Efficacy and Safety of Sirolimus-Eluting Stent with Biodegradable Polymer Ultimaster™ in Unselected Korean Population: A Multicenter, Prospective, Observational Study From Korean Multicenter Ultimaster Registry.

BACKGROUND AND OBJECTIVES: Ultimaster™, a third-generation sirolimus-eluting stent using biodegradable polymer, has been introduced to overcome long term adverse vascular events, such as restenosis or stent thrombosis. In the present study, we aimed to evaluate the 12-month clinical outcomes of Ultimaster™ stents in Korean patients with coronary artery disease. METHODS: This study is a multicenter, prospective, observational registry across 12 hospitals. To reflect real-world clinical evidence, non-selective subtypes of patients and lesions were included in this study. The study end point was target lesion failure (TLF) (the composite of cardiac death, target vessel myocardial infarction [MI], and target lesion revascularization [TLR]) at 12-month clinical follow up. RESULTS: A total of 576 patients were enrolled between November 2016 and May 2021. Most of the patients were male (76.5%), with a mean age of 66.0±11.2 years. Among the included patients, 40.1% had diabetes mellitus (DM) and 67.9% had acute coronary syndrome (ACS). At 12 months, the incidence of TLF was 4.1%. The incidence of cardiac death was 1.5%, MI was 1.0%, TLR was 2.7%, and stent thrombosis was 0.6%. In subgroup analysis based on the presence of ACS, DM, hypertension, dyslipidemia, or bifurcation, there were no major differences in the incidence of the primary endpoint. CONCLUSIONS: The present registry shows that Ultimaster™ stent is safe and effective for routine real-world clinical practice in non-selective Korean patients, having a low rate of adverse events at least up to 12 months.

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.

Impact of hyperuricemia on 5-year clinical outcomes in patients with critical limb ischemia following percutaneous transluminal angioplasty.

BACKGROUND: A growing evidence on the correlation between hyperuricemia and cardiovascular disease (CVD) has been previously reported. However, there have been limited data on the impact of hyperuricemia on long-term clinical outcomes in patients with critical limb ischemia (CLI) who underwent percutaneous transluminal angioplasty (PTA). METHODS: A total of 425 peripheral artery disease patients who underwent PTA for CLI were enrolled. The patients were divided into the hyperuricemia group (n = 101) and the normal group (n = 324). The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction, any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was a major adverse limb event (MALE), including any repeated PTA, and target extremity surgery. Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust for potential confounders. RESULTS: After IPTW matching analysis, compared to the normal group, the hyperuricemia group was associated with a higher incidence of MACCE (20.7% vs. 13.6%, hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.15-2.38, P  = 0.006) including non-cardiac death (11.7% vs. 6.3%, HR: 1.95, 95% CI: 1.19-3.19, P  = 0.006) and MALE (47.7% vs. 36.0%, HR: 1.62, 95% CI: 1.23-2.13, P  = 0.001) including non-target extremity revascularization (15.0% vs. 6.8%, HR: 2.42, 95% CI: 1.52-3.84, P  < 0.001). CONCLUSION: In the present study, hyperuricemia was associated with worse clinical outcomes in patients with CLI following PTA during 5-year clinical follow-up. Efficacy of controlling hyperuricemia in improving clinical outcomes should be evaluated in further studies.

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.

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.

Impact of hyperuricemia on 5-year clinical outcomes following percutaneous transluminal angioplasty.

