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. 2025 Dec 15;33:e00226025. doi: 10.5603/cj.103619

Comparisons of three-year outcomes according to the degree of left ventricular ejection fraction in patients with myocardial infarction with non-ST-segment elevation with and without chronic kidney disease

Yong Hoon Kim 1,2,*,✉, Ae-Young Her 1,2,*, Seung-Woon Rha 3,✉, Cheol Ung Choi 3, Byoung Geol Choi 4, Soohyung Park 3, Su Jin Hyun 5, Jung Rae Cho 6, Min-Woong Kim 7, Ji Young Park 8, Myung Ho Jeong 9
PMCID: PMC13189613  PMID: 41396029

Abstract

Background

Because renal and cardiac function are key to the prognosis of patients with coronary artery disease, we compared three-year clinical outcomes based on the degree of left ventricular ejection fraction (LVEF) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) with or without chronic kidney disease (CKD).

Methods

A total of 4567 patients diagnosed with NSTEMI were enrolled and stratified into CKD (1270 patients) and non-CKD (3297 patients) groups. Each group was further classified into heart failure (HF) with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF) subgroups. The primary outcome was all-cause death.

Results

In both the CKD and non-CKD groups, the adjusted rates of all-cause death (both p < 0.001) and cardiac death (CD, both p <0.001) in the HFrEF subgroup were significantly higher than in the HFmrEF and HFpEF subgroups. However, within the CKD group, the all-cause death rate was comparable between the HFmrEF and HFpEF subgroups. In contrast, within the non-CKD group, the rates of all-cause death (p = 0.005) and CD (p = 0.008) were significantly higher in the HFmrEF subgroup compared to the HFpEF subgroup. The increased all-cause death in the CKD group, relative to the non-CKD group, within the HFpEF subgroup contributed to these outcomes.

Conclusions

Regardless of CKD status, the HFrEF subgroup showed higher mortality rates compared with the HFmrEF and HFpEF subgroups. However, the mortality rate differed between the HFmrEF and the HFpEF subgroups in both the CKD and the non-CKD groups.

Keywords: chronic kidney disease, non-ST elevation myocardial infarction, ventricular ejection fraction

Introduction

Chronic kidney disease (CKD) is a significant comorbidity that significantly worsens cardiovascular outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) [1, 2]. In patients with acute myocardial infarction (AMI) and an estimated glomerular filtration rate (eGFR) < 81.0 mL/min/1.73 m2, each 10 mL/min/1.73 m2 decrease in eGFR is associated with a hazard ratio of 1.10 for death and nonfatal cardiovascular events [3]. Moreover, the effect of renal function on the prognosis of patients with coronary artery disease (CAD) is closely associated with cardiac function [4]. Left ventricular ejection fraction (LVEF) is a major criterion used for comparison in studies comparing mortality or morbidity in patients with AMI [5, 6]. However, the criteria for normal (preserved) LVEF vary slightly across studies [5, 7]. In 2016, the European Society of Cardiology (ESC) classified heart failure (HF) as HF with reduced EF (HFrEF, EF ≤ 40%), HF with mildly reduced EF (HFmrEF, EF 41–49%), and HF with preserved EF (HFpEF, EF ≥ 50%). ST-segment elevation myocardial infarction (STEMI) is associated with a high short-term mortality rate, whereas NSTEMI is associated with a high long-term mortality risk [8]. Therefore, investigating the long-term outcomes of patients with NSTEMI is crucial for understanding the long-term prognosis of patients with AMI. In particular, examining long-term outcomes based on the degree of LVEF (HFrEF, HFmrEF, or HFpEF) may provide valuable insights. However, while many studies have compared the outcomes of these three LVEF groups [9, 10], relatively few have focused on patients with NSTEMI. Even among patients with NSTEMI, percutaneous coronary intervention (PCI) is performed in > 60% of cases in real-world daily practice [11], and bare metal stents (BMSs) and first-generation (1G) drug-eluting stents (DESs) are rarely used [12]. Therefore, from the perspective of interventional cardiologists, when considering tailored therapy for patients with NSTEMI who have undergone PCI, it seems more beneficial to focus on those who have successfully received newer generation stents. Thus, we believe that investigating the outcomes based on the degree of LVEF in patients with NSTEMI with or without CKD will provide more useful information. Therefore, we compared the three-year clinical outcomes of these patients.

Methods

Study population

From November 2011 to December 2015, a total of 13,104 patients diagnosed with AMI were enrolled in the Korea AMI Registry-National Institute of Health (KAMIR-NIH) [13] dataset. KAMIR-NIH [13] is a prospective registry involving 20 high-volume PCI centers across the Republic of Korea that can perform on-site coronary artery bypass grafting (CABG), and it includes individuals aged ≥ 18 years. The exclusion criteria in the present study were patients (1) with STEMI (n = 6371, 48.6%); (2) who did had undergone or had had unsuccessful PCI (n = 1196, 9.1%); (3) who had undergone plain old balloon angioplasty (n = 426, 3.3%); (4) who had undergone CABG (n = 5, 0.03%); (5) who had received BMS or 1G-DES (n = 343, 2.6%); (6) with previous HF (n = 71, 0.5%); and (7) who could not be followed up (n = 125, 1.05%) (Fig. 1). Finally, 4567 patients with NSTEMI who had undergone successful PCI with a newer generation DES were evaluated. These patients were classified into a CKD group consisting of 1270 patients (27.8%) and a non-CKD group comprising 3297 patients (72.2%). The CKD and non-CKD groups were further classified into the following subgroups based on LVEF: HFrEF (group A, n = 163; group D, n = 374), HFmrEF (group B, n = 231; group E, n = 590), and HFpEF (group C, n = 876; group F, n = 2333) (Fig. 1).

Figure 1.

Figure 1

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Flowchart; AMI — acute myocardial infarction; CKD — chronic kidney disease; DES — drug-eluting stent; eGFR — estimated glomerular filtration rate; HF — heart failure; HFmrEF — HF with mildly reduced EF; HFpEF — HF with preserved EF; HFrEF — HF with reduced ejection fraction; NIH — National Institute of Health; NSTEMI — non-STEMI; PCI — percutaneous coronary intervention; STEMI — ST-segment–elevation myocardial infarction

This study was approved by the ethics committees of all participating centers, including the Korea University Guro Hospital Institutional Review Board Ethics Committee (approval number: KUGH MD11024), in compliance with the ethical guidelines of the 2004 Declaration of Helsinki. Before enrollment, written informed consent was obtained from all 4567 patients participating in the study. Throughout the three-year post-discharge follow-up period, all patients were scheduled for evaluation at 3, 6 and 12 months, with assessments continuing every 6 months. Echocardiography was recommended at 12 months post-AMI and annually thereafter. For patients who missed follow-up appointments, outcome data were collected through phone interviews or medical record reviews [14]. The event adjudication procedures were as previously described [13], with an impartial committee within the KAMIR-NIH carefully reviewing and assessing all events.

