Impact of Periprocedural Myocardial Injury on Long-Term Outcomes After Percutaneous Coronary Intervention Requiring Atherectomy.

The prognostic implications of cardiac troponin elevation after percutaneous coronary intervention (PCI) with atherectomy have not been established. The aim of this study was to investigate the incidence of periprocedural myocardial injury (PMI) and its association with cardiovascular events in patients with severely calcified lesions who underwent PCI with atherectomy. The study analyzed 346 patients (377 lesions) who underwent PCI with atherectomy between January 2018 and December 2021. Peak post-PCI high-sensitivity cardiac troponin (hs-cTn) was measured. The primary outcome was target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction, and clinically driven target lesion revascularization. A lesion-based analysis was conducted to assess the association of PMI with TLF up to 5 years after PCI. Increase of hs-cTn was seen with 362 lesions (96%), and significant PMI, defined as hs-cTn increase ≥70 × upper reference limit, was seen with 83 lesions (22%). Significant PMI was associated with a significantly greater risk of TLF (adjusted hazard ratio 1.93, 95% confidence interval 1.12 to 3.30, p = 0.017), primarily driven by an increased risk of cardiovascular death (adjusted hazard ratio 5.29, 95% confidence interval 1.46 to 19.16, p = 0.011). In conclusion, hs-cTn increase was frequently observed in patients who underwent PCI with atherectomy, and significant PMI was associated with an increased risk of TLF and cardiovascular death.

Use of human Caco-2 cells and HPAE-PAD for α-glucosidase assay.

To measure α-glucosidase activity, rat intestinal acetone powder is commonly used as a source of α-glucosidase, and the mutarotase-glucose oxidase (GOD) methods commonly used to quantitate glucose produced by enzymatic hydrolysis of the substrates. In this study, we compared human Caco-2 cell extracts with rat intestinal acetone powder extracts. We also compared high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) with the mutarotase-GOD method. The sensitivity of HPAE-PAD was higher than that of mutarotase-GOD. The glucose concentration quantified by HPAE-PAD was similar to that quantified using the mutarotase-GOD method. In the maltase reaction, 1-deoxynojirimycin (1-DNJ) exerted a more potent inhibitory effect on human enzymes than on rat enzymes. This order was reversed during the sucrase reaction. These results suggested that the combined use of Caco-2 cell extracts and HPAE-PAD is advantageous for use in α-glucosidase-related basic research.

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

Guideline-Directed Medical Therapy for Elderly Patients With Acute Myocardial Infarction Who Undergo Percutaneous Coronary Intervention　- Insights From a Retrospective Observational Study.

BACKGROUND: The efficacy of guideline-directed medical therapy (GDMT) in the elderly remains unclear. This study evaluated the impact of GDMT (aspirin or a P2Y12inhibitor, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ß-blocker, and statin) at discharge on long-term mortality in elderly patients with acute myocardial infarction (AMI) who had undergone percutaneous coronary intervention (PCI).Methods and Results: Of 2,547 consecutive patients with AMI undergoing PCI in 2009-2020, we retrospectively analyzed 573 patients aged ≥80 years. The median follow-up period was 1,140 days. GDMT was prescribed to 192 (33.5%) patients at discharge. Compared with patients without GDMT, those with GDMT were younger and had higher rates of ST-segment elevation myocardial infarction and left anterior descending artery culprit lesion, higher peak creatine phosphokinase concentration, and lower left ventricular ejection fraction (LVEF). After adjusting for confounders, GDMT was independently associated with a lower cardiovascular death rate (hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.16-0.81), but not with all-cause mortality (HR 0.77; 95% CI 0.50-1.18). In the subgroup analysis, the favorable impact of GDMT on cardiovascular death was significant in patients aged 80-89 years, with LVEF <50%, or with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2. CONCLUSIONS: GDMT in patients with AMI aged ≥80 years undergoing PCI was associated with a lower cardiovascular death rate but not all-cause mortality.

Multiple Blood Culture Sampling, Proper Antimicrobial Choice, and Adequate Dose in Definitive Therapy Supported by the Antimicrobial Stewardship Team Could Decrease 30-Day Sepsis Mortality Rates.

