Soichiro Fuke

Atrial Fibrillation in Patients With Brugada Syndrome : Relationships of Gene Mutation, Electrophysiology, and Clinical Backgrounds

OBJECTIVES The goal of our work was to examine the relationships of atrial fibrillation (AF) with genetic, clinical, and electrophysiological backgrounds in Brugada syndrome (BrS). BACKGROUND Atrial fibrillation is often observed in patients with BrS and indicates that electrical abnormality might exist in the atrium as well as in the ventricle. SCN5A, a gene encoding the cardiac sodium channel, has been reported to be causally related to BrS. However, little is known about the relationships of atrial arrhythmias with genetic, clinical, and electrophysiological backgrounds of BrS. METHODS Seventy-three BrS patients (49 +/- 12 years of age, men/women = 72/1) were studied. The existence of SCN5A mutation and clinical variables (syncopal episode, documented ventricular fibrillation [VF], and family history of sudden death) were compared with spontaneous AF episodes. Genetic and clinical variables were also compared with electrophysiologic (EP) parameters: atrial refractory period, interatrial conduction time (CT), repetitive atrial firing, and AF induction by atrial extra-stimulus testing. RESULTS Spontaneous AF occurred in 10 (13.7%) of the BrS patients and SCN5A mutation was detected in 15 patients. Spontaneous AF was associated with higher incidence of syncopal episodes (60.0% vs. 22.2%, p < 0.03) and documented VF (40.0% vs. 14.3%, p < 0.05). SCN5A mutation was associated with prolonged CT (p < 0.03) and AF induction (p < 0.05) in EP study, but not related to the spontaneous AF episode and other clinical variables. In patients with documented VF, higher incidence of spontaneous AF (30.8% vs. 10.0%, p < 0.05), AF induction (53.8% vs. 20.0%, p < 0.03), and prolonged CT was observed. CONCLUSIONS Spontaneous AF and VF are closely linked clinically and electrophysiologically in BrS patients. Patients with spontaneous AF have more severe clinical backgrounds in BrS. SCN5A mutation is associated with electrical abnormality but not disease severity.

Pro-apoptotic effects of imatinib on PDGF-stimulated pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension☆

BACKGROUND Remodeling of the pulmonary artery by an inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) is problematic in the treatment of idiopathic pulmonary arterial hypertension (IPAH). Effective treatment that achieves reverse remodeling is required. The aim of this study was to assess the pro-apoptotic effects of imatinib, a platelet-derived growth factor (PDGF)-receptor tyrosine kinase inhibitor, on PASMCs obtained from patients with IPAH. METHODS PASMCs were obtained from 8 patients with IPAH undergoing lung transplantation. Cellular proliferation was assessed by (3)H-thymidine incorporation. Pro-apoptotic effects of imatinib were examined using TUNEL and caspase-3,7 assays and using transmission electron microscopy. RESULTS Treatment with imatinib (0.1 to 10 μg/mL) significantly inhibited PDGF-BB (10 ng/mL)-induced proliferation of PASMCs from IPAH patients. Imatinib (1 μg/mL) did not induce apoptosis in quiescent IPAH-PASMCs, but it had a pro-apoptotic effect on IPAH-PASMCs stimulated with PDGF-BB. Imatinib did not induce apoptosis in normal control PASMCs with or without PDGF-BB stimulation. PDGF-BB induced phosphorylation of Akt at 15 min, and Akt phosphorylation was inhibited by imatinib in IPAH-PASMCs. Akt-I-1/2 (1 μmol/L), an Akt inhibitor, in the presence of PDGF-BB significantly increased apoptotic cells compared with the control condition. Thus, Akt-I-1/2 could mimic the effects of imatinib on PASMCs. CONCLUSION Imatinib has anti-proliferative and pro-apoptotic effects on IPAH-PASMCs stimulated with PDGF. The inhibitory effect of imatinib on Akt phosphorylation induced by PDGF plays an important role in the pro-apoptotic effect.

