Hideo Himeno

Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study

AIMnThis study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes.nnnMETHODSnWe enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event.nnnRESULTSnA total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]).nnnCONCLUSIONnrSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.

Platelet reactivity in the early and late phases of acute coronary syndromes according to cytochrome P450 2C19 phenotypes

BACKGROUNDnIt remains unknown whether the time course of the antiplatelet effects of clopidogrel differs according to cytochrome P450 (CYP) 2C19 phenotype in Japanese patients with acute coronary syndromes (ACS).nnnMETHODS AND RESULTSnPlatelet reactivity was serially assessed by VerifyNow-P2Y12 assay (Accumetrics, San Diego, CA, USA). Results were expressed as P2Y12-reaction-units (PRU) in 177 patients with ACS who underwent stent implantation and received aspirin plus a 300-mg loading dose of clopidogrel followed by 75 mg/day. High on-clopidogrel treatment platelet reactivity (HTPR) was defined as PRU>235. On the basis of the CYP2C19*2 and *3 alleles, 46 patients (26.0%) were classified as extensive metabolizers (EM), 103 (58.2%) as intermediate metabolizers (IM), and 28 (15.8%) as poor metabolizers (PM). At <7 days, the PRU level (232±102 vs. 279±70, 308±67, p<0.001) and the incidence of HTPR (49% vs. 74%, 86%, p=0.001) was lower in EM than in IM and PM. At 14-28 days the effects of CYP2C19 polymorphisms on PRU levels increased in a stepwise fashion (168±99 vs. 213±77 vs. 278±69, p<0.001), and EM and IM had lower percentages of HTPR than PM (28%, 37% vs. 73%, p<0.001). There was no significant difference in the cumulative frequency of 12-month adverse cardiovascular events among 3 phenotypes (16.5%, 14.1%, 9.2%; p=0.67).nnnCONCLUSIONnAbout three quarters of Japanese patients with ACS carried CYP2C19 variant alleles. The majority of IM and PM had increased platelet reactivity during the early phase of ACS. Although HTPR was frequently observed even 14-28 days after standard maintenance doses of clopidogrel in PM, the incidence of adverse outcomes did not differ, irrespective of CYP2C19 genotype.

Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease

OBJECTIVEnTo assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin.nnnMETHODSnCoronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks.nnnRESULTSnGreater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks.nnnCONCLUSIONnAlthough the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.

Constrictive Pericarditis Caused by Immunoglobulin G4–Related Disease

An 81-year-old man with congestive heart failure was admitted to our hospital. Computed tomography of the chest revealed pericardial thickening without calcification. Ultrasonic echocardiography and cardiac magnetic resonance imaging demonstrated diastolic dysfunction. Cardiac catheterization showed bilateral elevation of ventricular end-diastolic pressure with a square root sign. The preoperative serum immunoglobulin G4 (IgG4) level was abnormally high. Pericardiectomy and pericardiotomy were considered to be indicated and were performed. Histopathologic examination revealed tissue infiltration by IgG4-positive plasma cells, and constrictive pericarditis caused by IgG4-related disease was diagnosed. Postoperatively, the patient received additional corticosteroid therapy. The latest cardiac magnetic resonance image showed further improvement in diastolic function.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction

PurposeWe evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT).MethodsThis prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6xa0mg/day, nxa0=xa0424) or no drugs (nxa0=xa0435) for 2xa0years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure.ResultsThe age, ratio of males, and HbA1C were 65 vs. 65xa0years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan–Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82–1.86)]; there were no significant differences in secondary endpoints.ConclusionAlthough voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT.Trial RegistrationClinicaltrials.gov number: NCT00212017

Impact of n-3 polyunsaturated fatty acids in predicting ischemia/reperfusion injury and progression of myocardial damage after reperfusion in patients with ST-segment elevation acute myocardial infarction

BACKGROUNDnIn animal models of acute myocardial infarction, n-3 polyunsaturated fatty acids (PUFAs) administered before coronary occlusion have been suggested to prevent induction of ventricular arrhythmia and limit infarct size. However, the relation between the serum levels of n-3 PUFAs and ischemia/reperfusion (I/R) injury remains unclear.nnnMETHODSn211 patients with ST-segment elevation acute myocardial infarction received emergency percutaneous coronary intervention (PCI) within 6h from the onset. The patients were divided into two groups according to the sum of serum eicosapentaenoic acid (EPA) levels and docosahexaenoic acid (DHA) levels before PCI: group L (n=106), EPA+DHA <155μg/ml and group H (n=105), EPA+DHA ≥155μg/ml. The Selvester QRS-scoring system was used to estimate the serial change in infarct size.nnnRESULTSnTime to reperfusion was similar between the 2 groups. The QRS score before PCI was higher in group L than in group H (2.42±2.00 vs 1.85±2.01, p=0.015). The proportion of patients with I/R injury immediately after reperfusion, defined as reperfusion ventricular arrhythmias (25% vs 11%, p=0.006) and ST-segment re-elevation (44% vs 22%, p<0.001), was also higher in group L than in group H, followed by a greater increment in the QRS score during PCI (3.51±2.51 vs 2.54±1.91, p=0.006) and higher peak levels of creatinine phosphokinase (3552±241U/L vs 2660±242U/L, p<0.01). On multivariate analysis, serum level of EPA+DHA was an independent predictor of reperfusion injury (odds ratio 0.985, p=0.032).nnnCONCLUSIONnSerum level of n-3 PUFAs before PCI may be a predictor of I/R injury and the resultant extent of myocardial damage. These findings suggest a protective effect of serum n-3 PUFAs on ischemic myocardium.