BACKGROUND: Although the correlation between hyperuricemia and cardiovascular disease (CVD) is well known, there have been limited data regarding the impact of hyperuricemia on long-term clinical outcomes in patients with peripheral arterial disease (PAD) after percutaneous transluminal angioplasty (PTA). METHODS: A total of 718 patients who underwent PTA for PAD were enrolled. The patients were divided into the hyperuricemia group (N = 168) and the normal group (N = 550). Hyperuricemia was defined as a uric acid level ≥ 7.0 mg/dL in men, and ≥ 6.5 mg/dL in women. The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction (MI), any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was major adverse limb event (MALE), including any repeated PTA, and target extremity surgery (TES). Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust potential confounders. RESULTS: After IPTW matching analysis, compared to the normal group, the hyperuricemia group was not associated with increased MACCE but was associated with an increased incidence of MI (2.6 % vs. 0.5 %, p = 0.001), and coronary revascularization (6.7 % vs. 3.9 %, p = 0.018). Also, the hyperuricemia group was associated with a higher incidence of MALE (45.3 % vs. 28.9 %, p < 0.001), including target extremity revascularization (TER; 25.1 % vs. 15.9 %, p < 0.001), non-TER (11.5 % vs. 5.6 %, p < 0.001), and TES (22.8 % vs. 16.2 %, p = 0.002). CONCLUSIONS: In the present study, hyperuricemia was associated with worse clinical outcomes in PAD patients following PTA during 5-year clinical follow-up. Further investigations should be made regarding the clinical benefit of controlling hyperuricemia on clinical outcomes.

Visualizing the Low-Energy Electronic Structure of Prototypical Hybrid Halide Perovskite through Clear Band Measurements.

Organic-inorganic hybrid perovskites (OIHPs) are a promising class of materials that rival conventional semiconductors in various optoelectronic applications. However, unraveling the precise nature of their low-energy electronic structures continues to pose a significant challenge, primarily due to the absence of clear band measurements. Here, we investigate the low-energy electronic structure of CH3NH3PbI3 (MAPI3) using angle-resolved photoelectron spectroscopy combined with ab initio density functional theory. We successfully visualize the electronic structure of MAPI3 near the bulk valence band maximum by using a laboratory photon source (He Iα, 21.2 eV) at low temperature and explore its fundamental properties. The observed valence band exhibits a highly isotropic and parabolic band characterized by small effective masses of 0.20-0.21 me, without notable spectral signatures associated with a large polaron or the Rashba effect, subjects that are intensely debated in the literature. Concurrently, our spin-resolved measurements directly disprove the giant Rashba scenario previously suggested in a similar perovskite compound by establishing an upper limit for the Rashba parameter (αR) of 0.28 eV Å. Our results unveil the unusually complex nature of the low-energy electronic structure of OIHPs, thereby advancing our fundamental understanding of this important class of materials.

Spontaneous curvature generation by peptides in asymmetric bilayers.

Peptides and proteins play crucial roles in membrane remodeling by inducing spontaneous curvature. However, extracting spontaneous curvatures from simulations of asymmetric bilayers is challenging because differential stress (i.e., the difference of the leaflet surface tensions) arising from leaflet area strains can vary substantially among initial conditions. This study investigates peptide-induced spontaneous curvature δc 0 p in asymmetric bilayers consisting of a single lipid type and a peptide confined to one leaflet; δc 0 p is calculated from the Helfrich equation using the first moment of the lateral pressure tensor and an alternative expression using the differential stress. It is shown that differential stress introduced during initial system generation is effectively relaxed by equilibrating using P21 periodic boundary conditions, which allows lipids to switch leaflets across cell boundaries and equalize their chemical potentials across leaflets. This procedure leads to robust estimates of δc 0 p for the systems simulated, and is recommended when equality of chemical potentials between the leaflets is a primary consideration.

The impact of sex differences on 3-year outcomes of patients with non-ST-segment elevation myocardial infarction after successful stent implantation according to symptom-to-balloon time.

BACKGROUND: Because no data are available, we compared the 3-year outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) based on sex and symptom-to-balloon time (SBT). METHODS: This study included 4910 patients who were divided into two groups based on SBT: SBT <48 h (n = 3,293, 67.1%) and SBT ≥48 h (n = 1,617, 32.9%). The primary outcome was all-cause death during the 3-year follow-up period. The secondary outcome was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction, or repeat coronary revascularization. RESULTS: After adjustment, the in-hospital mortality rates for males and females in the SBT <48 h and SBT ≥48 h groups were similar. During a 3-year follow-up period, females in the SBT <48 h group had significantly higher rates of all-cause death (adjusted hazard ratio [aHR], 1.482; P = 0.006), cardiac death (CD, aHR, 1.617; P = 0.009), and MACE (aHR, 1.268; P = 0.024) than those males in the same groups. Females and males in the SBT ≥48 h group did not differ significantly in the primary and secondary outcomes. In males, the rates of all-cause death (P = 0.008) and CD (P = 0.024) were significantly higher in the SBT ≥48 h group than in the SBT <48 h group. CONCLUSIONS: This study has identified a higher 3-year mortality rate in female patients with NSTEMI and SBT <48 h compared to their male counterparts. As such, a more preventive approach may be required to reduce mortality in these female patients.

