Sex Differences in Process-of-Care and In-Hospital Prognosis Among Elderly Patients Hospitalized With Acute Myocardial Infarction.

BACKGROUND: Limited studies have demonstrated sex differences in the clinical outcomes and quality of care among elderly patients hospitalized with acute myocardial infarction (AMI).Methods and Results: Using nationwide cardiovascular registry data collected in Japan between 2012 and 2019, we enrolled patients aged ≥45 years. The 30-day and all in-hospital mortality rates, as well as process-of-care measures, were assessed, and mixed-effects logistic regression analysis was performed. A total 254,608 patients were included and stratified into 3 age groups: middle-aged, old and oldest old. The 30-day mortality rates for females and males were as follows: 3.0% vs. 2.7%, with an adjusted odds ratio (OR) of 1.17 (95% confidence interval (CI): 1.01-1.36, P=0.030) in middle-aged patients; 7.2% vs. 5.8%, with an OR of 1.14 (95% CI: 1.09-1.21, P<0.001) in old patients; and 19.6% vs. 15.5% with an OR of 1.17 (95% CI: 1.09-1.26, P<0.001) in the oldest old patients. Moreover, significantly higher numbers of female AMI patients across all age groups died in hospital, as well as having fewer invasive procedures and cardiovascular prescriptions, compared with their male counterparts. CONCLUSIONS: This nationwide cohort study revealed that female middle-aged and elderly patients experienced suboptimal quality of care and poorer in-hospital outcomes following AMI, compared with their male counterparts, highlighting the need for more effective management in consideration of sex-specific factors.

In-hospital mortality and cardiovascular treatment during hospitalization for heart failure among patients with schizophrenia: a nationwide cohort study.

AIMS: Schizophrenia is associated with cardiovascular disease (CVD) risk, and patients with schizophrenia are more likely to receive suboptimal care for CVD. However, there is limited knowledge regarding in-hospital prognosis and quality of care for patients with schizophrenia hospitalized for heart failure (HF). This study sought to elucidate the association between schizophrenia and in-hospital mortality, as well as cardiovascular treatment in patients hospitalized with HF. METHODS: Using the nationwide cardiovascular registry data in Japan, a total of 704,193 patients hospitalized with HF from 2012 to 2019 were included and stratified by age: young age, > 18 to 45 years (n = 20,289); middle age, >45 to 65 years (n = 114,947); and old age, >65 to 85 years (n = 568,957). All and 30-day in-hospital mortality as well as prescription of cardiovascular medications were assessed. After multiple imputation for missing values, mixed-effect multivariable logistic regression analysis was performed using patient and hospital characteristics with hospital identifier as a variable with random effects. RESULTS: Patients with schizophrenia were more likely to experience prolonged hospital stays, and incur higher hospitalization costs. In-hospital mortality for non-elderly patients with schizophrenia was significantly worse than for those without schizophrenia: the mortality rate was 7.6% vs 3.5% and the adjusted odds ratio (OR) was 1.96 (95% confidence interval (CI): 1.24-3.10, P = 0.0037) in young adult patients; 6.2% vs 4.0% and 1.49 (95% CI: 1.17-1.88, P < 0.001) in middle-aged patients. Thirty-day in-hospital mortality was significantly worse in middle-aged patients: the mortality rate was 4.7% vs 3.0% and an adjusted OR was 1.40 (95% CI: 1.07-1.83, P = 0.012). In-hospital mortality in elderly patients did not differ between those with and without schizophrenia. Prescriptions of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were significantly lower in patients with schizophrenia across all age groups. CONCLUSION: Schizophrenia was identified as a risk factor for in-hospital mortality and reduced prescription of cardioprotective medications in non-elderly patients hospitalized with HF. These findings highlight the necessity for differentiated care and management of HF in patients with severe mental illnesses.

Association between patient volume to cardiologist, process of care, and clinical outcomes in heart failure.

