Systemic reserve dysfunction and contrast-associated acute kidney injury following percutaneous coronary intervention.

BACKGROUND: Developing contrast-associated acute kidney injury (CA-AKI) following percutaneous coronary intervention (PCI) is closely related to patient-related risk factors as well as contrast administration. The diagnostic and prognostic roles of neutrophil gelatinase-associated lipocalin (NGAL) in CA-AKI following PCI are not well established. METHODS: Consecutive patients undergoing PCI were enrolled prospectively. CA-AKI was defined as an increase in the serum creatinine level ≥0.3 mg/dL within 48 hours or ≥1.5 times the baseline within 7 days after PCI. Serum NGAL concentrations were determined immediately before and 6 hours after PCI. The participants were classified into four NGAL groups according to the pre- and post-PCI NGAL values at 75th percentile. RESULTS: CA-AKI occurred in 38 (6.4%) of 590 patients. With chronic kidney disease status (hazard ratio [HR] 1.63, 95% confidence interval [CI]: 1.06-2.52), NGAL groups defined by the combination of pre- and 6 h post-PCI values were independently associated with the occurrence of CA-AKI (HR 1.69, 95% CI: 1.16-2.45). All-cause mortality for 29-month follow-ups was different among NGAL groups (log-rank p<0.001). Pre-PCI NGAL levels significantly correlated with baseline cardiac, inflammatory, and renal markers. Although post-PCI NGAL levels increased in patients with larger contrast administration, contrast media made a relatively limited contribution to the development of CA-AKI. CONCLUSION: In patients undergoing PCI, the combination of pre- and post-PCI NGAL values may be a useful adjunct to current risk-stratification of CA-AKI and long-term mortality. CA-AKI is likely caused by systemic reserve deficiency rather than contrast administration itself.

Clinical efficacy of angiotensin receptor-neprilysin inhibitor in de novo heart failure with reduced ejection fraction.

BACKGROUND/AIMS: We aimed to analyze the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) by the disease course of heart failure (HF). METHODS: We evaluated 227 patients with HF in a multi-center retrospective cohort that included those with left ventricular ejection fraction (LVEF) ≤ 40% undergoing ARNI treatment. The patients were divided into patients with newly diagnosed HF with ARNI treatment initiated within 6 months of diagnosis (de novo HF group) and those who were diagnosed or admitted for HF exacerbation for more than 6 months prior to initiation of ARNI treatment (prior HF group). The primary outcome was a composite of cardiovascular death and worsening HF, including hospitalization or an emergency visit for HF aggravation within 12 months. RESULTS: No significant differences in baseline characteristics were reported between the de novo and prior HF groups. The prior HF group was significantly associated with a higher primary outcome (23.9 vs. 9.4%) than the de novo HF group (adjusted hazard ratio 2.52, 95% confidence interval 1.06-5.96, p = 0.036), although on a higher initial dose. The de novo HF group showed better LVEF improvement after 1 year (12.0% vs 7.4%, p = 0.010). Further, the discontinuation rate of diuretics after 1 year was numerically higher in the de novo group than the prior HF group (34.4 vs 18.5%, p = 0.064). CONCLUSION: The de novo HF group had a lower risk of the primary composite outcome than the prior HF group in patients with reduced ejection fraction who were treated with ARNI.

Association Between Bleeding and New Cancer Detection and the Prognosis in Patients With Myocardial Infarction.

Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all-cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50-4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30-29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69-57.07]). The risk of all-cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04-8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81-9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.

Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts.

Heart failure (HF) is a frequent consequence of myocardial infarction (MI). Identification of the precise, time-dependent composition of inflammatory cells may provide clues for the establishment of new biomarkers and therapeutic approaches targeting post-MI HF. Here, we investigate the spatiotemporal dynamics of MI-associated immune cells in a mouse model of MI using spatial transcriptomics and single-cell RNA-sequencing (scRNA-seq). We identify twelve major immune cell populations; their proportions dynamically change after MI. Macrophages are the most abundant population at all-time points (>60%), except for day 1 post-MI. Trajectory inference analysis shows upregulation of Trem2 expression in macrophages during the late phase post-MI. In vivo injection of soluble Trem2 leads to significant functional and structural improvements in infarcted hearts. Our data contribute to a better understanding of MI-driven immune responses and further investigation to determine the regulatory factors of the Trem2 signaling pathway will aid the development of novel therapeutic strategies for post-MI HF.

