Publications by authors named "Kenichi Tsujita"

374 Publications

East Asian variant aldehyde dehydrogenase type 2 genotype exacerbates ischemia/reperfusion injury with ST-elevation myocardial infarction in men: possible sex differences.

Heart Vessels 2021 Jul 14. Epub 2021 Jul 14.

Department of Cardiovascular Medicine, Faculty of Life Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes generated during ischemia/reperfusion (I/R) injury in ST-elevation myocardial infarction (STEMI). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. Whether ALDH2*2 exacerbates I/R injury of in patients with STEMI is not known. The study subjects comprised 218 Japanese patients with STEMI (158 men and 60 women, mean age 67.9 ± 11.9) who underwent successful percutaneous coronary intervention. Of these, 120 (55.0%) were the carriers of variant ALDH2*2 and 98 (45.0%) those of wild ALDH2*1/*1 on genotyping. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit (14.2% vs 46.3%, P < 0.001) in the ALDH2*2 group. The peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, however, were significantly higher in the patients with ALDH2*2 than in those with ALDH2*1/*1 [a median 275.0 (175.8-407.5) vs 177.5 (126.9-344.3) U/L, P = 0.001] among men but not among women (P = 0.811). There was a significant interaction between men (male sex) and ALDH2*2 for I/R injury (χ2 = 4.425, P = 0.040). The variant ALDH2*2 was associated with more severe I/R injury than the wild ALDH2*1/*1 in STEMI patients in men with possible sex differences.
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http://dx.doi.org/10.1007/s00380-021-01907-xDOI Listing
July 2021

A simple method of sarcopenia detection can predict adverse cardiovascular events in patients with abdominal obesity.

Int J Obes (Lond) 2021 Jul 3. Epub 2021 Jul 3.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Background: Although sarcopenic obesity is associated with a higher risk of cardiovascular events compared with obesity without sarcopenia, it is difficult to diagnose sarcopenia in daily clinical settings. Recently, a simple scoring system has been developed to identify sarcopenia patients based on three variables (age, hand grip strength, and calf circumference). However, the utility of this score for cardiovascular risk stratification in patients with abdominal obesity is unknown.

Methods: We calculated the sarcopenia score in 262 patients with abdominal obesity, defined as a waist circumference ≥90 cm in women or ≥85 cm in men. The composite endpoint of this study was cardiovascular mortality, nonfatal myocardial infarction, stroke, unstable angina, and heart failure hospitalization.

Results: Of the 262 patients, 108 had a high sarcopenia score based on previously established criteria (≥105 in men and ≥120 in women). The patients with a high sarcopenia score had a significantly higher plasma level of B-type natriuretic peptide compared with those with a low sarcopenia score (median 56.7, interquartile range [28.2-142.9] vs. 37.9 [13.8-76.1] pg/mL; p < 0.0001). Kaplan-Meier curves revealed a significantly lower event-free survival rate in those with a high compared with a low sarcopenia score (log-rank test p = 0.001), even after adjustment for confounding factors using propensity score matching (log-rank test p = 0.009). Multivariate Cox proportional hazard analysis identified a high sarcopenia score (hazard ratio: 2.46; 95% confidence interval: 1.31-4.64, p = 0.005) as an independent predictor of the primary endpoints. The combination of a high sarcopenia score and low body mass index (<25 kg/m) predicted a significantly higher risk of future adverse events (p = 0.005). Furthermore, patients with a high sarcopenia score and high B-type natriuretic peptide level (≥200 pg/mL) had the poorest prognosis (p < 0.0001).

Conclusions: This simple screening test for sarcopenia can predict future adverse cardiovascular events in patients with abdominal obesity.
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http://dx.doi.org/10.1038/s41366-021-00895-2DOI Listing
July 2021

Coherent mapping helps identify abnormal potentials and improves the treatment of multiple ventricular tachycardia: A case report.

HeartRhythm Case Rep 2021 Jun 27;7(6):408-412. Epub 2021 Mar 27.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

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http://dx.doi.org/10.1016/j.hrcr.2021.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226306PMC
June 2021

Prognostic significance of liver stiffness assessed by fibrosis-4 index in patients with heart failure.

ESC Heart Fail 2021 Jun 22. Epub 2021 Jun 22.

Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Center for Metabolic Regulation of Healthy Aging (CMHA), Kumamoto University, Kumamoto, Japan.

Background: Heart failure (HF)-related congestive hepatopathy is a well-recognized problem in management of HF. The fibrosis-4 (FIB4) index calculated by [age × aspartate aminotransferase (IU/L)/platelet count (10 /L) × square root of alanine aminotransferase (IU/L)] is useful for evaluating liver stiffness. We aimed to investigate the impact of the FIB4 index on prognosis in patients with HF.

