Effect of Patient's Symptom Interpretation on In-Hospital Mortality in Acute Coronary Syndrome.

BACKGROUND: The association between symptom interpretation and prognosis has not been investigated well among patients with acute coronary syndrome (ACS). As such, the present study evaluated the effect of heart disease awareness among patients with ACS on in-hospital mortality.Methods and Results: We performed a post hoc analysis of 1,979 consecutive patients with ASC with confirmed symptom interpretation on admission between 2014 and 2018, focusing on patient characteristics, recanalization time, and clinical outcomes. Upon admission, 1,264 patients interpreted their condition as cardiac disease, whereas 715 did not interpret their condition as cardiac disease. Although no significant difference was observed in door-to-balloon time between the 2 groups, onset-to-balloon time was significantly shorter among those who interpreted their condition as cardiac disease (254 vs. 345 min; P<0.001). Moreover, the hazard ratio (HR) for in-hospital mortality was significantly higher among those who did not interpret their condition as cardiac disease based on the Cox regression model adjusted for established risk factors (HR 1.73; 95% confidence interval 1.08-2.76; P=0.022). CONCLUSIONS: This study demonstrated that prehospital symptom interpretation was significantly associated with in-hospital clinical outcomes among patients with ACS. Moreover, the observed differences in clinical prognosis were not related to door-to-balloon time, but may be related to onset-to-balloon time.

One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Detailed Lipid Profiles and Lipid-related Residual Risk after 12-week 10 mg Rosuvastatin Treatment for Acute Myocardial Infarction.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods and Results Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

Comparing In-Hospital Outcomes for Acute Myocardial Infarction Patients in High-Volume Hospitals Performing Primary Percutaneous Coronary Intervention vs. Regional General Hospitals.

BACKGROUND: It has been reported that patients with acute myocardial infarction (AMI) transferred to low-volume primary percutaneous coronary intervention (PCI) hospitals (<115/year) in low population density areas experience higher in-hospital mortality rates. This study compared in-hospital outcomes of patients admitted to high-volume primary PCI hospitals (≥115/year) with those for other regional general hospitals.Methods and Results: Retrospective analysis was conducted on data obtained from 2,453 patients with AMI admitted to hospitals in Iwate Prefecture (2014-2018). Multivariate analysis revealed that the in-hospital mortality rate of AMI among patients in regional general hospitals was significantly higher than among patients in high-volume hospitals. However, no significant difference in mortality rate was observed among patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI. Although no significant difference was found in the in-hospital mortality rate of patients with Killip class I STEMI, significantly lower in-hospital mortality rates were observed in patients admitted in high-volume hospitals for Killip classes II, III, and IV. CONCLUSIONS: Although in-hospital outcomes for patients with STEMI undergoing primary PCI were similar, patients with heart failure or cardiogenic shock exhibited better in-hospital outcomes in high-volume primary PCI hospitals than those in regional general hospitals.

Impact of the Great East Japan Earthquake and Tsunami on the Incidence of Takotsubo Syndrome Using a Multicenter, Long-Term Regional Registry.

BACKGROUND: This study aimed to clarify the incidence of takotsubo syndrome (TTS) after the Great East Japan earthquake (GEJ-E) between inland and coastal areas.Methods and Results:Consecutive hospitalized patients with TTS were registered between 2009 and 2016 in Iwate Prefecture. Patients were divided into 2 groups, by whether they lived inland or in the coastal area (both max. seismic intensity, 6-). The incidence of TTS was calculated using the standardized incidence ratio (SIR) before and after the earthquake. The long-term prognosis of the 2 groups was compared by Kaplan-Meier analysis. A total of 112 patients with TTS were registered from the acute coronary syndrome records of each hospital (n=4,163); 9 patients with TTS were registered within 2 months of the earthquake. A significant monthly variation was observed in March and April 2011 compared with the other months (P=0.029). At 2 years after the earthquake, the SIR was significantly increased in the coastal area (P<0.01), but decreased after ≥3 years. There were no significant differences in the long-term prognosis between the 2 groups (P=0.20). CONCLUSIONS: The incidence of TTS was increased in the acute phase after the GEJ-E, particularly in the coastal area. The magnitude of the tsunami damage is presumed to be a factor in the increased incidence of TTS, even though the seismic intensity in both areas was comparable.

