Multimodal Imaging-Assisted Intravascular Theranostic Photoactivation on Atherosclerotic Plaque.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.

Timing of fractional flow reserve-guided complete revascularization in patients with ST-segment elevation myocardial infarction with multivessel disease: Rationale and design of the OPTION-STEMI trial.

BACKGROUND: Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA. METHODS: The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least 1 non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into 2 groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50%-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis was revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025. CONCLUSIONS: The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457.

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Long-term clinical outcomes following successful percutaneous coronary intervention in patients with extremely long coronary chronic total occlusion lesions.

BACKGROUND: Lesion length is related to worse clinical outcomes following percutaneous coronary intervention (PCI) for the treatment of chronic total occlusion (CTO). However, the data to confirm the association between extremely long lesions and clinical hard endpoints have been limited. Therefore, we investigated the impact of extremely long CTO lesions (≥50 mm, treated lesion length) on the long-term clinical outcomes following successful PCI. METHODS: A total of 333 consecutive patients with CTO who underwent successful PCI with drug-eluting stents (DESs) were allocated to either the extremely long or the short CTO group according to their CTO lesion length. The 5-year clinical outcomes were compared between the two groups. The incidence of myocardial infarction, cardiac death (CD), revascularization, and major adverse cardiovascular events (MACE) was higher in the extremely long CTO group. The 5-year clinical outcomes were analyzed using the Cox hazard ratio (HR) model. RESULTS: In the entire study population, the extremely long CTO lesion was an independent predictor for higher rate of revascularization, MACE, CD, or mortality. CONCLUSIONS: In our study, CTO patients with extremely long lesions (≥50 mm) who underwent successful PCI were associated with a higher risk of worse long-term clinical outcomes, including hard clinical endpoints such as CD and mortality even in the DESs era.

Effects of delayed hospitalization on the 3-year clinical outcomes of patients with or without diabetes who had non-ST-segment-elevation myocardial infarction and underwent new-generation drug-eluting stent implantation.

Clinical outcomes after non-ST-segment-elevation myocardial infarction (NSTEMI) in patients with (symptom-to-door time [SDT] ≥ 24 h) or without (SDT < 24 h) delayed hospitalization among patients with or without diabetes were compared. From the Korea Acute Myocardial Infarction Registry-National Institute of Health, a total of 4517 patients with NSTEMI who underwent new-generation drug-eluting stents implantation were recruited and they were classified into the diabetes mellitus (DM) and non-DM groups. These two groups were subdivided into groups with and without delayed hospitalization. The primary clinical outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction, repeat coronary revascularization, and stroke. The secondary clinical outcome was the occurrence of individual components of MACCE and stent thrombosis. Although after multivariable and propensity score-adjusted analyses in the DM group, the primary and secondary clinical outcomes between the SDT < 24 h and SDT ≥ 24 h groups were similar; in the non-DM group, all-cause (p = 0.003 and p = 0.007, respectively) and cardiac (p = 0.001 and p = 0.008, respectively) death rates were significantly higher in the SDT ≥ 24 h group than in the SDT < 24 h group. Our results suggested that there was no significant difference in prognosis between diabetic patients with and without delayed SDT, but delayed SDT was associated with poor prognosis in nondiabetic patients.

Korean vs. Western Exercise Capacity Nomograms for Korean Patients With Cardiovascular Disease.

BACKGROUND: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most previous studies were based on Western populations. Further study is warranted for Asian patients according to ethnic or national standards. We aimed to compare prognostic values of Korean and Western nomograms for exercise capacity in Korean patients with cardiovascular disease (CVD). METHODS: In this retrospective cohort study, we enrolled 1,178 patients (62 ± 11 years; 78% male) between June 2015 and May 2020, who were referred for cardiopulmonary exercise testing in our cardiac rehabilitation program. The median follow-up period was 1.6 years. Exercise capacity was measured in metabolic equivalents by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean individuals and a previous landmark Western study was used to determine the percentage of predicted exercise capacity. The primary endpoint was the composite of major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, repeat revascularization, stroke and hospitalization for heart failure). RESULTS: A multivariate analysis showed that the risk of primary endpoint was more than double (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.10-4.40) in the patients with lower exercise capacity (< 85% of predicted) by Korean nomogram. The lower exercise capacity was one of the strong independent predictors along with left ventricular ejection fraction, age, and level of hemoglobin. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR, 1.33; 95% CI, 0.85-2.10). CONCLUSION: Korean patients with CVD with lower exercise capacity have higher risk of MACE. Considering inter-ethnic differences in cardiorespiratory fitness, the Korean nomogram provides more suitable reference values than the Western nomogram to determine lower exercise capacity and predict cardiovascular events in Korean patients with CVD.