Percutaneous coronary intervention and medical treatment

Coronary angiography and PCI were generally performed according to well-established guidelines [15]. Registered patients were administered a loading dose of aspirin (200–300 mg) in combination with clopidogrel (300–600 mg), ticagrelor (180 mg), or prasugrel (60 mg) before PCI. Patients who underwent PCI were required to receive dual antiplatelet therapy, which consisted of a daily dose of 100 mg aspirin and either 75 mg clopidogrel, 90 mg ticagrelor twice daily, or 5–10 mg prasugrel for at least one year. When performing PCI, the operators were not restricted in any aspect, including the choice of procedure method, procedure time, stent type, or revascularization strategy.

Study definitions and clinical endpoints

Acute myocardial infarction, STEMI, and NSTEMI were diagnosed based on the Fourth Universal Definition of MI [16]. Glomerular function for eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, and CKD was defined as an eGFR < 60m/min/1.73 m2 [17]. Because LVEF is a key factor in patient classification for HF in both randomized trials and observational studies, we performed a qualitative assessment via two-dimensional transthoracic echocardiography using the Simpson method [18]. Percutaneous coronary intervention was considered successful if the residual stenosis was < 30% and the infarct-related artery demonstrated thrombolysis in myocardial infarction (TIMI) flow grade 3. Symptom-to-door (SDT) and door-to-balloon (DBT) times were calculated based on recently published studies [19, 20]. During the three-year follow-up period, the primary outcome was the all-cause death rate. The secondary outcomes were cardiac death (CD), non-cardiac death (NCD), recurrent MI, repeat coronary revascularization, hospitalization for heart failure (HHF), and stroke. In the absence of definitive evidence indicating a noncardiac cause, all deaths were attributed to CD [21]. Definitions for recurrent MI and stroke were informed by established literature [16, 22]. Any repeat revascularization events were defined based on the criteria established by the Academic Research Consortium [23].

Statistical analysis

For discrete variables, differences among the three groups were analyzed using the chi-squared or Fisher’s exact test, as appropriate. These data are expressed as counts and percentages. For continuous variables, comparisons among the three groups were made using analysis of variance or the Jonckheere–Terpstra test. Post-hoc analyses between the two groups were conducted using either the Hochberg or Dunnett-T3 test, with results reported as means ± standard deviation or medians (interquartile range), as appropriate. p < 0.05 was considered statistically significant. We first identified variables in Table 1 that differed significantly among LVEF groups (p < 0.05). The multicollinearity test (Suppl. Tab. 1A) [24] was applied to exclude variables with a variance inflation factor > 5, tolerance value < 0.1, or condition index > 10 [25]. The final variables included in the multivariable Cox proportional hazard regression analysis are also presented in Supplementary Table 1A. Supplementary Table 1B shows the results of the collinearity testing for all-cause death between the CKD and non-CKD groups (B). We also performed propensity score-matched analyses to enhance statistical rigor, and the results are presented in Supplementary Tables 2A — J. Kaplan–Meier estimates were used to represent the cumulative incidence of adverse events throughout the follow-up period, with statistical significance tested using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models.

Table 1.

