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Tomohiko Taniguchi, MD, Hiroki Shiomi, MD, Takeshi Morimoto, MD, MPH, Hirotoshi
Watanabe, MD, Koh Ono, MD, Satoshi Shizuta, MD, Takao Kato, MD, Naritatsu
Saito, MD, Shuichiro Kaji, MD, Kenji Ando, MD, Kazushige Kadota, MD, Yutaka
Furukawa, MD, Yoshihisa Nakagawa, MD, Minoru Horie, MD, Takeshi Kimura, MD
PII: S0002-9149(17)30298-9
DOI: 10.1016/j.amjcard.2017.03.013
Reference: AJC 22474
Please cite this article as: Taniguchi T, Shiomi H, Morimoto T, Watanabe H, Ono K, Shizuta S, Kato
T, Saito N, Kaji S, Ando K, Kadota K, Furukawa Y, Nakagawa Y, Horie M, Kimura T, Incidence and
Prognostic Impact of Heart Failure Hospitalization During Follow Up After Primary Percutaneous
Coronary Intervention in ST-Segment Elevation Myocardial Infarction, The American Journal of
Cardiology (2017), doi: 10.1016/j.amjcard.2017.03.013.
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Incidence and Prognostic Impact of Heart Failure Hospitalization During Follow Up After
Tomohiko Taniguchi, MDa; Hiroki Shiomi, MDa; Takeshi Morimoto, MD, MPHb; Hirotoshi Watanabe, MDa;
Koh Ono, MDa; Satoshi Shizuta, MDa; Takao Kato, MDa; Naritatsu Saito, MDa; Shuichiro Kaji, MDc; Kenji
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Ando, MDd; Kazushige Kadota, MDe; Yutaka Furukawa, MDc; Yoshihisa Nakagawa, MDf; Minoru Horie,
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MDg; Takeshi Kimura, MDa
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Kyoto, Japan; bDepartment of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan;
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Division of Cardiology, Kobe City Medical Center General Hospital, Kobe, Japan; dDepartment of
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Cardiology, Kokura Memorial Hospital, Kokura, Japan; eDepartment of Cardiovascular Medicine, Kurashiki
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Central Hospital, Kurashiki, Japan; fDivision of Cardiology, Tenri Hospital, Tenri, Japan; g Departments of
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Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Email: taketaka@kuhp.kyoto-u.ac.jp
Funding Sources: Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices
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Abstract
The incidence of heart failure (HF) hospitalization and its impact on long-term outcomes have not been well evaluated in
contemporary patients with ST-segment elevation myocardial infarction (STEMI) following primary percutaneous
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coronary intervention (PCI). The CREDO-Kyoto Acute Myocardial Infarction (AMI) Registry is a multicenter registry
enrolling 5429 consecutive AMI patients undergoing PCI from 2005 to 2007. The present study population consisted of
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3682 patients with STEMI who underwent primary PCI within 24 hours of symptom onset and discharged alive. The
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incidence rate of HF hospitalization was 4.4%/year during the first year after the index STEMI, which attenuated to
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approximately 1.0%/year beyond 1-year to 5-year with the median follow-up period of 1956 days. The independent risk
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factors for HF hospitalization within 1 year included older age, prior myocardial infarction, heart failure at STEMI, left
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ventricular dysfunction, anterior AMI, and onset to balloon time >3 hours, use of beta blocker and non-use of statin at
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discharge. By the landmark analysis at 1-year, the cumulative incidences of all-cause death and HF hospitalization
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beyond 1-year and up to 5-year were significantly higher in patients with HF hospitalization within 1-year of STEMI
than in patients without (36.3% vs. 10.1%, P<0.001, and 40.4% vs. 4.3%, P<0.001, respectively). Even after adjusting for
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confounders, HF hospitalization within 1-year remained independently associated with a higher risk for death and HF
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hospitalization beyond 1-year (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.02-2.52, P=0.04, and HR: 5.72,
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95% CI: 3.46-9.22, P<0.001, respectively). In conclusion, HF hospitalization within 1-year was independently associated
with a higher risk for all-cause death and HF hospitalization beyond 1-year.