Stress-associated neurobiological activity is linked with acute plaque instability via enhanced macrophage activity: a prospective serial 18F-FDG-PET/CT imaging assessment.

AIMS: Emotional stress is associated with future cardiovascular events. However, the mechanistic linkage of brain emotional neural activity with acute plaque instability is not fully elucidated. We aimed to prospectively estimate the relationship between brain amygdalar activity (AmygA), arterial inflammation (AI), and macrophage haematopoiesis (HEMA) in acute myocardial infarction (AMI) as compared with controls. METHODS AND RESULTS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging was performed within 45 days of the index episode in 62 patients (45 with AMI, mean 60.0 years, 84.4% male; 17 controls, mean 59.6 years, 76.4% male). In 10 patients of the AMI group, serial 18F-FDG-PET/CT imaging was performed after 6 months to estimate the temporal changes. The signals were compared using a customized 3D-rendered PET reconstruction. AmygA [target-to-background ratio (TBR), mean ± standard deviation: 0.65 ± 0.05 vs. 0.60 ± 0.05; P = 0.004], carotid AI (TBR: 2.04 ± 0.39 vs. 1.81 ± 0.25; P = 0.026), and HEMA (TBR: 2.60 ± 0.38 vs. 2.22 ± 0.28; P < 0.001) were significantly higher in AMI patients compared with controls. AmygA correlated significantly with those of the carotid artery (r = 0.350; P = 0.005), aorta (r = 0.471; P < 0.001), and bone marrow (r = 0.356; P = 0.005). Psychological stress scales (PHQ-9 and PSS-10) and AmygA assessed by PET/CT imaging correlated well (P < 0.001). Six-month after AMI, AmygA, carotid AI, and HEMA decreased to a level comparable with the controls. CONCLUSION: AmygA, AI, and HEMA were concordantly enhanced in patients with AMI, showing concurrent dynamic changes over time. These results raise the possibility that stress-associated neurobiological activity is linked with acute plaque instability via augmented macrophage activity and could be a potential therapeutic target for plaque inflammation in AMI.

Age and sex dependent association of uric acid and incident hypertension.

BACKGROUND AND AIMS: A previous meta-analysis suggested that the relationship between hyperuricemia and hypertension may be stronger in younger individuals and women. We aimed to investigate the age and sex dependent association of uric acid (UA) and incident hypertension. METHODS AND RESULTS: We analyzed data from the Health Examinees Study, a community-based prospective cohort study conducted in Korea from 2004 to 2013. It included 29,088 non-hypertensive subjects aged 40-79 (age, 52.5 ± 7.8 years; men, 31.4%) who had serum UA measurement and participated in the follow-up survey. The risk factors of hypertension were assessed using Cox regression. Over a mean 3.8 years of follow-up, 1388 men (15.2%) and 1942 women (9.7%) were newly diagnosed with hypertension. Upon age- and sex-based stratification, the risk of hypertension was highest in hyperuricemic subjects aged 40-49 years (HR: women, 2.16; men, 1.30). Across the entire cohort, the risk of incident hypertension was higher in groups with higher serum UA levels, and highest in women aged 40-49 years (HR, 1.44; P < 0.001). On multivariable linear regression analysis, the higher the baseline serum UA level, the greater the increase in blood pressure during follow-up, and this effect was strongest in women aged 40-49 years (ß = 0.87 and P < 0.01 for systolic blood pressure). CONCLUSIONS: The relationship between uric acid and incident hypertension tended to be dependent on age and sex. Younger women are at highest risk of UA-related incident hypertension.

Targeted theranostic photoactivation on atherosclerosis.