Baseline characteristics

CKD (n =1270) Non-CKD (n = 3297)
Variables HFrEF LVEF ≤ 40% (n = 163) Group A HFmrEF LVEF 41–49% (n = 231) Group B HFpEF LVEF ≥ 50% (n = 876) Group C p-value HFrEF LVEF ≤ 40% (n = 374) Group D HFmrEF LVEF 41–49% (n = 590) Group E HFpEF LVEF ≥ 50% (n = 2333) Group F p-value
Male, n [%] 80 (49.1) 113 (48.9) 503 (57.4) 0.020 272 (62.7) 457 (77.5) 1885 (80.8) 0.001
Age [years] 72.7 ± 10.5 69.7 ± 10.7 66.2 ± 11.7 < 0.001 67.8 ± 10.9 65.2 ± 11.9 61.7 ± 11.9 < 0.001
SBP [mmHg] 131.2 ± 30.0 129.9 ± 25.1 135.3 ± 25.5 0.009 131.7 ± 27.4 132.6 ± 25.3 137.9 ± 25.8 < 0.001
DBP [mmHg] 79.1 ± 18.4 78.3 ± 14.1 81.3 ± 15.1 0.018 80.0 ± 16.4 80.0 ± 16.4 82.4 ± 15.0 < 0.001
Heart rate [beats/min] 93.1 ± 20.7 81.1 ± 18.7 76.9 ± 16.1 < 0.001 92.0 ± 19.9 80.2 ± 17.0 76.9 ± 15.8 < 0.001
Risk factors
 Hypertension, n (%) 100 (61.3) 132 (57.1) 495 (56.5) 0.517 231 (61.8) 282 (47.8) 1192 (51.1) < 0.001
 Diabetes mellitus, n (%) 78 (47.9) 78 (33.8) 242 (27.6) < 0.001 182 (48.7) 189 (32.0) 631 (27.0) < 0.001
 Dyslipidemia, n (%) 13 (8.0) 21 (9.1) 115 (13.1) 0.066 36 (9.6) 49 (8.3) 321 (13.8) < 0.001
 Previous MI, n (%) 20 (12.3) 20 (8.7) 48 (5.5) 0.004 60 (16.0) 53 (9.0) 114 (4.9) < 0.001
 Previous PCI, n (%) 26 (16.0) 19 (8.2) 85 (9.7) 0.029 65 (17.4) 69 (11.7) 187 (8.0) < 0.001
 Previous CABG, n (%) 2 (1.2) 5 (2.2) 6 (0.7) 0.134 11 (2.9) 3 (0.5) 10 (0.4) < 0.001
 Previous stroke, n (%) 20 (12.3) 9 (3.9) 46 (5.3) 0.001 43 (11.5) 49 (8.3) 113 (4.8) < 0.001
 Current smokers, n (%) 29 (17.8) 58 (25.1) 247 (28.2) 0.019 117 (31.3) 216 (36.6) 980 (42.0) < 0.001
Body mass index [kg/m2] 22.9 ± 3.7 23.5 ± 3.2 24.0 ± 3.3 0.001 23.4 ± 3.8 23.8 ± 3.1 24.5 ± 3.2 < 0.001
LVEF [%] 33.5 ± 6.0 45.8 ± 2.3 59.6 ± 6.4 < 0.001 32.2 ± 6.3 45.7 ± 2.5 59.4 ± 6.1 < 0.001
Killip class II/III, n (%) 70 (42.9) 54 (23.4) 117 (13.4) < 0.001 182 (48.7) 108 (18.3) 204 (8.7) < 0.001
Cardiogenic shock, n (%) 11 (6.7) 5 (2.2) 16 (1.8) 0.001 10 (2.7) 9 (1.5) 28 (1.2) 0.081
CPR on admission, n (%) 18 (11.0) 13 (5.6) 10 (1.1) < 0.001 48 (12.8) 17 (2.9) 23 (1.0) < 0.001
Symptom-to-door time [hours] 13.6 (3.4–68.9) 7.8 (3.3–31.1) 7.4 (2.5–24.0) 0.025 10.4 (3.2–43.0) 7.8 (2.3–25.7) 5.7 (2.0–24.0) 0.441
Door-to balloon time [hours] 17.1 (3.9–38.0) 13.1 (4.0–24.1) 13.6 (3.9–23.3) < 0.001 13.7 (3.5–40.3) 13.0 (3.2–24.3) 14.0 (4.0–25.0) < 0.001
Laboratory results
 Peak CK-MB [mg/dL] 16.3 (6.2–59.8) 36.9 (7.1–146.0) 17.4 (5.7–60.0) < 0.001 25.0 (6.7–71.6) 33.7 (8.8–120.7) 18.9 (5.5–73.8) < 0.001
 Peak troponin-I [ng/mL] 6.0 (1.6–20.1) 15.3 (2.5–32.7) 5.3 (1.3–18.9) < 0.001 9.8 (2.6–35.1) 10.3 (2.5–33.2) 5.8 (1.3–22.2) < 0.001
 Hemoglobin [mg/dL] 11.9 ± 2.4 13.0 ± 2.0 13.4 ± 2.0 < 0.001 12.6 ± 2.4 13.5 ± 2.2 14.1 ± 1.9 < 0.001
 Blood glucose [mg/dL] 190.0 ± 94.7 167.3 ± 84.0 152.8 ± 69.6 < 0.001 202.2 ± 86.9 162.6 ± 83.9 151.4 ± 68.8 < 0.001
 Serum creatinine [mg/dL] 1.56 ± 0.81 1.05 ± 0.88 1.04 ± 0.74 < 0.001 1.80 ± 0.82 1.20 ± 0.79 1.04 ± 0.67 < 0.001
 eGFR [mL/min/1.73 m2] 39.5 ± 17.2 41.1 ± 15.5 40.3 ± 15.8 0.597 100.4 ± 40.7 109.1 ± 89.8 108.2 ± 51.5 0.046
 Total cholesterol [mg/dL] 163.1 ± 44.2 175.6 ± 45.1 182.0 ± 44.0 < 0.001 169.8 ± 46.5 176.8 ± 47.2 181.5 ± 44.0 < 0.001
 Triglyceride [mg/dL] 100.1 ± 79.2 119.2 ± 83.5 130.9 ± 85.7 0.002 115.7 ± 81.5 112.4 ± 94.2 141.2 ± 96.3 < 0.001
 HDL-cholesterol [mg/dL] 42.2 ± 13.6 42.7 ± 10.8 43.4 ± 11.9 0.448 42.3 ± 12.8 42.6 ± 12.3 42.7 ± 11.1 0.862
 LDL-cholesterol [mg/dL] 100.0 ± 37.0 110.1 ± 36.9 115.6 ± 37.2 < 0.001 105.2 ± 42.1 111.0 ± 40.4 115.0 ± 38.2 < 0.001
Infarct-related artery
 Left main, n (%) 6 (3.7) 5 (2.2) 15 (1.7) 0.262 24 (6.4) 15 (2.5) 72 (3.1) 0.002
 LAD, n (%) 95 (58.3) 124 (53.7) 356 (40.6) < 0.001 181 (48.1) 299 (50.7) 896 (38.4) < 0.001
 LCx, n (%) 22 (13.5) 46 (19.9) 242 (27.6) < 0.001 61 (16.3) 138 (23.4) 655 (28.1) < 0.001
 RCA, n (%) 40 (24.5) 56 (24.2) 263 (30.0) 0.117 108 (28.9) 138 (23.4) 710 (30.4) 0.003
Treated vessel
 Left main, n (%) 8 (4.9) 10 (4.3) 28 (3.2) 0.459 34 (9.1) 28 (4.7) 101 (4.3) < 0.001
 LAD, n (%) 119 (73.0) 162 (70.1) 491 (56.0) < 0.001 255 (68.2) 369 (62.5) 1239 (53.1) < 0.001
 LCx, n (%) 47 (28.8) 77 (33.3) 354 (40.4) 0.006 132 (35.3) 215 (36.4) 943 (40.4) 0.057
 RCA, n (%) 52 (31.9) 76 (32.9) 348 (39.7) 0.047 158 (42.2) 202 (34.2) 891 (38.2) 0.040
Multivessel disease, n (%) 114 (69.9) 142 (61.5) 461 (52.6) < 0.001 262 (70.1) 343 (58.1) 1222 (52.4) < 0.001
IVUS/OCT, n (%) 25 (15.3) 52 (22.5) 185 (21.1) 0.181 70 (18.7) 157 (26.6) 653 (28.0) 0.001
FFR, n (%) 2 (1.2) 1 (0.4) 24 (2.7) 0.067 4 (1.1) 12 (2.0) 59 (2.5) 0.194
Drug-eluting stents*
 ZES, n (%) 40 (24.5) 57 (24.7) 212 (24.2) 0.987 84 (22.5) 137 (23.2) 545 (23.4) 0.929
 EES, n (%) 82 (50.3) 126 (54.5) 433 (49.4) 0.384 226 (60.4) 307 (52.0) 1178 (50.5) 0.002
 BES, n (%) 31 (19.0) 38 (16.5) 198 (22.6) 0.099 46 (12.3) 118 (20.0) 488 (20.9) 0.001
 Others, n (%) 10 (6.1) 10 (4.3) 33 (3.8) 0.378 18 (4.8) 28 (4.7) 122 (5.2) 0.862
Stent diameter [mm] 3.00 ± 0.39 3.01 ± 0.38 3.03 ± 0.41 0.445 3.09 ± 0.42 3.06 ± 0.38 3.10 ± 0.43 0.235
Stent length [mm] 31.1 ± 14.2 31.3 ± 15.1 29.5 ± 14.1 0.142 32.3 ± 15.6 31.1 ± 14.8 28.8 ± 13.5 < 0.001
Number of stents 1.20 ± 0.51 1.23 ± 0.51 1.21 ± 0.46 0.839 1.24 ± 0.49 1.22 ± 0.46 1.19 ± 0.44 0.044
Discharge medications
 Aspirin, n (%) 156 (95.7) 229 (99.1) 869 (99.2) 0.001 373 (99.7) 584 (99.0) 2315 (99.2) 0.422
 Clopidogrel, n (%) 129 (79.1) 180 (77.9) 645 (73.6) 0.181 289 (77.3) 430 (72.9) 1597 (68.5) 0.001
 Ticagrelor, n (%) 25 (15.3) 33 (14.3) 147 (16.8) 0.628 63 (16.8) 113 (19.2) 495 (21.2) 0.109
 Prasugrel, n (%) 9 (5.5) 18 (7.8) 84 (9.6) 0.205 22 (5.9) 47 (8.0) 241 (10.3) 0.010
 Beta-blocker, n (%) 126 (77.7) 190 (82.3) 758 (86.5) 0.006 298 (79.7) 505 (85.6) 1993 (85.4) 0.014
 RASI, n (%) 123 (75.5) 171 (74.0) 738 (84.2) < 0.001 295 (78.9) 485 (82.2) 1946 (83.4) 0.093
 Statin, n (%) 132 (81.0) 218 (94.4) 838 (95.7) < 0.001 331 (88.5) 559 (94.7) 2236 (95.8) < 0.001
 Anticoagulant, n (%) 9 (5.5) 10 (4.3) 11 (1.3) < 0.001 28 (7.5) 12 (2.0) 27 (1.2) < 0.001
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The p-values for categorical data from chi-square or Fisher’s exact test. The p-values for continuous data obtained from the analysis of variance or Jonckheere–Terpstra test. Values are means ± standard deviation or median (interquartile range) or numbers and percentages; BES — biolimus-eluting stent; CABG — coronary artery bypass graft; CKD — chronic kidney disease; CK-MB — creatine kinase myocardial band; CPR — cardiopulmonary resuscitation; DBP — diastolic blood pressure; EES — everolimus-eluting stent; eGFR — estimated glomerular filtration rate; FFR — fractional flow reserve; HDL — high-density lipoprotein; HFrEF — heart failure with reduced ejection fraction; HFmrEF — HF with mildly reduced EF; HFpEF — HF with preserved EF; IVUS/OCT — intravascular ultrasound/optical coherence tomography; LAD — left anterior descending artery; LCx — left circumflex artery; LDL — low-density lipoprotein; LVEF — left ventricular EF; MI — myocardial infarction; PCI — percutaneous coronary intervention; RCA — right coronary artery; RASI — renin-angiotensin system inhibitor; SBP — systolic blood pressure; ZES — zotarolimus-eluting stent;