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Mortality after ST-segment elevation myocardial infarction (STEMI) has been improved through widespread
and timely use of primary percutaneous coronary intervention (PCI),1,2 and through the optimal secondary prevention
therapies, with in-hospital mortality decreasing to about 5-10%.3-5 Primary PCI at early phase of STEMI reduces infarct
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size and decreases the risk of developing a substantial reduction of left ventricular ejection fraction (LVEF) and
subsequent development of heart failure (HF).6,7 On the other hand, improved survival of patients with myocardial
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infarction (MI) might have created a population with residual myocardial damage and a higher risk for developing HF.8,9
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Other factors such as an aging population and a decrease in sudden death due to penetration of implantable cardioverter
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defibrillator (ICD) therapy might contribute to the increasing prevalence of HF after MI. In previous studies with and
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without primary PCI, HF hospitalization after MI was declining,7,10,11 and HF on admission and after discharge was
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associated with increased short- and long-term mortality.12-14 However, the incidence of HF hospitalization and the
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impact of HF hospitalization after discharge on long-term clinical outcomes in STEMI patients following primary PCI
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have not been well evaluated in a contemporary cohort of STEMI patients except for the post hoc analysis of randomized
HORIZONS-AMI trial, which included less severe HF such as New York Heart Association (NYHA) class 1 or 2.15
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Therefore, we sought to investigate the incidence and predictors of HF hospitalization and the impact of HF
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hospitalization on long-term outcomes among STEMI patients treated with primary PCI in a large-scale multicenter acute
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Methods
The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) AMI registry is a
physician initiated, non-company sponsored, multicenter registry enrolling consecutive patients with AMI having
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coronary revascularization between January 2005 and December 2007 across 26 tertiary hospitals in Japan, excluding
those patients who underwent coronary revascularization after seven days of the onset of suspected AMI symptoms
(Supplementary Appendix A).16 The relevant review boards or ethics committees in all 26 participating centers approved
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the study protocol. Obtaining written informed consent from the patients was waived because of the retrospective study
design. Among 5429 patients enrolled in the CREDO-Kyoto AMI registry, 9 patients were excluded because of their
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refusal to participate in the study when contacted at follow-up. We also excluded 195 patients who had coronary artery
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bypass grafting surgery after the index AMI, 789 patients with non-STEMI, 494 patients who received PCI beyond 24
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hours after onset, and 260 patients who died during the index hospitalization (Figure 1). Therefore, the study population
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for the current analysis consisted of 3682 STEMI patients who had primary PCI within 24 hours of onset and survived to
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hospital discharge.
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Experienced clinical research coordinators in the independent research organization (Research Institute for
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Production Development, Kyoto, Japan) collected demographic, angiographic, and procedural data from the hospital
charts or hospital databases according to the pre-specified definitions (Supplementary Appendix B)17. Collection of
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follow-up information was mainly conducted through review of the inpatient and outpatient hospital charts by the clinical
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research coordinators, and additional follow-up information was collected through contact with patients, relatives and/or
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referring physicians by sending mail with questions regarding vital status and subsequent hospitalizations. Serious
adverse events such as death, MI, and HF hospitalization were adjudicated by the clinical event committee
(Supplementary Appendix C). HF hospitalization was defined as hospitalization due to worsening HF requiring
intravenous drug therapy. The detailed definitions of other baseline clinical characteristics were described previously.16,17
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Primary outcome measures for the current analysis included all-cause death and HF hospitalization. As the secondary
outcome measure, we also evaluated cardiac death, sudden death, non-cardiac death, MI, stroke, and any coronary
revascularizaion. Death was regarded as cardiac in origin unless obvious non-cardiac causes could be identified.
