BACKGROUND:The benefits of adding aspirin to warfarin and warfarin treatment intensity for Japanese patients with mechanical valve replacement (MeVR) are unclear. METHODS AND RESULTS:This multicenter non-randomized observational study recruited 158 Japanese patients who underwent MeVR in 11 university hospitals in Kyushu and Okinawa; 74 patients were allocated to the warfarin (W) group and 84 were allocated to the warfarin plus aspirin (W+A) group. Patients were followed for a mean (±SD) of 5.0±1.9 years. The primary and secondary endpoints were mainly atherosclerotic/thrombotic and bleeding events, respectively. There was no difference in the incidence of the primary endpoint between the W and W+A groups (14% vs. 22%, respectively; P=0.13). Univariate analysis revealed a higher incidence of the secondary endpoint in the W+A than W group (35% vs. 22%; P=0.032), but the difference was not significant in multivariate analysis. For the entire cohort, the postoperative mean international normalized ratio of prothrombin time (PT-INR) was relatively low (2.1±0.3). There were no differences in the incidence of events between PT-INR <2.0 and 2.0-3.0 (primary endpoint: 21% vs. 16%, respectively [P=0.41]; secondary endpoints: 33% vs. 26%, respectively [P=0.19]). CONCLUSIONS:Adding aspirin to warfarin treatment was not superior to warfarin alone, and relatively weak warfarin treatment (PT-INR <2.0) was not necessarily associated with an increased number of events (vs. PT-INR 2.0-3.0) in Japanese patients who underwent MeVR.

AIM:Notch signaling is a fundamental signal that regulates morphogenesis and cell differentiation during the embryonic period, and it plays a crucial role in macrophage differentiation. Macrophage-mediated inflammation promotes atherosclerosis from the initial lesion formation to acute thrombotic complications in advanced plaques. However, their role in atherosclerosis remains unclear. We herein focused on the Notch ligand Delta-like ligand 1 (Dll1), and examined its role in the pathobiology of atherosclerosis. METHODS:In Apoe-/- mice, a blocking antibody against Dll1 (Dll1 Ab) was administered for 12 weeks from 8 weeks (early phase) or 20 weeks (late phase) of age. RESULTS:Dll1 blockade suppressed both initial lesion development and plaque vulnerability compared with lesions in mice treated with non-immune IgG. Dll1 Ab decreased lipid accumulation in advanced lesions and increased the collagen content. In ex vivo cultured macrophages, the blockade of Dll1-Notch signaling by Dll1 blocking antibodies suppressed the mRNA expression of Tnf and the release of activated matrix metalloproteinase 9, which increased plaque vulnerability. In contrast, the stimulation of Dll1-Notch by recombinant Dll1 induced Il1b, Il6, and Tnf expression in macrophages, as well as NF-κB activation. An exploratory transcriptome analysis of atherosclerotic arteries suggested that Dll1-Notch signaling regulates the expression of genes associated with inflammation and mitosis. CONCLUSIONS:These results indicate that Dll1 promotes the pathobiology of atherosclerosis from the initial lesion development to plaque destabilization in advanced atherosclerotic lesions.

Aims Ischaemic heart disease is a leading cause of death worldwide, and heart failure after myocardial infarction (MI) is a growing issue in an ageing society. Macrophages play a central role in left ventricular (LV) remodelling after MI. Mitochondria consistently change their morphology, including fission and fusion; however, the role of these morphological changes, particularly in macrophages, remains unknown. This study investigated the role of dynamin-related protein 1 (Drp1), a key mediator of mitochondrial fission, in macrophages and its involvement in the mechanisms of left ventricular remodelling after myocardial infarction (MI).Methods and results This study utilized genetically altered mice lacking Drp1 in Lysozyme M-positive cells (Drp1-KO) to elucidate the specific role of macrophage Drp1 in post-infarct LV remodelling. Deletion of Drp1 in macrophages exacerbated LV remodelling, underpinned by reduced ejection fraction and increased LV diameter, which resulted in a poor prognosis after MI. Histological analysis indicated increased fibrosis and sustained macrophage accumulation in the infarcted hearts of Drp1-KO mice. Blockade of Drp1 in macrophages decreased mitochondrial fission and impaired mitophagy, leading to the subsequent release of mitochondrial DNA (mtDNA) into the cytosol and the induction of inflammatory cytokines. This induction was abrogated by the autophagy inducer Tat-beclin1 or siRNA-mediated knockdown of Z-DNA Binding Protein 1 (ZBP1). Deletion of ZBP1 in bone marrow-derived cells abrogated LV remodelling induced by the Drp1 inhibitor Mdivi-1.Conclusion Macrophage Drp1 plays a critical role in the pathobiology of post-infarct LV remodelling, particularly in mitochondrial quality control mechanisms. Macrophage Drp1 could be a novel therapeutic molecule to mitigate the progression of LV remodelling and consequent heart failure after MI.