A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK-ZNF890P locus in the Japanese general population.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor for CVD in the Japanese general population. METHODS: This was a genome-wide association study (GWAS) based on a cohort from the 2013 Tohoku Medical Megabank Project community study. The GWAS was performed using a HumanOmniExpressExome BeadChip array with 914,035 autosomal single-nucleotide polymorphisms. The Framingham Risk Score and the Suita score were used to evaluate the future risk of CVD. RESULTS: The GWAS identified 10 loci reaching suggestive significance in the discovery cohort. A replication analysis confirmed that one of the 10 loci, rs7798496, is associated with elevated hs-cTnT levels. The combined P value in the discovery and replication cohorts for the association between the rs7798496 and hs-cTnT levels was 3.4 × 10-8, which indicates that the novel variant reached genome-wide significance. The rs7798496 loci was located at an intergenic region between the retinoblastoma gene product (RB)-associated Krüppell-associated box (KRAB) zinc finger, zinc finger protein 890, and pseudogene (ZNF890P). Logistic regression analysis revealed that the presence of the rs7798496 T allele was strongly associated with a high risk for CVD. CONCLUSIONS: This study provides insights into a link between a novel genetic variant, T allele of rs7798269, and elevated hs-cTnT levels as a future risk for CVD in the general Japanese population.

Clinical outcomes of patients treated using very short duration dual antiplatelet therapy after implantation of biodegradable-polymer drug-eluting stents: rationale and design of a prospective multicenter REIWA registry.

Several studies have demonstrated the safety and feasibility of short (3-6 months) and very short duration (< 2 months) dual antiplatelet therapy (DAPT) in patients with a durable-polymer drug-eluting stent (DP-DES). However, the clinical importance of using very short duration DAPT has yet to be established in patients with a biodegradable polymer drug-eluting stent (BP-DES). The aim of this REIWA registry (multicenter and prospective registry; investigation of clinical outcomes of patients treated with short duration dual antiplatelet therapy after implantation of biodresorbable-polymer drug-eluting stent: a multicenter, prospective registry from Iwate medical university affiliated hospitals) is to determine the safety and feasibility of using 1-month DAPT followed by P2Y12 inhibitor monotherapy in patients after BP-DES implantation. This study is an observational, prospective, multicenter registry encompassing the entire local medical region of Iwate Prefecture (northern area of mainland Japan). A total of 1200 patients who underwent successful PCI with a novel thin strut BP-DES (Synergy, Ultimaster or Orsiro) and are considered to be appropriate patients for very short DAPT, are registered and subsequently administered 1-month DAPT followed by P2Y12 inhibitor monotherapy (clopidogrel 75 mg/day or prasugrel 3.75 mg/day). The primary endpoint was a composite of cardiovascular and bleeding events, which included cardiovascular death, spontaneous myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke, or TIMI major or minor bleeding at 12 months. The REIWA registry (UMIN000037321) will demonstrate both the safety and feasibility of using 1-month DAPT in patients with BP-DES. Furthermore, results of this study will also be able to provide supportive evidence for P2Y12 inhibitor monotherapy after 1-month DAPT following BP-DES implantation.

The Value of a Cystatin C-based Estimated Glomerular Filtration Rate for Cardiovascular Assessment in a General Japanese Population: Results From the Iwate Tohoku Medical Megabank Project.

BACKGROUND: Epidemiological studies have shown that high circulating cystatin C is associated with a risk of cardiovascular disease (CVD) independent of creatinine-based renal function measurements. The present study investigated the comparison between the cystatin C-based estimated glomerular filtration rate (GFRcys) and creatinine-based GFR (GFRcr) to determine whether these measurements are associated with CV biomarkers and elevated CVD risk in a general Japanese population. METHODS: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture (n = 29,375). Chronic kidney disease (CKD) was estimated using the GFRcys, GFRcr and the urine albumin-to-creatinine ratio (UACR). RESULTS: The prevalence of CKD in the participants was found to be higher based on the GFRcr than the GFRcys. Multiple variable analyses after adjusting for baseline characteristics showed that high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with the GFRcys. The area under the receiver operating characteristic (AUROC) curve for identifying individuals with a high Suita score was higher for the GFRcys (AUROC = 0.68) than it was for the GFRcr (AUROC = 0.64, P < 0.001). The GFRcys provided reclassification improvement for the CVD risk prediction model by the GFRcr (net reclassification improvement = 0.341; integrated discrimination improvement = 0.018, respectively, P < 0.001). CONCLUSIONS: The GFRcys is more closely associated with CV biomarkers, including hs-cTnT and NT-proBNP levels, and a high Suita score than the GFRcr, and it provides additional value in the assessment of CVD risk using GFRcr.

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project.

Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population. Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n = 30,193, age = 60.2 ± 11.5 year). Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90-3.89, p < 0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28-3.14, p < 0.001). Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.

Endovascular Embolization of Coronary Artery-Pulmonary Artery Fistulas with Double Coronary Aneurysms.

