Clinical characteristics of patients with asymptomatic recurrences of atrial fibrillation in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF) trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm. In a consistent percentage of cases, AF recurrences are asymptomatic, thus making its clinical management difficult in relation to both therapeutic efficacy and thromboembolic risk. METHODS: The GISSI-AF trial enrolled 1,442 patients in sinus rhythm with previous AF episodes. Patients were randomized to valsartan or placebo and followed for 12 months. To improve the likelihood of detecting arrhythmic recurrences, arrhythmic follow-up was based on both programmed or symptom-related control visits and transtelephonic electrocardiographic transmissions. The present post hoc analysis was performed on 1,638 arrhythmic episodes that occurred in 623 patients. RESULTS: Asymptomatic AF recurrences were present in 49.5% of patients. In multivariable analysis, asymptomatic AF recurrences were significantly associated with a longer duration of qualifying arrhythmias (odds ratio [95% CI] 1.57 (1.26-1.97), P < .0001). A lower ventricular response (P < .001) and a longer duration of the arrhythmic recurrence (P < .001) characterized asymptomatic episodes. Patients with asymptomatic events were more likely to be in AF at the time of electrocardiographic control at the end of the 12-month follow-up (adjusted odds ratio [95% CI] 4.9 (2.8-8.4), P < .001). Moreover, a higher CHADS(2) (Congestive heart failure, history of Hypertension, Age≥75 years, Diabetes mellitus, and past history of Stroke or TIA doubled) score and a more frequent use of amiodarone, calcium-channel blockers, and digitalis characterized patients with asymptomatic, whereas 1C drugs were more often used in subjects with symptomatic recurrences. CONCLUSION: Asymptomatic AF recurrences were frequent in the GISSI-AF study population in patients who were more likely to develop persistent-permanent AF and were characterized by an increased thromboembolic risk.

n-3 polyunsaturated fatty acids for the prevention of arrhythmia recurrence after electrical cardioversion of chronic persistent atrial fibrillation: a randomized, double-blind, multicentre study.

AIMS: Persistent atrial fibrillation (AF) often recurs after direct current electrical cardioversion (ECV). As several experimental and clinical studies suggest that n-3 polyunsaturated fatty acids (PUFAs) may have antiarrhythmic properties even at the atrial level, we aimed to evaluate whether oral supplementation with PUFAs, in addition to conventional antiarrhythmic drugs, could reduce the recurrence rate of the arrhythmia after ECV of persistent AF. METHODS AND RESULTS: Two hundred and four patients (mean age 69.3 years, 33% females) with persistent AF were randomly assigned to receive 3 g/day of PUFAs until ECV and 2 g/day thereafter (104 patients) or placebo (100 patients) for 6 months, beginning at least 1 week before ECV. Selection of conventional antiarrhythmic prophylaxis was left to local medical advice. The cardiac rhythm was assessed by both trans-telephonic monitoring and clinical visits. Primary end-point was the recurrence rate of AF. Sinus rhythm was restored, either spontaneously or after ECV, in 187 patients (91.7%); 95 patients (91.4%) on PUFAs and 92 patients (92.0%) on placebo (P=not significant). AF relapsed in 56 (58.9%) of the PUFAs patients and in 47 (51.1%) of the placebo patients (P=0.28). The mean time to AF recurrence was 83±8 days in the PUFAs group and 106±9 days in the placebo group (P=0.29). CONCLUSION: Our results do not support the hypothesis that, in patients undergoing ECV of chronic persistent AF, supplementation with PUFAs in addition to the usual antiarrhythmic treatment reduces recurrent AF.

Relation of C-reactive protein to long-term risk of recurrence of atrial fibrillation after electrical cardioversion.

The aim of this study is to assess the role of C-reactive protein (CRP) in predicting long-term risk of atrial fibrillation (AF) recurrence after electrical cardioversion. CRP levels are associated with the presence of AF and failure of electrical or pharmacologic cardioversion, but no previous study has assessed their predictive role in long-term follow-up after successful electrical cardioversion. One hundred two consecutive patients (age 67 +/- 11 years; 58 men) with nonvalvular persistent AF who underwent successful biphasic electrical cardioversion were studied. High-sensitivity CRP was measured immediately before cardioversion. Follow-up was performed up to 1 year in all cases. Patients were divided into 4 groups according to CRP quartiles. Patients in the lowest CRP quartile (<1.9 mg/L) had significantly lower rates of AF recurrence (4% vs 33% at 3 months in the other 3 groups combined, p = 0.007, and 28% vs 60% at 1 year, p = 0.01). The 4 groups were similar in age, gender, ejection fraction, and left atrial size. Survival analysis confirmed that patients in the lowest CRP quartile had a lower recurrence rate (p = 0.02). Cox regression analyses using age, gender, hypertension, diabetes, ejection fraction, left atrial diameter, use of antiarrhythmic drugs, angiotensin-converting enzyme inhibitors or angiotensin II antagonists, and statins, and CRP quartiles as covariates showed that only CRP was independently associated with AF recurrence during follow-up (hazard ratio 4.98, 95% confidence interval 1.75 to 14.26, p = 0.003). In conclusion, low CRP is associated with long-term maintenance of sinus rhythm after cardioversion for nonvalvular AF.

