increased diurnal QTe dynamicity is independently predictive of sudden death among patients with myocardial infarction. This simple parameter may help to stratify risk and select patients who may benefit from antiarrhythmic prophylaxis.

Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis.

OBJECTIVES: This meta-analysis compared amiodarone with placebo and class Ic drugs for the cardioversion of recent-onset atrial fibrillation (AF), defined as lasting less than seven days. BACKGROUND: Despite the lack of trials that support its efficacy convincingly, amiodarone is widely used for conversion of recent-onset AF. METHODS: We searched Medline and EMBASE databases, as well as the Cochrane Controlled Trials Register for randomized trials on recent-onset AF comparing amiodarone to placebo or class Ic drugs. Data were combined according to a fixed effect model. The primary end point was the rate of conversion at 24 h. To study time-dependency of the drugs, efficacy at 1 to 2 h, 3 to 5 h, 6 to 8 h, and at 24 h was analyzed. RESULTS: We found six studies randomizing amiodarone versus placebo (595 patients) and seven studies versus class Ic drugs (579 patients). There was no significant difference between amiodarone and placebo at 1 to 2 h, but significant efficacy was found after 6 to 8 h (relative risk [RR] 1.23, p = 0.022) and at 24 h (RR 1.44, p < 0.001). Efficacy with amiodarone was inferior to class Ic drugs for up to 8 h (RR 0.67, p < 0.001) but no difference was seen at 24 h (RR 0.95, p = 0.50). There were no major adverse effects. CONCLUSIONS: Amiodarone is superior to placebo for cardioversion of AF, and even though the onset of conversion is delayed, its efficacy is similar at 24 h compared with class Ic drugs. These results favor amiodarone as a reasonable alternative for patients with recent AF in whom class Ic and other, more rapidly acting antiarrhythmic drugs cannot be used.

Cardiac phantom measurement validating the methodology for a cardiac multi-centre trial with positron emission tomography.

In an ongoing international multi-centre trial, positron emission tomography (PET) is being used to evaluate the effect of a new P-selectin antagonist on the infarct size in patients with acute myocardial infarction, treated with thrombolysis. Although it is possible to correct for site-dependent factors, it is desirable to reduce these factors to a minimum. Therefore, acquisition and reconstruction protocols have been defined that can be closely followed by all participating centres. The resulting reconstructed images are transferred to the core centre for central processing with semi-automatic software. This paper reports on the multi-centre phantom experiment that was carried out to assess the inter-centre reproducibility of defect size determination with this protocol. Also, the spatial resolution of the short axis slices was examined. In addition, the analysis procedure was applied to normal PET studies to evaluate the specificity of perfusion defect detection. The transmural cold defect in the phantom occupied 14.8% of the left ventricular area. The automated analysis was applied to the phantom measurements from the 14 participating PET cameras. It yielded an accurate estimate of 15.1% with a standard deviation of 0.6%, indicating excellent reproducibility. The spatial resolution in the short axis slices was similar for all PET systems: 9.6+/-0.8 mm. The same procedure produced a defect size of zero in the studies of normal volunteers. This study indicates that cardiac studies from multiple PET systems can be pooled for statistical analysis.

Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study.

BACKGROUND: Although both prehospital fibrinolysis and primary angioplasty provide a clinical benefit over in-hospital fibrinolysis in acute myocardial infarction, they have not been directly compared. Our aim was to find out whether primary angioplasty was better than prehospital fibrinolysis. METHODS: We did a randomised multicentre trial of 840 patients (of 1200 planned) who presented within 6 h of acute myocardial infarction with ST-segment elevation, initially managed by mobile emergency-care units. We assigned patients to prehospital fibrinolysis (n=419) with accelerated alteplase or primary angioplasty (n=421), and transferred all to a centre with access to emergency angioplasty. Our primary endpoint was a composite of death, non-fatal reinfarction, and non-fatal disabling stroke at 30 days. Analyses were by intention to treat. FINDINGS: The median delay between onset of symptoms and treatment was 130 min in the prehospital-fibrinolysis group and 190 min (time to first balloon inflation) in the primary-angioplasty group. Rescue angioplasty was done in 26% of the patients in the fibrinolysis group. The rate of the primary endpoint was 8.2% (34 patients) in the prehospital-fibrinolysis group and 6.2% (26 patients) in the primary-angioplasty group (risk difference 1.96, 95% CI -1.53 to 5.46). 16 (3.8%) patients assigned prehospital fibrinolysis and 20 (4.8%) assigned primary angioplasty died (p=0.61). INTERPRETATION: A strategy of primary angioplasty was not better than a strategy of prehospital fibrinolysis (with transfer to an interventional facility for possible rescue angioplasty) in patients presenting with early myocardial infarction.