Methods And Results: Consecutive HF patients referred for hospitalization at Kumamoto University Hospital, Japan, were registered between 2006 and 2015. We observed cardiovascular outcomes in each type of HF [HF with reduced left ventricular ejection fraction (LVEF) (HFrEF), HF with mid-range LVEF (HFmrEF) and with preserved LVEF (HFpEF)] according to their FIB4 index; Group 1 (FIB4 index <1.3), Group 2 (FIB4 index: 1.3-2.67), and Group 3 (FIB4 index >2.67). This study enrolled 83 HFrEF patients, 117 HFmrEF patients, and 504 HFpEF patients. In HFpEF patients, the Kaplan-Meier curve revealed that Group 3 had a significantly higher rate of total cardiovascular events compared with the other two groups. By contrast, the occurrences of total cardiovascular events were not different among three groups in HFrEF and HFmrEF patients. Multivariate Cox proportional hazard analysis with significant factors in univariate analysis identified that the FIB4 index as an independent and significant predictor for future total cardiovascular events in HFpEF patients (hazard ratio: 1.09, 95% confidence interval: 1.03-1.15, P = 0.001).

Conclusions: The FIB4 index was a significant predictor for total cardiovascular events in HFpEF.
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http://dx.doi.org/10.1002/ehf2.13351DOI Listing
June 2021

Association of early administration of furosemide with improved oxygenation in patients with acute heart failure.

ESC Heart Fail 2021 Jun 15. Epub 2021 Jun 15.

Kumamoto University Hospital, Kumamoto, Japan.

Aims: Optimal pharmacological treatment for chronic heart failure has been established. However, treatments that can improve the prognosis of acute heart failure (AHF) are controversial. Although intravenous diuretics may be one optimal treatment option, little evidence has shown the effect of early administration of diuretics on clinical outcomes in patients with AHF. The aim of this study was to evaluate the association between door-to-furosemide (D2F) time, improved oxygenation, and in-hospital mortality in patients hospitalized for AHF.

Methods And Results: We screened 494 patients hospitalized for AHF in Miyazaki Prefectural Nobeoka Hospital. AHF patients who were treated with intravenous furosemide within 24 h of arrival at the hospital were included in this study. D2F time was defined as the time from patient arrival at the hospital to the first intravenous dose of furosemide. The early administration group was defined as those with D2F time ≤60 min, whereas the non-early group was defined as those with D2F time >60 min. The primary outcome was the rate of improved oxygenation at Day 1. The secondary outcomes were in-hospital mortality and cardiac death. There were 219 patients treated with the first intravenous dose of furosemide within 24 h analysed after the exclusion of 275 patients. The median D2F time was 55 min (interquartile range: 30-120 min) in the final cohort. The early administration group included 121 patients (55.3%). The rate of improved oxygenation was higher in the early group than the non-early group [median 16.7% (interquartile range: 0.0-40.0) vs. 0.0% (0.0-20.6), respectively, P < 0.001]. During the study period, there were six patients (5.0%) with in-hospital mortality in the early group and nine patients (9.2%) in the non-early group (P = 0.218). Cardiac death was observed less frequently in the early group than in the non-early group, but without statistical significance (3.3% and 9.2%, respectively) (P = 0.067). The univariable logistic regression analyses showed that early administration of furosemide was associated with improved oxygenation [odds ratio (OR): 2.26; 95% confidence interval (CI): 1.31-3.91; P = 0.004], but not with in-hospital mortality (OR: 0.52; 95% CI: 0.18-1.50; P = 0.225) or cardiac death (OR: 0.34; 95% CI: 0.10-1.13; P = 0.079). In multivariable analyses adjusted for risk score or relevant variables, early administration of furosemide was consistently associated with improvement of oxygenation.

Conclusions: The present study showed that in AHF patients, the early administration of furosemide was associated with improved oxygenation.
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http://dx.doi.org/10.1002/ehf2.13379DOI Listing
June 2021

Optical coherence tomography-versus intravascular ultrasound-guided stent expansion in calcified lesions.

Cardiovasc Interv Ther 2021 Jun 7. Epub 2021 Jun 7.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Optical coherence tomography (OCT) has a higher resolution than intravascular ultrasound (IVUS) and enables a more precise evaluation of calcium severity. We investigated the impact of the imaging method (OCT versus IVUS) on stent expansion during intravascular imaging-guided percutaneous coronary intervention (PCI) in calcified lesions. In this single-center, retrospective, observational study, 145 lesions with moderate to severe calcification were divided into four groups: 40 IVUS-guided rotational atherectomy (RA), 38 IVUS-guided non-RA, 35 OCT-guided RA, and 32 OCT-guided non-RA. Lesions without pre-procedural intravascular imaging were excluded. OCT-guided RA was associated with greater stent expansion at the target calcium compared with IVUS-guided RA (median 88.0%, interquartile range [78.0-96.0] vs. 76.5% [71.0-84.3], P = 0.008). Furthermore, stent expansion in OCT-guided non-RA was similar to OCT-guided RA. OCT-guided RA used a larger burr compared to IVUS-guided RA (1.75 mm [1.50-2.0] vs. 1.50 mm [1.50-1.75], P = 0.004). In OCT-guided RA, the median minimum calcium thickness was significantly reduced from 800 (640-980) µm to 550 (350-680) µm (P < 0.001). There was no significant difference in the incidence of ischemia driven target lesion revascularization between the four groups (P = 0.37). By determining the indication and endpoint of lesion modification by RA based on the thickness of calcium, OCT-guided PCI was associated with significantly greater stent expansion compared with IVUS-guided PCI.
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http://dx.doi.org/10.1007/s12928-021-00790-7DOI Listing
June 2021

Risk Prediction Score for Cancer Development in Patients With Acute Coronary Syndrome.