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We present continuous variables as the mean and standard deviation or median and interquartile range (IQR)
and categorical variables as numbers and percentages. We compared continuous variables with Students t test or a
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Wilcoxon rank-sum test on the basis of the distributions. We compared categorical variables with the 2 test when
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appropriate; otherwise, we used Fishers exact test. We used the Kaplan-Meier method to estimate the cumulative
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incidences of clinical event and assessed the differences with the log-rank test. We conducted a landmark analysis at 90
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days after the indexed STEMI to compare clinical outcomes between staged multivessel PCI strategy and culprit
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vessel-only PCI strategy in STEMI patients with multivessel disease. Staged PCI was defined as PCI for non-culprit
lesion scheduled during the index hospitalization and performed within 90 days of the index STEMI.18 To evaluate the
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late events beyond 1-year, we used landmark analysis at 1-year. We used Cox proportional hazard models to identify
predictors associated with HF hospitalization within 1 year after discharge from the index AMI hospitalization. The
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effects of HF hospitalization within 1-year after index AMI hospitalization for the primary outcome measures beyond
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1-year were expressed as hazard ratios (HR) with 95% confidence intervals (CI) by multivariable Cox proportional
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hazard models adjusting for the 35 clinically relevant factors indicated in Table 4. Consistent with our previous reports,
continuous variables were dichotomized using clinically meaningful reference values or median values. As a sensitivity
analysis, we conducted an adjusted analysis by the time-updated Cox regression model using heart failure hospitalization
as the time-updated variable together with other risk-adjusting 35 covariates at baseline to evaluate the impact of HF
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hospitalization on long-term mortality during the entire follow-up period. We also conducted a sensitivity analysis
excluding those patients with prior HF, because they are a different category of patients with increased risk of subsequent
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All statistical analyses were conducted using JMP version 10.0.2 (SAS Institute Inc, Cary, NC, USA) or IBM
SPSS Statistics, version 19.0.0 (IBM Corp., Armonk, NY, USA). All reported P values were two-tailed, and P values less
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than 0.05 were considered statistically significant.
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Results
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Baseline patient characteristics included 75% of men, 31% of diabetes mellitus, 9% of prior MI, and 27% of
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HF (prior and or current) (Table 1). The median length of follow-up was 1956 (IQR: 1668-2221) days. Cumulative
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5-year incidences of all-cause death and HF hospitalization were 14.8% and 8.5%, respectively (Figure 2 and Table 2).
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The annual incidence rate of HF hospitalization was 4.4%/year during the first year after the index STEMI, which
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attenuated to approximately 1.0%/year beyond 1-year and up to 5-year (Figure 2). Independent risk factors associated
with HF hospitalization within 1 year after STEMI identified by a multivariable Cox proportional hazard model were
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older age, prior MI, presence of HF at STEMI, thrombocytopenia, LVEF 40%, anterior AMI, onset-to balloon time >3
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hours, use of beta blocker and non-use of statin at discharge (Table 3).
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There were 1854 patients with multivessel coronary artery disease. After excluding 549 patients (multivessel
PCI at acute phase, Killip class 3, death or HF hospitalization within 90 days, or age 90), 680 multivessel disease
patients underwent staged PCI for angiographically significant non-culprit lesions within 90 days (staged non-culprit
lesion PCI group), while 625 multivessel disease patients received primary PCI only (culprit lesion only PCI group). The
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crude cumulative incidence of HF hospitalization was significantly lower in staged non-culprit lesion PCI group as
compared with culprit lesion only PCI group (5.1% versus 9.0%, P=0.006) (Supplementary Figure 1). During the entire
follow-up period, ICD/cardiac resynchronization therapy defibrillator (CRT-D) placement was more often performed in
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patients with HF hospitalization within 1 year than in those without (5/159 [3.1%] versus 22/3523 [0.6%]).
Among 3682 patients in the current study population, 157 patients died and 69 patients were lost to follow-up
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during 1-year after the index STEMI hospitalization. Among 159 patients with HF hospitalization within 1 year, 29
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patients died and 5 patients were lost to follow-up within 1-year after the index STEMI. Therefore, at the 1-year
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landmark point, there were 125 patients with and 3333 patients without HF hospitalization within 1-year after the index
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STEMI hospitalization. Baseline characteristics were significantly different between those patients with and without HF
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hospitalization within 1-year after the index AMI hospitalization (Table 4). Patients with HF hospitalization within 1-year
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were much older and more often had left ventricular (LV) dysfunction (LVEF 40%), HF (prior or current), prior MI,
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end-stage renal disease, atrial fibrillation, anemia and malignancy than those without HF hospitalization within 1-year.
