Masashi Fujino

Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism.

Background— Coronary artery embolism (CE) is recognized as an important nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical features, and prognosis remain insufficiently characterized. Methods and Results— We screened 1776 consecutive patients who presented with de novo acute myocardial infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing histological, angiographic, and other diagnostic imaging findings. The prevalence, clinical characteristics, treatment strategies, in-hospital outcomes, and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and the median international normalized ratio was 1.42 (range, 0.95–1.80). Eighteen of the 30 CE patients with nonvalvular atrial fibrillation had a CHADS2 score of 0 or 1. When those patients were reevaluated using CHA2DS2-VASc, 61% were reassigned to a higher risk category. During a median follow-up of 49 months, CE and thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of major adverse cardiac and cerebrovascular events was 27.1%. In the propensity score–matched cohorts (n=45 each), Kaplan–Meier analysis showed a significantly higher incidence of cardiac death in the CE group than in the non-CE group (hazard ratio, 9.29; 95% confidence interval, 1.13–76.5; P<0.001). Conclusions— Atrial fibrillation is the most frequent cause of CE. Patients with CE represent a high-risk subgroup of patients with acute myocardial infarction and require close follow-up.

Clinical Presentation, Management and Outcome of Japanese Patients With Acute Myocardial Infarction in the Troponin Era – Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) –

BACKGROUND New criteria for diagnosis of acute myocardial infarction (AMI) were proposed in 2000 as a universal definition, in which cardiac troponin (cTn) was the preferred biomarker. A large number of patients formerly classified by creatine kinase (CK) as unstable angina are now ruled-in by cTn as non-ST-elevation myocardial infarction (NSTEMI). METHODS AND RESULTS The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective and multicenter registry conducted in 28 institutions. We enrolled 3,283 consecutive patients with AMI diagnosed by cTn-based criteria who were admitted to participating institutions within 48 h of symptom onset. There were 2,262 patients (68.9%) with STEMI and 1,021 (31.1%) with NSTEMI. CK was not elevated more than twice the upper limit of normal in 458 patients (44.9%) with NSTEMI (NSTEMI-CK). Although there was no significant difference in the in-hospital mortality of STEMI and NSTEMI with CK elevation (NSTEMI+CK) patients (7.1% vs. 7.8%, P=0.57), it was significantly lower in patients with NSTEMI-CK than in those with STEMI or NSTEMI+CK (1.7%, P<0.001 for each). CONCLUSIONS J-MINUET revealed the clinical presentation, management and outcomes of Japanese patients with AMI in the current cTn era. We should be aware of the difference between AMI diagnosed by CK-based criteria and AMI diagnosed by cTn-based criteria when using universal definitions for the diagnosis of AMI.

The extent of heart rate reduction during hospitalization using beta-blockers, not the achieved heart rate itself at discharge, predicts the clinical outcome in patients with acute heart failure syndromes

AIM It has been uncertain whether patients with acute heart failure syndromes (AHFSs) benefit from a lower heart rate (HR) itself or from treatment for heart failure (HF) that reduces sympathetic tone with consequent HR reduction (HRR). The present study investigated the influence of HRR during hospitalization on the prognosis of AHFS patients. METHODS AND RESULTS In 421 AHFS patients, we analyzed the relationship between HRR during hospitalization and the prognosis after discharge. During a mean follow-up period of 1.9 years, 76 and 55 patients died or were re-hospitalized for HF, respectively. Although HR at discharge did not influence cardiac events (hazard ratio [HR]: 1.00 [95% CI; 0.99-1.02], p=0.22), the extent of HRR was a predictor of cardiac events (HR: 0.89 [0.84-0.96], p<0.001). Kaplan-Meier analysis revealed that the cardiac event rate of the HRR-positive group (≥ 27 bpm reduction of HR from 114 ± 24 at admission to 65 ± 11 bpm at discharge) was significantly lower than that of the HRR-negative group (≤ 26 bpm (=median value) reduction of HR from 74 ± 14 to 71 ± 14 bpm). In the HRR-positive group, the cardiac event rate was significantly lower in patients receiving beta-blockers. Furthermore, the extent of HR change was an important predictor of cardiac events among other markers, compared with the change in systolic blood pressure or B-type natriuretic peptide. CONCLUSION The HR itself at discharge was not associated with the prognosis, but the extent of HRR achieved by treatment of HF with beta-blockers was a strong predictor for the clinical outcome in AHFS patients.