Objective: This study aimed to identify factors that should be focused on by the antimicrobial stewardship team for treating patients with sepsis, by investigating the mortality of patients with sepsis within 30 days and the mortality-related factors in our hospital over a 10-year period from the perspective of appropriate antimicrobial use. Methods: Factors associated with 30-day mortality were investigated using hierarchical multiple logistic regression in 1406 patients with pathogen-identified sepsis in Hirosaki University Hospital. These factors were clinical data, microbiological data, antimicrobials used in empiric and definitive therapies, presence/absence of ineffective use, underdosing as evaluated using Monte Carlo simulation, and practice of de-escalation. Results: The ineffective use of antimicrobials in empiric therapy and the underdosing and ineffective use in definitive therapy were significantly associated with 30-day mortality (odds ratio [OR] = 2.70, 3.72, and 3.65, respectively). Multiple blood culture sampling was inversely associated with these inappropriate antimicrobial uses. Every year, the 30-day mortality rate has been decreasing, in line with the increase in multiple blood culture sampling and de-escalation; the inappropriate use of antimicrobials has also decreased. Conclusion: Multiple blood culture sampling, proper choice of antimicrobial, and using an adequate dose in definitive therapy could decrease the 30-day mortality rate in patients with sepsis and these factors could be supported by the antimicrobial stewardship team.

Calcium Fracture After Intravascular Lithotripsy as Assessed With Optical Coherence Tomography.

BACKGROUND: Plaque characteristics associated with effective intravascular lithotripsy (IVL) treatment of calcification have not been investigated. This study identified calcified plaque characteristics that favor the use of IVL.Methods and Results: Optical coherence tomography (OCT) was performed in 16 calcified lesions in 16 patients treated with IVL and coronary stenting. Cross-sectional OCT images in 262 segments matched across pre-IVL, post-IVL, and post-stenting time points were analyzed. After IVL, 66 (25%) segments had calcium fracture. In multivariable analysis, calcium arc (odds ratio [OR] 1.22; 95% confidence interval [CI] 1.13-1.32; P<0.0001), superficial calcification (OR 6.98; 95% CI 0.07-55.57; P=0.0182), minimum calcium thickness (OR 0.66; 95% CI 0.51-0.86; P=0.0013), and nodular calcification (OR 0.24; 95% CI 0.08-0.70; P=0.0056) were associated with calcium fracture. After stenting, stent area was larger for segments with fracture (8.0 [6.9-10.6] vs. 7.1 [5.2-8.9] mm2; P=0.004). CONCLUSIONS: Post-IVL calcium fracture is more likely in calcified lesions with lower thickness, a larger calcium arc, superficial calcification, and non-nodular calcification, leading to a larger stent area.

Intra- and Postprocedural Management of Coronary Artery Perforation During Percutaneous Coronary Intervention.

Background: Little is known regarding the postprocedural management of coronary artery perforation (CAP). Methods and Results: The characteristics, outcomes, and management of 115 CAP cases among 13,453 patients undergoing percutaneous coronary intervention (PCI) between 2001 and 2017 at Miyazaki Medical Association Hospital were analyzed retrospectively. The incidence of CAP was 0.85% (25 [0.19%] coronary ruptures [CRs], 90 [0.67%] wire perforations [WPs]). The most prevalent causes of CRs and WPs were rotational atherectomy (36.0%) and polymer-jacketed wires (41.1%), respectively. Fifty-two percent of CRs were treated using prolonged balloon inflation, whereas 50% of WPs were treated through embolization. Immediate and delayed cardiac tamponade (CT) occurred in 20% and 24% of CRs, respectively, and in 2.2% and 10% of WPs, respectively. The mean (±SD) right atrial pressure (RAP) during delayed CT in the CR and WP groups was 16.0±1.2 and 14.0±3.0 mmHg, respectively. New-onset atrial fibrillation developed in 24.0% and 11.1% of patients in the CR and WP groups, respectively, whereas late-onset coronary artery aneurysm (CAA) occurred in 24.0% and 0% of patients, respectively. One-year mortality rates in patients with immediate and delayed CT were 28.6% and 20.0%, respectively. Conclusions: Special attention should be paid to delayed CT, new-onset atrial fibrillation, and late-onset CAA after CAP treatment. Continuous monitoring of RAP after CAP during PCI may be useful for the early detection of delayed CT.

Outcomes of Elderly Patients With Acute Myocardial Infarction and Heart Failure Who Undergo Percutaneous Coronary Intervention.

