Eicosapentaenoic acid prevents atrial fibrillation associated with heart failure in a rabbit model.

Atrial fibrillation (AF) is associated with morbidity and mortality of heart failure. Eicosapentaenoic acid (EPA), which is contained in fish oil, was shown to reduce the risk of cardiovascular diseases. We investigated the effects of EPA on AF associated with heart failure in a rabbit model. Rabbits were subjected to ventricular tachypacing (VTP) for 4 wk with or without EPA treatment. Continuous VTP induced heart failure status in these rabbits. The duration of AF (DAF) induced by burst pacing was analyzed by electrophysiological studies. VTP resulted in increased DAF following burst pacing. EPA treatment attenuated increased DAF. Atrial fibrosis increased in response to VTP, accompanied by extracellular signal-regulated kinase (ERK) phosphorylation and transforming growth factor-ß1 (TGF-ß1) expression in the atrium. Treatment with EPA attenuated atrial fibrosis, ERK phosphorylation, and TGF-ß1 expression in response to VTP. EPA treatment increased adiponectin as an anti-inflammatory adipokine and decreased tumor necrosis factor-α as a proinflammatory adipokine in the atrium and epicardial adipose tissues. EPA attenuated VTP-induced AF promotion and atrial remodeling, which was accompanied by modulating the profiles of adipokine production from epicardial adipose tissue. EPA may be useful for prevention and treatment of AF associated with heart failure.

Pioglitazone, a peroxisome proliferator-activated receptor-gamma activator, attenuates atrial fibrosis and atrial fibrillation promotion in rabbits with congestive heart failure.

BACKGROUND: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activator pioglitazone antagonizes angiotensin II actions and possesses anti-inflammatory and antioxidant properties in vitro. There is evidence that pioglitazone improves ventricular remodeling in some experimental models. OBJECTIVE: The purpose of this study was to assess the effects of pioglitazone on arrhythmogenic atrial structural remodeling versus the effects of the angiotensin II type 1 receptor blocker candesartan in a rabbit model of congestive heart failure. METHODS: Rabbits subjected to ventricular tachypacing at 380 to 400 bpm for 4 weeks in the absence and presence of treatment with pioglitazone, candesartan, and combined pioglitazone and candesartan were assessed by electrophysiologic study, atrial fibrosis measurements, and cytokine expression analyses. RESULTS: Atrial fibrillation (AF) lasting longer than 2 seconds was induced in no nonpaced controls but in all ventricular tachypacing-only rabbits (mean duration of AF: 8.0 +/- 1.4 seconds). Pioglitazone reduced the duration of AF (3.5 +/- 0.2 seconds, P <.05) and attenuated atrial structural remodeling, with significant reductions in interatrial activation time (50 +/- 2 ms vs 41 +/- 2 ms, P <.05) and atrial fibrosis (16.8% +/- 0.8% vs 10.9% +/- 0.7%, P <.05; control 1.6% +/- 0.2%), effects comparable to those of candesartan (duration of AF: 3.0 +/- 0.2 seconds; activation time 44 +/- 2 ms; fibrosis: 9.4% +/- 0.6%). Both pioglitazone and candesartan reduced transforming growth factor-beta1, tumor necrosis factor-alpha, and activated extracellular signal-regulated kinase expression similarly, but neither affected p38-kinase or c-Jun N-terminal kinase activation. The effects of combined pioglitazone and candesartan therapy were not significantly different from the effects of pioglitazone or candesartan alone. CONCLUSION: Pioglitazone can attenuate congestive heart failure-induced atrial structural remodeling and AF promotion, with effects similar to those of candesartan. PPAR-gamma may be a potential therapeutic target for human AF.

Prognostic significance of the number of leads with ST depression during an anginal attack in high risk patients with unstable angina.

OBJECTIVE AND METHODS: We examined the prognostic significance of electrocardiographic predictors (number of leads with ST depression, maximal ST depression, QT dispersion), C-reactive protein, fibrinogen, myosin light chain 1 and creatine kinase MB fraction in 62 patients with unstable angina showing ST depression during an anginal attack. RESULTS: During the 90-day follow-up period, 15 patients (24%) exhibited new cardiac events (death, myocardial infarction or urgent revascularization). Using multivariate analysis, the number of leads with ST depression [relative risk 6.305 (95% confidence intervals 1.831-21.71), p<0.01] during an anginal attack was found to be an independent risk factor to predict cardiac events. Other predictors did not have prognostic significance. CONCLUSION: The number of leads with ST depression during an anginal attack is an independent risk predictor for new cardiac events in high risk patients with unstable angina.

Diagnosis of B-cell lymphoma. Utility of the polymerase chain reaction for detecting clonality from archival cytologic smears.