AIMS: The impact of hospital volume on clinical performance has been investigated by many researchers to date and thought that it is associated with quality of care and outcome for patients with heart failure (HF). This study sought to determine whether annual admissions of HF per cardiologist are associated with process of care, mortality, and readmission. METHODS AND RESULTS: Among the nationwide registry 'Japanese registry of all cardiac and vascular diseases - diagnostics procedure combination' data collected from 2012 to 2019, a total of 1 127 113 adult patients with HF and 1046 hospitals were included in the study. Primary outcome was in-hospital mortality, and secondary outcome was 30 day in-hospital mortality and readmission at 30 days and 6 months. Hospital and patient characteristics and process of care measures were also assessed. Mixed-effect logistic regression and Cox proportional-hazards model was used for multivariable analysis, and adjusted odds ratio and hazard ratio were evaluated. Process of care measures had inverse trends for annual admissions of HF per cardiologist (P < 0.01 for all measures: prescription rate of beta-blocker, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker, mineralocorticoid receptor antagonist, and anticoagulant for atrial fibrillation). Adjusted odds ratio for in-hospital mortality was 1.04 (95% confidence interval (CI): 1.04-1.08, P = 0.04) and 30 day in-hospital mortality was 1.05 (95% CI: 1.01-1.09, P = 0.01) for interval of 50 annual admissions of HF per cardiologist. Adjusted hazard ratio for 30 day readmission was 1.05 (95% CI: 1.02-1.08, P < 0.01) and 6 month readmission was 1.07 (95% CI: 1.03-1.11, P < 0.01). Plots of the adjusted odds indicated 300 as the threshold of annual admissions of HF per cardiologist for substantial increase of in-hospital mortality risk. CONCLUSIONS: Our findings demonstrated that annual admissions of HF per cardiologist are associated with worse process of care, mortality, and readmission with the threshold for mortality risk increased, emphasizing the optimal proportion of patients admitted with HF to cardiologist for better clinical performance.

Amelioration of Endotoxemia by a Synthetic Analog of Omega-3 Epoxyeicosanoids.

Sepsis, a systemic inflammatory response to pathogenic factors, is a difficult to treat life-threatening condition associated with cytokine and eicosanoid storms and multi-organ damage. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic (EPA) and docosahexaenoic acid, are the precursors of potent anti-inflammatory lipid mediators, including 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), the main metabolite of EPA generated by cytochrome P450 epoxygenases. Searching for novel therapeutic or preventative agents in sepsis, we tested a metabolically robust synthetic analog of 17,18-EEQ (EEQ-A) for its ability to reduce mortality, organ damage, and pro-inflammatory cytokine transcript level in a mouse model of lipopolysaccharide (LPS)-induced endotoxemia, which is closely related to sepsis. Overall survival significantly improved following preventative EEQ-A administration along with decreased transcript level of pro-inflammatory cytokines. On the other hand, the therapeutic protocol was effective in improving survival at 48 hours but insignificant at 72 hours. Histopathological analyses showed significant reductions in hemorrhagic and necrotic damage and infiltration in the liver. In vitro studies with THP-1 and U937 cells showed EEQ-A mediated repression of LPS-induced M1 polarization and enhancement of IL-4-induced M2 polarization of macrophages. Moreover, EEQ-A attenuated the LPS-induced decline of mitochondrial function in THP-1 cells, as indicated by increased basal respiration and ATP production as well as reduction of the metabolic shift to glycolysis. Taken together, these data demonstrate that EEQ-A has potent anti-inflammatory and immunomodulatory properties that may support therapeutic strategies for ameliorating the endotoxemia.

Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment.

Mitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed. Mitochondrial disease patient-derived fibroblasts regained respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. Mitochondrial DNA-replaced cells could be a resource for transplantation to treat maternal inherited mitochondrial diseases.

RNA decay in processing bodies is indispensable for adipogenesis.

The RNA decay pathway plays key regulatory roles in cell identities and differentiation processes. Although adipogenesis is transcriptionally and epigenetically regulated and has been thoroughly investigated, how RNA metabolism that contributes to the stability of phenotype-shaping transcriptomes participates in differentiation remains elusive. In this study, we investigated Ddx6, an essential component of processing bodies (PBs) that executes RNA decay and translational repression in the cytoplasm and participates in the cellular transition of reprogramming. Upon adipogenic induction, Ddx6 dynamically accumulated to form PBs with a binding partner, 4E-T, at the early phase prior to emergence of intracellular lipid droplets. In contrast, preadipocytes with Ddx6 knockout (KO) or 4E-T knockdown (KD) failed to generate PBs, resulting in significant suppression of adipogenesis. Transcription factors related to preadipocytes and negative regulators of adipogenesis that were not expressed under adipogenic stimulation were maintained in Ddx6-KO and 4E-T-KD preadipocytes under adipogenic induction. Elimination of Dlk1, a major negative regulator of adipogenesis, in 3T3L1 Ddx6-KO cells did not restore adipogenic differentiation capacity to any extent. Similar to murine cells, human primary mesenchymal stem cells, which can differentiate into adipocytes upon stimulation with adipogenic cocktails, required DDX6 to maturate into adipocytes. Therefore, RNA decay of the entire parental transcriptome, rather than removal of a strong negative regulator, could be indispensable for adipogenesis.