Circ J 2021 Jun 1. Epub 2021 Jun 1.

Department of Cardiovascular Medicine, Kumamoto University Hospital.

Background: Cancer is a known prognostic factor in patients with acute coronary syndrome (ACS), but few risk assessments of cancer development after ACS have been established.Methods and Results:Of the 573 consecutive ACS admissions between January 2015 and March 2018 in Nobeoka City, Japan, 552 were analyzed. Prevalent cancer was defined as a treatment history of cancer, and incident cancer as post-discharge cancer incidence. The primary endpoint was post-discharge cancer incidence, and the secondary endpoint was all-cause death during follow-up. All-cause death occurred in 9 (23.1%) patients with prevalent cancer, and in 17 (3.5%) without cancer. In the multivariable analysis, prevalent cancer was associated with all-cause death. To develop the prediction model for cancer incidence, 21 patients with incident cancer and 492 without cancer were analyzed. We compared the performance of D-dimer with that of the prediction model, which added age (≥65 years), smoking history, and high red blood cell distribution width to albumin ratio (RAR) to D-dimer. The areas under the receiver-operating characteristics curves of D-dimer and the prediction model were 0.619 (95% confidence interval: 0.512-0.725) and 0.774 (0.676-0.873), respectively. Decision curve analysis showed superior net benefits of the prediction model.

Conclusions: By adding elderly, smoking, and high RAR to D-dimer to the prediction model it became clinically useful for predicting cancer incidence after ACS.
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http://dx.doi.org/10.1253/circj.CJ-21-0071DOI Listing
June 2021

Impact of Chronic Kidney Disease on In-Hospital and 3-Year Clinical Outcomes in Patients With Acute Myocardial Infarction Treated by Contemporary Percutaneous Coronary Intervention and Optimal Medical Therapy - Insights From the J-MINUET Study.

Circ J 2021 Jun 3. Epub 2021 Jun 3.

Department of Cardiology, Gunma Prefectural Cardiovascular Center.

Background: The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m); moderate CKD (60>eGFR≥30 mL/min/1.73 m); and severe CKD (eGFR <30 mL/min/1.73 m). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788-0.841) to 0.831 (0.806-0.857), as well as 0.731 (0.708-0.755) to 0.740 (0.717-0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively.

Conclusions: CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.
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http://dx.doi.org/10.1253/circj.CJ-20-1115DOI Listing
June 2021

Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey.

Sci Rep 2021 Jun 1;11(1):11472. Epub 2021 Jun 1.

Department of Clinical Gene Therapy, Graduate School of Medicine, Center of Medical Innovation and Translational Research, Osaka University, 6th floor, Room 0611B, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.

In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund's adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.
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http://dx.doi.org/10.1038/s41598-021-91153-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169762PMC
June 2021

A Coronary Artery-Left Ventricular Fistula Through the Sinusoid.

Intern Med 2021 May 29. Epub 2021 May 29.

Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Japan.

A 78-year-old woman was referred to our hospital because of repetitive suppurative arthritis at the artificial left knee joint. Her plasma brain natriuretic peptide level was 122 pg/mL. A 12-lead electrocardiogram showed a QS pattern in the inferior leads. A two-dimensional echocardiogram revealed hypokinesis at the inferior wall and hypertrophy at the apical lateral wall. Color flow imaging revealed this hypertrophic region to be a myocardial sinusoid, demonstrating diastolic coronary to left ventricular flow and early systolic flow vice versa. This was a very rare case of coronary to left ventricular fistula through a sinusoid without cyanotic congenital heart disease or severe coronary artery disease.
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http://dx.doi.org/10.2169/internalmedicine.7454-21DOI Listing
May 2021

Cardiac computed tomography-derived extracellular volume fraction in late anthracycline-induced cardiotoxicity.

Int J Cardiol Heart Vasc 2021 Jun 18;34:100797. Epub 2021 May 18.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto, Japan.

Cardiotoxicity in the late phase after anthracycline drugs administration remains to be defined. Of the 44 patients who received anthracycline treatment, 7 were found to have cancer therapeutics-related cardiac dysfunction (CTRCD). The global longitudinal strain determined by echocardiography and myocardial extracellular volume fraction (ECV) determined by cardiac computed tomography (CCT) of the CTRCD(+) group were significantly higher than those of the control group and CTRCD(-) group, whereas there were no significant differences between the control and CTRCD(-) groups. Our findings indicated that CCT may be a tool comparable to echocardiography, indicating the effective evaluation of CTRCD by CCT.
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http://dx.doi.org/10.1016/j.ijcha.2021.100797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144341PMC
June 2021

Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group.

Eur Heart J 2021 May 26. Epub 2021 May 26.

Department of Cardiology, Cedars-Sinai Medical Center, Barbra Streisand Women's Heart Center, Smidt Heart Institute, Los Angeles, CA, USA.

Aims: To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA).

Methods And Results: The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365-744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05).

Conclusions: This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis.
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http://dx.doi.org/10.1093/eurheartj/ehab282DOI Listing
May 2021

Myocardial Tissue Characterization by Combining Extracellular Volume Fraction and T2 Mapping.