Background: As life expectancy rises, percutaneous coronary intervention (PCI) is being performed more frequently, even in elderly patients with acute myocardial infarction (AMI). This study evaluated outcomes of elderly patients with AMI complicated by heart failure (AMIHF), as defined by Killip Class ≥2 at admission, who undergo PCI. Methods and Results: We retrospectively analyzed 185 patients with AMIHF aged ≥80 years (median age 85 years) who underwent PCI between 2009 and 2019. The median follow-up period was 572 days. The rates of in-hospital major bleeding (Bleeding Academic Research Consortium Type 3 or 5) and in-hospital all-cause mortality were 20.5% and 25.9%, respectively. The proportion of frail patients increased during hospitalization, from 40.6% at admission to 59.2% at discharge (P<0.01). The cumulative incidence of all-cause mortality was 36.3% at 1 year and 44.1% at 2 years. After adjusting for confounders, advanced age, Killip Class 4, final Thrombolysis in Myocardial Infarction flow grade <3, and longer door-to-balloon time were associated with higher mortality, whereas higher left ventricular ejection fraction and cardiac rehabilitation were associated with lower mortality (all P<0.05). Progression of frailty during hospitalization was an independent risk factor for long-term mortality in hospital survivors (P<0.01). Conclusions: The management of patients with AMIHF aged ≥80 years who undergo PCI remains challenging, with high rates of in-hospital major bleeding, frailty progression, and mortality.

Left atrial appendage orifice dimensions in Japanese atrial fibrillation population measured by multiplane transesophageal echocardiography.

BACKGROUND: Successful implantation of the WATCHMAN device requires an accurate understanding of left atrial appendage (LAA) anatomy and orifice dimensions. Racial differences are observed in LAA size when comparing Asians with non-Asians. METHODS: A total of 170 patients (123 male, 67.4 ± 9.2 years) with paroxysmal or persistent atrial fibrillation (AF) underwent transesophageal echocardiography before catheter ablation or cardioversion (September 2018 to September 2019). As per the recommendations of the WATCHMAN device, the maximal LAA ostial diameters were measured at multiplane angles of 0°, 45°, 90°, and 135°. RESULTS: The majority of patients (121/170, 71%) had an LAA orifice size within 17-25 mm. Fifteen (8.8%) patients had undersized (< 17 mm) and eight (0.5%) had oversized (> 31 mm) LAA. One patient in this population had no LAA. LAA size was significantly larger in patients with persistent AF than in those with paroxysmal AF (23.3 ± 4.2 mm vs. 20.0 ± 3.0 mm, p < 0.001) and in male patients than in female patients (22.4 ± 4.2 vs. 20.9 ± 3.7 mm, p = 0.03). LAA orifice dimension was significantly correlated with CHADS2 score, the left atrial volume (LAV), E/e', and the left ventricular ejection fraction. Persistent AF, body mass index, and LAV were independently associated with LAA orifice dimension in multivariate analysis. CONCLUSION: This study demonstrated the distribution of LAA orifice dimension in the Japanese AF patients. This finding should be used as a reference to understand the racial characteristics of LAA size for the WATCHMAN procedure.

Inhibition of α-amylase and α-glucosidase by Morus australis fruit extract and its components iminosugar, anthocyanin, and glucose.

The inhibition of α-amylase and α-glucosidase are important for the maintenance of blood glucose level. Mammalian α-glucosidase includes maltase-glucoamylase and sucrase-isomaltase complexes. In this study, we examined the inhibitory effects of Morus australis fruit extract and its components, that is, three iminosugars (1-deoxynojirimycin [1-DNJ], fagomine, and 2-O-α-D-galactopyranosyl deoxynojirimycin), two anthocyanins (cyanidin-3-glucoside and cyanidin-3-rutinoside), and glucose, against α-amylase and α-glucosidase. We also quantified the concentration of each component in M. australis fruit extract. The IC50 values of the fruit extracts of four M. australis subspecies were >10 mg/ml for α-amylase, 1.1-1.7 mg/ml for maltase, 6.9-8.6 mg/ml for glucoamylase, 0.13-1.0 mg/ml for sucrase, and 0.46-1.4 mg/ml for isomaltase. When the IC50 value of each component and the concentration of each component in the fruit extract were taken into consideration, our results indicated that glucose are involved in the inhibition of α-amylase, and 1-DNJ and glucose are involved in the inhibition of α-glucosidase. This is in contrast to that in M. australis leaf, neither anthocyanin nor glucose are contained, and 1-DNJ is a main inhibitor. PRACTICAL APPLICATION: It is widely accepted that inhibition of α-amylase and α-glucosidase is one of the strategies to treat type-2 diabetes. Today, acarbose, miglitol, and voglibose are clinically used for this purpose. Our results that 1-DNJ and anthocyanin are present in Morus australis fruit and are involved in the inhibition of α-amylase and α-glucosidase suggest that M. australis fruit is a healthy sweetener.

Evaluation and development of a novel pre-treatment method for mulberry leaves to enhance their bioactivity via enzymatic degradation of GAL-DNJ to DNJ.