Regarding clinical presentation of STEMI, onset-to-admission time and total ischemic time were significantly longer in
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patients with HF hospitalization within 1-year than in those without, whereas door-to-balloon time was not different
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between the 2 groups. Anterior MI, Killip class 2-4, and multivessel coronary artery disease were more often seen in
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patients with HF hospitalization within 1-year than in those without. The infarct size estimated by peak creatinine
phosphokinase value was significantly larger in patients with HF hospitalization within 1-year than in those without.
Regarding medications at hospital discharge, statins were more often prescribed in patients without HF hospitalization
within 1-year, while the prescription rates for beta-blockers and inhibitors of renin angiotensin system were not different
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The cumulative incidences of all-cause death and HF hospitalization beyond 1-year and up to 5-year after the
index STEMI was significantly higher in patients with HF hospitalization within 1-year than in those without (36.3%
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versus 10.1%, P<0.001; 40.4% versus 4.3%, P<0.001, respectively) (Figure 3 and Table 5). After adjusting for
confounders, HF hospitalization within 1-year was independently associated with a higher risk for all-cause death and HF
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hospitalization beyond 1-year (adjusted HR: 1.64, 95% CI 1.02-2.52, P=0.04, and adjusted HR: 5.72, 95% CI: 3.46-9.22,
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P<0.001, respectively) (Table 5). The result from the sensitivity analysis to evaluate the impact of HF hospitalization on
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long-term mortality during the entire follow-up period by the time-updated Cox regression model was fully consistent
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with those from the 1-year landmark analysis (adjusted HR: 3.46, 95% CI 2.63-4.56, P<0.001). HF hospitalization within
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1-year was also associated with higher risk for cardiac death beyond 1-year, while the risk for non-cardiac death beyond
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1-year was neutral. The cumulative incidence of sudden death beyond 1-year and up to 5-year after the index STEMI was
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significantly higher in patients with HF hospitalization within 1-year than in those without (4.7% versus 1.0%, P<0.001)
(Table 5).
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The cumulative 1-year incidence of HF hospitalization was significantly higher in patients with prior HF than
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in patients with only current HF at time of the index STEMI (21.9% versus 4.1%, P<0.001). In the sensitivity analysis
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excluding those patients with prior HF, there were 117 patients and 3288 patients with and without HF hospitalization
within 1-year, respectively, at the 1-year landmark point. The cumulative incidences of all-cause death and HF
hospitalization beyond 1-year and up to 5-year after the index STEMI was significantly higher in patients with HF
hospitalization within 1-year than in those without (33.2% versus 9.8%, P<0.001; 38.2% versus 3.9%, P<0.001,
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respectively).
Discussion
The main findings of the present study are as follows; (1) The risk for HF hospitalization was higher during the
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first year in STEMI patients who underwent primary PCI (4.4% at 1-year), which attenuated to 1.0%/year beyond 1-year
and up to 5-year; (2) HF hospitalization within 1-year was independently associated with a higher risk for all-cause death
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and HF hospitalization beyond 1-year.