*

Newer generation DES included in the study were the zotarolimus-eluting stent (Resolute Integrity stent; Medtronic, Inc.), everolimus-eluting stent (Xience Prime stent; Abbott Vascular or Promus Element stent; Boston Scientific), and biolimus-eluting stent (BioMatrix Flex stent; Biosensors International or Nobori stent; Terumo Corporation)

Results

Baseline characteristics

Table 1 and Supplementary Table 3A present the baseline characteristics of the study population. In the CKD and non-CKD groups, the average age, mean heart rate, number of patients with diabetes mellitus (DM), numbers of patients with a history of MI, PCI, and stroke, number of patients classified as Killip class II/III, number of patients receiving cardiopulmonary resuscitation (CPR) on admission, average DBT, and number of patients with multivessel disease were highest in the HFrEF group. The peak creatine kinase myocardial band level was highest in the HFmrEF group, whereas the highest values for male sex, current smokers, average body mass index, average hemoglobin, total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol levels, as well as the number of patients prescribed statins upon discharge, were highest in the HFpEF group (Tab. 1).

Clinical outcomes

Tables 2 and 3 and Figure 2 present the key three-year outcome results.

Table 2.

Comparison of three-year clinical outcomes according to left ventricular ejection fraction (LVEF) subgroups in the chronic kidney disease (CKD) and non-CKD groups