Mulberry leaves are rich in 1-deoxynojirimycin (DNJ) and 2-O-α-D-galactopyranosyl-deoxynojirimycin (GAL-DNJ). Compared to DNJ, the bioactive potency of GAL-DNJ is low. We proposed that the conversion of GAL-DNJ into DNJ may improve its bioavailability. We evaluated this hypothesis and constructed a novel enzymatic-based method to induce the hydrolysis of GAL-DNJ to DNJ in order to improve the therapeutic potency of mulberry leaves.

Cardiac remodeling in acute myocardial infarction: Prospective insights from multimodality ultrasound imaging.

BACKGROUND: The severity of MI declined markedly in the last decade, and contemporary patterns of cardiac remodeling after MI are not defined. METHODS: We prospectively enrolled community patients with first MI and performed comprehensive two- and three-dimensional echocardiography. Remodeling was defined as left ventricular (LV) end-systolic volume index (ESVI) above American Society of Echocardiography normal values. Remodeling patterns were characterized as an increase in LVESVI or LV end-diastolic volume index (LVEDVI), or both. RESULTS: Between 2014 and 2016, 213 patients (63±13 years; 34% women) were enrolled within 3 days after MI (77% non-ST-elevation MI). Acute remodeling was present in 51% of patients. Higher troponin and wall motion score index were associated with greater remodeling (p < 0.001). Atrial annular area, leaflet tenting and papillary muscle areas increased with greater remodeling (p < 0.001). The greater the cardiac remodeling, the lower the LV ejection fraction and global longitudinal strain (p < 0.001). This decrease in LV function was accompanied by stroke volume augmentation and maintenance of cardiac index at the expense of increased LVEDVI. Different remodeling patterns were identified. Cases showing increased LVEDVI and normal LVESVI had smallest infarct size and better hemodynamics compared to cases with augmented LVESVI and normal LVEDVI. CONCLUSION: Acute remodeling occurs in more than half of first MI cases and exhibits different patterns defined by cavity size and hemodynamic profile. Acute remodeling is a global phenomenon, which also involves the left atrium and the mitral apparatus.

Inhibitory effect of Morus australis leaf extract and its component iminosugars on intestinal carbohydrate-digesting enzymes.

α-Amylase and α-glucosidase are central enzymes involved in the digestion of carbohydrates. α-Glucosidase includes maltase-glucoamylase and sucrase-isomaltase. We have previously performed the kinetic analysis of the inhibitory effects of powdered or roasted Morus australis leaf extract and its component iminosugars, such as 1-deoxynojirimycin (1-DNJ), fagomine, and 2-O-α-d-galactopyranosyl deoxynojirimycin (GAL-DNJ) on the activity of maltase. In this study, we analyzed the inhibitory effects of the aforementioned compounds against α-amylase, glucoamylase, sucrase, and isomaltase. At pH 6.0 and 37 °C, each leaf extract sample inhibited glucoamylase, sucrase, and isomaltase but not α-amylase. 1-DNJ and fagomine showed weak α-amylase inhibitory activity while GAL-DNJ exhibited none. 1-DNJ showed a strong glucoamylase, sucrase, and isomaltase inhibitory potential. The inhibitory potential against these three enzymes was 18-500 and 1500-3000-fold higher in the case of 1-DNJ than that observed in the case of fagomine and GAL-DNJ, respectively. We also observed that the indigestible dextrin could considerably inhibit α-amylase. When the powdered M. australis leaf extract was blended with indigestible dextrin, the mixture inhibited α-amylase, as well as maltase, glucoamylase, sucrase, and isomaltase. These results suggest that the ingestion of the leaf extract blended with indigestible dextrin might have the potential to efficiently suppress the postprandial blood glucose level increase.

Impact of osteogenic activity on degenerative aortic valve disease in patients with osteoporotic hip fracture.