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Several previous studies reporting an association between HF and mortality in patients with MI were based on
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cohorts including relatively large proportion of patients without revascularization in the acute phase of MI.9,12,14,19-21 The
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management of AMI has dramatically changed during the past decades, and these advances might have a beneficial
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impact on the incidence of HF and the prognosis of patients with post-discharge HF. The present study clearly
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demonstrated the incidence of HF hospitalization and the significant prognostic impact of HF hospitalization within 1
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year in the contemporary cohort of consecutive STEMI patients with primary PCI. In the present study, the rate of HF
hospitalization remained high (8.5% at 5-year), particularly during the first year of the index STEMI (4.4% at 1-year),
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even though all the patients underwent PCI within 24 hours from the onset. In high-risk patients for HF, severe HF often
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occurs relatively early after STEMI, if it does occur. The same trend was observed in post hoc analysis of the randomized
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HORIZONS-AMI trial, although the trial included relatively younger patients (mean age: approximately 60 years of age),
and patients with less severe HF at baseline (Killip class 3 at presentation: 0.4%).15 In the present study, HF
hospitalization within 1 year was independently associated with higher mortality risk beyond 1-year, suggesting that
prevention of HF hospitalization might lead to reduction in long-term mortality. Therefore, we should focus more on
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prevention of HF hospitalization after discharge in high-risk patients. The predictors of HF identified in the current
analysis confirmed the findings in previous studies.12,13,15 Elderly patients with large anterior MI carried particularly
higher risk for HF hospitalization. Consistent with our previous report,16 delay from symptom onset to reperfusion was
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independently associated with higher risk for HF hospitalization within 1-year, suggesting the importance of prompt
revascularization for myocardial salvage to reduce infarct size and future risk for HF.
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Moreover, the landmark analysis at 1 year showed that the crude cumulative incidence of HF hospitalization at
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4 year was approximately 10 times higher in patients with HF hospitalization within 1 year as compared with those
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without HF hospitalization within 1 year (40.4% versus 4.3%). More aggressive HF treatment of patients with HF
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hospitalization within 1 year may be warranted to improve prognosis. Furthermore, there also was a significant excess
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risk for sudden death in patients with HF hospitalization within 1 year as compared with those without. Appropriate risk
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stratification for sudden death and wider use of ICD might also be important to improve the mortality in patients with HF
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This study has several limitations. Firstly, HF hospitalization was an endpoint influenced by the judgment of
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physicians. We did not collect the data on less severe HF treated in outpatient settings. Secondly, the measured and
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unmeasured differences in baseline characteristics between patients with and without HF hospitalization within 1 year
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might limit the comparability of the groups, although we tried to make statistical adjustment as extensively as possible to
minimize the influence of the differences in baseline characteristics. Third, the follow-up not conducted in person, but
through secondary data collection, might lead to a substantial amount of data loss. Fourth, we did not collect information
on peak troponin and brain natriuretic peptide. Fourth, the use of DES in STEMI patients was different from the current
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standard. Finally, medical therapy at hospital discharge was not optimal from the current standard, and we could not
Acknowledgements
We appreciate the support and collaboration of the co-investigators participating in the CREDO-Kyoto AMI Registry. We
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are indebted to the outstanding effort of the clinical research coordinators for data collection.
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Funding Sources
This study was supported by Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices
Agency (PMDA) in Japan.
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Disclosures
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None. AN
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1. Schiele F, Meneveau N, Seronde MF, Descotes-Genon V, Oettinger J, Ecarnot F, Bassand JP. Changes in management
2. Nauta ST, Deckers JW, Akkerhuis KM, van Domburg RT. Age-dependent care and long-term (20 year) mortality of
PT
14,434 myocardial infarction patients: changes from 1985 to 2008. Int J Cardiol 2013;167:693-697.
3. Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, Go AS. Population trends in the incidence and outcomes of acute
RI
myocardial infarction. N Engl J Med 2010;362:2155-2165.
SC
4. Takii T, Yasuda S, Takahashi J, Ito K, Shiba N, Shirato K, Shimokawa H. Trends in acute myocardial infarction
U
incidence and mortality over 30 years in Japan: report from the MIYAGI-AMI Registry Study. Circ J 2010;74:93-100.
AN
5. Roe MT, Messenger JC, Weintraub WS, Cannon CP, Fonarow GC, Dai D, Chen AY, Klein LW, Masoudi FA, McKay C,
M
Hewitt K, Brindis RG, Peterson ED, Rumsfeld JS. Treatments, trends, and outcomes of acute myocardial infarction and
D
6. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP,
Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM,
EP
Ruschitzka F, Rutten FH, van der Meer P. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic
C
heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of
AC
Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart
J 2016;37:2129-2200.
7. Chen J, Hsieh AF, Dharmarajan K, Masoudi FA, Krumholz HM. National trends in heart failure hospitalization after
12
13
ACCEPTED MANUSCRIPT
8. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy.