One-step site-specific S-alkylation of full-length caveolin-1: Lipidation modulates the topology of its C-terminal domain.

Caveolin-1 is an integral membrane protein that is known to acquire a number of posttranslational modifications upon trafficking to the plasma membrane. In particular, caveolin-1 is palmitoylated at three cysteine residues (C133, C143, and C156) located within the C-terminal domain of the protein which could have structural and topological implications. Herein, a reliable preparation of full-length S-alkylated caveolin-1, which closely mimics the palmitoylation observed in vivo, is described. HPLC and ESI-LC-MS analyses verified the addition of the C16 alkyl groups to caveolin-1 constructs containing one (C133), two (C133 and C143), and three (C133, C143, and C156) cysteine residues. Circular dichroism spectroscopy analysis of the constructs revealed that S-alkylation does not significantly affect the global helicity of the protein; however, molecular dynamics simulations revealed that there were local regions where the helicity was altered positively or negatively by S-alkylation. In addition, the simulations showed that lipidation tames the topological promiscuity of the C-terminal domain, resulting in a disposition within the bilayer characterized by increased depth.

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.

Effect of delayed hospitalization on patients with non-ST-segment elevation myocardial infarction and complex lesions undergoing successful new-generation drug-eluting stents implantation.

In the absence of available data, we evaluated the effects of delayed hospitalization (symptom-to-door time [SDT] ≥ 24 h) on major clinical outcomes after new-generation drug-eluting stent implantation in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and complex lesions. In total, 4373 patients with NSTEMI were divided into complex (n = 2106) and non-complex (n = 2267) groups. The primary outcome was the 3-year rate of major adverse cardiac events (MACE), defined as all-cause death, recurrent MI, and any repeat revascularization. Secondary outcomes included the individual MACE components. In the complex group, all-cause death (adjusted hazard ratio [aHR], 1.752; p = 0.004) and cardiac death (aHR, 1.966; p = 0.010) rates were significantly higher for patients with SDT ≥ 24 h than for those with SDT < 24 h. In the non-complex group, all patients showed similar clinical outcomes. Patients with SDT < 24 h (aHR, 1.323; p = 0.031) and those with SDT ≥ 24 h (aHR, 1.606; p = 0.027) showed significantly higher rates of any repeat revascularization and all-cause death, respectively, in the complex group than in the non-complex group. Thus, in the complex group, delayed hospitalization was associated with higher 3-year mortalities.

The impact of renal function on the three-year outcomes in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Due to limited data availability, we compared the 3-year outcomes of patients with acute myocardial infarction (AMI) and nonobstructive coronary arteries (MINOCA) and those with obstructive coronary arteries (MIOCA) according to renal function. METHODS: From a final cohort of 10,774 patients with AMI were classified into 2 groups: the chronic kidney disease (CKD) group (estimated glomerular filtration rate <60 mL/min/1.73 m2, 2,854 patients; MINOCA, 123; MIOCA, 2,731) and the non-CKD group (7,920 patients; MINOCA, 256; MIOCA, 7,664). The primary outcome was the 3-year all-cause death rate, and the secondary outcomes included cardiac death (CD), non-CD death (NCD), recurrent myocardial infarction (MI), and any revascularization. RESULTS: In both the CKD and non-CKD groups, the adjusted in-hospital mortality, 3-year all-cause death, CD, and recurrent MI rates were similar between the MINOCA and MIOCA groups, but the adjusted 3-year any revascularization rates were significantly higher in the MIOCA group than in the MINOCA group. Characteristically, in the CKD group, the adjusted 3-year NCD rate (P = 0.032) was higher in the MINOCA group than in the MIOCA group, and sepsis was the main cause of NCD in this group. In both the MINOCA and MIOCA groups, all-cause death and NCD were significantly higher in the CKD group than in the non-CKD group. CONCLUSIONS: Regardless of renal function, the MINOCA and MIOCA groups had comparable mortality rates. However, patients with MINOCA and CKD had higher NCD rates. Close monitoring of renal function and enhanced strategies are required to reduce mortality in patients with MINOCA.