BACKGROUND: Previous studies have proposed that osteogenic and apoptotic processes of valve interstitial cells contribute to the mineralization and then calcification of the aortic valve. Osteoblast-like cells subsequently mediate calcification of the aortic valve as part of a highly regulated process analogous to skeletal bone formation. The objective of this study was to evaluate the pathogenesis of the sclerotic/calcific changes in the aortic valve from histological and biological findings, and investigate the role of osteoblasts in the calcified pathway of aortic stenosis. METHODS: Preoperative echocardiography in 550 consecutive patients with osteoporotic hip fracture were retrospectively examined (475 females, mean 25th-75th, 89 [85-93] years). One hundred sixteen patients were under medical treatment with anti-osteoporosis drugs. We evaluated the prevalence and degree of degenerative changes in the aortic valve and examined the associations of bone turnover biomarkers N-terminal pro-peptide of type 1 collagen (P1NP) and serum tartrate-resistant acid phosphatase (TRACP-5b) with degenerative calcific changes in the aortic valve. RESULTS: Of 550 patients, 112 patients (20.9%) showed no leaflet calcification; 296 (53.8%), 1 leaflet calcification; and 142 (25.8%), 2 ≥ leaflets calcification. Significant (peak velocity ≥ 3.0m/s) Aortic stenosis was found in 43 patients (7.8%). In patients who were not taking anti-osteoporotic drugs, P1NP was higher in the 2 ≥ leaflets calcification group than in the other groups (p < 0.01). TRACP-5b was not significantly different among the three groups (p = 0.15). CONCLUSIONS: Degenerative changes in the aortic valve were related to bone biomarker activation in osteoporotic hip fracture patients.

Transportal embolization for pancreatic arteriovenous malformation via a recanalized paraumbilical vein: A case report.

A 62-year-old man with liver cirrhosis presented with deterioration of liver function. Imaging studies revealed an arteriovenous malformation (AVM), with a dilated venous space, at the pancreatic head. Transarterial embolization of the AVM, using microcoils, was performed, although many feeding arteries remained. As the transarterial embolization was incomplete, further liver function deterioration was a possibility. In fact, 1 year after the procedure, the patient was referred back to our hospital for treatment of massive ascites and liver function deterioration. Transportal embolization of the dilated venous space was performed, using microcoils via the recanalized paraumbilical vein, with no enhancement of the AVM. No complications occurred. Based on our experience, we propose transportal embolization as an effective treatment option for pancreatic AVM.

Impact of frailty on outcomes in elderly patients with acute myocardial infarction who undergo percutaneous coronary intervention.

AIMS: Frailty is characterized by reduced biological reserves and weakened resistance to stressors, and is common in older adults. This study evaluated the prognostic implications of frailty at hospitalization in elderly patients with acute myocardial infarction (AMI) who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: We prospectively analysed 546 AMI patients aged ≥80 years undergoing PCI from 2009 to 2017. Frailty was classified based on impairment in walking (unassisted, assisted, and wheelchair/non-ambulatory), cognition (normal, mildly impaired, moderately to severely impaired), and basic activities of daily living. Impairment in each domain was scored as 0, 1, or 2, and patients were categorized into the following three groups based on total score: no frailty (0), mild frailty (1-2), moderate-to-severe frailty (≥3). The median follow-up period was 589 days. Of the 546 patients, 27.8% were frail (mild or moderate-to-severe), and this proportion significantly increased to 35.5% at discharge (P < 0.001). Compared to non-frail patients, frail patients were older, less likely to be male, and had a higher rate of advanced Killip class. Major bleeding (no frailty, 9.6%; mild frailty, 16.9%; moderate-to-severe frailty, 31.8%; P < 0.001) and in-hospital mortality (no frailty, 8.4%; mild frailty, 15.4%; moderate-to-severe frailty, 27.3%; P < 0.001) increased as frailty worsened. After adjusting for confounders, frailty was independently associated with higher mid-term all-cause mortality (hazard ratio, 1.81; 95% confidence interval, 1.23-2.65; P = 0.002). CONCLUSION: Frailty in AMI patients aged ≥80 years undergoing PCI was associated with major bleeding, in-hospital death, and mid-term mortality.

Combined Effect of Quercetin and Fish Oil on Oxidative Stress in the Liver of Mice Fed a Western-Style Diet.

To study the combined effect of the flavonoid quercetin and fish oil containing ω-3 fatty acids on preventing diet-induced metabolic syndrome, we fed mice with a control diet, a high-fat, high-sucrose, and high-cholesterol Western-style diet (Western diet), a Western diet supplemented with 0.05% quercetin, a Western diet containing 5% fish oil rich in docosahexaenoic acid (DHA) (DHA diet), or a DHA diet supplemented with 0.05% quercetin. After 18 weeks of feeding, fish oil potentiated the suppression of lipid peroxidation by quercetin in the liver but not in the epididymal adipose tissue. Fish oil but not quercetin suppressed the accumulation of non-esterified fatty acids and the expression of fatty acid synthase in the liver of Western-diet-fed mice. Thus, the combination of quercetin and DHA-rich fish oil may partly alleviate non-alcoholic fatty liver disease by reducing oxidative stress and suppressing fatty acid synthesis.