N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial.

OBJECTIVES: The aim of this study was to assess the efficacy of preoperative and postoperative treatment with n-3 polyunsaturated fatty acids (PUFAs) in preventing the occurrence of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). BACKGROUND: Postoperative AF is a common complication of CABG. There is growing clinical evidence that PUFAs have cardiac antiarrhythmic effects. METHODS: A total of 160 patients were prospectively randomized to a control group (81 patients, 13 female, 64.9 +/- 9.1 years) or PUFAs 2 g/day (79 patients, 11 female, 66.2 +/- 8.0 years) for at least 5 days before elective CABG and until the day of discharge from the hospital. The primary end point was the development of AF in the postoperative period. The secondary end point was the hospital length of stay after surgery. All end points were independently adjudicated by two cardiologists blinded to treatment assignment. RESULTS: The clinical and surgical characteristics of the patients in the two groups were similar. Postoperative AF developed in 27 patients of the control group (33.3%) and in 12 patients of the PUFA group (15.2%) (p = 0.013). There was no significant difference in the incidence of nonfatal postoperative complications, and postoperative mortality was similar in the PUFA-treated patients (1.3%) versus controls (2.5%). After CABG, the PUFA patients were hospitalized for significantly fewer days than controls (7.3 +/- 2.1 days vs. 8.2 +/- 2.6 days, p = 0.017). CONCLUSIONS: This study first demonstrates that PUFA administration during hospitalization in patients undergoing CABG substantially reduced the incidence of postoperative AF (54.4%) and was associated with a shorter hospital stay.

Atrial flutter and atrial fibrillation: which relationship? New insights into the electrophysiological mechanisms and catheter ablation treatment.

Atrial fibrillation (AF) and atrial flutter (AFL) are two arrhythmias commonly associated in clinical practice. This association generally reflects a similar arrhythmogenic substrate. It has been observed that the development of isthmus-dependent AFL is often preceded by AF. The conversion from AF to AFL develops thanks to a line of functional block in the right atrial free wall. In this subset a particular condition is represented by typical AFL that occurs during the treatment with class IC or III antiarrhythmic drugs in patients with previous AF. A hybrid approach (antiarrhythmic drugs and catheter ablation) has been proposed as a possible treatment of drug-induced AFL. The conversion from AFL to AF is less frequent and may be due to several mechanisms: a shortening of the length of the line of functional block, atrial ectopic beats or rapid atrial rhythm, focal activation from the pulmonary veins, alternans of atrial action potentials. Also, atypical right and left AFL can determine AF. Finally, atypical AFL may occur after AF ablation, and could be prevented by associated cavotricuspid isthmus ablation.

[Severe aortic stenosis successfully treated with percutaneous aortic valve implantation]. / Stenosi aortica severa inoperabile trattata con successo mediante impianto di valvola aortica per via percutanea.

Patients with severe calcific aortic stenosis are occasionally not amenable to surgery because of advanced age or severe co-morbidities. Percutaneous aortic valve dilation is used but has only limited time relief. While preclinical evidence on percutaneous aortic valve replacement seems promising, only very limited clinical data are available worldwide. We hereby present the first case of percutaneous aortic valve replacement successfully performed in Italy in a 74-year-old high-risk female. This case emphasizes the technical challenges inherent to this procedure and its promising role in selected very high-risk patients with severe aortic stenosis, notwithstanding the early and long-term risk of adverse events.

Electropharmacological effects of antiarrhythmic drugs on atrial fibrillation termination. Part I: Molecular and ionic fundamentals of antiarrhythmic drug actions.

In the last few years many studies have been performed with the aim of gaining a better understanding of the pathophysiological nature of atrial fibrillation. These recent observations provide new insights into the initiation and perpetuation of atrial fibrillation, underlying the importance of the pulmonary veins as major sources of atrial triggers and introducing new concepts such as the atrial electrical remodeling and the spatial heterogeneity of the electrophysiological characteristics of this arrhythmia. The increasing knowledge about the cardiac ion channel structure and function and about the electrophysiological actions of the antiarrhythmic drugs may contribute to a better comprehension of the mechanisms of the pharmacological termination of the arrhythmia. In part I of the review we try to give a unified vision of the old models and new concepts about the molecular and ionic fundamentals of antiarrhythmic drug actions.

Electropharmacological effects of antiarrhythmic drugs on atrial fibrillation termination. Part II: New insights into the electrophysiological mechanisms of atrial fibrillation termination.

Antiarrhythmic drugs have been largely used to convert atrial fibrillation to sinus rhythm. Classes Ia, Ic and III antiarrhythmic agents are all known to be effective. Nevertheless, the electrophysiological properties of such agents even of the same class are very different. The mechanisms of the pharmacological termination of atrial fibrillation is an interesting issue that has not been so extensively studied yet. In this review we try to summarize the principal concepts about the electrophysiological substrate of atrial fibrillation and to give a unified and modern overview of the issue of the mechanisms of the pharmacological termination of the arrhythmia.