Circulation 2000;101:2981-2988.
9. Ezekowitz JA, Kaul P, Bakal JA, Armstrong PW, Welsh RC, McAlister FA. Declining in-hospital mortality and
PT
increasing heart failure incidence in elderly patients with first myocardial infarction. J Am Coll Cardiol 2009;53:13-20.
10. Hellermann JP, Jacobsen SJ, Redfield MM, Reeder GS, Weston SA, Roger VL. Heart failure after myocardial
RI
infarction: clinical presentation and survival. Eur J Heart Fail 2005;7:119-125.
SC
11. Shafazand M, Rosengren A, Lappas G, Swedberg K, Schaufelberger M. Decreasing trends in the incidence of heart
U
failure after acute myocardial infarction from 1993-2004: a study of 175,216 patients with a first acute myocardial
AN
infarction in Sweden. Eur J Heart Fail 2011;13:135-141.
M
12. Gerber Y, Weston SA, Enriquez-Sarano M, Berardi C, Chamberlain AM, Manemann SM, Jiang R, Dunlay SM, Roger
D
VL. Mortality Associated With Heart Failure After Myocardial Infarction: A Contemporary Community Perspective. Circ
TE
13. Kaul P, Ezekowitz JA, Armstrong PW, Leung BK, Savu A, Welsh RC, Quan H, Knudtson ML, McAlister FA.
EP
Incidence of heart failure and mortality after acute coronary syndromes. Am Heart J 2013;165:379-385.e372.
C
14. Steg PG, Dabbous OH, Feldman LJ, Cohen-Solal A, Aumont MC, Lopez-Sendon J, Budaj A, Goldberg RJ, Klein W,
AC
Anderson FA, Jr. Determinants and prognostic impact of heart failure complicating acute coronary syndromes:
observations from the Global Registry of Acute Coronary Events (GRACE). Circulation 2004;109:494-499.
15. Kelly DJ, Gershlick T, Witzenbichler B, Guagliumi G, Fahy M, Dangas G, Mehran R, Stone GW. Incidence and
predictors of heart failure following percutaneous coronary intervention in ST-segment elevation myocardial infarction:
13
14
ACCEPTED MANUSCRIPT
16. Shiomi H, Nakagawa Y, Morimoto T, Furukawa Y, Nakano A, Shirai S, Taniguchi R, Yamaji K, Nagao K, Suyama T,
Mitsuoka H, Araki M, Takashima H, Mizoguchi T, Eisawa H, Sugiyama S, Kimura T. Association of onset to balloon and
PT
door to balloon time with long term clinical outcome in patients with ST elevation acute myocardial infarction having
primary percutaneous coronary intervention: observational study. BMJ (Clinical research ed) 2012;344:e3257.
RI
17. Kimura T, Morimoto T, Furukawa Y, Nakagawa Y, Kadota K, Iwabuchi M, Shizuta S, Shiomi H, Tada T, Tazaki J,
SC
Kato Y, Hayano M, Abe M, Tamura T, Shirotani M, Miki S, Matsuda M, Takahashi M, Ishii K, Tanaka M, Aoyama T, Doi
U
O, Hattori R, Tatami R, Suwa S, Takizawa A, Takatsu Y, Takahashi M, Kato H, Takeda T, Lee JD, Nohara R, Ogawa H,
AN
Tei C, Horie M, Kambara H, Fujiwara H, Mitsudo K, Nobuyoshi M, Kita T. Long-term safety and efficacy of
M
sirolimus-eluting stents versus bare-metal stents in real world clinical practice in Japan. Cardiovasc Interv Ther
D
2011;26:234-245.
TE
18. Toyota T, Shiomi H, Taniguchi T, Morimoto T, Furukawa Y, Nakagawa Y, Horie M, Kimura T. Culprit Vessel-Only vs.
Staged Multivessel Percutaneous Coronary Intervention Strategies in Patients With Multivessel Coronary Artery Disease
EP
Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction. Circ J
C
2016;80:371-378.