Impact of symptom presentation on in-hospital outcomes in patients with acute myocardial infarction

BACKGROUND Limited data exist regarding the association between symptom presentation of acute myocardial infarction (AMI) and in-hospital outcomes. METHODS We analyzed data of the Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET). This was a prospective and multicenter registry consisting of 3085 AMI patients with available data of symptoms, who were hospitalized within 48h from onset during July 2012 to March 2014. We defined typical symptoms as any of chest pain or pressure due to myocardial ischemia. RESULTS Of this study population, 642 patients (20.8%) had atypical symptoms (atypical group) and the remaining 2443 patients (79.2%) showed typical symptoms (typical group). Compared to the typical group, the atypical group was associated with higher age, more females, hypertension, diabetes, chronic kidney disease, history of cardiovascular disease, non-ST elevation MI, and Killip class ≥2. In the atypical group, urgent percutaneous coronary intervention was less frequently performed than in the typical group, and in STEMI patients door-to-balloon time was longer in the atypical than typical group. Atypical group had larger infarct size than typical group. Furthermore, in-hospital mortality was significantly higher in atypical than in typical group (19.5% vs. 3.3%, p<0.001). In multivariable analysis, presence of atypical symptoms was an independent predictor of in-hospital mortality (odds ratio 3.12, 95% confidence interval 2.19 to 4.47, p<0.001). Moreover, the association between atypical symptoms and mortality was consistent across each subgroup. CONCLUSIONS Atypical symptoms of AMI were associated with less invasive therapy and poor outcome. Attention should be directed to these high-risk patients.

Risk stratification based on nutritional screening on admission: Three-year clinical outcomes in hospitalized patients with acute heart failure syndrome

BACKGROUND Several blood tests are commonly used to assess nutritional status, including serum albumin levels (SAL) and lymphocyte counts (LC). The aim of this study is to investigate whether nutritional screening on admission can be used to determine risk levels for adverse clinical events in acute heart failure syndrome (AHFS) patients. METHODS In 432 consecutive AHFS patients, we measured SAL and LC and prospectively followed the patients for their combined clinical events (all-cause death and re-hospitalization for heart failure) for three years from admission. The classification and regression tree (CART) tool identified the cut-off criteria for SAL and LC to differentiate among patients with different risks of clinical events as 3.5g/dl and 963/mm3, respectively. RESULTS The CART tool classified 15.5% patients as high risk, 15.7% as intermediate risk, and 68.8% as low risk. The CART for nutritional status (CART-NS) values were strongly correlated with combined clinical events [hazard ratio of 2.13 (low vs high risk), 95% confidence interval of 1.42-3.16, p<0.001], even after adjusting for plasma brain natriuretic peptide levels. The CART-NS analysis improved the specificity (89.5%) of predictions of clinical outcomes with the comparable sensitivity (36.3%) compared with the use of a single criterion (SAL <3.5g/dl: 70.2, 42.4% or LC <963/mm3: 73.4, 41.7%, respectively). CONCLUSION A substantial proportion of AHFS patients are at risk of malnutrition, and this risk is associated with poor clinical outcomes. We demonstrate that this algorithm for nutritional screening, even in emergency clinical settings, can determine risk levels for further adverse events in AHFS patients.