BACKGROUND: Photoactivation targeting macrophages has emerged as a therapeutic strategy for atherosclerosis, but limited targetable ability of photosensitizers to the lesions hinders its applications. Moreover, the molecular mechanistic insight to its phototherapeutic effects on atheroma is still lacking. Herein, we developed a macrophage targetable near-infrared fluorescence (NIRF) emitting phototheranostic agent by conjugating dextran sulfate (DS) to chlorin e6 (Ce6) and estimated its phototherapeutic feasibility in murine atheroma. Also, the phototherapeutic mechanisms of DS-Ce6 on atherosclerosis were investigated. RESULTS: The phototheranostic agent DS-Ce6 efficiently internalized into the activated macrophages and foam cells via scavenger receptor-A (SR-A) mediated endocytosis. Customized serial optical imaging-guided photoactivation of DS-Ce6 by light illumination reduced both atheroma burden and inflammation in murine models. Immuno-fluorescence and -histochemical analyses revealed that the photoactivation of DS-Ce6 produced a prominent increase in macrophage-associated apoptotic bodies 1 week after laser irradiation and induced autophagy with Mer tyrosine-protein kinase expression as early as day 1, indicative of an enhanced efferocytosis in atheroma. CONCLUSION: Imaging-guided DS-Ce6 photoactivation was able to in vivo detect inflammatory activity in atheroma as well as to simultaneously reduce both plaque burden and inflammation by harmonic contribution of apoptosis, autophagy, and lesional efferocytosis. These results suggest that macrophage targetable phototheranostic nanoagents will be a promising theranostic strategy for high-risk atheroma.

Impact of Sleep-Disordered Breathing on Functional Outcomes in Ischemic Stroke: A Cardiopulmonary Coupling Analysis.

BACKGROUND AND PURPOSE: Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up. METHODS: A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort. CPC analysis was conducted, and SDB was defined by the presence of narrow-band coupling during sleep time. We investigated the association between SDB and functional impairment at 3 months as measured by the modified Rankin Scale. RESULT: Narrow-band coupling was present in 191 (31.1%) of 615 patients (mean age 64.5±12.6 years). The narrow-band group showed a significantly higher rate of severe functional impairment (modified Rankin Scale score >2; 45.5% versus 12.9%, P<0.001) and persistent disability (Δmodified Rankin Scale score ≤0; 53.9% versus 39.8%, P<0.001) at the 3-month follow-up. In multivariate analysis, narrow-band coupling was an independent predictor of higher risk of severe and persistent functional impairment at 3 months (odds ratio, 3.98 [95% CI, 2.34-6.78]; P<0.001; and odds ratio, 1.81 [95% CI, 1.23-2.66]; P<0.001, respectively). The results remained consistent after propensity-score matched analysis with 157 patient pairs (C-statistic=0.770). CONCLUSIONS: SDB assessed by CPC analysis at the early stage of ischemic stroke could predict severe and prolonged functional impairment at 3 months. CPC analysis using Holter monitoring can help predicting functional impairment in acute ischemic stroke.

Cilostazol-based triple versus potent P2Y12 inhibitor-based dual antiplatelet therapy in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

Although potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) has replaced clopidogrel-based therapy as the standard treatment in patients with acute myocardial infarction (AMI), there is a concern about the risk of bleeding in East Asian patients. We compared the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAT) with potent P2Y12 inhibitor-based DAPT in Korean patients. A total of 4152 AMI patients who underwent percutaneous coronary intervention (PCI) in the Korea Acute Myocardial Infarction Registry were analyzed retrospectively. Patients were divided into two groups: the TAT group (aspirin + clopidogrel + cilostazol, n = 3161) and the potent DAPT group (aspirin + potent P2Y12 inhibitors [ticagrelor or prasugrel], n = 991). Major clinical outcomes at 30 days and 2 years were compared between the two groups using propensity score matching (PSM) analysis. After PSM (869 pairs), there were no significant differences between the two groups in the incidence of total death, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and stroke at 30 days and 2 years. However, the Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were significantly lower in the TAT group compared with the potent DAPT group at 2 years (6.4% vs. 3.6%, p = 0.006). In Korean AMI patients undergoing PCI, TAT with cilostazol was associated with lower bleeding than the potent P2Y12 inhibitor-based DAPT without increased ischemic risk. These results could provide a rationale for the use of TAT in East Asian AMI patients.

Three-Year Clinical Outcomes With the Cilotax Dual Drug-Eluting Stent vs Everolimus-Eluting Stents in Patients With Acute Myocardial Infarction.