JACC Cardiovasc Imaging 2021 May 11. Epub 2021 May 11.

Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

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http://dx.doi.org/10.1016/j.jcmg.2021.02.029DOI Listing
May 2021

Prospective multicenter registry of hybrid coronary artery revascularization combined with non-saphenous vein graft surgical bypass and percutaneous coronary intervention using everolimus eluting metallic stents (PRIDE-METAL study).

Cardiovasc Interv Ther 2021 May 18. Epub 2021 May 18.

Department of Cardiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan.

The concept of hybrid coronary revascularization (HCR) combines the advantages of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) to improve the treatment of patients with complex multivessel disease. This study aimed to investigate a 1-year clinical follow-up of a prospective multicenter registry of HCR combined with non-saphenous vein graft surgical bypass and PCI using everolimus-eluting metallic stents (the PRIDE-METAL study). From June 2016 to June 2018, a total of 54 patients with multivessel coronary disease from six Japanese institutes were enrolled in this study. The primary endpoint of the study was the occurrence of major adverse cardiovascular event (MACE; all-cause death, myocardial infarction, stroke, and repeat revascularization) at 1 year. Three patients declined before complete HCR, and two patients were lost by the 1-year follow-up. All-cause mortality at 30 days and at 1 year was 0% and 4.1%, respectively. The rates of myocardial infarction, repeat revascularization, stroke, and MACE were 0% at 30 days, and 0%, 2.0%, 2.0%, and 8.2% at 1-year follow-up, respectively. No occlusion of arterial bypass graft at the 30-day follow-up was observed, and was observed in 1.7% at the 1-year follow-up. HCR was safe and feasible and associated with a low risk of MACE at the 1-year follow-up. Further validation in multicenter and randomized studies is needed.
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http://dx.doi.org/10.1007/s12928-021-00784-5DOI Listing
May 2021

Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy.

J Am Heart Assoc 2021 Jun 15;10(11):e019525. Epub 2021 May 15.

Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka Japan.

Background Statin-mediated efficacy of lowering low-density lipoprotein (LDL) cholesterol varies in each individual, and its diminished response is associated with worse outcomes. However, there is no established approach to predict hyporesponse to statins. PCSK9 (proprotein convertase subxilisin/kexin type 9) is a serine-protease associated with LDL metabolism, which circulates as mature and furin-cleaved PCSK9. Since mature PCSK9 more potently degrades the LDL receptor, its evaluation may enable the identification of statin hyporesponders. Methods and Results We analyzed 101 statin-naive patients with coronary artery disease who commenced a statin. PCSK9 subtypes at baseline and 1 month after statin use were measured by ELISA. Hyporesponse to statins was defined as a percent reduction in LDL cholesterol <15%. The relationship between each PCSK9 subtype level and hyporesponse to statins was investigated. Statins significantly lowered LDL cholesterol level (percent reduction, 40%±21%), whereas 11% of study participants exhibited a hyporeseponse to statins. Multivariable logistic regression analysis demonstrated that baseline mature PCSK9 level was an independent predictor for hyporesponse to statins even after adjusting clinical characteristics (mature PCSK9 per 10-ng/mL increase: odds ratio [OR], 1.12; 95% CI, 1.01-1.24 [=0.03]), whereas furin-cleaved level was not (per 10-ng/mL increase: OR, 1.37; 95% CI, 0.73-2.58 [=0.33]). Receiver operating characteristic curve analysis identified mature PCSK9 level of 228 ng/mL as an optimal cutoff to predict hyporesponse to statins (area under the curve, 0.73 [sensitivity, 0.91; specificity, 0.56]). Conclusions Baseline mature PCSK9 level >228 ng/mL is associated with hyporesponse to statins. This finding suggests that mature PCSK9 might be a potential determinant of hyporesponse to statins.
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http://dx.doi.org/10.1161/JAHA.120.019525DOI Listing
June 2021

Long-Term Clinical Impact of Cardiogenic Shock and Heart Failure on Admission for Acute Myocardial Infarction.

Int Heart J 2021 May 15;62(3):520-527. Epub 2021 May 15.

Department of Cardiology, Fukuoka University School of Medicine.

Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.
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http://dx.doi.org/10.1536/ihj.20-646DOI Listing
May 2021

The association between the extent of lipidic burden and delta-fractional flow reserve: analysis from coronary physiological and near-infrared spectroscopic measures.

Cardiovasc Diagn Ther 2021 Apr;11(2):362-372

Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, Osaka, Japan.

Background: Vulnerable plaque features including lipidic plaque have been shown to affect fractional flow reserve (FFR). Given that formation and propagation of lipid plaque is accompanied by endothelial dysfunction which impairs vascular tone, the degree of lipidic burden may affect vasoreactivity during hyperemia, potentially leading to reduced FFR. Our aim is to elucidate the relationship of the extent of lipidic plaque burden with coronary physiological vasoreactivity measure.

Methods: We analyzed 89 subjects requeuing PCI due to angiographically intermediate coronary stenosis with FFR ≤0.80. Near-infrared spectroscopy (NIRS) and intravascular ultrasound were used to evaluate lipid-core burden index (LCBI) and atheroma volume at both target lesion (maxLCBI; maximum value of LCBI within any 4 mm segments) and entire target vessel (LCBI: LCBI within entire vessel). In addition to FFR, delta-FFR was measured by difference of distal coronary artery pressure/aortic pressure (Pd/Pa) between baseline and hyperemic state.