Anticoagulation combined with antiplatelet therapy in patients with left ventricular thrombus after first acute myocardial infarction

Aims There are limited data about the optimal anti-thrombotic therapy for preventing embolism while minimizing bleeding events in patients with first acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). Methods and results Among 2301 consecutive patients with AMI hospitalized between 2001 and 2014, we studied 1850 patients with first AMI who discharged alive to investigate clinical characteristics, incidence of systemic embolism (SE), and association between anticoagulation and embolic or bleeding events. Left ventricular thrombus was diagnosed by echocardiography, left ventriculography, or cardiac magnetic resonance imaging in 92 (5.0%) patients (62 ± 12 years). During a median follow-up period of 5.4 years (interquartile range 2.1-9.1 years), SE occurred in 15 of 92 patients with LVT (16.3%) and 51 of 1758 patients without LVT (2.9%), respectively. Kaplan-Meier analysis showed a significantly higher incidence of SE in the LVT group (log-rank test, P < 0.001). Multivariate analysis showed that LVT was an independent predictor of SE. Among the LVT patients treated with vitamin K antagonists (n = 84), we compared the patients with therapeutic range (TTR) ≥50% (n = 34) and those with TTR <50% (n = 50). Only one embolic event developed in the TTR ≥50% group and nine embolic events developed in the TTR <50% group (2.9% vs. 19%, P = 0.036). There was no difference in major bleeding events (TTR ≥50%; 9% vs. TTR <50%; 8%, P = 0.89). Conclusion Appropriate anticoagulation therapy may decrease the incidence of embolic events without increasing the incidence of bleeding events in patients with first AMI complicated by LV thrombus.

Early development of acute kidney injury is an independent predictor of in-hospital mortality in patients with acute myocardial infarction

BACKGROUND Acute kidney injury (AKI) often occurs in patients with acute myocardial infarction (AMI), and is associated with adverse outcomes. However, it remains unclear how timing of AKI affects it. This study assessed impact of timing of AKI on prognosis after AMI. METHODS This study consisted of 760 patients with AMI who were admitted within 48h after symptom onset. AKI was diagnosed as increase in creatinine ≥0.3mg/dl or ≥50% within any 48h after admission. Patients were classified into 3 groups according to the occurrence and timing of AKI: no-AKI, early-AKI (within 48h after admission) and late-AKI (>48h). Early-AKI was classified into transient early-AKI, defined as creatinine returning to the level below the criteria of AKI, and persistent early-AKI. RESULTS Early-AKI occurred in 64 patients (9%) and late-AKI in 32 patients (4%). Patients with early-AKI had significantly higher mortality (35%) than those with late-AKI (7%, p<0.001) and no-AKI (3%, p<0.001). Multivariate analysis showed early-AKI was an independent predictor of in-hospital mortality (OR: 3.38, 95% CI: 1.30-8.76, p=0.013), but late-AKI was not. Among patients with early-AKI, mortality was significantly higher even if AKI was transient (23%, p<0.001). Patients with persistent early-AKI had the highest mortality (66%, p<0.001). CONCLUSIONS Early-AKI was associated with worse outcome. Even if renal function once returned to baseline level, patients with early-AKI tended to be at high risk of mortality.

Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute Myocardial InfarctionHighlights

Objective— Coronary artery ectasia (CAE) is an infrequently observed vascular phenotype characterized by abnormal vessel dilatation and disturbed coronary flow, which potentially promote thrombogenicity and inflammatory reactions. However, whether or not CAE influences cardiovascular outcomes remains unknown. Approach and Results— We investigated major adverse cardiac events (MACE; defined as cardiac death and nonfatal myocardial infarction [MI]) in 1698 patients with acute MI. The occurrence of MACE was compared in patients with and without CAE. CAE was identified in 3.0% of study subjects. During the 49-month observation period, CAE was associated with 3.25-, 2.71-, and 4.92-fold greater likelihoods of experiencing MACE (95% confidence interval [CI], 1.88–5.66; P<0.001), cardiac death (95% CI, 1.37–5.37; P=0.004), and nonfatal MI (95% CI, 2.20–11.0; P<0.001), respectively. These cardiac risks of CAE were consistently observed in a multivariate Cox proportional hazards model (MACE: hazard ratio, 4.94; 95% CI, 2.36–10.4; P<0.001) and in a propensity score–matched cohort (MACE: hazard ratio, 8.98; 95% CI, 1.14–71.0; P=0.03). Despite having a higher risk of CAE-related cardiac events, patients with CAE receiving anticoagulation therapy who achieved an optimal percent time in target therapeutic range, defined as ≥60%, did not experience the occurrence of MACE (P=0.03 versus patients with percent time in target therapeutic range <60% or without anticoagulation therapy). Conclusions— The presence of CAE predicted future cardiac events in patients with acute MI. Our findings suggest that acute MI patients with CAE are a high-risk subset who might benefit from a pharmacological approach to controlling the coagulation cascade.