Efficacy and safety of cilostazol-based triple antiplatelet therapy compared with clopidogrel-based dual antiplatelet therapy in patients with acute ST-elevation myocardial infarction undergoing percutaneous coronary intervention: A multicenter, randomized, open-label, phase 4 trial.

BACKGROUND: Previous studies reported that compared to conventional dual antiplatelet therapy (DAT; aspirin + clopidogrel), triple antiplatelet therapy (TAT), involving the addition of cilostazol to DAT, had better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). However, the optimal duration of TAT is yet to be determined. METHODS: In total, 985 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) were prospectively enrolled in 15 PCI centers in South Korea and China. We randomly assigned patients into 3 groups: DAT (aspirin and clopidogrel for 12 months), TAT 1M (aspirin, clopidogrel, and cilostazol for 1 month), and TAT 6M (aspirin, clopidogrel, and cilostazol for 6 months). The primary endpoint was 1-year major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, recurrent myocardial infarction, stroke, or repeat revascularization. RESULTS: The primary endpoint did not differ among the 3 groups (8.8% in DAT, 11.0% in TAT 1M, and 11.6% in TAT 6M; hazard ratio for TAT 1M vs DAT, 1.302; 95% confidence interval [CI], 0.792-2.141; P = .297; hazard ratio for TAT 6M vs DAT, 1.358; 95% CI, 0.829-2.225; P = .225). With respect to in-hospital outcomes, more bleeding events occurred in the TAT group than in the DAT group (1.3% vs 4.7% vs 2.6%, P = .029), with no significant differences in major bleeding events. Additionally, the TAT group had a higher incidence of headaches (0% vs 1.6% vs 2.6%, P = .020). CONCLUSIONS: The addition of cilostazol to DAT did not reduce the incidence of 1-year MACEs compared with DAT alone. Instead, it may be associated with an increased risk of drug intolerance and side effects, including in-hospital bleeding and headaches.

Promoting the activity of a receptor tyrosine phosphatase with a novel pH-responsive transmembrane agonist inhibits cancer-associated phenotypes.

Cell signaling by receptor protein tyrosine kinases (RTKs) is tightly controlled by the counterbalancing actions of receptor protein tyrosine phosphatases (RPTPs). Due to their role in attenuating the signal-initiating potency of RTKs, RPTPs have long been viewed as therapeutic targets. However, the development of activators of RPTPs has remained limited. We previously reported that the homodimerization of a representative member of the RPTP family (protein tyrosine phosphatase receptor J or PTPRJ) is regulated by specific transmembrane (TM) residues. Disrupting this interaction by single point mutations promotes PTPRJ access to its RTK substrates (e.g., EGFR and FLT3), reduces RTK's phosphorylation and downstream signaling, and ultimately antagonizes RTK-driven cell phenotypes. Here, we designed and tested a series of first-in-class pH-responsive TM peptide agonists of PTPRJ that are soluble in aqueous solution but insert as a helical TM domain in lipid membranes when the pH is lowered to match that of the acidic microenvironment of tumors. The most promising peptide reduced EGFR's phosphorylation and inhibited cancer cell EGFR-driven migration and proliferation, similar to the PTPRJ's TM point mutations. Developing tumor-selective and TM-targeting peptide binders of critical RPTPs could afford a potentially transformative approach to studying RPTP's selectivity mechanism without requiring less specific inhibitors and represent a novel class of therapeutics against RTK-driven cancers.

Unsaturated Lipids Facilitate Partitioning of Transmembrane Peptides into the Liquid Ordered Phase.