A 75-year-old woman with chest discomfort and a continuous murmur was admitted to our hospital. During noninvasive examination, computed tomography angiography showed a coronary artery-pulmonary artery fistula with double giant coronary aneurysms (one was 42 mm× 32 mm× 32 mm, and the other was 25 mm× 20 mm× 17 mm) arising from the proximal part of the left anterior descending (LAD) artery. Stress myocardial scintigraphy showed ischemia at the LAD area. Given her frailty, the heart team, including cardiac surgeons, judged that surgical treatment would be difficult. Thus, endovascular embolization for the abnormal vessels was selected. After coronary angiography, two coronary aneurysms were embolized by 53 coils, and the feeding artery was embolized by two coils and one Amplatzer Vascular Plug 4™. A small pulmonary artery fistula remained after the procedures; thus, additional embolization was performed 3 months after the index procedure. Thereafter, angiography showed no flow into the aneurysms, and her symptoms improved.Endovascular embolization might be an effective treatment to achieve aneurysm occlusion in patients at high risk for surgical treatment. Although the present case had double coronary aneurysms with a large feeder vessel, the combination procedure of coils and vascular plug was able to embolize this abnormal vessel.

Expression of miR-23a induces telomere shortening and is associated with poor clinical outcomes in patients with coronary artery disease.

Telomeric repeat binding factor (TRF) 2 (TRF2) plays an important role in telomere maintenance. miR-23a may directly inhibit TRF2 expression, thereby, inducing telomere shortening and cellular senescence. The present study aimed to determine whether miR-23a and TRF2 are expressed in patients with coronary artery disease (CAD), and whether pitavastatin might affect these levels. The present study included 104 patients with CAD and 50 controls. Patients with CAD were randomly divided into two subgroups (a moderate lipid lowering therapy (LLT) group and an aggressive LLT group). Peripheral blood mononuclear cells (PBMCs) were taken from patients with CAD and from controls at baseline and after 12 months. Levels of miR-23a were higher in the CAD group than in the controls. Levels of TRF2 protein were lower in the CAD group than in the controls. Our randomized clinical study showed that aggressive LLT decreased miR-23a and increased TRF2 levels, whereas moderate LLT generated no change in these levels. Our transfected cell model showed that miR-23a controlled TRF2 expression. After a mean follow-up of 339 days, cardiovascular events were associated with high miR-23a, low TRF2 or low relative telomere length. Multivariate analysis showed that levels of miR-23a (RR: 4.9, 95% CI: 1.9-14.3) were a strong predictor of cardiovascular events after adjustment for baseline characteristics. In conclusion, elevated levels of miR-23a play an important role in coronary atherosclerosis via down-regulated TRF2, and may provide important prognostic information in patients with CAD. Additionally, aggressive LLT may prevent telomere erosion via down-regulated miR-23a.

Thrombospondin-1 contributes to slower aortic aneurysm growth by inhibiting maladaptive remodeling of extracellular matrix.

In this issue of Clinical Science, Krishna and colleagues describe recent work on thrombospondin-1 (TSP-1) maturation and its association with slower growth of aortic aneurysm in TSP-1 knockdown mouse models. The authors conclude that TSP-1 deficiency promotes maladaptive remodeling of the extracellular matrix (ECM) leading to accelerated aortic aneurysm progression. We comment on a causal relation between TSP-1 and the progression of aortic aneurysm.

Dysregulation of ossification-related miRNAs in circulating osteogenic progenitor cells obtained from patients with aortic stenosis.

CAVD (calcific aortic valve disease) is the defining feature of AS (aortic stenosis). The present study aimed to determine whether expression of ossification-related miRNAs is related to differentiation intro COPCs (circulating osteogenic progenitor cells) in patients with CAVD. The present study included 46 patients with AS and 46 controls. Twenty-nine patients underwent surgical AVR (aortic valve replacement) and 17 underwent TAVI (transcatheter aortic valve implantation). The number of COPCs was higher in the AS group than in the controls (P<0.01). Levels of miR-30c were higher in the AS group than in the controls (P<0.01), whereas levels of miR-106a, miR-148a, miR-204, miR-211, miR-31 and miR-424 were lower in the AS group than in the controls (P<0.01). The number of COPCs and levels of osteocalcin protein in COPCs were positively correlated with levels of miR-30a and negatively correlated with levels of the remaining miRNAs (all P<0.05). The degree of aortic valve calcification was weakly positively correlated with the number of COPCs and miR-30c levels. The number of COPCs and miR-30c levels were decreased after surgery, whereas levels of the remaining miRNAs were increased (all P<0.05). Changes in these levels were greater after AVR than after TAVI (all P<0.05). In vitro study using cultured peripheral blood mononuclear cells transfected with each ossification-related miRNA showed that these miRNAs controlled levels of osteocalcin protein. In conclusion, dysregulation of ossification-related miRNAs may be related to the differentiation into COPCs and may play a significant role in the pathogenesis of CAVD.