Corrigendum to "Oncostatin M mediates cardioprotection via angiogenesis in ischemic heart disease" [Am. Heart J. Plus Cardiol. Res. Pract. vol. 35, 2023, 100331].

[This corrects the article DOI: 10.1016/j.ahjo.2023.100331.].

Takotsubo syndrome associated with coronary microvascular dysfunction: A case study.

The patient, a 68-year-old man, presented to our emergency room with chest pain, prompting an emergency cardiac catheterization due to elevated cardiac troponin-I levels. While no obvious coronary artery stenosis was found, there was evidence of apical ballooning wall motion in the left ventricle, leading to a diagnosis of takotsubo syndrome. Three months later, he occasionally experienced chest pain at rest, prompting us to conduct another cardiac catheterization. Left ventriculography showed normal contraction. Suddenly, he experienced chest pain accompanied by ST elevation, which occurred spontaneously. Subsequently, slow-flow phenomenon was observed in the intermediate part of left anterior descending artery (LAD). We promptly administered nitroglycerin to alleviate the symptoms. Following the diagnosis of coronary microvascular dysfunction (CMD), he started calcium-channel blocker therapy and remained asymptomatic. One year later, we re-performed cardiac catheterization to further explore his condition. Acetylcholine provocation test was performed, which showed no epicardial coronary spasm. However, lactic acid elevation was observed in the coronary sinus blood sample. Additionally, a coronary physiological measurement in the LAD revealed a high index of microcirculatory resistance and low coronary flow reserve. Based on this series of clinical events, we inferred a significant contribution of CMD to the patient's condition. Learning objective: Coronary microvascular dysfunction (CMD) is increasingly recognized as an important cardiovascular disease, leading to myocardial ischemia, which is occasionally associated with takotsubo syndrome (TTS). In this report, we present a case of spontaneous CMD associated with TTS. This case emphasizes the significance of accurate diagnosis and appropriate treatment, highlighting the importance of recognizing CMD in patients with TTS.

Oncostatin M mediates cardioprotection via angiogenesis in ischemic heart disease.

Objective: Oncostatin M (OSM) is an inflammatory cytokine belonging to the interleukin-6 family member, which plays an important role in various cardiovascular diseases. We recently reported increased serum OSM levels in patients with coronary artery disease. However, the specific role in HF with ischemic heart disease (IHD) remains unclear. Methods and results: A total of 120 patients with HF and 48 control subjects were enrolled in this study. Serum OSM levels were measured using a sandwich technique immunoassay during the compensated state. The results revealed significantly higher serum OSM levels in HF patients compared to controls. Importantly, HF patients with IHD had higher OSM levels, and those with collateral flow showed the even higher levels, indicating a potential involvement in angiogenesis. Furthermore, a positive correlation was found between serum OSM levels and levels of vascular endothelial growth factor (VEGF). In vitro experiments demonstrated that recombinant OSM upregulated VEGF production in cultured human coronary artery endothelial cells. We additionally observed that endogenous OSM levels were enhanced through exercise. Lastly, we identified the potential of SGLT2 inhibitors to enhance OSM production. Conclusions: Serum OSM levels were elevated in HF patients, particularly in those with IHD Our data indicated that endogenous OSM induces VEGF production in the heart, suggesting the activation of angiogenesis, which can be further enhanced by exercise or SGLT2 inhibitors.

A case of ventricular fibrillation without left ventricular systolic dysfunction induced by trastuzumab emtansine for breast cancer.