Effect of smoking on clinical outcomes in patients receiving rotational atherectomy in calcified coronary lesions: from the ROCK Registry, South Korea.

BACKGROUND: Tobacco smoking and its harmful health effects also increase economic burdens globally. Surprisingly, despite the detrimental health consequences of smoking, some studies have shown better survival among smokers compared with non-smokers, a phenomenon called "smoker's paradox". However, the impact of smoking status on clinical outcomes in severe calcified coronary artery disease (CAD) patients has yet to be reported. OBJECTIVES: Investigate the impact of smoking on clinical outcomes in calcified CAD receiving rotational atherectomy (RA). DESIGN: Retrospective review of medical records. SETTING: Multicenter registry in South Korea. PATIENTS AND METHODS: This multicenter registry included consecutive patients with calcified CAD who underwent RA at nine tertiary centers in Korea between January 2010 and October 2019. MAIN OUTCOME MEASURES: Target-vessel failure (TVF) which included the composite of cardiac death, target-vessel myocardial infarction (TVMI), and target-vessel revascularization (TVR). SAMPLE SIZE: 583 lesions in 540 patients followed for a median of 16.1 months. RESULTS: Lesions were divided into two groups: non-smokers (n=472, 81.0%) and smokers (n=111, 19.0%). TVF in the smoker group was significantly more frequent than in non-smoker group (log rank P=.016). The inverse probability of treatment weighting analysis also showed that smoking was significantly associated with a higher incidence of the primary outcome (HR: 1.617; 95% CI: 1.127-2.320; P=.009), cardiac death (HR 1.912; 95% CI: 1.105-3.311; P=.021), myocardial infarction (HR: 3.914; 95% CI: 1.884-8.132; P<.001), TVMI (HR: 3.234; 95% CI: 1.130-9.258; P=.029), and TVR (HR: 1.661; 95% CI: 1.043-2.643; P=.032). However, any bleeding was significantly observed less in the smokers. CONCLUSION: Smoking is significantly associated with adverse clinical outcomes in CAD patients requiring RA. LIMITATIONS: Retrospective design. CONFLICTS OF INTEREST: None.

AIMP3 induces laminopathy and senescence of vascular smooth muscle cells by reducing lamin A expression and leads to vascular aging in vivo.

Aminoacyl-tRNA synthetase-interacting multifunctional protein 3 (AIMP3), a tumor suppressor, mediates a progeroid phenotype in mice by downregulating lamin A. We investigated whether AIMP3 induces laminopathy and senescence of human aortic smooth muscle cells (HASMCs) and is associated with vascular aging in mice and humans in line with decreased lamin A expression. Cellular senescence was evaluated after transfecting HASMCs with AIMP3. Molecular analyses of genes encoding AIMP3, lamin A, chemokine (C-C motif) ligand 2 (CCL2), and C-C chemokine receptor type 2 (CCR2) and histological comparisons of aortas were performed with mice at various ages (7 weeks, 5 months, 12 months, 24 months, and 32 months), AIMP3-transgenic mice, and human femoral arteries of cadavers. AIMP3-transfected HASMCs exhibited increased AIMP3 and senescence marker p16 protein expression and decreased lamin A protein expression in accordance with their disrupted nuclear morphology in histological analyses. AIMP3-transgenic mice displayed increased AIMP3 protein expression and decreased lamin A protein expression in aortas together with typical aging pathologies. Similar changes were observed in wild-type aging (24-month-old) mice but not in wild-type young (7-week-old) mice. In humans, AIMP3 and lamin A protein expression was higher and lower, respectively, in femoral arteries of elderly individuals than in those of their younger counterparts. This study found that AIMP3 overexpression in vitro decreased lamin A expression and induced nuclear laminopathy and cellular senescence. Similar findings were made in the vasculature of aging mice and elderly humans.

Impact of chronic total occlusion lesions on clinical outcomes in patients receiving rotational atherectomy: results from the ROCK registry.