Prognostic impact of chronic total coronary occlusion on long-term outcomes in implantable cardioverter-defibrillator recipients with ischaemic heart disease

Aims The prognostic impact of chronic total coronary occlusion (CTO) on implantable cardioverter-defibrillator (ICD) recipients remains unclear. Methods and results Eighty-four consecutive patients with ischaemic heart disease who received ICD therapy for primary or secondary prevention were analysed. We investigated all-cause mortality and major adverse cardiac events (MACEs) including cardiac death, appropriate device therapy, hospitalization for heart failure, and ventricular assist device implantation. Of the study patients (mean age 70 ± 8 years; 86% men), 34 (40%) had CTO. There were no significant differences in age, left ventricular ejection fraction (LVEF), New York Heart Association functional class III or IV status, and proportion who underwent secondary prevention between patients with CTO (CTO group) and without CTO (non-CTO group). During a median follow-up of 3.8 years (interquartile range 2.7-5.4 years), the CTO group tended to have a higher MACE rate (log-rank P = 0.054) than the non-CTO group. Within the CTO group, there was no difference in the MACE rate between patients with and without viable myocardium. In patients with ICD for secondary prevention (n = 47), 16 patients (34%) with CTO had a higher MACE rate than patients without CTO (log-rank P < 0.01). Cox proportional hazards regression analysis showed that the presence of CTO, but not LVEF, was associated with a higher MACE rate. Multivariate analysis showed that the presence of CTO was a predictor of MACE (P < 0.05). Conclusion In patients with ischaemic heart disease receiving ICD implantation, the presence of CTO has an adverse impact on long-term prognosis, especially as secondary prevention.

Long-Term Outcomes of Non-ST-Elevation Myocardial Infarction Without Creatine Kinase Elevation ― The J-MINUET Study ―

BACKGROUND According to troponin-based criteria of myocardial infarction (MI), patients without elevation of creatine kinase (CK), formerly classified as unstable angina (UA), are now diagnosed as non-ST-elevation MI (NSTEMI), but little is known about their outcomes.Methods and Results:Between July 2012 and March 2014, 3,283 consecutive patients with MI were enrolled. Clinical follow-up data were obtained up to 3 years. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure and urgent revascularization for UA. There were 2,262 patients with ST-elevation MI (STEMI), 563 NSTEMI with CK elevation (NSTEMI+CK) and 458 NSTEMI without CK elevation (NSTEMI-CK). From day 0, Kaplan-Meier curves for the primary endpoint began to diverge in favor of NSTEMI-CK for up to 30 days. The 30-day event rate was significantly lower in patients with NSTEMI-CK (3.3%) than in STEMI (8.6%, P<0.001) and NSTEMI+CK (9.9%, P<0.001). Later, the event curves diverged in favor of STEMI. The event rate from 31 days to 3 years was significantly lower in patients with STEMI (19.8%) than in NSTEMI+CK (33.6%, P<0.001) and NSTEMI-CK (34.2%, P<0.001). Kaplan-Meier curves from 31 days to 3 years were almost identical between NSTEMI+CK and NSTEMI-CK (P=0.91). CONCLUSIONS Despite smaller infarct size and better short-term outcomes, long-term outcomes of NSTEMI-CK after convalescence were as poor as those for NSTEMI+CK and worse than for STEMI.