CKD, n = 1270
HFrEF (n = 163) Group A HFmrEF (n = 231) Group B Log-rank Unadjusted Multivariable-adjusted* Propensity score-adjusted†
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 49 (30.1) 25 (10.8) < 0.001 3.236 (1.998–5.240) < 0.001 3.597 (2.084–6.210) < 0.001 3.552 (2.012–5.741) < 0.001
Cardiac death 34 (20.9) 13 (5.6) < 0.001 4.253 (2.243–8.061) < 0.001 5.239 (2.509–10.94) < 0.001 4.946 (2.315–10.50) < 0.001
Non-cardiac death 15 (9.2) 12 (5.2) 0.047 2.120 (0.992–4.530) 0.053 2.519 (0.991–6.401) 0.052 2.251 (0.847–5.417) 0.108
Recurrent MI 10 (7.5) 8 (3.6) 0.105 2.120 (0.836–5.374) 0.113 2.709 (0.910–8.065) 0.073 2.980 (0.982–9.039) 0.054
Any repeat revascularization 13 (10.0) 19 (8.7) 0.660 1.171 (0.578–2.372) 0.660 1.194 (0.599–2.747) 0.647 1.179 (0.503–2.651) 0.721
Hospitalization for HF 15 (11.4) 13 (5.9) 0.068 1.971 (0.937–4.145) 0.073 1.734 (0.713–4.017) 0.125 1.968 (0.800–4.843) 0.102
Stroke 9 (7.0) 3 (1.4) 0.006 5.211 (1.409–19.26) 0.013 6.081 (1.532–24.14) 0.010 5.532 (1.317–23.23) 0.019
HFrEF (n = 163) Group A HFpEF (n = 876) Group C Log-rank Unadjusted Multivariable-adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 49 (30.1) 53 (6.1) < 0.001 5.977 (4.051–8.817) < 0.001 5.065 (3.205–8.005) < 0.001 4.076 (2.555–6.501) < 0.001
Cardiac death 34 (20.9) 26 (3.0) < 0.001 7.279 (4.966–13.80) < 0.001 7.237 (3.984–13.14) < 0.001 5.737 (3.109–10.59) < 0.001
Non-cardiac death 15 (9.2) 27 (3.1) < 0.001 3.701 (1.968–6.960) < 0.001 2.935 (1.374–6.271) 0.005 2.465 (1.143–5.314) 0.021
Recurrent MI 10 (7.5) 35 (4.1) 0.064 1.920 (0.950–3.877) 0.069 1.772 (0.804–3.728) 0.156 1.708 (0.764–3.321) 0.201
Any repeat revascularization 13 (10.0) 71 (8.4) 0.500 1.225 (0.678–2.213) 0.501 1.408 (0.715–2.772) 0.323 1.473 (0.731–2.968) 0.273
Hospitalization for HF 15 (11.4) 29 (3.4) < 0.001 3.535 (1.894–6.598) < 0.001 2.453 (1.180–5.099) 0.016 2.344 (1.121–4.898) 0.024
Stroke 9 (7.0) 16 (1.9) 0.001 3.775 (1.667–8.548) 0.001 5.288 (2.102–13.30) < 0.001 3.961 (1.584–9.907) 0.003
HFmrEF (n = 231) Group B HFpEF (n = 876) Group C Log-rank Unadjusted Multivariable-adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 25 (10.8) 53 (6.1) 0.011 1.837 (1.142–2.955) 0.012 1.573 (0.922–2.682) 0.096 1.405 (0.818–2.413) 0.218
Cardiac death 13 (5.6) 26 (3.0) 0.046 1.944 (0.999–3.783) 0.050 1.617 (0.759–3.442) 0.213 1.445 (0.671–3.110) 0.347
Non-cardiac death 12 (5.2) 27 (3.1) 0.108 1.733 (0.878–3.421) 0.113 1.540 (0.717–3.306) 0.269 1.399 (0.645–3.035) 0.395
Recurrent MI 8 (3.6) 35 (4.1) 0.775 0.894 (0.415–1.927) 0.775 0.933 (0.498–2.184) 0.872 0.793 (0.891–2.089) 0.789
Any repeat revascularization 19 (8.7) 71 (8.4) 0.864 1.045 (0.630–1.734) 0.864 1.424 (0.809–2.505) 0.220 1.505 (0.852–2.659) 0.150
Hospitalization for HF 13 (5.9) 29 (3.4) 0.082 1.773 (0.922–3.411) 0.086 1.585 (0.793–3.167) 0.192 1.351 (0.664–2.745) 0.406
Stroke 3 (1.4) 16 (1.9) 0.610 0.726 (0.212–2.493) 0.611 0.864 (0.231–3.229) 0.828 0.741 (0.196–2.800) 0.659
Non-CKD, n = 3297
HFrEF (n = 374) Group D HFmrEF (n = 590) Group E Log-rank Unadjusted Multivariable-adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 97 (25.9) 57 (9.7) < 0.001 2.981 (2.163–4.161) < 0.001 3.179 (2.167–4.662) < 0.001 2.847 (1.935–4.187) < 0.001
Cardiac death 69 (18.4) 30 (5.1) < 0.001 4.036 (2.628–6.197) < 0.001 4.854 (2.887–8.160) < 0.001 4.394 (2.602–7.421) < 0.001
Non-cardiac death 28 (7.5) 27 (4.6) 0.021 1.844 (1.087–3.129) 0.023 1.688 (0.919–3.100) 0.092 1.406 (0.759–2.605) 0.278
Recurrent MI 22 (6.8) 19 (3.4) 0.015 2.107 (1.140–3.893) 0.017 2.067 (1.052–3.602) 0.035 2.014 (1.025–3.591) 0.042
Any repeat revascularization 43 (13.6) 50 (8.9) 0.029 1.567 (1.042–2.356) 0.031 1.706 (1.060–2.746) 0.028 1.629 (1.010–2.627) 0.046
Hospitalization for HF 45 (14.0) 19 (3.4) < 0.001 4.398 (2.572–7.520) < 0.001 3.325 (1.854–5.962) < 0.001 3.450 (1.923–6.189) < 0.001
Stroke 11 (3.6) 15 (2.7) 0.491 1.313 (0.603–2.860) 0.493 1.085 (0.422–2.790) 0.866 1.071 (0.417–2.654) 0.901
HFrEF (n = 374) Group D HFpEF (n = 2333) Group F Log-rank Unadjusted Multivariable-adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 97 (25.9) 95 (4.1) < 0.001 6.784 (5.012–9.682) < 0.001 5.340 (3.849–7.408) < 0.001 4.370 (3.153–6.056) < 0.001
Cardiac death 69 (19.1) 49 (2.1) < 0.001 9.936 (6.888–14.33) < 0.001 7.013 (4.631–10.62) < 0.001 6.023 (3.964–9.152) < 0.001
Non-cardiac death 28 (7.5) 46 (2.0) < 0.001 4.236 (2.773–7.098) < 0.001 3.479 (1.998–6.056) < 0.001 2.558 (1.483–4.412) 0.001
Recurrent MI 22 (6.8) 55 (2.4) < 0.001 2.951 (1.799–4.839) < 0.001 2.367 (1.341–4.178) 0.003 2.326 (1.319–4.102) 0.004
Any repeat revascularization 43 (13.6) 187 (8.2) 0.001 1.720 (1.234–2.396) 0.001 1.810 (1.237–2.649) 0.001 1.795 (1.221–2.492) 0.003
Hospitalization for HF 45 (14.0) 34 (1.5) < 0.001 9.970 (6.384–15.57) < 0.001 7.918 (4.674–13.41) < 0.001 7.252 (4.282–12.28) < 0.001
Stroke 11 (3.6) 46 (2.0) 0.092 1.747 (0.905–3.373) 0.097 1.163 (0.506–2.672) 0.722 1.109 (0.482–2.551) 0.807
HFmrEF (n = 590) Group E HFpEF (n = 2333) Group F Log-rank Unadjusted Multivariable-adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 57 (9.7) 95 (4.1) < 0.001 2.437 (1.755–3.385) < 0.001 1.745 (1.188–2.562) 0.005 1.642 (1.121–2.405) 0.008
Cardiac death 30 (5.1) 49 (2.1) < 0.001 2.483 (1.576–3.912) < 0.001 2.069 (1.205–3.550) 0.008 1.908 (1.116–3.216) 0.018
Non-cardiac death 27 (4.6) 46 (2.0) < 0.001 2.388 (1.485–3.841) < 0.001 1.528 (0.885–2.637) 0.128 1.440 (0.836–2.418) 0.189
Recurrent MI 19 (3.4) 55 (2.4) 0.196 1.408 (0.836–2.373) 0.198 1.412 (0.853–2.483) 0.151 1.404 (0.797–2.398) 0.241
Any repeat revascularization 50 (8.9) 187 (8.2) 0.571 1.094 (0.801–1.495) 0.571 1.002 (0.696–1.442) 0.990 1.023 (0.710–1.473) 0.904
Hospitalization for HF 19 (3.4) 34 (1.5) 0.003 2.284 (1.303–4.004) 0.004 2.472 (1.353–4.517) 0.003 2.312 (1.268–4.218) 0.006
Stroke 15 (2.7) 46 (2.0) 0.337 1.329 (0.742–2.381) 0.339 1.305 (0.670–2.273) 0.434 1.247 (0.637–2.044) 0.520
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BMI — body mass index; CABG — coronary artery bypass graft CK-MB — creatine kinase myocardial band; CPR — cardiopulmonary resuscitation; DBP — diastolic blood pressure; DBT — door-to-balloon time; DM — diabetes mellitus; HFmrEF — HF with mildly reduced EF; HFpEF — HF with preserved EF; HFrEF — heart failure with reduced ejection fraction; HR — hazard ratio; CI — confidence interval; LDL — low-density lipoprotein; MI — myocardial infarction; PCI — percutaneous coronary intervention; SBP — systolic blood pressure; SDT — symptom-to-door time.

*

Adjusted by male sex, age, SBP, DBP, heart rate, hypertension, DM, dyslipidemia, previous MI, previous PCI, previous CABG, previous stroke, current smokers, BMI, Killip class II/III, cardiogenic shock, CPR on admission, SDT, DBT, peak CK-MB, peak troponin-I, hemoglobin, blood glucose, and triglyceride (Supplementary Table S1A).

†

The propensity score-matching results for each group are provided in Supplementary Tables 3A–F

Table 3.

Comparison of three-year clinical outcomes between chronic kidney disease (CKD) and non-CKD groups according to left ventricular ejection fraction (LVEF) subgroups