Trastuzumab-induced cardiomyopathy is a known complication of its use in breast cancer treatment. However, cardiac complications of trastuzumab without left ventricular systolic dysfunction have been rarely reported. These include left bundle branch block, sinus node dysfunction, and ventricular tachycardia. We herein report a case of a 47-year-old female with human epidermal growth factor receptor 2-positive, stage IV breast cancer without a history of cardiovascular disease. During treatment with trastuzumab emtansine (T-DM1), she presented with out-of-hospital cardiac arrest and was resuscitated by automated cardioverter defibrillator (AED). Emergent cardiac catheterization revealed no organic obstruction and coronary vasospasm in her coronary arteries, and no left ventricular systolic dysfunction. Ventricular fibrillation (VF) was documented by an event memory of AED. T-DM1 was withdrawn and implantable cardioverter defibrillator was implanted. Thereafter, VF or life-threatening arrhythmia were not documented for 36 months until her death by breast cancer. We concluded that the etiology of her VF event was T-DM1-induced cardiotoxicity. We believe this is the first report of life-threatening VF event without cardiomyopathy induced by T-DM1. .

Unique left pulmonary vein isolation in straight common trunk based on longitudinal conduction of left lateral ridge.

BACKGROUND: A left common pulmonary vein (LCPV) is the most common anatomical variation in the pulmonary vein (PV) and often influences strategies of PV isolation for atrial fibrillation (AF). Our objective was to elucidate the electrical properties of the specific shape of LCPV and to apply it to an ablation procedure. METHODS AND RESULTS: We investigated consecutive 12 out of 204 paroxysmal AF patients who had the shape of a straight common trunk in LCPV defined by the formation of a single conduit with parallel cranial and caudal walls after the coalescence of superior and inferior PVs on the distal side. The distance between the top of the bifurcation of LPVs and the level coinciding with the middle of the anterior wall of LCPV (left lateral ridge: LLR) was more than 10 mm in all the patients. The activation pattern of the LLR showed longitudinal conduction without outside connections. All the LCPV except one were successfully isolated without ablating the LLR (C-shape ablation). Only one patient had AF recurrence during the follow-up period. CONCLUSION: The LLR in LCPV with a straight common trunk has longitudinal conduction without outside connections, which permits the isolation of LCPV without ablating LLR.

Oncostatin M is a novel biomarker for coronary artery disease - A possibility as a screening tool of silent myocardial ischemia for diabetes mellitus.

OBJECTIVE: Oncostatin M (OSM) is an inflammatory cytokine of the interleukin-6 family which plays a crucial role in the pathogenesis of atherosclerosis. Therefore, we tested our hypothesis that serum OSM levels are increased in patients with coronary artery diseases (CAD). METHODS AND RESULTS: Serum OSM level was measured by sandwich technique immunoassay in 315 consecutive patients and who underwent coronary angiography at the International University of Health and Welfare Hospital from April 2019 to March 2021. A diagnosis of CAD was made in 169 patients. Serum OSM levels were significantly higher in patients with significant coronary stenosis compared to those without it. [123.0 ± 46.7 pg/mL (n = 169) vs. 98.3 ± 47.9 pg/mL (n = 146), p < 0.001]. A positive correlation was noted between serum OSM levels and severity and complexity of coronary stenosis. Importantly, the coronary revascularization significantly decreased the serum OSM levels. We furthermore detected a positive correlation between serum OSM levels and HbA1c levels. Finally, our data suggested that 120 pg/mL of serum OSM was the potential cutoff value for screening of silent myocardial ischemia related with diabetic mellitus (DM). CONCLUSION: Serum OSM can be a novel biomarker for CAD and may be useful for the screening of asymptomatic CAD in patients with DM.

A case of vasospastic angina with exertional sign.

We herein report a case of a 56-year-old woman with angina pectoris. She visited our emergency room because of chest pain. She finally underwent emergency percutaneous coronary intervention in right coronary artery due to acute coronary syndrome. Several months later, she complained of exertional chest pain again. Exercise-stress electrocardiogram showed ST-segment depression in V2-V6. However, coronary angiography showed no organic stenosis and we conducted acetylcholine provocation test. We finally detected severe coronary artery spasm and diagnosed exercise-induced vasospastic angina (VSA). This case highlights the importance of the recognition of exercise-induced VSA. Exercise-induced VSA needs the definite diagnosis and appropriate treatment. Learning objective Many patients felt chest pain even if they have undergone percutaneous coronary intervention (PCI). This case highlights the importance of the recognition of exercise-induced vasospastic angina (VSA). Exercise-induced VSA needs definite diagnosis and appropriate treatment. This case report describes the importance of precise diagnosis and highlights the recognition of exercise-induced VSA. We recommend the acetylcholine provocation test after PCI in order to determine the diagnosis of exercise-induced VSA.