BACKGROUND: This study compared the safety and effectiveness of paclitaxel/cilostazol-eluting Cilotax stents with those of everolimus-eluting stents in patients with acute myocardial infarction. Real-world data from the Korea Acute Myocardial Infarction Registry were examined. METHODS: A total of 5,472 patients with acute myocardial infarction underwent percutaneous coronary intervention with Cilotax stents (n = 212) or everolimus-eluting stents (n = 5,260). The primary end point was the 3-year rate of target lesion failure. The other end points were major adverse cardiovascular events (a composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization), target vessel revascularization, and stent thrombosis. A propensity score matching analysis was performed to adjust for potential confounders by using a logistic regression model; propensity score matching generated 2 well-balanced groups (Cilotax group, n = 180; everolimus-eluting stents group, n = 170; N = 350). After propensity score matching, baseline clinical characteristics were similar between the groups. RESULTS: After percutaneous coronary intervention, compared with the everolimus-eluting stents group, the Cilotax group more often had major adverse cardiovascular events (24.1% vs 18.5%; P = .042), myocardial infarction (8.0% vs 3.2%; P < .001), target lesion revascularization (8.0% vs 2.6%; P < .001), target vessel revascularization (11.3% vs 4.5%; P < .001), and stent thrombosis (4.7% vs 0.5%; P < .001) before matching. Even after matching, the Cilotax group had more frequent target lesion revascularization (9.4% vs 2.9%; P = .22) and stent thrombosis (5.6% vs 1.2%; P = .34). CONCLUSION: In patients with acute myocardial infarction who underwent percutaneous coronary intervention, use of the Cilotax stent was associated with higher rates of target lesion revascularization, target vessel revascularization, and stent thrombosis than were everolimus-eluting stents. Use of the Cilotax dual drugeluting stent should be avoided in the treatment of myocardial infarction.

Effect of diabetes mellitus on 3-year outcomes in patients with acute myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Diabetes mellitus (DM) is a significant factor in increased mortality rates among patients with acute myocardial infarction (AMI), but research on its impact on the long-term outcomes in patients with MI with nonobstructive coronary arteries (MINOCA) is limited. Thus, a comparison of the 3-year clinical outcomes between the DM and non-DM groups among patients with MINOCA was undertaken. METHODS: From the Korea AMI Registry-National Institute of Health dataset, 10,774 AMI patients were enrolled. After applying the exclusion criteria, 379 patients with MINOCA were included. The primary clinical outcomes were major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction (MI), repeat coronary revascularization, and stroke. The secondary outcomes were the individual components of MACCE. RESULTS: The adjusted hazard ratios for 3-year MACCE (2.287, p = 0.010), all-cause death (2.845, p = 0.004), and non-cardiac death (non-CD, 3.914, p = 0.008) were higher in the DM group than in the non-DM group. It is speculated that the higher non-CD rate in the MINOCA group is attributable to a higher proportion of patients with non-ST-segment elevation MI in the total study population. The CD, recurrent MI, revascularization, and stroke rates were similar between the DM and non-DM groups. DM, advanced age, cardiopulmonary resuscitation on admission, and non-use of statin medications were significant predictors of MACCE. CONCLUSIONS: In this study involving patients with MINOCA, the DM group exhibited a higher 3-year mortality rate than the non-DM group. Thus, DM demonstrated a hazardous effect even in patients with MINOCA.

Assessing lung fluid status using noninvasive bioelectrical impedance analysis in patients with acute heart failure: A pilot study.

BACKGROUND: Outpatient monitoring of pulmonary congestion in heart failure (HF) patients may reduce hospitalization rates. This study tested the feasibility of non-invasive high-frequency bioelectrical impedance analysis (HF-BIA) for estimating lung fluid status. METHODS: This prospective study included 70 participants: 50 with acute HF (HF group) and 20 without HF (control group). All participants underwent a supine chest CT scan to measure lung fluid content with lung density analysis software. Concurrently, direct segmental multi-frequency BIA was performed to assess the edema index (EI) of the trunk, entire body, and extremities. RESULTS: The correlation coefficients between lung fluid content and EI measured using HF-BIA were r = 0.566 (p < 0.001) and r = 0.550 (p < 0.001) for the trunk and whole body, respectively. In the HF group, the trunk EI (0.402 ± 0.015) and whole body EI (0.402 ± 0.016) were significantly higher than those of the control group (trunk EI, 0.383 ± 0.007; whole body EI, 0.383 ± 0.007; all p < 0.001). The lung fluid content was significantly higher in the HF than that in the control group (23.7 ± 5.3 vs. 15.5 ± 2.8%, p < 0.001). The log value of NT pro-BNP was significantly correlated with trunk EI (r = 0.688, p < 0.001) and whole-body EI (r = 0.675, p < 0.001) measured by HF-BIA, and the lung fluid content analyzed by CT (r = 0.686, p < 0.001). CONCLUSIONS: BIA-based EI measurements of the trunk and whole body significantly correlated with lung fluid content and NT pro-BNP levels. Non-invasive BIA could be a promising screening tool for lung fluid status monitoring in acute HF patients.