The aim of this study was to investigate the impact of chronic total occlusion (CTO) on clinical outcomes in patients with calcified coronary lesions receiving rotational atherectomy (RA). This multi-center registry enrolled consecutive patients with calcified coronary artery disease who underwent RA during percutaneous coronary intervention (PCI) from 9 tertiary centers in Korea between January 2010 and October 2019. The primary outcome was target-vessel failure (TVF) which included the composite of cardiac death, target-vessel myocardial infarction (TVMI), and target-vessel revascularization (TVR). A total of 583 lesions were enrolled in this registry and classified as CTO (n = 42 lesions, 7.2%) and non-CTO (n = 541 lesions, 92.8%). The CTO group consisted of younger patients who were more likely to have a history of previous percutaneous coronary intervention or coronary artery bypass graft surgery. The incidence of the primary outcome was 14.1% and 16.7% for the non-CTO group and CTO group, respectively. The primary outcomes observed in the two groups were not significantly different (log-rank p = 0.736). The 18-month clinical outcomes of the CTO group were comparable to those of the non-CTO group in multivariate analysis. About 7% of patients requiring RA have CTO lesions and these patients experience similar clinical outcomes compared with those having non-CTO lesions. Use of RA for CTO lesions was safe despite higher procedural complexity.

Effects of Smoking on Long-Term Clinical Outcomes and Lung Cancer in Patients with Acute Myocardial Infarction.

BACKGROUND AND OBJECTIVES: Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the "smoker's paradox". This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization. RESULTS: Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594-0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443-0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009-1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026-1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensity-score matched HR, 2.749; 95% CI, 1.416-5.338; p=0.003). CONCLUSIONS: In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.

Soluble neprilysin and long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention: a retrospective cohort study.

BACKGROUND: Neprilysin has an essential role in regulating fluid balance and vascular resistance, and neprilysin inhibitors have shown beneficial effects in patients with heart failure. However, the potential predictive value of neprilysin levels as a biomarker for cardiovascular risk remains unclear. The aim of this study was to assess the prognostic value of soluble neprilysin (sNEP) levels in patients with ischemic heart disease. METHODS: Neprilysin levels were measured in 694 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). These patients were classified into two groups according to their serum levels of neprilysin and categorized into the lower neprilysin group (n = 348) and the higher neprilysin group (n = 346). The primary clinical endpoint was all-cause mortality, and the secondary endpoint was a composite of major adverse cardiac events (MACE). RESULTS: The median sNEP level was 76.0 pg/ml. The median sNEP levels were higher in patients with left ventricular ejection fraction (LVEF) ≥40% (77.6 pg/ml, interquartile range 46.6-141.3) than in those with LVEF < 40% (70.0 pg/ml, interquartile range 47.1-100.6; P = 0.032). Among all patients, each clinical outcome and MACE did not differ significantly according to the groups divided into median, tertile, or quartile of sNEP levels during a median follow-up of 28.4 months. We did not find a significant relationship between sNEP levels and clinical outcomes in multivariate Cox regression analysis. Among patients with LVEF < 40%, an increased sNEP level was associated with a higher rate of all-cause death (adjusted hazard ratio 2.630, 95% confidence interval 1.049-6.595, P = 0.039). CONCLUSION: Serum sNEP levels are not associated with long-term mortality or cardiovascular outcomes after PCI in patients with CAD. In the LVEF < 40% group, increased sNEP levels may be associated with a higher risk of all-cause death.

Ticagrelor Does Not Improve Endothelial Dysfunction in Stable Survivors of Acute Coronary Syndrome.

BACKGROUND: Ticagrelor is an intriguing antiplatelet agent with a potentially beneficial impact on endothelial dysfunction and confers a mortality benefit beyond 1 month after acute coronary syndrome (ACS). However, little data exist on whether ticagrelor improves endothelial dysfunction in stable patients who survive the acute period and receive guideline-directed medical therapy. METHODS AND RESULTS: This study is a prospective, randomized, parallel, open-labeled study that enrolled 30-day survivors of non-ST-segment elevation ACS (NSTE-ACS). Forty patients with NSTE-ACS were randomly assigned to ticagrelor or clopidogrel groups. The primary end point was the change in the percentage brachial artery flow-mediated dilation (baFMD) from baseline. Baseline characteristics were not different between the 2 groups. The median time from the stent implantation to screening was 269 days. After 30 days of study medication administration, the change in the percentage baFMD value was similar between the ticagrelor and clopidogrel groups (-0.08 [1.42] vs 0.30 [1.69], P = .66). There was no difference in the change in high-sensitive C-reactive protein (-0.61 [1.48] vs -0.01 [0.57], P = .28); however, the change in platelet inhibition significantly differed (P2Y12 reaction units, -140.5 [49.5] vs -3.9 [51.4], P < .001). CONCLUSIONS: This dual time point baFMD study demonstrated that treatment with ticagrelor was not superior to clopidogrel for improving endothelial dysfunction in stabilized patients with NSTE-ACS.