AC
19. Lewis EF, Velazquez EJ, Solomon SD, Hellkamp AS, McMurray JJ, Mathias J, Rouleau JL, Maggioni AP, Swedberg
K, Kober L, White H, Dalby AJ, Francis GS, Zannad F, Califf RM, Pfeffer MA. Predictors of the first heart failure
hospitalization in patients who are stable survivors of myocardial infarction complicated by pulmonary congestion and/or
14
15
ACCEPTED MANUSCRIPT
20. Lewis EF, Moye LA, Rouleau JL, Sacks FM, Arnold JM, Warnica JW, Flaker GC, Braunwald E, Pfeffer MA.
Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study. J Am Coll
Cardiol 2003;42:1446-1453.
PT
21. Hung J, Teng TH, Finn J, Knuiman M, Briffa T, Stewart S, Sanfilippo FM, Ridout S, Hobbs M. Trends from 1996 to
2007 in incidence and mortality outcomes of heart failure after acute myocardial infarction: a population-based study of
RI
20,812 patients with first acute myocardial infarction in Western Australia. J Am Heart Assoc 2013;2:e000172.
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Figure Legends
AMI=acute myocardial infarction; CABG=coronary artery bypass grafting; HF=heart failure; PCI=percutaneous
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coronary intervention; STEMI=ST-segment elevation myocardial infarction.
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Figure 2. Cumulative Incidences of All-cause Death (A) and Heart Failure Hospitalization (B) in the Entire Study
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Population.
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Figure 3. Cumulative Incidences of All-cause Death (A), and Heart Failure Hospitalization (B) Beyond 1-Year:
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Tables
N=3682
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(A) Patient characteristics
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Age (years) 67.012.2
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Age 75 years 1080 (29%)
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Men 2747 (75%)
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Body mass index (kg/m2) 23.73.5
2624 (71%)
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Prior stroke (symptomatic) 312 (8%)
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Peripheral vascular disease 105 (3%)
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eGFR <30 ml/min/1.73m2, without dialysis 121 (3%)
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Hemodialysis AN 45 (1%)
3 867/3230 (27%)
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Killip class
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1 2879 (78%)
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2 301 (8%)
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3 AN 80 (2%)
4 422 (13%)
Target of proximal LAD (including culprit and non-culprit lesions) 2002 (54%)
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Total stent length >28 mm (including culprit and non-culprit lesions) 1456/3391 (43%)
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Minimum stent size <3.0 mm (including culprit and non- culprit lesions) 1063/3391 (31%)
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DES use (culprit lesions) 647 (18%)
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DES use (including culprit and non-culprit lesions)
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Warfarin 430 (12%)
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Proton pump inhibitors 1284 (35%)
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Histamine H2-receptor antagonists 1301 (35%)
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Categorical variables were presented as number of patients (percentage), and continuous
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variables as mean standard deviation or median with interquartile range.
Body mass index was calculated as weight in kilograms divided by height in meters