OBJECTIVE:Vasoplegia after cardiac surgery with cardiopulmonary bypass is an important cause of postoperative hemodynamic instability. This study evaluated clinical factors associated with vasoplegia and its association with delayed postoperative recovery. DESIGN:Single-center retrospective observational study. SETTING:University hospital. PARTICIPANTS:Adult patients undergoing cardiac or thoracic aortic surgery with cardiopulmonary bypass between January 2014 and December 2024. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Vasoplegia was defined as simultaneous fulfillment of at least 3 of 4 hemodynamic criteria for more than 30 minutes between separation from cardiopulmonary bypass and 12 hours after intensive care unit admission: mean arterial pressure <60 mmHg, systemic vascular resistance index <1500 dyn·s/cm⁵/m², cardiac index >2.5 L/min/m², and vasopressor support. Among 572 patients, 101 (17.7%) developed vasoplegia. In multivariable logistic regression, lower geriatric nutritional risk index, impaired left ventricular systolic function, prior percutaneous coronary intervention, and aortic-involving surgery were independently associated with vasoplegia. Vasoplegia occurred in 13.9%, 13.7%, and 43.2% of patients with 0, 1, and 2 to 3 nutritional/functional deficits, respectively. After propensity score overlap weighting, vasoplegia was associated with prolonged mechanical ventilation ≥48 hours (odds ratio [OR], 2.20; 95% confidence interval (CI), 1.35-3.59), prolonged intensive care unit stay ≥7 days (OR, 2.08; 95% CI, 1.26-3.45), in-hospital mortality (OR, 3.09; 95% CI, 1.02-9.32), and composite poor postoperative outcome (OR, 2.03; 95% CI, 1.26-3.29). CONCLUSIONS:Vasoplegia after cardiopulmonary bypass was associated with preoperative nutritional/functional vulnerability, impaired ventricular function, prior percutaneous coronary intervention, aortic surgical exposure, and delayed early postoperative recovery after measured-risk balancing.

Basal interventricular septum (IVS) hypertrophy (BSH) is characterized by a reduced aortoseptal angle and thickened basal IVS. The BSH shape suggests compression by the longitudinally elongated ascending aorta (pseudohypertrophy), further suggesting the possibility of surgical aortic wall shortening to improve the BSH. We report the case of a 77-year-old woman with an asymptomatic dissecting thoracic ascending aortic aneurysm and clear BSH. Surgical aortic root replacement with longitudinal wall shortening clearly improved the BSH, demonstrating the beneficial effects on BSH of surgical aortic wall shortening.

Left ventricular basal posterior wall (LVbp) inward bending in patients with rheumatic mitral regurgitation and giant left atrium (LA) is a risk for low cardiac output after mitral valve (MV) surgery, which is dramatically improved by aggressive LA plication. However, the effects of LA plication on LVbp bending in patients with atrial functional mitral regurgitation (aFMR) and giant LA have not yet been reported. In 2 patients with LVbp bending, aFMR, and giant LA, MV replacement/repair with aggressive LA plication improved LVbp bending. However, compared to patient 1, in which MV replacement with posterior MV chordal preservation was followed by LA plication, improvements in LVbp bending was greater in patient 2, in which LA plication was followed by MV repair. These findings suggest that aggressive LA plication followed by MV repair has greater benefits (vs MV replacement with posterior MV chordal preservation before LA plication) on LVbp bending in patients with aFMR and giant LA.