HFrEF (LVEF ≤ 40%), n = 537
Outcomes CKD (n = 163) Group A Non-CKD (n = 374) Group D Log-rank Unadjusted Adjusted* Propensity score-adjusted†
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 49 (30.1) 97 (25.9) 0.250 1.223 (0.867–1.724) 0.252 1.199 (0.811–1.703) 0.363 1.270 (0.874–1.847) 0.210
Cardiac death 34 (20.9) 69 (18.4) 0.413 1.187 (0.787–1.790) 0.414 1.204 (0.790–1.933) 0.387 1.273 (0.822–1.974) 0.280
Non-cardiac death 15 (9.2) 28 (7.5) 0.395 1.312 (0.701–2.456) 0.396 1.238 (0.609–2.385) 0.555 1.263 (0.613–2.628) 0.482
Recurrent MI 10 (7.5) 22 (6.8) 0.797 1.103 (0.522–2.329) 0.797 1.381 (0.603–3.160) 0.445 1.298 (0.599–2.810) 0.509
Any repeat revascularization 13 (10.0) 43 (13.6) 0.308 0.725 (0.390–1.349) 0.310 0.856 (0.439–1.670) 0.648 0.779 (0.402–1.510) 0.460
Hospitalization for HF 15 (11.4) 45 (14.0) 0.468 0.806 (0.449–1.445) 0.469 0.739 (0.394–1.384) 0.344 0.764 (0.400–1.483) 0.427
Stroke 9 (7.0) 11 (3.6) 0.102 2.052 (0.850–4.951) 0.105 1.429 (0.457–4.464) 0.539 1.512 (0.501–4.825) 0.309
HFmrEF (LVEF 41–49%), n = 821
Outcomes CKD (n = 231) Group B Non-CKD (n = 590) Group E Log-rank Unadjusted Adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 25 (10.8) 57 (9.7) 0.619 1.127 (0.704–1.803) 0.619 1.085 (0.656–1.795) 0.749 1.148 (0.791–1.919) 0.467
Cardiac death 13 (5.6) 30 (5.1) 0.745 1.114 (0.581–2.135) 0.745 1.039 (0.519–2.078) 0.914 1.010 (0.504–1.691) 0.969
Non-cardiac death 12 (5.2) 27 (4.6) 0.704 1.141 (0.578–2.252) 0.704 1.148 (0.598–2.386) 0.688 1.359 (0.795–2.635) 0.262
Recurrent MI 8 (3.6) 19 (3.4) 0.827 1.097 (0.480–2.505) 0.827 1.046 (0.431–2.474) 0.921 1.127 (0.652–2.741) 0.685
Any repeat revascularization 19 (8.7) 50 (8.9) 0.925 0.975 (0.575–1.654) 0.925 0.939 (0.538–1.641) 0.826 0.906 (0.468–1.229) 0.524
Hospitalization for HF 13 (5.9) 19 (3.4) 0.106 1.774 (0.876–3.593) 0.111 1.548 (0.746–3.211) 0.241 1.495 (0.704–3.180) 0.225
Stroke 3 (1.4) 15 (2.7) 0.277 0.509 (0.147–1.760) 0.286 0.835 (0.227–3.075) 0.786 0.796 (0.208–3.041) 0.739
HFpEF (≥ 50%), n = 3209
Outcomes CKD (n = 876) Group C Non-CKD (n = 2333) Group F Log-rank Unadjusted Adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 53 (6.1) 95 (4.1) 0.018 1.497 (1.070–2.095) 0.019 1.597 (1.111–2.295) 0.011 1.510 (1.079–2.114) 0.016
Cardiac death 26 (3.0) 49 (2.1) 0.145 1.422 (0.884–2.288) 0.147 1.404 (0.842–2.241) 0.193 1.431 (0.889–2.303) 0.140
Non-cardiac death 27 (3.1) 46 (2.0) 0.058 1.577 (0.980–2.536) 0.060 1.844 (1.100–3.093) 0.020 1.758 (1.054–2.875) 0.035
Recurrent MI 35 (4.1) 55 (2.4) 0.011 1.720 (1.126–2.628) 0.012 1.716 (1.113–2.607) 0.014 1.666 (1.090–2.547) 0.014
Any repeat revascularization 71 (8.4) 187 (8.2) 0.884 1.020 (0.777–1.341) 0.884 1.051 (0.788–1.401) 0.737 1.032 (0.764–1.325) 0.835
Hospitalization for HF 29 (3.4) 34 (1.5) 0.001 2.299 (1.401–3.773) 0.001 2.846 (1.676–4.830) < 0.001 2.383 (1.446–3.928) 0.001
Stroke 16 (1.9) 46 (2.0) 0.807 0.932 (0.527–1.645) 0.807 0.824 (0.442–1.536) 0.542 0.935 (0.529–1.653) 0.818
Total, n = 4567
Outcomes CKD (n = = 1270) Group A + B+ C Non-CKD (n = 3297) Group D + E + F Log-rank Unadjusted Adjusted * Propensity score-adjusted †
HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value
All-cause death 127 (10.0) 249 (7.6) 0.007 1.343 (1.085–1.663) 0.007 1.375 (1.089–1.735) 0.007 1.331 (1.073–1.651) 0.009
Cardiac death 73 (5.7) 148 (4.5) 0.068 1.297 (0.980–1.717) 0.069 1.294 (0.951–1.761) 0.100 1.278 (0.963–1.696) 0.089
Non-cardiac death 54 (4.3) 101 (3.1) 0.040 1.411 (1.014–1.964) 0.041 1.483 (1.039–2.117) 0.030 1.409 (1.009–1.968) 0.044
Recurrent MI 53 (4.3) 96 (3.0) 0.025 1.466 (1.048–2.050) 0.025 1.542 (1.088–2.186) 0.015 1.438 (1.028–2.011) 0.034
Any repeat revascularization 103 (8.6) 280 (8.9) 0.787 0.969 (0.773–1.215) 0.787 0.952 (0.714–1.204) 0.737 0.976 (0.779–1.224) 0.834
Hospitalization for HF 57 (4.7) 98 (3.1) 0.009 1.540 (1.111–2.135) 0.010 1.610 (1.145–2.263) 0.007 1.545 (1.114–2.144) 0.009
Stroke 28 (2.3) 72 (2.3) 0.912 1.025 (0.662–1.586) 0.912 1.137 (0.694–1.864) 0.610 1.017 (0.657–1.574) 0.941
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CABG — coronary artery bypass graft; CPR — cardiopulmonary resuscitation; DBP — diastolic blood pressure; DM — diabetes mellitus; HFmrEF — HF with mildly reduced EF; HFpEF — HF with preserved EF; HFrEF — heart failure with reduced ejection fraction; IRA — infarct-related artery; LAD — left anterior descending coronary artery; LDL — low-density lipoprotein; MI — myocardial infarction; PCI — percutaneous coronary intervention; SBP — systolic blood pressure.

*

Adjusted by male sex, age, SBP, DBP, hypertension, DM PCI, CABG, CPR, hemoglobin, triglyceride, LDL-cholesterol, IRA, and LAD (Supplementary Table S1B).

†

The propensity score-matching results for each group are provided in Supplementary Tables 3G–J

Figure 2.

Figure 2

Figure 2

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Kaplan–Meier analysis for all-cause death (A), cardiac death (B), non-cardiac death (C), recurrent MI (D), any repeat revascularization (E), hospitalization for HF (F), and stroke (G) during a three-year follow-up period; CKD — chronic kidney disease; EF — ejection fraction; HF — heart failure; PCI — percutaneous coronary intervention Kaplan–Meier analysis for all-cause death (A), cardiac death (B), non-cardiac death (C), recurrent MI (D), any repeat revascularization (E), hospitalization for HF (F), and stroke (G) during a three-year follow-up period; CKD — chronic kidney disease; EF — ejection fraction; HF — heart failure; PCI — percutaneous coronary intervention