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 …

Clinical features of and effects of angiotensin system antagonists on amiodarone-induced pulmonary toxicity

BACKGROUND Amiodarone (AMD) is a strong antiarrhythmic drug but has severe side effects such as pulmonary toxicity. There are no indicators or drugs that can prevent the development of amiodarone-induced pulmonary toxicity (AIPT). METHODS We collected data for 96 consecutive patients treated with AMD and analyzed clinical factors related to AIPT. In addition, we examined the effect of AMD and angiotensin II (Ang II) on human lung alveolar epithelial cells (AEC) and verified the protective efficacy of an Ang II type 1 receptor blocker (ARB) in vitro. RESULTS During a follow-up period of 33.8+/-34.6 months, AIPT developed in 11 patients (11.5%). There were no differences in the dose of AMD, left ventricular ejection fraction, serum KL-6 and %DLCO level before starting AMD between patients with and those without AIPT. However, repeated episodes of congestive heart failure (CHF) were observed more frequently in patients with AIPT than in patients without AIPT (81.8% vs. 41.2%, P<0.011). In vitro examination, AMD progressively increased apoptosis of AEC and Ang II enhanced this effect of AMD (P<0.001). However, ARB inhibited the enhancement by Ang II of the AMD-induced apoptosis effect (P<0.001). Furthermore, patients with AIPT were administrated a lower dose of angiotensin system antagonists than were those without AIPT (P<0.05). CONCLUSIONS The results indicate that Ang II induced by CHF increases the risk of AMD-induced pulmonary toxicity. An angiotensin-converting enzyme inhibitor or ARB should be given at a sufficient dose during AMD treatment.

Right but not left ventricular function recovers early after living-donor lobar lung transplantation in patients with pulmonary arterial hypertension

OBJECTIVE The aim of this study was to evaluate right and left ventricular functions in patients with pulmonary arterial hypertension after living-donor lobar lung transplantation compared with those without hypertension. METHODS Thirty-three recipients of living-donor lobar lung transplantation were divided into two groups: those with pulmonary arterial hypertension (PAH group; n = 12) and those without (non-PAH group; n = 21). Their systolic pulmonary artery pressure was 93.1 +/- 6.7 mm Hg versus 31.4 +/- 2.9 mm Hg, respectively. Right and left ventricular ejection fractions, systolic pulmonary artery pressure, and cardiac index were serially measured by radionuclide ventriculography and right heart catheterization, respectively. RESULTS Pretransplant right and left ventricular ejection fractions were lower in the PAH group (29.8% +/- 7.0%, 49.9% +/- 6.6%) than in the non-PAH group (49.7% +/- 3.3%, 65.2% +/- 1.9%) (P = .010, .068). Two months after living-donor lobar lung transplantation, right ventricular ejection fraction and systolic pulmonary artery pressure in the PAH group (57.3% +/- 5.1%, 25.7 +/- 1.8 mm Hg) improved dramatically, equal to those in the non-PAH group. In contrast, left ventricular ejection fraction and cardiac index in the PAH group (50.9% +/- 3.7%, 2.66 +/- 0.12 L x min(-1) x m(-2)) were still significantly lower than in the non-PAH group (65.4% +/- 2.8%, 3.13 +/- 0.15 L x min(-1) x m(-2)) (P = .0038, .037). At 6 to 12 months, the PAH group demonstrated a significant rise in left ventricular ejection fraction and cardiac index that reached similar values in the non-PAH group measured at 2 months. These values were stable for up to 3 years. CONCLUSIONS Right ventricular function recovered early after living-donor lobar lung transplantation in the PAH group. In contrast, recovery of left ventricular function required 6 to 12 months. Improved cardiac function was sustained for up to 3 years, suggesting long-term durability of cardiac function recovery after living-donor lobar lung transplantation.

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.

COMPARISON OF THE EFFECTS OF NITROPRUSSIDE VERSUS NICORANDIL ON THE SLOW/NO-REFLOW PHENOMENON DURING CORONARY INTERVENTIONS FOR ACUTE MYOCARDIAL INFARCTION

Although slow/no-reflow is a serious problem complicating primary percutaneous coronary interventions (PCI) for acute myocardial infarction (AMI) and is associated with a poor prognosis, its efficacious treatment remains problematic. We compared the acute, in-hospital and long-term (1 year) effects