Results: The averaged FFR and delta-FFR was 0.74 (0.69-0.77), and 0.17±0.05, respectively. On target lesion-based analysis, maxLCBI was negatively correlated to FFR (ρ=-0.213, P=0.040), and it was positively correlated to delta-FFR (ρ=0.313, P=0.002). Furthermore, target vessel-based analysis demonstrated similar relationship of LCBI with FFR (ρ=-0.302, P=0.003) and delta-FFR (ρ=0.369, P<0.001). Even after adjusting clinical characteristics and lesion/vessel features, delta-FFR (by 0.10 increase) was independently associated with maxLCBI (β=57.2, P=0.027) and LCBI (β=24.8, P=0.007) by mixed linear model analyses.

Conclusions: A greater amount of lipidic plaque burden at not only "target lesion" alone but "entire target vessel" was associated with a greater delta-FFR. The accumulation of lipidic plaque materials at both local site and entire vessel may impair hyperemia-induced vasoreactivity, which causes a reduced FFR.
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http://dx.doi.org/10.21037/cdt-20-1024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102241PMC
April 2021

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

Cardiovasc Interv Ther 2021 Apr 29. Epub 2021 Apr 29.

Department of Cardiovascular Medicine, Faculty of Life Science, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by chronic stenosis or obstruction of the pulmonary arteries due to thromboembolism. Although previous studies have shown untreated CTEPH has a poor prognosis, the establishment of gold-standard therapies including pulmonary endarterectomy, balloon pulmonary angioplasty (BPA), and medical therapy has improved hemodynamics and right ventricular function, leading to good long-term survival. BPA is an important therapy for patients with inoperable CTEPH, although the procedure is currently limited to specific institutions and operators. This review discusses the development of the rapidly evolving field of CTEPH that includes improvements in imaging modalities and advances in surgical and interventional techniques.
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http://dx.doi.org/10.1007/s12928-021-00775-6DOI Listing
April 2021

Validation of the atherothrombotic risk score for secondary prevention in patients with acute myocardial infarction: the J-MINUET study.

Heart Vessels 2021 Apr 21. Epub 2021 Apr 21.

Department of Cardiology, Gunma Prefectural Cardiovascular Center, Maebashi, Japan.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) is a contemporary risk scoring system for secondary prevention based on nine clinical factors. However, this scoring system has not been validated in other populations. The aim of this study was to validate the TRS2°P in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI) in a nationwide registry cohort. Among 3283 consecutive patients with AMI enrolled in the Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET), a total of 2611 patients who underwent primary PCI were included in this study. The performance of the TRS2°P to predict major adverse cardiovascular events (MACE) composed of all-cause death, non-fatal MI, and non-fatal stroke up to 3 years in the present cohort was evaluated. The TRS2°P had modest discriminative performance in this J-MINUET cohort with a c-statistic of 0.63, similar to that in the derived cohort (TRA2°P-TIMI50, c-statistic 0.67). A strong graded relationship between the TRS2°P and 3-year cardiovascular event rates was also observed in the J-MINUET cohort. Age ≥ 75 years, Killip ≥ 2, prior stroke, peripheral artery disease, anemia, and non-ST-elevation myocardial infarction were identified as independent factors for the incidence of MACE. The TRS2°P modestly predicted secondary cardiovascular events among patients with AMI treated by primary PCI in a nationwide cohort of Japan. Further studies are needed to develop a novel risk score better predicting secondary cardiovascular events.
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http://dx.doi.org/10.1007/s00380-021-01840-zDOI Listing
April 2021

Inhibitory Effect of Rivaroxaban on Atrial Arrhythmogenesis via Protease-Activated Receptor 2 Pathway.

Circ J 2021 Apr 2. Epub 2021 Apr 2.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University.

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http://dx.doi.org/10.1253/circj.CJ-21-0157DOI Listing
April 2021

Current trends and future perspectives for heart failure treatment leveraging cGMP modifiers and the practical effector PKG.

J Cardiol 2021 Apr 1. Epub 2021 Apr 1.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Cyclic guanosine monophosphate (cGMP), an intracellular second messenger molecule synthesized by guanylated cyclases (GCs), controls various myocardial properties, including cell growth and survival, interstitial fibrosis, endothelial permeability, cardiac contractility, and cardiovascular remodeling. These processes are mediated by the main cGMP effector protein kinase G (PKG) activation of which exerts intrinsic protective responses against the adverse effects of neurohormonal stimulation and pathological cardiac stress. Therapeutic strategies that enhance cGMP levels and PKG activation have been used for heart failure, which can be executed by reducing natriuretic peptide (NP) proteolysis, enhancing cGMP synthesis, or blocking cGMP hydrolysis. Among these, reducing NP clearance with neprilysin inhibitor combined with angiotensin receptor blocker has been shown to greatly improve the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) compared to the prognosis of patients on standard therapy using angiotensin-converting enzyme inhibitors. Moreover, in a recent phase III clinical trial, soluble GC-derived cGMP generation was shown to have potential efficacy in the management of HFrEF. Despite the clinical significance of cGMP/PKG signaling activated by either soluble or particulate GCs in heart failure, the differential signaling events downstream of intracellular cGMP, which are precisely controlled not only by PKG activation but also by the changes in its targeting and compartmentalization depending on the pathophysiology of heart disease, are not yet completely understood. Hitherto, the importance of the latter PKG regulatory mechanisms in developing therapeutic strategies has not been elucidated. Further investigation of redox-based PKG modulation will aid in the successful development of clinical therapies and could also lead to the establishment of improved personalized treatments for patients with heart failure.
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http://dx.doi.org/10.1016/j.jjcc.2021.03.004DOI Listing
April 2021