Outcomes among the three LVEF subgroups in the CKD and non-CKD groups

In the CKD group, the HFrEF subgroup had higher rates of all-cause death compared with the HFmrEF and HFpEF subgroups (adjusted HR [aHR] 3.597, 95% CI: 2.084–6.210, p < 0.001 and aHR 5.065, 95% CI: 3.205–8.005, p < 0.001, respectively), as well as higher rates of CD (aHR 5.239, 95% CI: 2.509–10.94, p < 0.001 and aHR 7.237, 95% CI: 3.984–13.14, p < 0.001, respectively) and stroke (aHR 6.081, 95% CI: 1.532–24.14, p = 0.010 and aHR 5.288, 95% CI: 2.102–13.30, p < 0.001, respectively). Furthermore, the HFrEF subgroup had significantly higher rates of NCD (aHR 2.935, 95% CI: 1.374–6.271, p = 0.005) and HHF (aHR 2.453, 95% CI: 1.180–5.099, p = 0.016) than the HFpEF subgroup. However, the primary and secondary outcomes did not differ significantly between the HFmrEF and HFpEF subgroups (Tab. 2). In the non-CKD group, the HFrEF subgroup had higher rates of all-cause death than the HFmrEF and HFpEF subgroups (aHR 3.179, 95% CI: 2.167–4.662, p < 0.001 and aHR 5.340, 95% CI: 3.849–7.408, p < 0.001, respectively), as well as higher rates of cardiac death (CD) (aHR 4.854, p < 0.001 and aHR 7.013, p < 0.001, respectively), recurrent MI (p = 0.035 and p = 0.003, respectively), any repeat revascularization (p = 0.028 and p = 0.001, respectively), and HHF (p < 0.001 and p < 0.001, respectively). Furthermore, the HFrEF subgroup had significantly higher rates of NCD (aHR 3.479, p < 0.001) than the HFpEF subgroup. The HFmrEF subgroup had higher rates of all-cause death (aHR 1.745, 95% CI: 1.188–2.562, p = 0.005), CD (aHR 2.069, p = 0.008), and HHF (p = 0.003) than the HFpEF subgroup. The propensity score-adjusted analyses confirmed the robustness of the multivariate-adjusted results (Tab. 2).

Outcomes between the CKD and the non-CKD groups according to LVEF subgroups

Neither the HFrEF nor HFmrEF subgroups showed significant differences in any outcomes between the CKD and non-CKD groups. However, in the HFpEF subgroup and the total study population, the CKD group had higher rates of all-cause death (aHR 1.597, 95% CI: 1.111–2.295, p = 0.011 and aHR 1.375, 95% CI: 1.089–1.735, p = 0.007, respectively), NCD (aHR 1.844, p = 0.020 and aHR 1.483, p = 0.030, respectively), recurrent MI (p = 0.014 and p = 0.015, respectively), and HHF (p < 0.001 and p = 0.007, respectively) than the non-CKD group. The propensity score-adjusted findings aligned closely with the multivariate-adjusted outcomes (Tab. 3).

Independent predictors

In both the CKD and non-CKD groups, male sex, older age (≥ 65 years), Killip class II/III status, CPR on admission, non-use of beta-blockers, non-use of renin angiotensin system inhibitor (RASI), and non-use of statins were significant independent predictors of all-cause death (Suppl. Tab. 3B).

Discussion

The main findings of this multicenter prospective cohort study were as follows: first, in the CKD group, the three-year adjusted rates of all-cause death, CD, and stroke were significantly higher in the HFrEF subgroup than in the HFmrEF and HFpEF subgroups. However, all clinical outcomes were similar between the HFmrEF and HFpEF subgroups. Second, in the non-CKD group, the three-year adjusted rates of all-cause death, CD, recurrent MI, repeat revascularization, and HHF were significantly higher in the HFrEF subgroup than in the HFmrEF and HFpEF subgroups. The adjusted three-year rates of all-cause death, CD, and HHF were significantly higher in the HFmrEF subgroup than in the HFpEF subgroup. Third, although the adjusted three-year clinical outcomes in the HFrEF and HFmrEF subgroups were similar between the CKD and non-CKD groups, the HFpEF subgroup and total study population showed higher adjusted three-year all-cause death, NCD, and recurrent MI rates in the CKD group than in the non-CKD group. Fourth, in both the CKD and non-CKD groups, male sex, older age, Killip class II/III status, CPR on admission, non-use of beta-blockers, non-use of RASI, and non-use of statin were significant independent predictors of all-cause death.

Approximately 25–30% of patients with NSTEMI experience a moderate reduction in kidney function [3]. In the present study, 27.8% (1270/4567) of patients with NSTEMI showed an eGFR of < 60 mL/min/1.73 m2. Previous studies have reported that CKD contributes to adverse outcomes in patients with HFpEF [26]. Similarly, in the present study, the CKD group in the HFpEF subgroup showed higher rates of all-cause death, NCD, recurrent MI, and HHF (Tab. 3). These worse outcomes may explain the similar clinical outcomes between the HFmrEF and HFpEF subgroups in the CKD group (Tab. 2). A recent meta-analysis [27] also showed a lower all-cause death for HFmrEF compared with HFrEF (risk ratio [RR] 0.92, 95% CI: 0.85–0.98, p < 0.001) but a similar prognosis compared with HFpEF (RR 1.02, 95% CI: 0.96–1.09, p = 0.63). Another study [28] reported that a reduced eGFR was a stronger predictor of all-cause death in patients with HFrEF than in those with HFpEF. These conflicting results are likely due to differences in study populations [29].

In this study, the baseline characteristics did not differ significantly between the CKD and non-CKD groups, except for sex, age, hypertension, current smoking status, Killip class II/III, hemoglobin, triglycerides, intravascular ultrasound/optical coherence tomography, and stent diameter (Suppl. Tab. 3A). These baseline characteristics were comparable to those of the CKD and non-CKD groups in the HFpEF (EF ≥ ≥ 50%) and HFrEF (EF ≤ 40%) subgroups in a recent study [29]. Hypertension and DM are the two primary causes of CKD worldwide and are significant risk factors for CVD [30]. In the present study, the number of hypertensive patients was higher in the CKD group than in the non-CKD group across the HFmrEF and HFpEF subgroups and the total study population. However, the number of patients did not differ significantly between the CKD and non-CKD groups in any of the three LVEF groups. This may be attributed to the exclusion of many patients based on the exclusion criteria shown in Figure 1 and could also explain the similar clinical outcomes of the CKD and non-CKD groups in the HFrEF and HFmrEF subgroups (Tab. 3). Despite this, the HFrEF subgroup within the CKD group in the present study showed higher rates of all-cause death and CD compared with the HFmrEF and HFpEF subgroups (Tab. 2).

Heart failure with mildly reduced EF may be more similar to HFpEF or HFrEF; it may be a transition between the two, or it may be a distinct syndrome [18, 27]. The long-term clinical outcomes in HFmrEF patients are still unclear, and the link between CKD and both HFmrEF and HFpEF is not well established [26, 31]. Many patients with AMI exhibit a gradual reduction in EF, potentially progressing to ischemic heart disease. This decrease in cardiac output frequently leads to reduced renal blood flow, which exacerbates renal injury [4]. No other studies have compared outcomes based solely on LVEF in patients with NSTEMI who underwent successful PCI according to CKD presence or absence. Therefore, comparison of our results with those of other studies is limited. However, a recent nationwide cohort study comparing the effects of CKD in patients with NSTEMI [1] showed a 1.55-fold increased risk of five-year mortality (95% CI: 1.53–1.58) among patients with CKD compared (p < 0.001) to patients without CKD (p < 0.001). The CKD group in the present study showed higher all-cause death (aHR 1.375, 95% CI: 1.089–1.735, p = 0.007) than the non-CKD group in the overall study population. Other recent registry results [32] showed a significantly lower all-cause death rate among patients with HFmrEF compared with those with HFrEF (aHR 0.89, 95% CI: 0.83–0.95, p < 0.001) and HFpEF (aHR 1.25, 95% CI: 1.17–1.33, p < 0.001). Similarly, the HFrEF subgroup in the non-CKD group in the present study demonstrated higher all-cause death (aHR 3.179, p < 0.001) and CD (aHR 4.854, p < 0.001) rates than the HFmrEF subgroup, whereas the HFmrEF subgroup showed higher rates of all-cause death (aHR 1.745, p = 0.005) and CD (aHR 2.069, p = 0.008) compared with the HFpEF subgroup (Tab. 2).