Background: Macrophage-mediated inflammation plays an important role in the healing process after myocardial infarction (MI). We have previously reported in macrophages that inhibition of dynamin-related protein 1 (Drp1), which induces mitochondrial fission, restrains skewing toward inflammatory phenotype. It is, however, obscure whether macrophage Drp1 promotes left ventricular (LV) remodeling after MI. Aims: The aim of this study is to elucidate the role of macrophage Drp1 in the mechanisms of LV remodeling after MI. Methods: C57Bl/6J mice specifically deficient Drp1 in Lysozyme-M + macrophages (Drp1KO) were created by Cre/loxP technology and underwent ligation of the left anterior descending coronary artery at 8 to 12 weeks of age. Results: Deletion of macrophage Drp1 decreased LV ejection fraction (38±14 vs. 23±9% at day 28. N=9, p<0.05) and increased LV diameter (LVDd/Ds 5.7±0.4/4.8±0.3 vs. 4.6±0.2/3.7±0.3mm at day 28, N=9, p<0.05) (Figure). Survival rates until 28 days after MI were significantly lower in Drp1KO mice (25 vs. 64%. N=24 and 33, p<0.05). Deletion of Drp1 led to sustained macrophage accumulation and fibrosis of infarcted tissues. TEM revealed that mitophagosomes are decreased in Drp1-deficient macrophages in infarcted hearts. In ex vivo cultured macrophages, siRNA-mediated knockdown of Drp1 impaired mitochondrial fission and LC3-dependent mitophagy. In these macrophages, inhibition of Drp1 by Mdivi-1 for 96 hr, but not for 24 hr, induced mitochondrial DNA (mtDNA) leakage to the cytosol accompanied by increased expression of inflammatory cytokines. Hypoxia and starvation, in addition to Mdivi-1, induced leakage of mtDNA and expression of inflammatory cytokines at 24 hr. These results suggest that impairment of mitochondrial quality maintenance machinery causes leakage of mtDNA that induces inflammation. Conclusions: Macrophage Drp1 protects the heart from sustained inflammation and adverse cardiac remodeling after MI. Drp1-LC3-mediated mitophagy could be a mechanism that maintains mitochondrial quality and prevents excessive inflammation after MI.

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.

Background and aims: In advanced atherosclerotic lesions, macrophage deaths result in necrotic core formation and plaque vulnerability. Cyclophilin D (CypD) is a mitochondria-specific cyclophilin involved in the process of cell death after organ ischemia-reperfusion. However, the role of CypD in atherosclerosis, especially in necrotic core formation, is unknown. Therefore, this experiment aims to clarify the role of CypD in necrotic core formation. Methods: To clarify the specific role of CypD, encoded by Ppif in mice, apolipoprotein-E/CypD-double knockout (Apoe- /-Ppif- /- ) mice were generated. These mice were fed a high-fat diet containing 0.15 % cholesterol for 24 weeks to accelerate atherosclerotic lesion development. Results: Deletion of CypD decreased the necrotic core size, accompanied by a reduction of macrophage apoptosis compared to control Apoe- /- mice. In RAW264.7 cells, siRNA-mediated knockdown of CypD attenuated the release of cytochrome c from the mitochondria to the cytosol induced by endoplasmic reticulum stress inducer thapsigargin. In addition, necroptosis, induced by TNF-alpha and caspase inhibitor, was attenuated by knockdown of CypD. Ly-6Chigh inflammatory monocytes in peripheral blood leukocytes and mRNA expression of Il1b in the aorta were decreased by deletion of CypD. In contrast, siRNA-mediated knockdown of CypD did not significantly decrease Il1b nor Ccl2 mRNA expression in RAW264.7 cells treated with LPS and IFN-gamma, suggesting that inhibition of inflammation in vivo is likely due to decreased cell death in the atherosclerotic lesions rather than a direct action of CypD deletion on the macrophage. Conclusions: These results indicate that CypD induces macrophage death and mediates necrotic core formation in advanced atherosclerotic lesions. CypD could be a novel therapeutic target for treating atherosclerotic vascular diseases.