Risk of Out-of-Hospital Cardiac Arrest in Aged Individuals in Relation to Cold Ambient Temperature　- A Report From North Tochigi Experience.

BACKGROUND: The impact of cold ambient temperature on out-of-hospital cardiac arrest (OHCA) in aged individuals caused by cardiovascular events in indoor environments has not been investigated sufficiently.Methods and Results:We conducted a case-crossover study. The relationship between OHCA caused by cardiovascular events and exposure to minimum temperature <0℃ was analyzed. Conditional logistic regression analysis was performed to estimate the odds ratios for the relationship between exposure to minimum temperature <0℃ and the risk of OHCA. Between January 1, 2011, and December 31, 2015, a total of 1,452 cases of OHCA were documented, and patients were screened for enrollment. A total of 458 individuals were enrolled in this analysis, and were divided into 2 groups of 110 (elderly group: 65-74 years old) and 348 (aged group: ≥75 years old). The aged individuals had a significant increased risk of OHCA after exposure to minimum temperature <0℃ (odds ratio [OR]: 1.528, 95% confidence interval [CI] 1.009-2.315, P=0.045). Cold ambient temperature was an especially significant increased risk for OHCA occurrence for males (OR: 1.997, 95% CI 1.036-3.773, P=0.039) and during winter (OR: 2.391, 95% CI 1.312-4.360, P=0.004) in the aged group. CONCLUSIONS: Cold ambient temperature significantly affected aged individuals (≥75 years old) experiencing an OHCA caused by cardiovascular events in indoor environments.

Impaired glucose tolerance and albuminuria in patients with chronic heart failure: a subanalysis of the SUPPORT trial.

AIMS: The study aims to evaluate the prognostic significance of impaired glucose tolerance (IGT) with reference to albuminuria in patients with chronic heart failure (CHF). METHODS AND RESULTS: We examined 535 CHF patients (mean 66 years, women 25%) in the control arm of our SUPPORT trial, in which we examined additive impact of olmesartan in hypertensive patients with symptomatic CHF treated with ß-blockers and/or angiotensin-converting enzyme inhibitors. We examined the association between glycaemic abnormality (assessed by 75 g of oral glucose tolerance test) and albuminuria for a composite outcome of all-cause death, myocardial infarction, stroke, and HF hospitalization. IGT patients (N = 113, mean 67.2 years) were older and more frequently treated with ß-blockers compared with those with normal glucose regulation (N = 142, mean 64.0 years) and those with diabetes mellitus (N = 280, mean 65.7 years). Multivariable Cox proportional hazard models revealed that, as compared with normal glucose regulation (NGR), IGT was associated with increased risk of the outcome when complicated by albuminuria [hazard ratio (HR) 2.25; 95% confidence interval (CI) 1.14-4.42; P = 0.019] but not when uncomplicated by albuminuria (HR 0.76; 95% CI 0.35-1.60, P = 0.47) (P for interaction = 0.041). This was also the case for diabetes mellitus and albuminuria (HR 2.06; 95% CI 1.17-3.61; P = 0.012). Among IGT patients without albuminuria, 21 (29%) developed albuminuria at 1-year visit, which was again associated with poor prognosis (HR 7.36; 95% CI 1.39-38.98, P = 0.019). CONCLUSIONS: These results indicate that IGT is associated with poor prognosis when complicated by albuminuria in CHF patients, demonstrating the importance of combined early stages of glucose intolerance and renal dysfunction in the management of CHF.

Stent collapse caused by balloon occlusion and aspiration system in saphenous vein graft intervention.