B-type natriuretic peptide as a predictor of ischemia/reperfusion injury immediately after myocardial reperfusion in patients with ST-segment elevation acute myocardial infarction

Background: In animal models of acute myocardial infarction (AMI), B-type natriuretic peptide (BNP) administered before and during coronary occlusion limits infarct size. However, the relation between plasma BNP levels and ischemia/reperfusion injury remains unclear. Methods: 302 patients with ST-segment elevation AMI (STEMI) received emergency percutaneous coronary intervention within six hours from the onset. The patients were divided into two groups according to the plasma BNP level before angiography: group L (n=151), BNP ≤32.2 pg/ml; group H (n=151), BNP >32.2 pg/ml. The Selvester QRS-scoring system was used to estimate infarct size. Results: The rate of ischemia/reperfusion injury immediately after reperfusion, defined as reperfusion ventricular arrhythmias (26% vs. 11%, p=0.001) and ST-segment re-elevation (44% vs. 22%, p=0.008), was higher in group L than in group H. Group L had a greater increase in the QRS score during percutaneous coronary intervention (3.55±0.17 vs. 2.09±0.17, p<0.001) and a higher QRS score 1 h after percutaneous coronary intervention (5.77±0.28 vs. 4.51±0.28, p=0.002). On multivariate analysis, plasma BNP levels in the lower 50th percentile were an independent predictor of reperfusion injury (odds ratio, 2.620; p<0.001). The odds ratios of reperfusion injury according to decreasing quartiles of BNP level, as compared with the highest quartile, were 1.536, 3.692 and 4.964, respectively (p trend=0.002). Conclusions: Plasma BNP level before percutaneous coronary intervention may be a predictor of ischemia/reperfusion injury and the resultant extent of myocardial damage. Our findings suggest that high plasma BNP levels might have a clinically important protective effect on ischemic myocardium in patients with STEMI who receive percutaneous coronary intervention.

Longitudinal stent deformation elongating to left main trunk

A 67-year-old woman was admitted with an acute coronary syndrome. Angiographic examination revealed diffuse severe stenosis of the left circumflex artery. A Pressure Wire Certus (St. Jude Medical, St. Paul, MN, USA) was passed to the second post-lateral (PL) branch. To prevent side-branch occlusion, a SION wire (Asahi Intecc Co., Aichi, Japan) was left in the first PL branch, and a SION blue wire (Asahi Intecc) was placed in the second obtuse marginal branch. We implanted an everolimus-eluting stent (PROMUS Element 2.5xa0×xa024xa0mm, Boston Scientific, Natick, MA, USA) in the culprit lesion. After retrieving the protection wire in first PL branch with resistance, we performed post-dilatation. However, the intravascular ultrasound images showed that the proximal portion of the implanted stent had elongated approximately 2xa0mm to the left main trunk (LMT), although the position of the distal edge of the stent was unchanged. We decided to additionally place a stent from the ostium of the LMT to the proximal left anterior descending coronary artery, and a biolimus-eluting stent (NOBORI 3.0xa0×xa018xa0mm, Terumo Co., Tokyo, Japan) was implanted successfully. Longitudinal stent elongation might be caused by the small number of links between the hoops of a stent, originally intended to improve deliverability.

Coronary plaque characteristics in computed tomography and 2-year outcomes: The PREDICT study

BACKGROUNDnCoronary computed tomography angiography (CCTA) not only provides information regarding luminal stenoses but also allows for visualization of mural atheromatous changes (coronary plaques).nnnOBJECTIVEnWe sought to elucidate whether plaques seen on CCTA enable prediction of 2-year outcomes in patients with suspected and known coronary artery disease (CAD).nnnMETHODSnOf 3015 patients who underwent CCTA, the images and 2-year clinical courses of 2802 patients were independently analyzed. The primary endpoint was the composite of all-cause death and acute coronary syndrome.nnnRESULTSnDuring the 2-year observation period, 49 (1.7%) patients developed the primary outcome. The 2-year rates of the primary outcome in the normal (nu202f=u202f515, no mural lesions), calcium (nu202f=u202f654, calcified lesion alone), and plaque groups (nu202f=u202f1633, presence of noncalcified or partially calcified plaques) were 0.2%, 2.0%, and 2.1%, respectively (Pu202f=u202f0.0028). Adverse plaque features such as low attenuation, positive remodeling, spotty calcification, and the napkin-ring sign (low-attenuation core with a higher-attenuation rim) were assessed by an independent core laboratory. Stepwise multivariate Cox proportional hazard analysis showed that a plaque with two or more characteristics (adjusted hazard ratio, 1.98; 95% confidence interval, 1.09-3.60; Pu202f=u202f0.0254), age of ≥67 years (mean), statin treatment after CCTA, and obstructive stenosis remained independent predictors of the primary outcome.nnnCONCLUSIONSnPlaque imaging in CCTA has predictive value for the 2-year outcome and is a useful identifier for high-risk patients among those with known and suspected CAD.

Takotsubo Cardiomyopathy in a Patient with Previously Undiagnosed Hypertrophic Cardiomyopathy with Latent Obstruction

A 62-year-old woman with takotsubo cardiomyopathy (TCM) accompanied by cardiogenic shock due to the obstruction of left ventricular outflow tract (LVOT) and massive mitral regurgitation (MR) was admitted to the emergency department. After successful treatment with intensive care, dobutamine stress-echocardiography was performed, which reproduced a dynamic LVOT gradient, severe MR and cardiogenic shock. A histological examination obtained from the right ventricular septum demonstrated hypertrophied and bizarre myocytes, with myocyte disarray. Besides TCM, a diagnosis of preexisting hypertrophic cardiomyopathy with latent obstruction was made. She was discharged with medical therapy including a beta-blocker, which would not be routinely employed in the treatment of a patient with TCM.