Basic mechanism of ventricular functional mitral regurgitation (FMR) is subvalvular tethering. Left ventricular (LV) dilatation, in association with mitral valve (MV) annular dilatation, causes outward displacement of papillary muscles (PMs), which abnormally pulls or tethers MV leaflets, resulting in MV tenting, reduction in leaflets coaptation and MR. Because surgical annuloplasty does shorten distance between anterior and posterior MV annuli to improve coaptation but does not address this subvalvular tethering, ventricular FMR frequently persists or recurs in the chronic stage after surgical annuloplasty. This high incidence of persistent/recurrent MR requires additional procedures to reduce subvalvular tethering. Although patients occasionally show marked improvements after annuloplasty with surgical tethering reduction procedures such as PM approximation, evidence to support benefits of such surgery is limited, requiring further trials. Recently, MV adaptation or MV leaflets tissue growth associated with LV dilatation attracts attention. Patients with larger MV leaflets with significant LV dilatation/dysfunction show less MV tethering and MR compared to those with smaller MV leaflets but with similar LV remodeling, suggesting the protective or beneficial role of MV leaflets tissue growth against LV remodeling. The MV leaflets tissue growth has the potential to lead to novel strategies of treatment for ventricular FMR. It is well known that atrial FMR is frequent in patients with left atrial dilatation, typically in those with isolated atrial fibrillation. The degree of atrial FMR is usually mild, even when it is present, and occasionally moderate, and severe atrial FMR is really rare. It is known that only severe regurgitation causes heart failure in primary MR, resulting in description on indications of surgery or intervention for only severe MR in current guidelines. Therefore, this atrial FMR up to moderate degree did not attract attention for a long time. However, recent studies have shown that patients with only moderate atrial FMR develop severe heart failure, suggesting more aggressive indication of MV surgery or intervention for “moderate” regurgitation in patients with atrial FMR. Therefore, atrial FMR is now recognized highly important. The unveiled malignant nature of atrial FMR arises many questions, including (1) why patients with only moderate atrial FMR develop heart failure? (2) do patients with mild atrial FMR develop heart failure or not?, and many others. Atrial FMR seems even more mysterious after the unveiling of its significance.

Infective endocarditis (IE) is a severe illness characterized by vegetation of bacterial thrombosis. We hypothesized that adding recombinant tissue-type plasminogen activator (rt-PA) to antibiotics would contribute to good results in the treatment of IE. As an in vitro study, we injected labeled Staphylococcus aureus (S. aureus) and either rt-PA or PBS + plasminogen into a polydimethylsiloxane flow chamber with fibrin on a coverslip, and then performed immunofluorescent area assessment. As an in vivo experiment, IE model rats that had suffered mechanical damage in the aortic valve by catheter and revealed bacterial vegetation caused by S. aureus injection were treated with either a control, cefazolin (CEZ), rt-PA, or rt-PA + CEZ, for 7 days. Survival was assessed for 14 days after the appearance of vegetation, with daily monitoring of the vegetation by transthoracic echocardiography (TTE). The in vitro investigation showed that perfusion of rt-PA could detach S. aureus significantly more efficiently than PBS could. In the in vivo research, the rt-PA + CEZ group survived significantly longer than the other groups, and rt-PA + CEZ was more effective than CEZ in the dissolution of vegetation, as observed by TTE. In conclusion, adding rt-PA to antibiotic treatment could dissolve the vegetation component synergistically and improve the survival rate.