The affinity of single-pass transmembrane (TM) proteins for ordered membrane phases has been reported to depend on their lipidation, TM length, and lipid accessible surface area. In this work, the raft affinities of the TM domain of the linker for activation of T cells and its depalmitoylated variant are assessed using free energy simulations in a binary bilayer system composed of two laterally patched bilayers of ternary liquid ordered (Lo) and liquid disordered (Ld) phases. These phases are modeled by distinct compositions of distearoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine (POPC), and cholesterol, and the simulations were carried out for 4.5 µs/window. Both peptides are shown to preferentially partition into the Ld phase in agreement with model membrane experiments and previous simulations on ternary lipid mixtures but not with measurements on giant plasma membrane vesicles where the Lo is slightly preferred. However, the 500 ns average relaxation time of lipid rearrangement around the peptide precluded a quantitative analysis of free energy differences arising from peptide palmitoylation and two different lipid compositions. When in the Lo phase, peptides reside in regions rich in POPC and interact preferentially with its unsaturated tail. Hence, the detailed substructure of the Lo phase is an important modulator of peptide partitioning, in addition to the inherent properties of the peptide.

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.

Three-Year Clinical Outcomes Based on Pre-Percutaneous Coronary Intervention Coronary Blood Flow Grade and Symptom-to-Balloon Time in Patients with Non-ST-Segment Elevation Myocardial Infarction.

We compared the 3-year clinical outcomes according to the degree of pre-percutaneous coronary intervention thrombolysis in myocardial infarction flow grade (pre-PCI TIMI) and symptom-to-balloon time (SBT) individuals who underwent successful stent implantation with a diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI). A total of 4910 patients with NSTEMI were divided into two groups: pre-PCI TIMI 0/1 (SBT < 48 h: n = 1328, SBT ≥ 48 h: n = 558) and pre-PCI TIMI 2/3 (SBT < 48 h: n = 1965, SBT ≥ 48 h: n = 1059). The primary outcome was a 3-year all-cause death rate, and the secondary outcome was the composite endpoint of 3-year all-cause death, recurrent MI, or any repeat revascularization rate. After adjustment, in the pre-PCI TIMI 0/1 group, the 3-year all-cause death (p = 0.003), cardiac death (CD, p < 0.001), and secondary outcome (p = 0.030) values were significantly higher in the SBT ≥ 48 h group than in the SBT < 48 h group. However, patients with pre-PCI TIMI 2/3 had similar primary and secondary outcomes, regardless of the SBT group. Within the SBT < 48 h group, the pre-PCI TIMI 2/3 group exhibited significantly higher rates of 3-year all-cause death, CD, recurrent MI, and secondary outcome values than the pre-PCI TIMI 0/1 group. Patients in the SBT ≥ 48 h group with either pre-PCI TIMI 0/1 or TIMI 2/3 had similar primary and secondary outcomes. Our results suggest that shortening the SBT may confer a survival benefit in patients with NSTEMI and those in the pre-PCI TIMI 0/1 group compared to those in the pre-PCI TIMI 2/3 group.

Effect of delayed hospitalization on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: We evaluated the effect of delayed hospitalization (symptom-to-door time [STD] ≥ 24 h) on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing new-generation drug-eluting stent (DES) implantation. METHODS: A total of 4513 patients with NSTEMI were classified into chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m², n = 1118) and non-CKD (eGFR ≥ 60 mL/min/1.73 m², n = 3395) groups. They were further sub-classified into groups with (STD ≥ 24 h) and without (STD < 24 h) delayed hospitalization. The primary outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction, any repeat coronary revascularization, and stroke. The secondary outcome was stent thrombosis (ST). RESULTS: After multivariable-adjusted and propensity score analyses, the primary and secondary clinical outcomes were similar in patients with or without delayed hospitalization in both CKD and non-CKD groups. However, in both the STD < 24 h and STD ≥ 24 h groups, MACCE (p < 0.001 and p < 0.006, respectively) and mortality rates were significantly higher in the CKD group than in the non-CKD group. However, ST rates were similar between the CKD and non-CKD groups and between the STD < 24 h and STD ≥ 24 h groups. CONCLUSIONS: Chronic kidney disease appears to be a much more important determinant of MACCE and mortality rates than STD in patients with NSTEMI.