We present the case of an 82-year-old male patient with unstable angina pectoris referred for percutaneous coronary intervention in the saphenous vein graft (SVG) to left circumflex coronary artery. An everolimus-eluting cobalt chrome stent was successfully deployed, using an embolic protection device with balloon occlusion and aspiration system. During the procedure of aspiration thrombectomy, the deployed stent unexpectedly collapsed. We re-dilated the collapsed stent using the same distal protection and aspiration system. However, the stent collapsed again during the aspiration procedure. As we could successfully re-dilate the collapsed stent using the same balloon occlusion and aspiration system after pulling the guide catheter out from the ostium of SVG, we concluded that the collapse of the stent was caused by the excess negative pressure generated by the distal occlusion and aspiration procedure under the completely wedged guide catheter into the ostium of SVG. We believe this is the first report of stent collapse due to excess negative pressure during aspiration thrombectomy. .

Influence of Left Ventricular Ejection Fraction on the Effects of Supplemental Use of Angiotensin Receptor Blocker Olmesartan in Hypertensive Patients With Heart Failure.

BACKGROUND: There is no robust evidence of pharmacological interventions to improve mortality in heart failure (HF) patients with preserved left ventricular ejection fraction (LVEF) (HFpEF). In this subanalysis study of the SUPPORT Trial, we addressed the influence of LVEF on the effects of olmesartan in HF. METHODS AND RESULTS: Among 1,147 patients enrolled in the SUPPORT Trial, we examined 429 patients with reduced LVEF (HFrEF, LVEF <50%) and 709 with HFpEF (LVEF ≥50%). During a median follow-up of 4.4 years, 21.9% and 12.5% patients died in the HFrEF and HFpEF groups, respectively. In HFrEF patients, the addition of olmesartan to the combination of angiotensin-converting enzyme inhibitor (ACEI) and ß-blocker (BB) was associated with increased incidence of death (hazard ratio (HR) 2.26, P=0.002) and worsening renal function (HR 2.01, P=0.01), whereas its addition to ACEI or BB alone was not. In contrast, in HFpEF patients, the addition of olmesartan to BB alone was significantly associated with reduced mortality (HR 0.32, P=0.03), whereas with ACEIs alone or in combination with BB and ACEI was not. The linear mixed-effect model showed that in HFpEF, the urinary albumin/creatinine ratio was unaltered when BB were combined with olmesartan, but significantly increased when not combined with olmesartan (P=0.01). CONCLUSIONS: LVEF substantially influences the effects of additive use of olmesartan, with beneficial effects noted when combined with BB in hypertensive HFpEF patients. (Circ J 2016; 80: 2155-2164).

Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial.

We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96-1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19-2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and ß-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11-1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01-2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24-2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and ß-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

Prevalence, predictors and prognosis of patients with heart failure requiring nursing care.

BACKGROUND: Although the need for nursing care (NC) in heart failure (HF) patients is recognized, detailed information on the current status in Japan is lacking. METHODS AND RESULTS: In the CHART-2 Study, we obtained information on daily life, physical ability, nutrition and mental status for 4,174 patients (mean age, 67.1±10.8 years; 73.3% male) out of 10,219 patients. We examined the prevalence, baseline characteristics and clinical outcomes of stage B and C/D HF patients requiring NC. The prevalence of HF requiring NC was significantly higher in stage C/D (38.6%) than in stage B (30.4%; P<0.001). Among the reasons for requiring NC, physical dysfunction was most prevalent in both stage B (20.6%) and C/D (29.0%). Compared with the non-NC group, the NC group was characterized by higher age, higher prevalence of female gender and cerebrovascular disease, and increased plasma brain natriuretic peptide regardless of HF stage. During a median follow-up of 12.7 months after the survey, the NC group had a significantly higher mortality compared with the non-NC group (9.6% vs. 3.6%, P<0.001). On multivariate logistic analysis depressive mental status (hazard ratio [HR], 3.61; P<0.001) and dementia (HR, 2.70; P<0.001) were significantly associated with NC need. CONCLUSIONS: In HF patients, NC need is considerably high and is associated with increased mortality regardless of HF stage in Japan.