In our previous study, we reported that 2, 5-dimethyl-celecoxib (DM -C), a derivative of celecoxib, prevents cardiac remodeling in different mouse models of heart failure, including myocardial infarction (MI). The inflammatory response after MI affects the progression of cardiac remodeling, wherein the immune cells, mainly macrophages, play crucial roles. Therefore, we evaluated the effect of DM -C on macrophages in a cryoinjuryinduced myocardial infarction (CMI) mouse model. We observed that DM -C attenuated the deterioration of left ventricular ejection fraction and cardiac fibrosis 14 d after CMI. Gene expression of pro-inflammatory cytokines at the infarct site was reduced by DM -C treatment. Analysis of macrophage surface antigens revealed that DM -C induced transient accumulation of macrophages at the infarct site without affecting their polarization. In vitro experiments using peritoneal monocytes/macrophages revealed that DM -C did not directly increase the phagocytic ability of the macrophages but increased their number, thereby upregulating the clearance capacity. Moreover, DM -C rapidly excluded the cells expressing necrotic cell marker from the infarct site. These results suggested that DM -C enhanced the clearance capacity of macrophages by transiently increasing their number at the infarct site, and terminated the escape from the inflammatory phase earlier, thereby suppressing excessive cardiac remodeling and ameliorating cardiac dysfunction.

BACKGROUND:The long-term mortality of end-stage renal disease (ESRD) patients is still unsatisfactory. Therefore, long-term risk assessments in ESRD patients undergoing cardiac surgery are needed. Recently, sarcopenia is major concern in cardiac surgery because of its association with poor long-term survival. However, the impact of sarcopenia on the long-term survival of ESRD patients undergoing cardiac surgery is not well understood. METHODS:Eighty-two ESRD patients who underwent elective cardiac surgery were enrolled. Sarcopenia was identified based on noncontrast abdominal computed tomography. The impact of preoperative and intraoperative factors on long-term survival was investigated. RESULTS:Forty-three patients (52%) were diagnosed with sarcopenia. The in-hospital mortality rate was 4.9%. The 5-year overall survival rate was 48%. The multivariate analyses revealed that STS score ≥ 4 (odds ratio, 6.0; confidence interval, 2.5-14.7; p < 0.01) and presence of sarcopenia (odds ratio, 2.4; confidence interval, 1.3-4.5; p  =  0.03) were independent risk factors for overall survival. The 5-year survival rates of low-risk (Society of Thoracic Surgeons score of < 4) patients without sarcopenia, low-risk with sarcopenia, more than intermediate-risk (Society of Thoracic Surgeons score of ≥ 4) without sarcopenia, and more than intermediate-risk with sarcopenia groups were 80%, 51%, 50%, and 26%, respectively. CONCLUSIONS:Among the ESRD patients, the low risk without sarcopenia group showed an excellent long-term survival, in contrast to more than intermediate-risk patients with sarcopenia, who can expect poor long-term survival. Preoperative assessment of sarcopenia in addition to the surgical risk score can be useful in developing a therapeutic strategy.

Background Cardiac hemangiomas are rare, accounting for only 5% of benign cardiac tumors. In the past, there have been few reports of giant cardiac hemangiomas that were > 100 mm in size but were asymptomatic. Case presentation A 44-year-old woman presented with a large asymptomatic intracardiac mass that was accidentally detected on echocardiography. The tumor was surgically resected. During surgery, a sharply margined tumor was located in the right atrium; the tumor was histopathologically diagnosed as a cavernous hemangioma. The patient was discharged uneventfully on the 18th postoperative day. No signs of recurrence were observed at 1 year postoperatively. Conclusions We report on a surgical case of an asymptomatic giant cardiac hemangioma 115 mm × 92 mm in size, as measured by echocardiography. It is difficult to diagnose cardiac tumors before surgery based on symptoms and imaging. Surgical resection is the most reliable treatment because of its accurate diagnosis and favorable prognosis.