Renin-angiotensin system inhibitors and non-ST-elevation myocardial infarction outcomes based on left ventricular ejection fraction.

BACKGROUND: We assessed left ventricular ejection fraction (LVEF) to compare the effects of renin-angiotensin system inhibitors (RASI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We categorized 4558 patients with NSTEMI as either RASI users (3752 patients) or non-users (806 patients). The 3-year patient-oriented composite outcomes (POCO), which included all-cause death, recurrent MI, any repeat revascularization, or hospitalization for heart failure (HF), were the primary outcomes. To compare clinical outcomes, a multivariable-adjusted hazard ratio (aHR) was calculated after performing multicollinearity tests on all significant confounding variables (P <0.05) RESULTS: Among RASI users, the aHRs for POCO, all-cause death, and cardiac death were significantly higher in the HF with reduced EF (HFrEF) subgroup than in the HF with mildly reduced EF (HFmrEF; 1.610, 2.120, and 2.489, respectively; P <0.001, <0.001, and <0.001, respectively) and HF with preserved EF (HFpEF; 2.234, 3.920, 5.215, respectively; P <0.001, <0.001, and <0.001, respectively) subgroups. The aHRs for these variables were significantly higher in the HFmrEF subgroup than the HFpEF subgroup (1.416, 1.843, and 2.172, respectively). Among RASI non-users, the aHRs for these variables were significantly higher in the HFrEF subgroup than the HFmrEF (2.573, 3.172, and 3.762, respectively) and HFpEF (2.425, 3.805, and 4.178, respectively) subgroups. In three LVEF subgroups, RASI users exhibited lower aHRs for POCO and all-cause death than RASI non-users. CONCLUSIONS: In the RASI users group, the aHRs for POCO and mortality were highest in the HFrEF subgroup, intermediate in the HFmrEF subgroup, and lowest in the HFpEF subgroup.

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption.

Importance: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear. Objective: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes. Design, Setting, and Participants: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females. Exposures: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking. Main Outcomes and Measures: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death. Results: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants. Conclusions and Relevance: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

Long-term air pollution exposure is associated with higher incidence of ST-elevation myocardial infarction and in-hospital cardiogenic shock.

Previous studies have reported the association between myocardial infarction (MI) and air pollution (AP). However, limited information is available regarding the long-term effects of AP on the relative incidence rates of ST-elevation MI (STEMI) and Non-ST-elevation MI (NSTEMI). We investigated the association between long-term exposure to AP and the incidence of STEMI. Between January 2006 and December 2015, a total of 45,619 eligible patients with Acute Myocardial Infarction (AMI) were enrolled in the Korea Acute MI Registry (KAMIR) and KAMIR-National Institutes of Health. Mixed-effect regression models were used to examine the association between the annual average ambient AP before MI onset and the incidence of STEMI, and to evaluate the association of AP with the incidence of in-hospital cardiogenic shock. After mixed-effect regression model analysis, particulate matter (PM) 10 µm or less in diameter (PM10) was associated with increased incidence of STEMI compared with NSTEMI (odds ratio [OR] 1.009, 95% Confidence Interval [CI] 1.002-1.016; p = 0.012). For in-hospital cardiogenic shock complication, PM10 and SO2 were associated with increased risk, PM10 (OR 1.033, 95% CI 1.018-1.050; p < 0.001), SO2 (OR 1.104, 95% CI 1.006-1.212; p = 0.037), respectively. Policy-level strategies and clinical efforts to reduce AP exposure are necessary to prevent the incidence of STEMI and severe cardiovascular complications.