Usefulness of combined risk stratification with heart rate and systolic blood pressure in the management of chronic heart failure. A report from the CHART-2 study.

BACKGROUND: The appropriate target ranges of heart rate (HR) and systolic blood pressure (SBP) for the management of chronic heart failure (CHF) patients remain to be elucidated in a large-scale cohort study. METHODS AND RESULTS: We examined 3,029 consecutive CHF patients with sinus rhythm (SR) (mean age, 67.9 years) registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 Study (CHART-2; NCT00418041). There were 357 deaths (11.8%) during the median follow-up of 3.1 years. We first performed the classification and regression tree analysis for mortality, identifying SBP <89 mmHg, HR >70 beats/min and SBP <115 mmHg as the primary, secondary and tertiary discriminators, respectively. According to these, we divided the patients into low- (n=1,131), middle- (n=1,624) and high-risk (n=274) groups with mortality risk <10%, 10-20% and >20%, respectively. The low-risk group was characterized by SBP >115 mmHg and HR <70 beats/min and the high-risk group by SBP <89 mmHg regardless of HR values or SBP 89-115 mmHg and HR >76 beats/min. Multivariate Cox regression analysis revealed that the hazard ratio of all-cause death for low-, middle- and high-risk groups was 1.00 (reference), 1.48 (95% confidence interval (CI): 1.10-1.99, P=0.009) and 2.44 (95% CI 1.66-3.58, P<0.001), respectively. Subgroup analysis revealed that age ≥70 years, diabetes, or reduced left ventricular function had higher hazard ratios in the high-risk group. CONCLUSIONS: The results demonstrate the usefulness of combined risk stratification of HR and SBP in CHF patients with SR.

Prognostic impact of nutritional status in asymptomatic patients with cardiac diseases: a report from the CHART-2 Study.

BACKGROUND: The prognostic impact of nutritional status is poorly understood in asymptomatic patients with structural and/or functional heart diseases, classified as stage B in the ESC/AHA/ACC chronic heart failure (HF) guidelines. METHODS AND RESULTS: We evaluated the impact of nutrition, using the controlling nutritional status (CONUT) score, calculated by the serum albumin and total cholesterol levels,and lymphocyte number, in 3,421 stage B patients from the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 Study (mean age: 66.9±12.7 years, male: 71.6%). During a median follow-up of 2.89 years, 224 patients died from cardiovascular (45%, n=102) and noncardiovascular (55%, n=123) causes and 139 experienced hospitalization for HF. Survival at 3 years in patients with CONUT 0-1 (reference, n=2,121), 2 (n=693) and ≥3 (n=607) was 95.5, 92.3, and 73.2%, respectively (P<0.001). The adjusted Cox hazard analyses revealed that the CONUT score was significantly associated with increased incidence of all-cause death (hazard ratio 1.27 per point increase; 95% confidence interval, 1.16-1.39, P<0.001). Subgroup analysis showed that per point increase in the CONUT score was significantly associated with a 17% increase in HF hospitalization in patients ≥70 years old (P=0.049), but not in those aged <70 years. CONCLUSIONS: In the current stage B patients, poor nutritional status was associated with increased incidence of death for the overall population and of HF hospitalization for the elderly proportion.

Supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial--rationale and design.