C-reactive protein and left atrial appendage velocity are independent determinants of the risk of thrombogenesis in patients with atrial fibrillation.

BACKGROUND: The association between inflammatory status and thrombosis in patients with atrial fibrillation (AF) is unclear. We studied the correlation between inflammation and the risk of thrombogenesis in patients with AF and the relationship of inflammation with other factors associated with thrombotic risk. METHODS: We studied 150 consecutive patients (69 men, age 65+/-12 years) with persistent non-valvular AF who had transesophageal echocardiography prior to cardioversion. Patients underwent also measurements of high-sensitivity C-reactive protein, fibrinogen, D-dimer, and hematocrit levels. RESULTS: Patients were divided into two groups according to the presence (n=52) or absence (n=98) of dense spontaneous echo contrast (SEC) in left atrium or left atrial appendage. The two groups were similar for age, sex, and major clinical risk factors. Patients with dense SEC had significantly larger left atrium diameter (p=0.007), lower left atrial appendage mean velocity (p<0.0001), and higher levels of C-reactive protein (p=0.003), D-dimer (p=0.008), and fibrinogen (p=0.006). At multivariate analysis, only left atrial appendage velocity (odds ratio: 19.11; 95% confidence interval 4.2-80.9) and C-reactive protein (odds ratio: 3.41; 95% confidence interval 1.2-9.8) were significantly associated with thrombus and/or dense SEC. However, there was no relationship between C-reactive protein levels and left atrial appendage velocity (p=0.24, r=-0.09). CONCLUSIONS: Our results show that left atrial appendage velocity and C-reactive protein are independently associated with the risk of thromboembolism in AF. Thus, blood stasis and inflammation appear to constitute two major distinct components of thrombogenesis.

Fast cardiologist-administered midazolam for electrical cardioversion of atrial fibrillation.

AIM: To evaluate the safety and the feasibility of sedation administered by cardiologists with rapid intravenous bolus of midazolam followed by flumazenil infusion during transthoracic biphasic electrical cardioversion (TEC) for atrial fibrillation (AF). METHODS: Two hundred and sixty-five consecutive patients (119 females, mean age 67.4 +/- 8.5 years) with either acute (24 patients) or persistent AF (mean arrhythmia duration 3.7 +/- 3.0 months) underwent TEC. Midazolam (0.05 mg/kg) was administered as rapid intravenous bolus by the cardiologist, whereas the anaesthesiologist was simply alerted. At the end of the procedure, intravenous flumazenil 0.25 mg was given, followed by 0.25 mg over 1 h. Patients received continuous electrocardiographic and pulse-oxymetric monitoring. RESULTS: Adequate sedation was obtained in 262 patients (98.9%), with a mean midazolam dose of 4.4 +/- 0.9 mg. After drug administration, the mean time to patient's sedation and reawakening were 3.1 +/- 1.9 and 6.1 +/- 2.7 min, respectively. The mean reduction in oxygen saturation was 5.4 +/- 3.7%. Sinus rhythm was restored in 254 patients (95.8%). All but 41 patients (15.5%) were completely amnesic. None reported pain. No adverse events were registered. No urgent call for the anaesthesiologist was made. CONCLUSIONS: Conscious sedation with fast-administered midazolam followed by flumazenil for cardioversion of atrial fibrillation is safe, effective and well tolerated, easing the procedure and shortening its duration.

Left atrial ablation versus biatrial ablation for persistent and permanent atrial fibrillation: a prospective and randomized study.

OBJECTIVES: The aim of this study was to compare--in patients with persistent and permanent atrial fibrillation (AF)--the efficacy and safety of left atrial ablation with that of a biatrial approach. BACKGROUND: Left atrium-based catheter ablation of AF, although very effective in the paroxysmal form of the arrhythmia, has an insufficient efficacy in patients with persistent and permanent AF. METHODS: Eighty highly symptomatic patients (age, 58.6 +/- 8.9 years) with persistent (n = 43) and permanent AF (n = 37), refractory to antiarrhythmic drugs, were randomized to two different ablation approaches guided by electroanatomical mapping. A procedure including circumferential pulmonary vein, mitral isthmus, and cavotricuspid isthmus ablation was performed in 41 cases (left atrial ablation group). In the remaining 39 patients (biatrial ablation group), the aforementioned approach was integrated by the following lesions in the right atrium: intercaval posterior line, intercaval septal line, and electrical disconnection of the superior vena cava. RESULTS: During follow-up (mean duration 14 +/- 5 months), AF recurred in 39% of patients in the left atrial ablation group and in 15% of patients in the biatrial ablation group (p = 0.022). Multivariable Cox regression analysis showed that ablation technique was an independent predictor of AF recurrence during follow-up. CONCLUSIONS: In patients with persistent and permanent AF, circumferential pulmonary vein ablation, combined with linear lesions in the right atrium, is feasible, safe, and has a significantly higher success rate than left atrial and cavotricuspid ablation alone.