OBJECTIVE: To apply the polymerase chain reaction (PCR) to detect clonality for potentially helping to establish a definitive diagnosis of lymphoma in cytologic material. STUDY DESIGN: In this retrospective study, Papanicolaou-stained cytologic smears and formalin-fixed, paraffin-embedded tissues from 17 cases of B-cell lymphoma were examined to investigate their clonality by a PCR technique using three different approaches (FR3, FR3A and FR2) for amplification of immunoglobulin heavy chain genes. Cytologic smears from 10 cases of nonneoplastic lymphoid tissues and T-cell lymphomas served as negative controls. RESULTS: Monoclonality was detected in 9 of 17 cases (53%) of B-cell lymphoma in cytologic smears as compared with 8 of 16 cases (50%) in tissue sections. Semi-nested PCRs (FR3A/FR2) were superior to the single PCR (FR3) in the detection rate (41% vs. 18%). Five of seven cases (71%) of marginal zone B-cell lymphomas showed monoclonality, whereas only 4 of 10 cases (40%) of diffuse large B-cell lymphomas did so. Monoclonality was demonstrated in none of the negative controls. CONCLUSIONS: Clonality detection in B-cell lymphomas by PCR using cytologic smears is specific and equal in sensitivity to that using formalin-fixed, paraffin-embedded tissues. The detection rate is especially excellent in marginal zone B-cell lymphoma, in which the cytologic diagnosis is particularly challenging. Combined seminested PCRs for FR3A and FR2 are advocated for a reliable assessment of clonality.

Novel transitional zone index allows more accurate differentiation between idiopathic right ventricular outflow tract and aortic sinus cusp ventricular arrhythmias.

BACKGROUND: Although several ECG algorithms have been proposed for differentiating the origins of outflow tract ventricular arrhythmia (OT-VA), their accuracy still is limited in cases with cardiac rotation. OBJECTIVE: The purpose of this study was to assess whether a novel "cardiac rotation-corrected" transitional zone (TZ) index would be a useful marker for differentiating right ventricular outflow tract (RVOT) origin from aortic sinus cusp (ASC) origin. METHODS: Surface ECGs of OT-VAs with left bundle branch block morphology and inferior axis in 112 patients who were successfully ablated in the RVOT (n = 87) or the ASC (n = 25) were analyzed. The TZ index was defined according to the site of R-wave transition of sinus beats and OT-VAs. RESULTS: The TZ index was significantly lower in the ASC origin than in the RVOT origin (-1.2 ± 0.9 vs 0.3 ± 0.7, P <.0001). A cutoff value of the TZ index <0 predicted the ASC origin with 88% sensitivity and 82% specificity. The previously reported R-wave duration index ≥ 50% had a high specificity of 85% but a low sensitivity of 44%, and R/S-wave amplitude index ≥ 30% had 68% sensitivity and 79% specificity. The area under the curve by receiver operating characteristic curve analysis was 0.90 for the TZ index, which was significantly higher than the R-wave duration index and R/S-wave amplitude index of 0.74 and 0.76, respectively. CONCLUSION: This novel TZ index can be a more useful marker for differentiating RVOT origin from ASC origin.

Combined assessment of left ventricular dyssynchrony and contractility by speckled tracking strain imaging: a novel index for predicting responders to cardiac resynchronization therapy.

BACKGROUND: Mechanical dyssynchrony is an important factor in the response to cardiac resynchronization therapy (CRT). However, no echocardiographic measure can improve prediction of case selection for CRT. OBJECTIVE: The purpose of this study was to assess the efficacy of a newly combined echocardiographic index for ventricular dyssynchrony and contractility using speckled tracking strain analysis to predict responders to CRT. METHODS: Forty-seven patients with severe heart failure in New York Heart Association functional class III/IV, left ventricular ejection fraction /=130 ms were included in the study. Echocardiography was performed, and a novel index (i-Index), the product of radial dyssynchrony and radial strain, was calculated. Responder to CRT was defined as a patient with a >/=15% decrease in left ventricular end-systolic volume at 6-month follow-up. RESULTS: Thirty-two patients (68%) were classified as responders. The i-Index was significantly higher in responders than in nonresponders (3,450 +/- 1180 vs 1,481 +/- 841, P <.001). The area under receiver operator characteristic curve was 0.92 for the i-Index, which was better than the index of radial dyssynchrony only (0.74). A cutoff value of i-Index >2,000 predicted responders with 94% sensitivity and 80% specificity. The index using only radial dyssynchrony had 81% sensitivity and 53% specificity. Furthermore, i-Index decreased in responders (1,985 +/- 1261, P <.001) but not in nonresponders (1,684 +/- 866, P = .48). CONCLUSION: Our findings suggest that a novel combined index by radial strain echocardiography might be a predictor of response to CRT. The value of this novel echocardiographic index requires further assessment in larger studies.