BACKGROUND: Although angiotensin receptor blockers (ARBs) are now one of the first-line drug classes for the management of hypertension, recommendations for the management of chronic heart failure (CHF) are limited. The supplemental benefit of angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial investigates whether an additive treatment with an ARB, olmesartan, reduces the mortality and morbidity in hypertensive patients with stable chronic heart failure. METHODS AND RESULTS: The SUPPORT trial is a prospective randomized open-label blinded endpoint study. Between October 2006 and March 2010, 1147 stable CHF patients treated with evidence-based medications were successfully randomized to either olmesartan or control group. In the olmesartan group, the ARB was initiated at the dose of 5.0-10mg, and was then increased up to 40mg/day, when possible. No ARBs were allowed in the control group. Primary outcome measure in the SUPPORT trial is the composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke and hospital admission due to worsening heart failure. The participants will be followed for at least 3 years until March 2013. CONCLUSIONS: The SUPPORT trial will elucidate the supplemental benefits of an ARB, olmesartan, in hypertensive patients with CHF.

Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation.

OBJECTIVE: The pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) independent of cholesterol-lowering effects are thought to be mediated through inhibition of the Rho/Rho-kinase pathway. However, we have previously demonstrated that the pleiotropic effects of regular-dose statins are mediated mainly through inhibition of the Rac1 signaling pathway rather than the Rho/Rho-kinase pathway, although the molecular mechanisms of the selective inhibition of the Rac1 signaling pathway by regular-dose statins remain to be elucidated. In this study, we tested our hypothesis that small GTP-binding protein GDP dissociation stimulator (SmgGDS) plays a crucial role in the molecular mechanisms of the Rac1 signaling pathway inhibition by statins in endothelial cells. APPROACH AND RESULTS: In cultured human umbilical venous endothelial cells, statins concentration-dependently increased SmgGDS expression and decreased nuclear Rac1. Statins also enhanced SmgGDS expression in mouse aorta. In control mice, the protective effects of statins against angiotensin II-induced medial thickening of coronary arteries and fibrosis were noted, whereas in SmgGDS-deficient mice, the protective effects of statins were absent. When SmgGDS was knocked down by its small interfering RNA in human umbilical venous endothelial cells, statins were no longer able to induce Rac1 degradation or inhibit angiotensin II-induced production of reactive oxygen species. Finally, in normal healthy volunteers, statins significantly increased SmgGDS expression with a significant negative correlation between SmgGDS expression and oxidative stress markers, whereas no correlation was noted with total or low-density lipoprotein-cholesterol. CONCLUSIONS: These results indicate that statins exert their pleiotropic effects through SmgGDS upregulation with a resultant Rac1 degradation and reduced oxidative stress in animals and humans.

Prognostic impact of blood urea nitrogen changes during hospitalization in patients with acute heart failure syndrome.

BACKGROUND: Elevated blood urea nitrogen (BUN) observed in patients hospitalized for acute heart failure syndrome (AHFS) may represent increased neurohumoral activation. The purpose of this study was to examine the prognostic impact of BUN changes during hospitalization on the long-term prognosis of AHFS patients. METHODS AND RESULTS: The Tohoku Acute Heart Failure Registry (n=497) is a multicenter retrospective cohort study enrolling AHFS patients who were admitted in 2007. The 337 survivors (mean age, 76 years; 52% male) were divided into 3 groups according to tertiles of BUN change during hospitalization: Decreased (D-BUN, ΔBUN (BUN level at discharge-BUN level at hospitalization)≤-1.63 mg/dl, n=112); Unchanged (U-BUN, ΔBUN-1.64 to 5.73 mg/dl, n=113); Increased (I-BUN, ΔBUN>5.73 mg/dl, n=112). The D-BUN group had higher prevalence of lowest glomerular filtration rate during hospitalization, whereas the I-BUN group had higher systolic blood pressure. During a median follow-up period of 2.3 years after discharge, the Kaplan-Meier curve showed that D-BUN and I-BUN had worse prognosis compared with U-BUN. Multivariable logistic model showed that all-cause death was more frequent in I-BUN (hazard ratio, 2.94; 95% confidence interval, 1.51-5.73; P<0.001). Subgroup analysis revealed that BUN increase during hospitalization was associated with all-cause death, regardless of renal function. CONCLUSIONS: AHFS patients with a BUN increase during hospitalization have worse long-term prognosis, independent of renal function.