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Background Large-scale clinical trials have demonstrated that patients with atrial fibrillation (AF), when treated with a rhythm-control strategy, are still at risk for embolic events. We hypothesized that left atrial (LA) dysfunction persisted even after successful maintenance of sinus rhythm for > 3 months. Methods A total of 93 patients with AF and satisfactory rhythm control for > 3 months were included. Satisfactory rhythm control was defined as being free of AF based on patient-reported symptoms, monthly ECG follow-up, and ambulatory Holter ECG if needed. Among the 93 patients, 25 patients had sustained AF that was terminated by electrical or pharmacologic cardioversion, while 68 patients had paroxysmal AF under good medical control. Clinical data were obtained, and transthoracic and transesophageal echocardiography were performed after satisfactory rhythm control for > 3 months. Results Among the 93 patients, 34 patients (37%) had LA dysfunction, defined as LA appendage (LAA) peak emptying velocity 65 years, and prior cerebral vascular accident. LA dysfunction was found in 10 of 17 patients (59%) with three or more risk factors. The odds ratio for having LA dysfunction was 3.1 (p = 0.04; 95% confidence interval, 1.1 to 9.1) when compared with patients with less than three risk factors. Conclusions LA dysfunction was present in more than one third of AF patients after satisfactory rhythm control for > 3 months. Patients with higher burden (three or more) of clinical risk factors were more likely to have impaired LA function.

Accumulation of somatic mutations of mitochondrial DNA (mtDNA) contributes to the aging process and progressive organ dysfunction. We investigated the mitochondrial DNA with 4977-base-pair mtDNA deletion mutation (mtDNA(4977)) in human atrial tissue and correlated the amount of mtDNA(4977) to clinical atrial fibrillation (AF).Atrial tissue from the right atrial appendage was obtained in 88 patients during open-heart surgery (22 children/adolescents and 66 adults). The amount of mtDNA(4977) was measured using a nested polymerase chain reaction protocol and normalized to wild-type mtDNA. We found that the mtDNA(4977) was absent in all 22 pediatric/adolescent patients. In the adult group, the relative amount of mtDNA(4977) was significantly higher in patients with AF than in patients without AF (0.55 +/- 0.26 vs 0.35 +/- 0.29, p0.007) [mean +/- SD]. The amount of mtDNA(4977) was also positively associated with age (r = 0.29, p0.01). Left and right atrial pressures, left atrial dimension, hypertension, and cardiac diagnosis did not influence the amount of mtDNA(4977) significantly. Further multivariate analysis showed that both aging and AF contributed independently to the accumulation of mtDNA(4977).AF is associated with an increase of mtDNA(4977). This change is similar to the aging process of atrial tissue and might contribute to atrial dysfunction in AF.

Although the pig has been used as an experimental model for ischemic heart disease and sudden death, relatively little is known about the anatomy of the conduction system (CS) of this animal. We attempted to correlate electrophysiologic and anatomic differences between the pig and human CS. Invasive electrophysiologic studies were performed in five healthy anesthetized pigs. In contrast to the adult human, the pig has sinus tachycardia, shortened PR and H-V intervals, and a relatively short sinoatrial conduction time. Compared with the human CS, serial sections of the CS of pig hearts showed the following differences: (1) the atrioventricular node is located more to the right of the summit of the ventricular septum; (2) the penetrating bundle is very short, and the bifurcation of the bundle into bundle branches occurs more proximally; (3) there is more connective tissue and less elastic tissue; and (4) there is a copious amount of nerve fibers (about 50 percent throughout the CS). The presence of the abundant neural tissue implies that there is an important neurogenic component to conduction in the pig. Because of the above differences from the human, the pig should be used with caution as an experimental model in ischemic heart disease and sudden death where arrhythmias are studied.

Large-scale clinical trials have demonstrated that patients with atrial fibrillation (AF), when treated with a rhythm-control strategy, are still at risk for embolic events. We hypothesized that left atrial (LA) dysfunction persisted even after successful maintenance of sinus rhythm for3 months.A total of 93 patients with AF and satisfactory rhythm control for3 months were included. Satisfactory rhythm control was defined as being free of AF based on patient-reported symptoms, monthly ECG follow-up, and ambulatory Holter ECG if needed. Among the 93 patients, 25 patients had sustained AF that was terminated by electrical or pharmacologic cardioversion, while 68 patients had paroxysmal AF under good medical control. Clinical data were obtained, and transthoracic and transesophageal echocardiography were performed after satisfactory rhythm control for3 months.Among the 93 patients, 34 patients (37%) had LA dysfunction, defined as LA appendage (LAA) peak emptying velocity40 cm/s or spontaneous echo contrast and/or thrombus in the LA or LAA. When compared to the other 59 patients without LA dysfunction, they had larger LA dimension (40 +/- 6 mm vs 36 +/- 8 mm [+/- SD], p = 0.018) but did not differ significantly regarding the left ventricular (LV) chamber size, LV ejection fraction, mitral or tricuspid inflow, and ratio of the amplitude of the waves created by early diastolic filling and atrial contraction. We also analyzed the relationship between LA function and clinical risk factors for stroke, including hypertension, diabetes mellitus, coronary artery disease, age65 years, and prior cerebral vascular accident. LA dysfunction was found in 10 of 17 patients (59%) with three or more risk factors. The odds ratio for having LA dysfunction was 3.1 (p = 0.04; 95% confidence interval, 1.1 to 9.1) when compared with patients with less than three risk factors.LA dysfunction was present in more than one third of AF patients after satisfactory rhythm control for3 months. Patients with higher burden (three or more) of clinical risk factors were more likely to have impaired LA function.

The calcineurin-nuclear factor of activated T-cell (NFAT) signal transduction pathway regulates the expression of a plethora of genes in the myocardium. Cytosolic calcium overloading occurs in atrial fibrillation (AF), and this fulfills the condition needed for activation of this pathway. We therefore investigated the NFAT pathway in atrial tissue in a porcine model of AF.AF was induced in eight adult pigs by rapid atrial pacing. Investigations on the calcineurin and NFAT pathway were performed on transmural left atrial tissue obtained 6 weeks after implantation of the pacemaker (pacing for 4 weeks, and AF without pacing for 2 weeks). In the AF group, the left atrial dimension increased significantly (26 +/- 4 mm vs 31 +/- 4 mm, respectively, p0.05 [mean +/- SD]). Calcineurin enzyme activity increased significantly in pigs with AF (n = 8) when compared to control pigs (n = 6) [0.143 +/- 0.034 vs 0.038 +/- 0.063 mmol PO(4)(-) released, p0.01]. We found that both NFAT-c3 and NFAT-c4, the downstream effectors of calcineurin, increased significantly in the nuclei in AF tissue using immunoblotting. Translocation of NFAT-c3 and NFAT-c4 into the nuclei was also demonstrated in AF tissue microsections using immunohistochemistry. The electrophoresis mobility shift assay further demonstrated that nuclear extracts from AF tissue had a significantly larger binding capacity for NFAT-specific oligonucleotide probes.Our results demonstrate that calcineurin activity was increased in AF with subsequent NFAT-c3 and NFAT-c4 translocation into the nucleus. Activation of this signal transduction pathway may play an important role in the pathogenesis of AF.

To assess the left ventricular function during sustained stable ventricular tachycardia (VT), ten patients, aged 58 to 74, underwent simultaneous echo-Doppler and hemodynamic studies during sinus rhythm and induced sustained stable monomorphic VT. The VT cycle length was 447 ± 92 ms (mean ± SD). During VT, cardiac index fell from 2.32 ± 0.54 to 1.62 ± 0.63 L/min/m 2 (p (Chest 1989; 96:275–80)