High throughput single cell analysis of mitochondrial heteroplasmy in mitochondrial diseases.

Mitochondrial heteroplasmy, which fundamentally means intracellular heterogeneity of mitochondrial DNA (mtDNA), has been measured in a group of cells, regardless of intercellular heterogeneity. Ordinal methods for mitochondrial heteroplasmy cannot discriminate between an intercellular homogenic population composed of cells with similar intracellular heterogeneity for mtDNA and an intercellular heterogenic population composed of cells with different rates of mutated mtDNA. A high-throughput method to determine mitochondrial heteroplasmy in a single cell was developed by using droplet digital PCR with TaqMan polymerase in this study. This technique revealed that there are three different cell populations of cultured fibroblasts derived from patients with mitochondrial disease carrying a mutation in the mtDNA; cells with homoplasmy of either mutated or healthy mtDNA; and cells mixed with mutated and healthy mtDNA. The presence of intercellular heterogeneity, even in uniformed cultured fibroblasts, suggests that heterogeneity should exist among different kinds of cells. The diagnosis of intercellular heterogeneity with respect to mitochondrial heteroplasmy by this methodology could provide novel insight into developing a treatment strategy for mitochondrial diseases.

Bifurcation Intervention in Single Coronary Artery.

A 77-year-old man was referred to our hospital for angina on effort. Coronary angiography and computed tomography demonstrated a single coronary artery arising from the right sinus of Valsalva. The left circumflex coronary artery (LCx) anomalously deriving near from the ostium of right coronary artery exhibited severe stenosis in the bifurcation of the obtuse marginal branch. Although the bifurcation lesion still remains a therapeutic challenge for guide extension catheter (GEC)-based percutaneous coronary intervention, under the guidance of intravascular ultrasound imaging, we successfully implanted an everolimus-eluting stent at the bifurcated LCx lesion and performed kissing balloon inflation using 0.014- and 0.010-inch systems through GECs.

Stent-less percutaneous coronary intervention using rotational atherectomy and drug-coated balloon: A case series and a mini review.

BACKGROUND: Experiences of rotational atherectomy (RA) followed by drug-coated balloon (DCB) dilation alone (RA/DCB) for de novo coronary artery lesion have been limited. CASE SERIES: Case 1 (65 year-old male) with silent myocardial ischemia and hemodialysis had old anterior myocardial infarction and intact LM/LCx, and underwent RA/DCB against a diffuse calcified lesion in the proximal LAD and a tandem lesion in the proximal RCA. Case 2 (88 year-old female) with post-infarction unstable angina had severe thrombocytopenia and anemia due to myelodysplastic syndrome (platelet 6000/µL, hemoglobin 8.3 g/dL), and underwent RA/DCB against a severe stenosis in the mid LCx after transfusions. Case 3 (47 year-old male) with silent myocardial ischemia due to possible sequelae of Kawasaki disease underwent RA/DCB against a restenotic lesion at the in-let of the calcified aneurysm in the proximal LAD. In all of the patients, PCI was successfully completed under optical frequency domain imaging (OFDI) without complications. Follow-up CAG performed 6-7 months after the procedure revealed no restenosis in case 1 and case 3, and all of the 3 cases have been free of cardiovascular/hemorrhagic events for 11-37 months since the last stent-less procedures. CONCLUSIONS: These cases suggest that RA/DCB under OFDI might be an alternative stent-less revascularization therapy of choice for patients who may be unsuitable for drug-eluting stent implantation.

Rotational Atherectomy Followed by Drug-Coated Balloon Dilation for Left Main In-Stent Restenosis in the Setting of Acute Coronary Syndrome Complicated with Right Coronary Chronic Total Occlusion.