In both the CKD and non-CKD groups, the all-cause death and CD rates were significantly higher in the HFrEF subgroup than in the HFmrEF and HFpEF subgroups (Tab. 2), consistent with previous reports [33] that did not consider CKD status. These results suggest that although we conducted a multivariate-adjusted analysis, the HFrEF subgroup may be associated with worse baseline characteristics than the HFmrEF or HFpEF subgroups, as shown in Table 1 and Supplementary Table 3A. However, in our study, the clinical outcomes of the HFmrEF and HFpEF subgroups showed different patterns between the CKD and non-CKD groups. Specifically, the long-term prognoses of the HFmrEF and HFpEF subgroups remain controversial. Further research is needed to address this issue. We hope our findings provide valuable information for cardiologists treating patients with NSTEMI and CKD.

Study limitations

This study has several limitations. First, owing to the nature of the registry dataset, underreported and/or missing data are possible. Second, although we conducted multivariate analyses, variables outside the KAMIR-NIH dataset may have influenced the study outcomes. Third, the three-year follow-up period may be too short to compare long-term outcomes. Fourth, although monitoring LVEF changes over a three-year follow-up period is key to understanding clinical outcomes, owing to substantial missing data in the registry, we could not assess the changes in LVEF for each group throughout the entire follow-up period. Fifth, we acknowledge as an important limitation that patients treated with angiotensin receptor–neprilysin inhibitors or sodium–glucose cotransporter-2 inhibitors — both recommended as Class IA therapies for patients with HFrEF [34] — were not included, which may limit the extent to which our findings reflect current clinical practice. Finally, although the albumin-to-creatinine ratio is clinically important for diagnosing CKD and for prognostic assessment, it was not a mandated variable in KAMIR-NIH and was therefore largely unavailable. Accordingly, ACR could not be incorporated into the present analyses, which constitutes a limitation

Conclusions

The results of this multicenter, prospective cohort study demonstrated higher mortality rates in the HFrEF subgroup compared to those in the HFmrEF and HFpEF subgroups in both the CKD and non-CKD groups. However, the mortality rates between the HFmrEF and HFpEF subgroups showed different patterns between the CKD and non-CKD groups. Further research is required to confirm these findings.

Supplementary Information

Acknowledgements

Investigators of KAMIR-NIH (Korea Acute Myocardial Infarction Registry — National Institutes of Health): Myung Ho Jeong, Chonnam National University Hospital Chonnam, Gwangju, Korea; Young Jo Kim, Yeungnam University Medical Center, Daegu, Korea; Chong Jin Kim, Kyunghee University Hospital at Gangdong, Seoul, Korea; Myeong Chan Cho, Chungbuk National University Hospital, Cheongju, Korea; Hyo-Soo Kim, Seoul National University Hospital, Seoul, Korea; Hyeon-Cheol Gwon, Samsung Medical Center, Seoul, Korea; Ki Bae Seoul St. Mary’s Hospital, Seoul, Korea; Dong Joo Oh, Korea University Guro Hospital, Seoul, Korea; Shung Chull Chae, Kyungpook National University Hospital, Daegu, Korea; Kwang Soo Cha, Pusan National University Hospital, Busan, Korea; Junghan Yoon, Wonju Severance Christian Hospital, Wonju, Korea; Jei-Keon Chae, Chonbuk National University Hospital, Jeonju, Korea; Seung Jae Joo, Jeju National University Hospital, Jeju, Korea; Dong-Ju Choi, Seoul National University Bundang Hospital, Bundang, Korea; Seung-Ho Hur, Keimyung University Dongsan Medical Center, Daegu, Korea; In Whan Seong, Chungnam National University Hospital, Daejeon, Korea; Doo Il Kim, Inje University Haeundae Paik Hospital, Busan, Korea; Seok Kyu Oh, Wonkwang University Hospital, Iksan, Korea; Tae Hoon Ahn, Gachon University Gil Medical Center, Incheon, Korea; Jin-Yong Hwang, Gyeongsang National University Hospital, Jinju, Korea.

Footnotes

Ethics statement: This study received approval from the ethics committees of all participating centers, including the Korea University Guro Hospital Institutional Review Board Ethics Committee (approval number: KUGH MD11024), in compliance with the ethical guidelines of the 2004 Declaration of Helsinki.

Author contributions: Conceptualization: Y.H.K., A.-Y.H., S.-W.R., C.U.C., S.P., J.R.C., J.Y.P., M.H.J.; data curation: Y.H.K., A.-Y.H., B.G.C., S.P., S.J.H.; formal analysis: Y.H.K., A.-Y.H., B.G.C., S.P., S.J.H.; funding acquisition: M.H.J.; investigation: Y.H.K., A.-Y.H., S.-W.R., C.U.C., B.G.C., S.P., J.R.C., J.Y.P., M.H.J.; methodology: Y.H.K., A.-Y.H., S.-W.R., C.U.C., B.G.C., J.R.C., J.Y.P., M.H.J.; project administration: Y.H.K., A.-Y.H., S.-W.R., C.U.C., J.R.C., J.Y.P., M.H.J.; resources: S.-W.R., C.U.C., S.P., M.H.J.; software: Y.H.K., A.-Y.H., B.G.C., S.P., S.J.H.; supervision: Y.H.K., S.-W.R., M.H.J.; validation: Y.H.K., A.-Y.H., S.-W.R., C.U.C., B.G.C., J.R.C., J.Y.P., M.H.J.; visualization: Y.H.K., A.-Y.H., S.-W.R., C.U.C., B.G.C., S.J.H., J.R.C., J.Y.P., M.H.J.; writing — original draft: Y.H.K., A.-Y.H.; writing — review & editing: Y.H.K., A.-Y.H., S.-W.R., C.U.C., B.G.C., S.P., S.J.H., J.R.C., J.Y.P., M.H.J.

Funding: This research was supported by a fund (2016-ER6304-02) by Research of Korea Centers for Disease Control and Prevention.

Conflicts of interest: The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

Supplementary material: Supplementary Tables 1–3 (available on Journal’s website).

Data availability statement

Data is contained within the article or supplementary material.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

18_33-0_[103619]_Supp-9.docx (24.5KB, docx)
19_33-0_[103619]_Supp-10.docx (203.4KB, docx)
20_33-0_[103619]_Supp-11.docx (56.9KB, docx)

Data Availability Statement

Data is contained within the article or supplementary material.

Articles from Cardiology Journal are provided here courtesy of Via Medica sp. z o.o. sp. k.

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