Hironori Saito

Carvedilol decreases elevated oxidative stress in human failing myocardium

Background—Oxidative stress has been implicated in the pathogenesis of heart failure. However, direct evidence of oxidative stress generation in the human failing myocardium has not been obtained. Furthermore, the effect of carvedilol, a vasodilating &bgr;-blocker with antioxidant activity, on oxidative stress in human failing hearts has not been assessed. This study was therefore designed to determine whether levels of lipid peroxides are elevated in myocardia of patients with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid peroxidation level. Methods and Results—Endomyocardial biopsy samples obtained from 23 patients with DCM and 13 control subjects with normal cardiac function were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation product. Expression of HNE-modified protein was found in all myocardial biopsy samples from patients with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial HNE-modified protein levels in patients with DCM were significantly increased compared with the levels in control subjects (P <0.0001). Endomyocardial biopsy samples from 11 patients with DCM were examined before and after treatment (mean, 9±4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22±8 mg/d). After treatment with carvedilol, myocardial HNE-modified protein levels decreased by 40% (P <0.005) along with amelioration of heart failure. Conclusions—Oxidative stress is elevated in myocardia of patients with heart failure. Administration of carvedilol resulted in a decrease in the oxidative stress level together with amelioration of cardiac function.

Severe Endothelial Dysfunction After Sirolimus-Eluting Stent Implantation

A 40-year-old man with a recent anterior myocardial infarction but with no history of coronary spasm and no risk factors for endothelial dysfunction such as diabetes mellitus, hypertension, smoking, or hypercholesterolemia was admitted to our hospital. Coronary angiography showed diffuse 90% proximal left anterior descending artery stenosis (Figure 1A). He received a sirolimus-eluting stent (Cypher, Cordis Corporation, Miami Lakes, Fla) to treat diffuse …

Direct evidence for increased hydroxyl radicals in angiotensin II-induced cardiac hypertrophy through angiotensin II type 1a receptor.

Summary: Oxidative stress is known to contribute to numerous cardiac disease processes. However, the contribution of reactive oxygen species to cardiac hypertrophy has not yet been fully investigated. The aim of the present study was therefore to determine whether levels of reactive oxygen species were increased in angiotensin IIinduced cardiac hypertrophy. We continuously administered angiotensin II (1.1 mg/kg per day) into wild‐type and angiotensin II type‐1a receptor knockout mice for 2 weeks. The angiotensin II treatment increased blood pressure and heart weight/body weight ratio in wild‐type mice but not in knockout mice. The generation of hydroxyl radicals in heart tissue homogenate was directly assessed with electron spin resonance spectroscopy using a spin trapping agent, alphaphenyl‐ N‐tert butylnitrone. Angiotensin II significantly increased hydroxyl radical production 2.2‐fold (p < 0.01) in the hearts of wildtype mice but not in knockout mice. The present study provided direct evidence for increased production of hydroxyl radicals in angiotensin II‐induced cardiac hypertrophy through angiotensin II type‐1a receptor. These findings in this study may provide important insights into the development of hypertrophy and the transition of hypertrophy to heart failure.

Atrial Electrograms and Activation Sequences in the Transition Between Atrial Fibrillation and Atrial Flutter

Transition Between Atrial Fibrillation and Flutter. Introduction: The eletrophysiologic mechanism of atrial fibrillation (AF) has a wide spectrum, and it seems that some atrial regions are essential for the occurrence of a particular type of AF. We focused on one type of AF: AF associated with typical atrial flutter (AFI), which was right atrial (RA) arrhythmia, and sought to investigate intra‐atrial electrograms and activation sequences in the transition between AF and AFL.

Differences in clinical and angiographic outcomes with different drug-eluting stents in Japanese patients with and without diabetes mellitus

BACKGROUND Although percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with worse clinical outcomes, the efficacy of drug-eluting stents (DES) in Japanese patients and differences in effectiveness between different DES types remain unknown. METHODS AND SUBJECTS Five-hundred and sixty-two consecutive patients (183 with DM, 379 without DM) with 676 lesions were treated with sirolimus-eluting stents (SES, n=531; 160 DM group, 371 non-DM group) or paclitaxel-eluting stents (PES, n=145; 64 and 81, respectively). We assessed the initial and 8-month follow-up clinical and angiographic outcomes. RESULTS There were no significant differences in clinical and lesion characteristics, although the pre-minimum luminal diameter was smaller in the DM group (p=0.016). The risk of major adverse cardiac events (MACE), defined as cardiac death, non-fatal myocardial infarction, congestive heart failure, or recurrent angina pectoris, was higher in the DM group compared with the non-DM group (17.4% vs 9.5%, p=0.007). Among diabetic patients, although SES reduced late loss by 0.45 mm (p<0.001) and the binary restenosis rate by 66.4% (7.4% vs 22.0%, p<0.001) compared with PES at 8 months, it did not reduce target lesion revascularization or MACE, as in the non-DM group. CONCLUSIONS Diabetic patients have worse mid-term prognosis than non-diabetic patients undergoing PCI with DES. Although the superiority of SES in terms of late loss or restenosis may not play a clinically meaningful role in the treatment of diabetic patients, this phenomenon was independent of the presence of diabetes.

