Yoshiyuki Kamiyama

Synergetic Antioxidant and Vasodilatory Action of Carbon Monoxide in Angiotensin II–Induced Cardiac Hypertrophy

The aim of this study was to determine the effects of carbon monoxide (CO) at a nontoxic low concentration on the cardiac and vascular hypertrophic response and reactive oxygen species generation, compared with the action of a vasodilator, hydralazine. Twelve- to 16-week-old low-density lipoprotein receptor knockout mice were subjected to angiotensin II (Ang II) infusion using osmotic minipumps (Ang II group; n=11) for 2 weeks. Controls were administered saline (n=10). Animals were exposed to CO in a chamber at 60 ppm for 2 hours per day with or without Ang II infusion (Ang II+CO group, n=10; CO group, n=9). Hydralazine was administered with Ang II infusion (n=10). Animals exhibited elevated arterial carboxyhemoglobin after CO exposure. Although the CO exposure did not affect systolic blood pressure without Ang II infusion, the hypertensive response after Ang II infusion was significantly attenuated by CO. Accordingly, the mice in the Ang II+CO group showed lesser left ventricular hypertrophy compared with those in the Ang II group. CO treatment also attenuated aortic hypertrophy. Interestingly, these changes were accompanied by the reduction of reactive oxygen species production, p47phox and p67phox subunit expressions of reduced nicotinamide-adenine dinucleotide phosphate oxidase, and Akt phosphorylation. Although hydralazine showed stronger antihypertensive action, superior inhibition on cardiac hypertrophy was obtained by CO (P<0.05). Furthermore, Ang II-dependent myocardial reactive oxygen species generation was more effectively suppressed by CO. Low-dose exogenous CO treatment attenuates Ang II-dependent reactive oxygen species generation, suggesting that appropriate CO administration alleviates hypertension and reduces organ hypertrophy mediated by Ang II.

Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy

BACKGROUND Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. METHODS AND RESULTS Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. CONCLUSIONS ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV.

Association of Serum n-3/n-6 Polyunsaturated Fatty Acid Ratio With T-Wave Alternans in Patients With Ischemic Heart Disease

Several studies have demonstrated that oral intake of n-3 polyunsaturated fatty acids, specifically eicosapentaenoic acid (EPA), prevents ventricular tachyarrhythmias (VT) with ischemic heart disease, but the underlying mechanisms still remain unclear. Thus, we examined the relation between the serum EPA/arachidonic acid (AA) ratio and electrophysiological properties in patients with ischemic heart disease. The study subjects consisted of 57 patients (46 males, mean age, 66 ± 13 years) with ischemic heart disease. T-wave alternans (TWA) and heart rate variability were assessed by 24hour Holter ECG, and left ventricular ejection fraction (LVEF) was determined by echocardiography. Fasting blood samples were collected, and the serum EPA/AA ratio was determined. Based on a median value of the serum EPA/AA ratio, all subjects were divided into two groups: serum EPA/AA ratio below 0.33 (Group-L, n = 28) or not (Group-H, n = 29). We compared these parameters between the two groups. LVEF was not different between the two groups. The maximum value of TWA was significantly higher in Group-L than in Group-H (69.5 ± 22.8 μV versus 48.7 ± 12.0 μV, P = 0.007). In addition, VT defined as above 3 beats was observed in 7 cases (25%) in Group-L, but there were no cases of VT in Group-H (P = 0.004). However, low-frequency (LF) component, high-frequency (HF) component, LF to HF ratio, and standard deviation of all R-R intervals were not different between the two groups. These results suggest that a low EPA/AA ratio may induce cardiac electrical instability, but not autonomic nervous imbalance, associated with VT in patients with ischemic heart disease.

Serum phosphate levels reflect responses to cardiac resynchronization therapy in chronic heart failure patients.

Recent studies have shown that high levels of serum phosphate are associated with adverse cardiovascular events. However, little is known about the relation between phosphate levels and improvement of cardiac function in chronic heart failure (CHF) patients who underwent cardiac resynchronization therapy (CRT). The purpose of this study was to examine whether serum phosphate levels were able to predict responders to CRT and adverse cardiac events.