Validation of Acute Myocardial Infarction and Heart Failure Diagnoses in Hospitalized Patients With the Nationwide Claim-Based JROAD-DPC Database.

Circ Rep 2021 Feb 20;3(3):131-136. Epub 2021 Feb 20.

Department of Cardiovascular Medicine, Tohoku University Hospital, Tohoku University Graduate School of Medicine Sendai Japan.

Big data systems such as diagnosis procedure combination (DPC) datasets have recently been used for research purposes. However, there have been few validation studies to determine the accuracy of diagnoses. The aim of this study was to validate and evaluate 2 diagnoses, namely acute myocardial infarction (AMI) and heart failure (HF), using International Classification of Diseases, 10th revision (ICD-10) codes in the Japanese Registry Of All cardiac and vascular Disease (JROAD)-DPC database. ICD-10 codes I21.0-I21.9 and I50.0-I50.9 were used to identify AMI and HF, respectively, in the JROAD-DPC database. Diagnoses of AMI and HF were validated in clinical datasets assessing sensitivity and positive predictive value (PPV). Over 1-2 years, 742 patients hospitalized for AMI and 1,368 patients hospitalized for HF were identified in the DPC dataset. Sensitivity and PPV for AMI were 78.9% and 78.8%, respectively. When emergency hospitalization was included as a criterion, PPV increased to 84.9%. For HF, sensitivity and PPV were 84.7% and 57.0%, respectively. When emergency hospitalization and acute HF were included as criteria, PPV increased to 83.0%. Using ICD-10 codes for AMI and HF diagnoses among hospitalized patients, the DPC dataset showed acceptable concordance with clinical datasets. PPV increased when any conditions of hospitalization were included, especially in HF.
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http://dx.doi.org/10.1253/circrep.CR-21-0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956876PMC
February 2021

Impact of Reactive Oxidative Metabolites Among New Categories of Nonischemic Heart Failure.

J Am Heart Assoc 2021 Apr 18;10(7):e016765. Epub 2021 Mar 18.

Department of Cardiovascular Medicine Faculty of Life Sciences Graduate School of Medical Science and Center for Metabolic Regulation of Healthy Aging (CMHA) Kumamoto University Kumamoto Japan.

Background We investigated the clinical significance of derivatives of reactive oxygen metabolites (DROMs), a new marker of reactive oxygen species, in patients with nonischemic heart failure (HF) and compared them among new categories of HF. Methods and Results We recruited 201 consecutively hospitalized patients with HF and measured DROM under stable conditions. Then, we divided them according to new categories of HF (HF with reduced ejection fraction [EF], HF with midrangeEF, and HF with preserved EF) without coronary artery disease. In subgroup analysis, we followed EF changes in patients with HF with reduced EF and classified them into HF with recovered EF or nonrecovered EF according to whether EF had improved to >40%. DROMs are significantly and independently associated with HF-related events in patients with NIHF. There were no significant differences in DROM and the probability of HF-related events among HF categories in Kaplan-Meier analysis. However, patients with HF with reduced EF and HF with preserved EF but not HF with midrange EF with HF-related events had higher DROM than those without HF-related events. In subgroup analysis, Kaplan-Meier analysis demonstrated that the probabilities of HF-related events in HF with recovered EF were dramatically decreased. DROM were significantly higher in patients with HF with nonrecovered EF than in HF with recovered EF. In receiver operating characteristic analysis, the cutoff level of DROM for predicting improvements in HF with recovered EF was 347 Carratelli units. Furthermore, the C-statistic value for predicting EF improvement for the DROM levels was 0.703. In multivariable logistic regression analysis, DROM was independently and significantly associated with the prediction of HF with recovered EF. Conclusions DROM measurements can provide important prognostic information for risk stratification in any category of NIHF. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000035827.
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http://dx.doi.org/10.1161/JAHA.120.016765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174381PMC
April 2021

The feasibility and limitation of coronary computed tomographic angiography imaging to identify coronary lipid-rich atheroma in vivo: Findings from near-infrared spectroscopy analysis.

Atherosclerosis 2021 04 24;322:1-7. Epub 2021 Feb 24.

Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, Osaka, Japan; Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Background: Coronary computed tomography angiography (CCTA) non-invasively visualizes lipid-rich plaque. However, this ability is not fully validated in vivo. The current study aimed to elucidate the association of CCTA features with near-infrared spectroscopy-derived lipidic plaque measure in patients with coronary artery disease.