Clinical significance of platelet reactivity during prasugrel therapy in patients with acute myocardial infarction

BACKGROUND Although some studies have examined platelet reactivity (PR) during prasugrel treatment, little is known about PR during the early treatment period and its clinical significance in Japan. METHODS We investigated the early and medium-term efficacy and safety of prasugrel in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Seventy-eight patients were enrolled and PR was measured (in P2Y12 reaction units; PRU) by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). RESULTS In 44 patients, serial measurement revealed that PR was significantly higher at 2h after administration of the 20-mg loading dose of prasugrel than on the morning of the second day at 17.6±6.6h after administration (191.6±75.5 vs. 138.5±68.9PRU). During the 8-month follow-up period, bleeding events occurred in 18 patients (23.1%) (GUSTO minor: 15 patients). Multivariate regression analysis identified oral anticoagulant use as a significant predictor of bleeding events during admission [odds ratio (OR): 4.214, 95% confidence interval (CI): 1.005-17.669, p=0.049]. Administration of prasugrel via a nasogastric tube was a significant predictor of high on-treatment platelet reactivity (HTPR) (PRU≥230) (OR: 43.100, 95% CI: 4.517-411.251, p=0.001). In addition, HTPR was a significant predictor of major adverse cardiac events (cardiovascular death, non-fatal myocardial infarction, stent thrombosis, stroke, and sustained ventricular tachycardia) during the 8-month follow-up period (OR: 4.911, 95% CI: 1.164-20.722, p=0.030). CONCLUSIONS It is feasible to treat AMI patients with prasugrel. HTPR is a significant independent risk factor for adverse events in AMI patients receiving prasugrel after primary PCI.

Diagnostic Accuracy of Three Different Protocols for 3.0T Coronary Magnetic Resonance Angiography

The usefulness of coronary magnetic resonance angiography (cMRA) has been reported, although the difference in the diagnostic accuracy of different protocols has not been established.We compared conventional coronary angiography (CAG) and cMRA, conducted within 6 months in 24 consecutive patients between September 2012 and July 2014. Three cMRA protocols were examined, cMRA1, free-breathing wholeheart coronary angiography (WHCA) without contrast; cMRA2, free-breathing WHCA with contrast; and cMRA3, breath-hold steady-state free precession with contrast using a 3.0 T scanner. Image quality was graded on a 4-point scale: 1) nonassessable; 2) assessable, fair vessel contrast; 3) assessable, good vessel contrast; and 4) assessable, excellent vessel contrast. Significant narrowing of the coronary arteries was visually assessed.Stenosis was observed in 34 segments, with a prevalence of 10.3%. For cMRA1, cMRA2, and cMRA3, the numbers of assessable segments were 245 (74.2%), 287 (87.0%), and 164 (49.7%), respectively (P < 0.001 by the McNemar test). For assessable segments, the sensitivity, specificity, positive predictive value, and negative predictive value were 89.3%, 99.1%, 92.6%, and 98.6% for cMRA1, 90.0%, 98.1%, 84.4%, and 98.8% for cMRA2, and 76.5%, 93.9%, 59.1%, and 97.1% for cMRA3, respectively. For the assessable segments, the image quality score was better with cMRA2 than with the other two protocols.cMRA is a useful modality to rule out coronary artery disease, especially the cMRA2 protocol, which performed better than the other two protocols.

Myocardial clearance of I-123 metaiodobenzylguanidine in dilated cardiomyopathy

We present the results of sequential imaging studies conducted in two patients with dilated cardiomyopathy whose responses to long-term beta-blocker therapy differed. We evaluated the time course of the myocardial clearance and the heart to upper mediastinal ratios of I-123 metaiodobenzylguanidine (MIBG) scintigraphy. In the first patient, the left ventricular ejection fraction as well as the clinical symptoms were improved by long-term beta-blocker therapy with a concurrent normalization of the myocardial clearance and the heart to upper mediastinal ratio of I-123 MIBG scintigraphy. The myocardial clearance and the upper mediastinal ratio of I-123 MIBG indicated no improvement in the second patient, and the left ventricular function did not change. The myocardial clearance and the heart to upper mediastinal ratio of I-123 MIBG scintigraphy were useful in evaluating the efficacy of long-term beta-blocker therapy in patients with dilated cardiomyopathy.