Left ventricular plasty improved cardiac function in a case of takotsubo cardiomyopathy with persistent aneurysm

A 72-year-old woman was admitted to a local hospital due to repeated chest pain in December 2011. On admission, blood tests showed elevation of cardiac enzyme and B-type natriuretic peptide levels. Electrocardiography showed ST-segment elevation in almost all leads. Echocardiography showed akinesis in left ventricular (LV) apex, and hyperkinesis in basal LV. Urgent cardiac catheterization was performed. Coronary angiography showed no significant organic stenosis and the acetylcholine provocation test did not evoke coronary spasm. The left ventriculography revealed marked akinesis of the apical ballooning with hyperkinesis of the basal LV segments, suggesting takotsubo cardiomyopathy. Following the diagnosis, she started treatment for LV dysfunction with standard pharmacotherapy including beta blocker, aldosterone receptor blocker, and angiotensin-converting enzyme inhibitor. Even after 3 months, echocardiography demonstrated that LV wall motion was not recovered, and her symptoms of heart failure were not improved. Based on these findings, we considered that surgical LV plasty was necessary for the treatment of cardiac dysfunction in this patient. She underwent surgical operation (aneurysma resection and LV volume reduction) in April 2011. Pathological examination of the excised myocardial tissue from the aneurysm revealed damaged cardiomyocytes replaced with interstitial fibrosis and adipose tissue. After surgery, her LV systolic function and clinical symptoms dramatically improved. <Learning objective: Generally, patients with takotsubo cardiomyopathy have a favorable prognosis because the wall motion abnormality returns to normal without severe complications. There are only a few cases where surgical interventions were applied for takotsubo cardiomyopathy. This is an interesting case suffered from persistent severe heart failure and underwent surgical LV plasty for the LV aneurysm. After surgery, her LV systolic function and clinical symptoms dramatically improved. Pathological findings of the resected LV tissue showed that fibrosis and adipose tissue replaced myocardial fibers.>.

Anatomical predisposing factors of transmural thermal injury after pulmonary vein isolation.

Aims Transmural thermal injury (TTI), such as oesophageal erosion/ulcer and perioesophageal nerve injury leading to gastric hypomotility, is an important complication associated with pulmonary vein isolation (PVI). However, a predictor of TTI concerning anatomical structures surrounding the oesophagus has not yet been fully elucidated. Therefore, we sought to identify the predisposing factors of TTI after PVI. Methods and results Consecutive 110 patients, who underwent PVI for atrial fibrillation, received oesophagogastroduodenoscopy 2 days later, were investigated. The relationships between TTI and clinical and anatomical parameters were examined. Based on the computed tomography data, we measured the angle of the left atrial (LA) posterior wall to the descending aorta (Ao) (LA-Ao angle), the branching angle of the left inferior pulmonary vein (LIPV) to the coronal plane (LIPV angle), and the minimum distance between the LA posterior wall and descending Ao enclosing the oesophagus (LA-Ao distance). Transmural thermal injuries occurred in 21 patients (oesophageal erosion in 5 and gastric hypomotility in 16). Age, gender, body mass index, LA diameter, and LA volume index in echocardiography were not associated with TTI. However, the LIPV angle was larger and the LA-Ao distance was shorter in the TTI (+) group compared to the TTI (-) group. With multivariate logistic regression analysis, the LIPV angle [odds ratio (OR): 2.144, P = 0.0031] and LA-Ao distance (OR: 0.392, P = 0.0229) were independent predictors of TTI. Conclusion The anatomical proximities of the LA posterior wall, LIPV, and descending Ao surrounding the oesophagus are strongly associated with the prevalence of TTI.

Crucial role of pulmonary vein firing as an initiator of typical atrial flutter: Evidence of a close relationship between atrial fibrillation and typical atrial flutter

Several studies reported that cavotricuspid isthmus‐dependent atrial flutter (typical AFL) frequently coexists with atrial fibrillation (AF); however, the underlying mechanisms have not been fully investigated. This study aimed to reveal the mechanisms of the initiation of typical AFL and the association between typical AFL and AF.

Prognostic value of T-wave alternans in survivors of ventricular fibrillation or hemodynamically unstable ventricular tachycardia

T‐wave alternans is useful for predicting the occurrence of ventricular tachyarrhythmias and sudden cardiac death in various heart diseases. However, little is known about the clinical significance of T‐wave alternans measurement in survivors of ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT).