Masaharu Ishihara

Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials.

BACKGROUND Patients who have acute myocardial infarction remain at major risk of cardiovascular events. We aimed to assess the effects of either human atrial natriuretic peptide or nicorandil on infarct size and cardiovascular outcome. METHODS We enrolled 1216 patients who had acute myocardial infarction and were undergoing reperfusion treatment in two prospective, single-blind trials at 65 hospitals in Japan. We randomly assigned 277 patients to receive intravenous atrial natriuretic peptide (0.025 microg/kg per min for 3 days) and 292 the same dose of placebo. 276 patients were assigned to receive intravenous nicorandil (0.067 mg/kg as a bolus, followed by 1.67 microg/kg per min as a 24-h continuous infusion), and 269 the same dose of placebo. Median follow-up was 2.7 (IQR 1.5-3.6) years for patients in the atrial natriuretic peptide trial and 2.5 (1.5-3.7) years for those in the nicorandil trial. Primary endpoints were infarct size (estimated from creatine kinase) and left ventricular ejection fraction (gauged by angiography of the left ventricle). FINDINGS 43 patients withdrew consent after randomisation, and 59 did not have acute myocardial infarction. We did not assess infarct size in 50 patients for whom we had fewer than six samples of blood. We did not have angiographs of left ventricles in 383 patients. Total creatine kinase was 66,459.9 IU/mL per h in patients given atrial natriuretic peptide, compared with 77,878.9 IU/mL per h in controls, with a ratio of 0.85 between these groups (95% CI 0.75-0.97, p=0.016), which indicated a reduction of 14.7% in infarct size (95% CI 3.0-24.9%). The left ventricular ejection fraction at 6-12 months increased in the atrial natriuretic peptide group (ratio 1.05, 95% CI 1.01-1.10, p=0.024). Total activity of creatine kinase did not differ between patients given nicorandil (70 520.5 IU/mL per h) and controls (70 852.7 IU/mL per h) (ratio 0.995, 95% CI 0.878-1.138, p=0.94). Intravenous nicorandil did not affect the size of the left ventricular ejection fraction, although oral administration of nicorandil during follow-up increased the left ventricular ejection fraction between the chronic and acute phases. 29 patients in the atrial natriuretic peptide group had severe hypotension, compared with one in the corresponding placebo group. INTERPRETATION Patients with acute myocardial infarction who were given atrial natriuretic peptide had lower infarct size, fewer reperfusion injuries, and better outcomes than controls. We believe that atrial natriuretic peptide could be a safe and effective adjunctive treatment in patients with acute myocardial infarction who receive percutaneous coronary intervention.

Implications of Prodromal Angina Pectoris in Anterior Wall Acute Myocardial Infarction: Acute Angiographic Findings and Long-Term Prognosis

OBJECTIVES This study was undertaken to assess how prodromal angina affects long-term prognosis after acute myocardial infarction. BACKGROUND Although it has been reported that prodromal angina occurring shortly before the onset of acute myocardial infarction has protective effects against ischemia, its implication for long-term prognosis remains unclear. METHODS We studied consecutive 350 patients with anterior myocardial infarction who underwent coronary angiography within 24 h after the onset of chest pain. Follow-up was achieved for 340 patients (97%). RESULTS Eighty-nine patients had one or more episodes of angina within 24 h before infarction. On initial angiography, patients with prodromal angina in the 24 h before infarction had a patent infarct-related artery more frequently than did those without prodromal angina (34% vs. 22%, p = 0.03). Among 213 patients who underwent thrombolytic therapy for an occluded infarct-related artery, reperfusion was more frequently achieved in patients with prodromal angina in the 24 h before infarction (76% vs. 56%, p = 0.01). Prodromal angina in the 24 h before infarction was associated with a lower in-hospital mortality rate (6% vs. 14%, p = 0.02) and better 5-year survival (p = 0.009). There was no significant difference in survival between patients with previous angina at any time (n = 202) and those without. Multivariate analysis showed that prodromal angina in the 24 h before infarction was an independent factor related to 5-year survival after acute myocardial infarction (odds ratio 0.49, p = 0.04). CONCLUSIONS Prodromal angina occurring shortly before the onset of infarction, but not previous angina itself, has a beneficial effect on long-term prognosis after infarction, suggesting a relation to ischemic preconditioning.

Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction.

OBJECTIVES This study was undertaken to assess whether prodromal angina could have beneficial effects in diabetic patients with acute myocardial infarction (AMI). BACKGROUND Prodromal angina occurring shortly before the onset of AMI is associated with favorable outcomes by the mechanism of ischemic preconditioning. However, little is known about the impact of diabetes on ischemic preconditioning. METHODS We studied 611 patients with a first anterior wall AMI who underwent emergency catheterization within 12 h after the onset of chest pain: 490 patients without diabetes and 121 patients with non-insulin treated diabetes. Prodromal angina was defined as angina episode(s) occurring within 24 h before the onset of AMI. Serial contrast left ventriculograms were obtained in 424 patients at the time of acute and predischarge catheterization. RESULTS In non-diabetic patients, prodromal angina was associated with lower peak creatine kinase (CK) value (3,068 +/- 2,647 IU/l vs. 3,601 +/- 2,462 IU/l, p = 0.037), larger increase in left ventricular ejection fraction (LVEF) (10.1 +/- 13.0% vs. 5.8 +/- 13.4%, p = 0.004) and lower in-hospital mortality (3.4% vs. 9.3%, p = 0.015). On the contrary, in diabetic patients, there was no significant difference in peak CK value (3,382 +/- 2,520 IU/l vs. 3,233 +/- 2,412 IU/l, p = NS), the change in LVEF (6.7 +/- 13.8% vs. 7.1 +/- 12.4%, p = NS) and in-hospital mortality (8.8% vs. 11.0%, p = NS) between patients with and patients without prodromal angina. CONCLUSIONS Prodromal angina limited infarct size, enhanced recovery of LV function and improved survival in non-diabetic patients with AMI. However, such beneficial effects of prodromal angina were not observed in diabetic patients, suggesting that diabetes might prevent ischemic preconditioning.

Assessment of outcomes and differences between in- and out-of-hospital cardiac arrest patients treated with cardiopulmonary resuscitation using extracorporeal life support☆

AIM Cardiopulmonary resuscitation (CPR) using extracorporeal life support (ECLS) for in-hospital cardiac arrest (IHCA) patients has been assigned a low-grade recommendation in current resuscitation guidelines. This study compared the outcomes of IHCA and out-of-hospital cardiac arrest (OHCA) patients treated with ECLS. METHODS A total of 77 patients were treated with ECLS. Baselines characteristics and outcomes were compared for 38 IHCA and 39 OCHA patients. RESULTS The time interval between collapse and starting ECLS was significantly shorter after IHCA than after OHCA (25 (21-43)min versus 59 (45-65)min, p<0.001). The weaning rate from ECLS (61% versus 36%, p=0.03) and 30-day survival (34% versus 13%, p=0.03) were higher for IHCA compared with OHCA patients. IHCA patients had a higher rate of favourable neurological outcome compared to OHCA patients, but the difference was not statistically significant (26% versus 10%, p=0.07). Kaplan-Meier analysis showed improved 30-day and 1-year survival for IHCA patients treated with ECLS compared to OHCA patients who had ECLS. However, multivariate stepwise Cox regression model analysis indicated no difference in 30-day (odds ratio 0.94 (95% confidence interval 0.68-1.27), p=0.67) and 1-year survival (0.99 (0.73-1.33), p=0.95). CONCLUSION CPR with ECLS led to more favourable patient outcomes after IHCA compared with OHCA in our patient group. The difference in outcomes for ECLS after IHCA and OHCA disappeared after adjusting for patient factors and the time delay in starting ECLS.

Should We Emergently Revascularize Occluded Coronaries for Cardiac Arrest? Rapid-Response Extracorporeal Membrane Oxygenation and Intra-Arrest Percutaneous Coronary Intervention

Background— Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation. Methods and Results— This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%; P =0.01), the intra-arrest PCI was higher (88% versus 70%; P =0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25–51] versus 54 minutes [34–74 minutes]; P =0.002). Conclusions— Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed. # Clinical Perspective {#article-title-28}Background— Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation. Methods and Results— This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%; P=0.01), the intra-arrest PCI was higher (88% versus 70%; P=0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25–51] versus 54 minutes [34–74 minutes]; P=0.002). Conclusions— Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed.

Impact of acute hyperglycemia on left ventricular function after reperfusion therapy in patients with a first anterior wall acute myocardial infarction

OBJECTIVE This study was undertaken to assess the relationship between acute hyperglycemia and left ventricular function after reperfusion therapy for acute myocardial infarction (AMI). METHODS This study consisted of 529 patients with a first anterior wall AMI who underwent coronary angiography followed by coronary angioplasty or thrombolysis within 12 hours after the onset of chest pain. Plasma glucose was measured at the time of hospital admission. Acute hyperglycemia was defined as plasma glucose >10 mmol/L. RESULTS Although acute hyperglycemia was associated with both lower acute left ventricular ejection fraction (LVEF) (46% +/- 12% vs 48% +/- 10%, P =.026) and lower predischarge LVEF (51% +/- 15% vs 56% +/- 15%, P =.001), the difference was more pronounced in the latter and the change in LVEF was significantly smaller in patients with acute hyperglycemia (4.8% +/- 11.2% vs 8.0% +/- 13.8%, P =.022). Multivariable analysis showed that there was a significant correlation between plasma glucose and impaired predischarge LVEF, even after adjustment of acute LVEF (r = -0.13, P =.005). Thirty-day mortality tended to be higher in patients with acute hyperglycemia than in patients without (7.1% vs 3.5%, P =.06). Multivariable analysis showed that plasma glucose (per 1 mmol/L increase) was an independent predictor of 30-day mortality after AMI (odds ratio 1.12, 95% CI 1.03-1.22, P =.009). CONCLUSION Acute hyperglycemia was independently associated with impaired left ventricular function and higher 30-day mortality after AMI. These results may provide a potential explanation for poor outcomes of patients with AMI and acute hyperglycemia.

High-intensity signals in coronary plaques on noncontrast T1-weighted magnetic resonance imaging as a novel determinant of coronary events.

OBJECTIVES The aim of this study was to determine whether coronary high-intensity plaques (HIPs) visualized by noncontrast T1-weighted imaging can predict future coronary events. BACKGROUND Coronary HIPs are associated with characteristics of vulnerable plaques, including positive remodeling, lower Hounsfield units, and ultrasound attenuation. However, it remains unclear whether the presence of HIPs is associated with increased risk for coronary events. METHODS The signal intensity of coronary plaques was prospectively examined in 568 patients with suspected or known coronary artery disease (CAD) who underwent noncontrast T1-weighted imaging to determine the plaque-to-myocardium signal intensity ratio (PMR). RESULTS During the follow-up period (median 55 months), coronary events were observed in 55 patients. Receiver-operating characteristic curve analysis identified a PMR of 1.4 as the optimal cutoff for predicting prognosis. Multivariate Cox regression analysis identified the presence of plaques with PMRs ≥1.4 as the significant independent predictor of coronary events (hazard ratio: 3.96; 95% confidence interval: 1.92 to 8.17; p < 0.001) compared with the presence of CAD (hazard ratio: 3.56; 95% confidence interval: 1.76 to 7.20; p < 0.001) and other traditional risk factors. Among the 4 groups based on PMR cutoff and the presence of CAD, coronary event-free survival was lowest in the group with PMRs ≥1.4 and CAD and highest in the group with PMRs <1.4 but no CAD. Importantly, the group with PMRs ≥1.4 and no CAD had an intermediate rate of coronary events, similar to the group with PMRs <1.4 and CAD. CONCLUSIONS HIPs identified in a noninvasive, quantitative manner are significantly associated with coronary events and may thus represent a novel predictive factor.

Beneficial effect of prodromal angina pectoris is lost in elderly patients with acute myocardial infarction

BACKGROUND Prodromal angina pectoris occurring shortly before the onset of acute myocardial infarction is associated with a favorable outcome by the mechanism of ischemic preconditioning. Recent experiments have reported that the beneficial effect of ischemic preconditioning are reversed in the aged heart. METHODS We studied 990 patients who underwent coronary angiography within 12 hours after the onset of acute myocardial infarction. Patients were divided into 2 groups: those aged <70 years (nonelderly patients, n = 722) and those aged >/=70 years (elderly patients, n = 268). Prodromal angina in the 24 hours before infarction was found in 190 of 722 nonelderly patients and in 66 of 268 elderly patients (26% vs 25%, P =.61). RESULTS In nonelderly patients, prodromal angina was associated with lower peak creatine kinase levels (2438 +/- 1939 IU/L vs 2837 +/- 2341 IU/L, P =.04), lower in-hospital mortality rates (3.7% vs 8.8%, P =.02), and better 5-year survival rates (P =. 007). On the contrary, in elderly patients there was no significant difference in peak creatine kinase levels (2427 +/- 2142 IU/L vs 2256 +/- 1551 IU/L, P =.51), in-hospital mortality rate (21.2% vs 17. 4%, P =.49), and 5-year survival rates (P =.47). A multivariate analysis showed that prodromal angina in the 24 hours before infarction was associated with 5-year survival rate in nonelderly patients (odds ratio 0.49, P =.009) but not in elderly patients (odds ratio l.12, P =.65). CONCLUSIONS In nonelderly patients, prodromal angina in the 24 hours before infarction was associated with a smaller infarct size and better short- and long-term survival, suggesting a relation to ischemic preconditioning. However, such a beneficial effect was not observed in elderly patients.

Attenuation of the no-reflow phenomenon after coronary angioplasty for acute myocardial infarction with intracoronary papaverine

The no-reflow phenomenon is observed as reduction of coronary blood flow on the angiograms (angiographic no-reflow) after immediate percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI). To assess whether a potent coronary microvascular dilator--papaverine--could attenuate the no-reflow phenomenon, nine patients with AMI who were found to have angiographic no-reflow after PTCA were studied. Angiographic no-reflow was defined as the Thrombolysis in Myocardial Infarction flow grade 1 or 2 without any mechanical obstructions in the epicardial artery. A bolus dose of 10 mg of intracoronary papaverine was administered, and the flow grade was again evaluated. Intracoronary papaverine caused a significant improvement of the flow grade (p= 0.0152). The number of cineframes that were required for the contrast medium to pass two selected landmarks on the angiograms also significantly decreased (41 +/- 17 frames to 18 +/- 8 frames, p= 0.0039). Thus intracoronary papaverine attenuated angiographic no-reflow that occurred after PTCA for AMI.

Intraaortic balloon pumping as the postangioplasty strategy in acute myocardial infarction

Abstract To assess the usefulness of intraaortic balloon pumping (IABP) in acute myocardial infarction (AMI), 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty (PTCA) for total occlusion of the left anterior descending artery were studied. After successful PTCA 66 patients were treated with conventional therapy (group I), and 48 patients were treated with IABP for 25 ± 8 hours (group II). The reocclusion rate was significantly lower in group II (2.4% vs 17.7% p p = 0.08). Vascular complications occurred in two patients, but there were no deaths from IABP. These results suggest that after successful PTCA for acute myocardial infarction, IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function.