Methods: 95 coronary lesions (culprit/non-culprit = 51/44) in 35 CAD subjects were evaluated by CCTA and NIRS imaging. CT density, positive remodeling, spotty calcification, napkin-ring sign and NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI) were analyzed by two independent physicians. The association of CCTA-derived plaque features with maxLCBI ≥ 400 was evaluated.

Results: The median CT density and maxLCBI were 57.7 Hounsfield units (HU) and 304, respectively. CT density (r = -0.75, p < 0.001) and remodeling index (RI) (r = 0.58, p < 0.001) were significantly associated with maxLCBI, respectively. Although napkin-ring sign (p < 0.001) showed higher prevalence of maxLCBI ≥ 400 than those without it, spotty calcification did not (p = 0.13). On multivariable analysis, CT density [odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.93-0.97; p < 0.001] and positive remodeling [OR = 7.71, 95%CI = 1.37-43.41, p = 0.02] independently predicted maxLCBI ≥ 400. Receiver operating characteristic curve analysis demonstrated CT density <32.9 HU (AUC = 0.92, sensitivity = 85.7%, specificity = 91.7%) and RI ≥ 1.08 (AUC = 0.83, sensitivity = 74.3%, specificity = 85.0%) as optimal cut-off values of maxLCBI ≥ 400. Of note, only 52.6% at lesions with one of these plaque features exhibited maxLCBI ≥ 400, whereas the frequency of maxLCBI ≥ 400 was highest at those with both features (88.5%, p < 0.001 for trend).

Conclusions: CT density <32.9 HU and RI ≥ 1.08 were associated with lipid-rich plaque on NIRS imaging. Our findings underscore the synergistic value of CT density and positive remodeling to detect lipid-rich plaque by CCTA.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.02.019DOI Listing
April 2021

Current Awareness and Status of Transthoracic Echocardiography in Kumamoto Prefecture - A Report of the Kumamoto Cardiovascular Echocardiography Standardization Project.

Circ Rep 2020 Apr 21;2(6):297-305. Epub 2020 Apr 21.

Department of Laboratory Medicine, Kumamoto University Hospital Kumamoto Japan.

There are few reports on current awareness and status of transthoracic echocardiography (TTE), including the actual performance rate according to echocardiographic guidelines, in a specific area or region. This cross-sectional survey study was conducted in Kumamoto Prefecture from October 2018 to March 2019. There are 366 medical institutions advocating cardiology in Kumamoto Prefecture. Of these, 259 (101 hospitals and 158 clinics) returned questionnaires regarding TTE. In all, 150,570 TTEs were performed in 2017. Of these, 132,771 (88%) were performed in hospitals and 17,799 (12%) were performed in clinics. Physicians performed only 5% of TTEs, whereas sonographers performed 86%. Although the modified Simpson method was performed in 90% of hospitals, 3-dimensional echocardiography was performed in only 2% of hospitals. In addition, the left atrial volume index was not examined in approximately 60% of hospitals, and the mean E/E' ratio was not examined in 80% of hospitals. Multivariable logistic regression analysis revealed that having a Fellow of the Japan Society of Ultrasonic in Medicine was significantly and independently associated with guideline-oriented TTE (odds ratio 9.43; 95% confidence interval 1.22-72.71, P<0.05). The rate of echocardiographic measurements performed according to echocardiographic guidelines is exceptionally low in Kumamoto Prefecture. Sufficient dissemination of echocardiographic guidelines may be important in improving this rate.
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http://dx.doi.org/10.1253/circrep.CR-20-0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925316PMC
April 2020

Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice.

Circ Rep 2020 Mar 4;2(3):158-166. Epub 2020 Mar 4.

Department of Cardiovascular Medicine and Center for Metabolic Regulation of Healthy Aging, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan.

Direct-activated factor X (FXa) plays an important role in thrombosis and is also involved in inflammation via the protease-activated receptor (PAR)-1 and PAR-2 pathway. We hypothesized that rivaroxaban protects against cardiac remodeling after myocardial infarction (MI). MI was induced in wild-type mice by permanent ligation of the left anterior descending coronary artery. At day 1 after MI, mice were randomly assigned to the rivaroxaban and vehicle groups. Mice in the rivaroxaban group were provided with a regular chow diet plus rivaroxaban. We evaluated cardiac function by echocardiography, pathology, expression of mRNA and protein at day 7 after MI. Rivaroxaban significantly improved cardiac systolic function, decreased infarct size and cardiac mass compared with the vehicle. Rivaroxaban also downregulated the mRNA expression levels of tumor necrosis factor-α, transforming growth factor-β, PAR-1 and PAR-2 in the infarcted area, and both A-type and B-type natriuretic peptides in the non-infarcted area compared with the vehicle. Furthermore, rivaroxaban attenuated cardiomyocyte hypertrophy and the phosphorylation of extracellular signal-regulated kinase in the non-infarcted area compared with the vehicle. Rivaroxaban protected against cardiac dysfunction in MI model mice. Reduction of PAR-1, PAR-2 and proinflammatory cytokines in the infarcted area may be involved in its cardioprotective effects.
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http://dx.doi.org/10.1253/circrep.CR-19-0117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921351PMC
March 2020

Two-Year Outcomes of Asymptomatic vs. Symptomatic Patients After Deferral of Revascularization Based on Fractional Flow Reserve - Insights From the J-CONFIRM Registry.