An 83-year-old man presented with recurrent acute coronary syndrome (ACS) at the left main coronary artery (LMCA) complicated with ostial chronic total occlusion (CTO) in the right coronary artery (RCA) (RCA-CTO). At the first LMCA-ACS approximately 1 year earlier, he had undergone LMCA-crossover stenting with a biolimus-eluting stent in the presence of RCA-CTO. At the second LMCA-ACS, we angiographically confirmed severe in-stent restenosis in the distal LMCA, in addition to angled severe stenosis in the just proximal LCx, and performed primary PCI for the LMCA bifurcation lesion under intra-aortic balloon pumping support. Because of difficulty in crossing a guidewire through the just proximal LCx lesion, we first performed rotational atherectomy against the LMCA in-stent eccentric lesion. After successfully crossing the guidewire into the LCx, we added balloon dilation with kissing balloon inflation followed by alternate drug-coated balloon dilation. An eight-month follow-up coronary angiography revealed no further vessel narrowing in the LMCA bifurcation lesion.

Primary Percutaneous Coronary Intervention Followed by Valve Surgery for Acute Coronary Syndrome at Left Main Trunk Complicated With Severe Aortic Stenosis.

An 89-year-old woman appeared to have acute coronary syndrome at the left main trunk (LMT) complicated with severe aortic stenosis, moderate-severe mitral regurgitation, depressed left ventricular (LV) function, and multivessel disease. Because of sustained hypotension even under intra-aortic balloon pumping support during emergency coronary angiograhy, we performed primary percutaneous coronary intervention solely for the LMT lesion using a bare metal stent, leading to recovery from the shock state. On the second hospital day, based on our heart-team consensus, we performed aortic valve replacement and coronary artery bypass grafting surgery, and added edge-to-edge repair (Alfieri stitch) of the mitral valve, resulting in complete revascularization and dramatically improved LV function.

Relationship Between Mean Blood Pressure at Admission and In-Hospital Outcome After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

A J-shaped or U-shaped curve phenomenon might exist between systolic blood pressure (SBP) or pulse pressure (PP) at admission and in-hospital mortality in Japanese patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). However, data regarding a relationship between mean blood pressure (MBP) at admission and in-hospital outcome in AMI patients undergoing primary PCI are still lacking in Japan.A total of 1,413 primary PCI-treated AMI patients were classified into quintiles based on admission MBP (< 79 n = 283, 79-91 n = 285, 92-103 n = 285, 104-115 n = 279, and ≥ 116 mmHg n = 281). Patients with MBP < 79 mmHg had a significantly higher in-hospital mortality, while mortality was not significantly different among the other quintiles: 16.6% (< 79), 4.9% (79-91), 3.9% (92-103), 3.2% (104-115), and 5.0% (≥ 116 mmHg). On multivariate analysis, Killip class ≥ 3 at admission, LMT or multivessels as culprit lesions, admission MBP < 79 mmHg, and age were independent positive predictors of in-hospital mortality, whereas hypercholesterolemia and TIMI 3 flow before/after PCI were negative predictors, while the other MBP categories were not.These results suggest that admission MBP < 79 mmHg might be associated with in-hospital death, and the in-hospital prognostic effects of MBP, the steady component of blood pressure, at admission might be different from those of SBP or PP, the pulsatile component of blood pressure, at admission in Japanese AMI patients undergoing primary PCI.

Rotational Atherectomy Followed by Drug-Coated Balloon Dilation in Possible Coronary Sequelae of Kawasaki Disease.

Rotational atherectomy with/without low-pressure balloon dilation has been a mainstay of interventional treatment for stenosis due to the coronary sequelae of Kawasaki disease (KD). Here, we report a restenosis case of probable coronary sequelae of KD treated with rotational atherectomy with low-pressure 2.5-mm balloon dilation 6 months previously. Under the guidance of optical frequency domain imaging, we performed rotational atherectomy followed by 2.5-mm drug-coated balloon (DCB) dilation for an atherosclerotic restenosis at the inlet of a calcified aneurysm in the proximal left anterior descending coronary artery. Coronary angiography 6 months later showed no apparent progression of vessel narrowing, and we could defer repeat intervention. The present case suggests that rotational atherectomy followed by DCB dilation could be an alternative revascularization therapy of choice in coronary KD sequelae complicated with atherosclerosis.