Triangular radial Nb2O5 nanorod growth on c-plane sapphire for ultraviolet-radiation detection.

Nb2O5 nanostructures with excellent crystallinities were grown on c-plane sapphire and employed for ultraviolet-(UV)-radiation detection. The triangular radial Nb2O5 grown on the c-sapphire substrate had a 6-fold symmetry with domain matching epitaxy on the substrate. Owing to the radial growth, the nanorods naturally connected when the deposition time increased. This structure can be used as a UV-detector directly by depositing macroscale electrodes without separation of a single nanorod and e-beam lithography process. It was confirmed that electric reactions occur at different UV irradiation wavelengths (254 nm and 365 nm).

Computed Tomography Angiography Images of Coronary Artery Stenosis Provide a Better Prediction of Risk Than Traditional Risk Factors in Asymptomatic Individuals With Type 2 Diabetes: A Long-term Study of Clinical Outcomes.

OBJECTIVE: We investigated the efficacy of coronary computed tomography angiography (CCTA) in predicting the long-term risks in asymptomatic patients with type 2 diabetes and compared it with traditional risk factors. RESEARCH DESIGN AND METHODS: We analyzed 933 patients with asymptomatic type 2 diabetes who underwent CCTA. Stenosis was considered obstructive (≥50%) in each coronary artery segment using CCTA. The extent and severity scores for coronary artery disease (CAD) were evaluated. The primary end point was major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization during a mean follow-up period of 5.5 ± 2.1 years. RESULTS: Ninety-four patients with MACE exhibited obstructive CAD with a greater extent and higher severity scores (P < 0.001 for all). After adjusting for confounding risk factors, obstructive CAD remained an independent predictor of MACE (hazard ratio 3.11 [95% CI 2.00-4.86]; P < 0.001]). The performance of a risk prediction model based on C-statistics was significantly improved (C-index 0.788 [95% CI 0.747-0.829]; P = 0.0349) upon the addition of a finding of obstructive CAD using CCTA to traditional risk factors, including age, male, hypertension, hyperlipidemia, smoking, estimated glomerular filtration rate, and HbA1c. Both integrated discrimination improvement (IDI) and net reclassification improvement (NRI) analyses further supported this finding (IDI 0.046 [95% CI 0.020-0.072], P < 0.001, and NRI 0.55 [95% CI 0.343-0.757], P < 0.001). In contrast, the risk prediction power of the coronary artery calcium score remained unimproved (C-index 0.740, P = 0.547). CONCLUSIONS: Based on our data, the addition of CCTA-detected obstructive CAD to models that include traditional risk factors improves the predictions of MACE in asymptomatic patients with type 2 diabetes.

Impact of cystatin-C level on the prevalence and angiographic characteristics of vasospastic angina in Korean patients.

Cystatin-C, a marker of mild renal dysfunction, has been reported to be associated with cardiovascular diseases including vasospastic angina (VSA). We aimed to investigate the impact of cystatin-C level on the prevalence and angiographic characteristics of VSA in Korean patients.A total of 549 patients in the VA-KOREA (Vasospastic Angina in KOREA) registry who underwent ergonovine provocation tests were consecutively enrolled. Estimated glomerular filtration rate (eGFR) and levels of serum creatinine (Cr) and cystatin-C were assessed before angiography.The patients were classified into two groups: the VSA group (n = 149, 27.1%) and the non-VSA group (n = 400). Although eGFR and Cr levels were similar between the two groups, the VSA group had a significantly higher level of cystatin-C (P < 0.05). A high level of cystatin-C (second tertile, hazard ratio 1.432; 95% confidence interval [1.1491.805]; P = 0.026, third tertile, 1.947 [1.132-2.719]; P = 0.003) and current smoking (2.710 [1.415-4.098]; P < 0.001) were independently associated with the prevalence of VSA. Furthermore, the highest level of cystatin-C (> 0.96 ng/mL) had a significant impact on the incidence of multivessel spasm (2.608 [1.061-4.596]; P = 0.037).A high level of cystatin-C was independently associated with the prevalence of VSA and with a high-risk type of VSA in Korean patients, suggesting that proactive investigation of VSA should be considered for patients with mild renal dysfunction indicated by elevated cystatin-C.