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squared.
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eGFR was calculated by the Modification of Diet in Renal Disease formula modified
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The infarct size estimated by peak creatinine phosphokinase (CPK) value was evaluated
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(N=3682)
All-cause death 580 (14.8%)
Cardiac death 233 (6.0%)
RI
Sudden death 64 (1.6%)
Non-cardiac death 347 (9.4%)
SC
Myocardial infarction 218 (6.0%)
Stroke 211 (5.8%)
Heart failure hospitalization 306 (8.5%)
U
Any coronary revascularization 1309 (36.8%)
AN
The number of patients with at least 1 event was counted through the entire follow-up
Univariate Multivariable
PT
Variable Unadjusted HR P value Adjusted HR P
RI
95%CI 95%CI value
SC
Age 75 years 3.54 (2.59-4.87) <0.001 1.64 (1.05-2.57) 0.03
U
Body mass index <25.0 1.52 (1.05-2.26) 0.02 0.95 (0.60-1.57) 0.84
AN
Men 0.57 (0.42-0.80) 0.001 0.73 (0.47-1.14) 0.16
M
Diabetes mellitus on insulin therapy 1.65 (0.81-2.96) 0.15 1.15 (0.47-2.40) 0.75
D
TE
dialysis
PT
Anemia (Hemoglobin <11.0 g/dl) 2.14 (1.35-3.24) 0.002 0.65 (0.34-1.18) 0.16
RI
Thrombocytopenia (Platelet count 3.21 (1.36-6.34) 0.01 4.15 (1.70-8.66) 0.003
SC
<100*109/L)
U
Chronic obstructive pulmonary 1.17(0.46-2.42) 0.71 0.92 (0.27-2.27) 0.87
AN
disease
M
Heart failure (prior and/or at the 5.32 (3.86-7.41) <0.001 3.03 (1.81-5.06) <0.001
index admission)
EP
Left ventricular ejection fraction 4.80 (3.36-6.81) <0.001 2.44 (1.59-3.74) <0.001
AC
40%
Hours from onset to balloon 3 0.52 (0.33-0.79) 0.002 0.56 (0.33-0.89) 0.01
hours
ACCEPTED MANUSCRIPT
PT
ACE-I/ARB 0.72 (0.52-1.02) 0.06 0.86 (0.54-1.41) 0.55
RI
Mineralocorticoid Receptor 3.46 (2.46-4.81) <0.001 1.51 (0.96-2.35) 0.07
SC
Antagonist
U
CI=confidence interval; HR=hazard ratio.
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
Within 1 Year.
PT
Variable Yes No P value
RI
(N=125) (N=3333)
SC
(A) Baseline characteristics
U
Age (years) AN 74.011.0 66.311.9 <0.001
Left ventricular ejection fraction 40%* 42/100 (42%) 357/2695 (13%) <0.001
PT
Left ventricular ejection fraction 30% 19/100 (19%) 87/2695 (3%) <0.001
RI
Severe mitral regurgitation* 9 (7%) 77 (2%) 0.004
SC
Prior stroke (symptomatic) * 13 (10%) 258 (8%) 0.28
U
Peripheral vascular disease * AN 6 (5%) 85 (3%) 0.14
PT
12-24 22/108 (20%) 338/2924 (12%)
RI
Door to balloon time (hours) 1.5 (1.0-2.3) 1.5 (1.0-2.2) 0.71
SC
Killip class
U
1 AN 63 (50%) 2700 (81%)
PT
6 (5%) 75 (2%) 0.06
and non-culprit lesions) *
RI
Target of CTO (non-culprit lesions) * 10 (8%) 94 (3%) <0.001
SC
Target of bifurcation (including culprit and non-
37 (30%) 844 (25%) 0.28
U
culprit lesions) * AN
Side-branch stenting (including culprit and
5 (4%) 95 (3%) 0.45
non-culprit lesions) *
M
PT
Aspirin 123 (98%) 3317 (99.5%) 0.09
RI
Cilostazol 50 (40%) 1191 (36%) 0.33
SC
Statin 51 (41%) 1955 (59%) <0.001
U
Beta-blocker AN 59 (47%) 1452 (44%) 0.42
models.
The infarct size estimated by peak CPK value was evaluated in 3449/3458 patients
PT
(99.7%).
RI
U SC
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
PT
Heart Failure Hospitalization 1 year
RI
Unadjusted Adjusted
P P
Yes HR HR
No value value
SC
Number of patients (95% CI) (95% CI)
Number of patients
with at least one
with at least one
event (Cumulative
U
event (Cumulative
Incidence)
Incidence) (N=3333)
AN
(N=125)
4.17 1.64
All-cause death 46 (36.3%) 379 (10.1%) <0.001 0.04
(3.03-6.00) (1.02-2.52)
M
5.63 2.45
Cardiac death 21 (19.1%) 128 (3.3%) <0.001 0.01
(3.45-8.74) (1.20-4.66)
TE
4.96
Sudden death 6 (4.7%) 42 (1.0%) 0.003 N/A -
(1.89-10.8)
3.42 1.19
EP
Number of patients with event was assessed through the entire follow-up period beyond
the 1-year landmark point, while cumulative incidence was truncated at 5-year from the
onset of STEMI.
ACCEPTED MANUSCRIPT
N/A=not assessed.
PT
RI
U SC
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC