Tomohiro Uchikawa

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.

Reactive oxidative metabolites are associated with atrial conduction disturbance in patients with atrial fibrillation

BACKGROUND Oxidative stress is associated with atrial fibrillation (AF). However, little is known about the relationship between serum markers of oxidation and electrical activity in patients with AF. OBJECTIVE The purpose of this study was to investigate the possible association between serum markers of reactive oxidative metabolism and atrial remodeling in paroxysmal and persistent AF. METHODS Derivatives of reactive oxidative metabolites (DROM), an index of oxidative stress, were measured in 306 consecutive patients with AF (225 paroxysmal, 81 persistent) undergoing radiofrequency (RF) catheter ablation. Filtered P-wave duration by P-wave signal-averaged ECG and levels of high-sensitivity C-reactive protein (CRP) as an inflammatory marker also were measured. RESULTS Patients were followed up for 1.2 +/- 0.8 years. DROM levels in patients with persistent AF were significantly higher than in patients with paroxysmal AF (341.6 +/- 85.5 Carratelli [Carr] units vs 305.0 +/- 77.7 Carr units, P <.001). DROM levels showed a tighter, positive correlation with filtered P-wave duration in persistent AF patients (r = 0.56, P <.001) than in all AF patients (r = 0.13, P <.05). DROM levels also showed a weaker but significant correlation with high-sensitivity CRP in patients with AF. Kaplan-Meier analysis revealed that the highest quartile of basal DROM levels exhibited a significantly higher AF recurrence rate after RF catheter ablation in patients with paroxysmal AF (P <.01). CONCLUSION Serum markers of oxidative stress reflect atrial conduction disturbance and predict AF recurrence after RF catheter ablation in paroxysmal AF patients. DROM could serve as a biomarker for predicting risk of AF recurrence after RF catheter ablation.

Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation.

AIMS This study investigated the potential association between homocysteine levels and cardiovascular events or atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) in patients with AF. METHODS AND RESULTS Blood samples were obtained prior to the RFCA procedure. Levels of homocysteine and carboxy-terminal telopeptide of collagen type I (CITP), a collagen type I degradation marker, were measured in 96 patients receiving RFCA; 62 paroxysmal or persistent AF patients and 34 paroxysmal supra-ventricular tachycardia patients. Patients were followed up for 2.1 +/- 1.5 years. Plasma homocysteine levels were significantly higher in patients with persistent AF (P < 0.05) compared with levels in paroxysmal AF and control patients. Homocysteine levels also positively correlated with left atrial dimension (LAD) (P < 0.01) and CITP levels (P < 0.001). While no significant correlation was found between basal homocysteine levels and recurrent AF after RFCA in AF patients, patients in the high homocysteine group exhibited a significantly higher rate of cardiovascular events without AF recurrence compared with those in the low homocysteine group (P < 0.05). CONCLUSION High homocysteine levels are associated with the presence of persistent AF, which is accompanied by increased CITP levels and LAD. Also confirmed is the role of homocysteine as a risk factor for the pathogenesis of cardiovascular events after RFCA in AF patients. Measurement of homocysteine level may provide useful information for the managing cardiovascular risk in patients with AF.

Elevation of red blood cell distribution width during hospitalization predicts mortality in patients with acute decompensated heart failure

BACKGROUND Increased red blood cell distribution width (RDW) is associated with adverse outcomes in heart failure. In the present study, we assessed the association between changes in RDW values during hospitalization and long-term prognosis in patients with acute decompensated heart failure (ADHF). METHODS We measured the RDW value in 229 consecutive patients with ADHF. Blood samples were obtained at the time of hospital admission and at discharge. Changes in RDW were calculated as the mean difference between RDW values on admission and those at the time of hospital discharge. RESULTS Patients were followed up for a median of 692 days. A Kaplan-Meier survival analysis demonstrated that patients whose RDW levels increased during hospitalization had significantly higher all-cause and cardiac-based mortality following heart failure than did patients whose RDW levels decreased during hospitalization. A multivariate Cox regression analysis revealed that change in RDW values during hospitalization, but not the values of RDW and hemoglobin on admission, was independently correlated with all-cause and cardiac-based mortality after adjusting for other risk factors in patients with ADHF. CONCLUSIONS These data document that the change in RDW values during hospitalization independently predicts poor outcomes in patients with ADHF. Continuous follow-up of RDW values could provide useful information for long-term prognosis after heart failure.

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 </=35%, and QRS duration >/=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.

Normalisation of plasma growth hormone levels improved cardiac dysfunction due to acromegalic cardiomyopathy with severe fibrosis

A 51-year-old man was referred to the Department of Cardiology in our hospital due to severe congestive heart failure and ventricular arrhythmias in March 2008. He had repeated ventricular tachycardia for years and the left ventricular ejection fraction (EF) was 11% on admission. A myocardial biopsy revealed that over 50% cardiomyocytes were replaced by fibrosis. Due to the typical acromegalic features, he was referred to the endocrinology department and diagnosed as acromegaly. He was treated with octreotide for 8 months followed by trans-sphenoidal surgery. The plasma levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) decreased by octreotide and normalised by surgery after which the cardiac function improved drastically. The current case demonstrates that cardiac dysfunction in acromegaly could be recovered by normalisation of GH and IGF-1 even in the presence of severe fibrosis in the myocardium.

Safety and Efficacy of Long-Term Use of Tolvaptan in Patients With Heart Failure and Chronic Kidney Disease

BACKGROUND We assessed the long-term safety and efficacy of tolvaptan in 102 patients with heart failure (HF) and chronic kidney disease (CKD). Median follow-up duration was 1.6 years (1.0-4.4 years).Methods and Results:One patient discontinued tolvaptan because of hypernatremia. There were no changes in renal function or electrolytes during the 1-year follow-up. The cardiac-related death-free or HF-related hospitalization-free survival rate was significantly higher in patients receiving tolvaptan than in propensity score-matched patients who did not receive tolvaptan. CONCLUSIONS In patients with HF and CKD, long-term administration of tolvaptan was well-tolerated, relatively safe and effective, suggesting its utility for long-term management of these conditions.

Early Spontaneous Remission of Intramyocardial Dissecting Hematoma

Intramyocardial dissecting hematoma is a rare but potentially fatal complication of myocardial infarction. The decision to adopt a surgical or conservative strategy may depend on the clinical and hemodynamic stability of patients. Regardless, the precise and temporal assessment of the structure of hematoma is imperative. We herein report the first case of a patient with early spontaneous remission of intramyocardial dissecting hematoma successfully managed by a conservative approach with multimodality imaging.

Morphological characteristics of the Holter P-waves associated with pulmonary vein pacing.

AIMS Identification of arrhythmogenic pulmonary veins (PVs) initiating atrial fibrillation is helpful for catheter ablation. The aim of this study was to examine the possibility to recognize the arrhythmogenic PV using Holter ECG. METHODS AND RESULTS In 20 patients, P-wave characteristics were studied during pacing from four PVs. Holter ECG was recorded using two leads: the modified CC5 (Lead 1) and NASA (Lead 2), and the P-wave amplitude and duration were evaluated. In Lead 1, P-waves produced by left PV pacing were significantly lower in amplitude than right PV pacing (-3 +/- 75 vs. 86 +/- 43 microV, P < 0.001). In Lead 2, pacing in superior PVs produced P-waves with higher amplitude than inferior PVs (210 +/- 74 vs. 125 +/- 66 muV, P < 0.001). The criteria proposed by the morphological characteristics of P-waves identified putative arrhythmogenic PVs with an accuracy of 78%. CONCLUSION It might be possible to identify putative arrhythmogenic PVs by modified Holter ECG recording.