Circ Rep 2020 Nov 18;2(12):744-752. Epub 2020 Nov 18.

Department of Cardiology, Tokyo Medical University Hachioji Medical Center Tokyo Japan.

The effect of symptoms on clinical outcomes after deferral of revascularization based on fractional flow reserve (FFR) remains poorly understood. From the J-CONFIRM (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter) Registry, this study evaluated 1,215 patients with stable coronary artery disease, including symptomatic and asymptomatic patients (n=571 and 644, respectively). The primary endpoint was the cumulative 2-year incidence of target vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). An inverse probability weighted analysis was performed to adjust for the differences in baseline clinical characteristics between the 2 groups. At 2 years, the TVF rate did not differ significantly between symptomatic and asymptomatic patients (6.5% vs. 4.9%, respectively; P=0.15) or between symptomatic and asymptomatic patients with lesions with an FFR ≤0.80 (8.0% vs. 12.3%, respectively; P=0.20). Conversely, symptomatic patients showed significantly higher rates of TVF (6.2% vs. 3.3%; P=0.01) and CDTVR (6.2% vs. 3.1%; P=0.009) than asymptomatic patients, regardless of negative FFR values (>0.80). Despite negative FFR values, symptomatic patients were at higher risk of TVF than asymptomatic patients, driven primarily by a higher rate of CDTVR. Conversely, those with a positive FFR were likely to develop TVF regardless of their symptoms.
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http://dx.doi.org/10.1253/circrep.CR-20-0110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937522PMC
November 2020

Temporal Change in Longitudinal Strain After Domino Liver Transplantation With Liver Grafts Explanted From Patients With Hereditary Amyloidogenic Transthyretin Amyloidosis.

Circ Rep 2020 Nov 10;2(12):730-738. Epub 2020 Nov 10.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan.

Using transthoracic echocardiography, including 2D speckle tracking imaging (STI), this study examined cardiac function after domino liver transplantation (DLT) with liver grafts explanted from patients with hereditary amyloidogenic transthyretin amyloidosis. In all, 14 patients who underwent DLT at Kumamoto University Hospital and for whom 2D STI information was available were enrolled in the study; time-dependent echocardiographic changes were evaluated in 7. Although left ventricular (LV) systolic and diastolic function did not differ between the pre- and post-DLT periods (mean [±SD] 5.4±1.0 years after DLT), there were significant (P<0.05 for all) increases in the post- vs. pre-DLT period in basal longitudinal strain (LS; -13.4±2.3 vs. -19.3±4.4), relative apical LS index (=apical LS/[basal LS+mid LS]; 0.75±0.20 vs. 0.58±0.08), and LV ejection fraction/global LS (3.91±0.58 vs. 3.06±0.44). Age at the time of DLT was significantly higher in the group with impaired (>-14%) than preserved basal LS (57.2±3.5 vs. 39.6±16.0 years; P<0.05). When control subjects (n=14) were added to the enrolled DLT recipients, multivariable logistic regression analysis revealed that a history of DLT was significantly associated with impaired basal LS (>-14%; odds ratio 28.39, 95% confidence interval 1.89-427.45, P<0.05). LV systolic and diastolic function was preserved in the long term after DLT. However, 2D STI revealed subtle cardiac dysfunction in DLT recipients, which may be an early manifestation of cardiac amyloidosis.
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http://dx.doi.org/10.1253/circrep.CR-20-0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937528PMC
November 2020

Sirt7 Deficiency Attenuates Neointimal Formation Following Vascular Injury by Modulating Vascular Smooth Muscle Cell Proliferation.

Circ J 2021 Mar 5. Epub 2021 Mar 5.

Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University.

Background: Sirt7 is a recently identified sirtuin and has important roles in various pathological conditions, including cancer progression and metabolic disorders. It has previously been reported that Sirt7 is a key molecule in acute myocardial wound healing and pressure overload-induced cardiac hypertrophy. In this study, the role of Sirt7 in neointimal formation after vascular injury is investigated.Methods and Results:Systemic (Sirt7) and smooth muscle cell-specific Sirt7-deficient mice were subjected to femoral artery wire injury. Primary vascular smooth muscle cells (VSMCs) were isolated from the aorta of wild type (WT) and Sirt7mice and their capacity for cell proliferation and migration was compared. Sirt7 expression was increased in vascular tissue at the sites of injury. Sirt7mice demonstrated significant reduction in neointimal formation compared to WT mice. In vitro, Sirt7 deficiency attenuated the proliferation of serum-induced VSMCs. Serum stimulation-induced upregulation of cyclins and cyclin-dependent-kinase 2 (CDK2) was significantly attenuated in VSMCs of Sirt7compared with WT mice. These changes were accompanied by enhanced expression of the microRNA 290-295 cluster, the translational negative regulator of CDK2, in VSMCs of Sirt7mice. It was confirmed that smooth muscle cell-specific Sirt7-deficient mice showed significant reduction in neointima compared with control mice.

Conclusions: Sirt7 deficiency attenuates neointimal formation after vascular injury. Given the predominant role in vascular neointimal formation, Sirt7 is a potentially suitable target for treatment of vascular diseases.
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http://dx.doi.org/10.1253/circj.CJ-20-0936DOI Listing
March 2021