Background In advanced atherosclerotic lesions, apoptotic cell death of plaque macrophages results in necrotic core formation and plaque vulnerability. Cyclophilin D (CypD) is a mitochondria-specific cyclophilin involved in the process of cell death after organ ischemia-reperfusion. However, the role of CypD in atherosclerosis, especially in necrotic core formation, is unknown. Methods To clarify the specific role of CypD, apolipoprotein-E/CypD-double knockout (ApoE-/-CypD-/-) mice were generated. These mice were fed a high-fat diet containing 0.15% cholesterol for 24 weeks to accelerate atherosclerotic lesion development. Results The deletion of CypD decreased the necrotic core size, accompanied by a reduction of macrophage apoptosis compared to control ApoE-/- mice. In RAW264.7 cells treated with endoplasmic reticulum stress inducer thapsigargin, the release of cytochrome c to the cytosol was attenuated by siRNA-mediated knockdown of CypD. Ly-6Chigh inflammatory monocytes in the peripheral blood leukocytes and mRNA expression of Il1b in the aorta were decreased by the deletion of CypD. In contrast, siRNA-mediated knockdown of CypD did not significantly decrease Il1b nor Ccl2 mRNA expression in RAW264.7 cells treated with LPS and IFN-γ, suggesting that inhibition of inflammation in vivo is likely due to decreased cell death in the atherosclerotic lesions rather than a direct action of CypD deletion on the macrophage. Conclusions This is the first report showing that CypD induces macrophage death and promotes necrotic core formation in advanced atherosclerotic lesions. CypD could be a novel therapeutic target for treating atherosclerotic vascular diseases.

We previously reported that 2,5-dimethylcelecoxib (DM-C), a derivative of celecoxib, lacks cyclooxygenase-2 inhibitory effects and suppresses cardiac remodeling by activating glycogen synthase kinase-3 (GSK-3). However, it remains unclear whether DM-C attenuates fibroblast-to-myofibroblast transformation (FMT), which plays a key role in cardiac fibrosis. Therefore, we evaluated the effect of DM-C on FMT using a cryoinjury-induced myocardial infarction (CMI) mouse model. We found that DM-C attenuated the deterioration of left ventricular ejection fraction after CMI by decreasing cardiac fibrosis. Analysis of the expression level of α-smooth muscle actin (α-SMA), a marker for myofibroblasts, indicated that DM-C decreased FMT at the cardiac injury site. To investigate the mechanism by which DM-C attenuated FMT, fibroblasts obtained from the heart were stimulated with TGF-β to induce FMT, and the effect of DM-C was analyzed. DM-C suppressed the expression of α-SMA and the phosphorylation levels of Smad 2/3 and GSK-3, indicating that DM-C suppressed α-SMA expression by inhibiting the transforming growth factor (TGF)-β signaling pathway via activation of GSK-3. DM-C decreased the expression of collagen, connective tissue growth factor (CTGF) and Snail, which are also known to accelerate cardiac fibrosis. These results suggested that DM-C attenuated cardiac fibrosis by suppressing FMT at the injured site after CMI by inhibiting the TGF-β signaling pathway via activation of GSK-3. Thus, DM-C has potential against cardiac disease as a novel anti-fibrotic agent.

We previously reported the 2,5-dimethylcelecoxib (DM-C) attenuated cardiac remodeling in different types of cardiac hypertrophy model. However, it remains unclear whether DM-celecoxib attenuates fibroblast-to-myofibroblast transformation (FMT) which plays the key role in cardiac fibrosis after myocardial infarction (MI). Therefore, we investigated the effect of DM-C on FMT using cryoinjury induced myocardial infarction (CMI) mouse model and TGF-β1-stimulated cardiac fibroblasts. We found that DM-celecoxib attenuated deterioration of left ventricular ejection fraction after CMI by decreasing cardiac fibrosis. Analysis of the expression level of α-smooth muscle actin, a marker for myofibroblast, indicated that DM-celecoxib decreased FMT in cardiac injured site. In the cardiac fibroblasts, DM-celecoxib suppressed expression of α-SMA and phosphorylation levels of Smad 2/3 and GSK-3, indicating that DM-celecoxib suppressed α-SMA expression by inhibiting TGF-β signaling pathway via activation of GSK-3. These results suggested that DM-celecoxib attenuated cardiac fibrosis via suppressing fibroblast-to-myofibroblast transformation in injured site after CMI by suppressing TGF-β signaling pathway via activation of GSK-3. Thus, DM-celecoxib has a potential as a novel anti-fibrotic agent after MI in clinical setting.

Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Background Aortic dilatation may occur in some patients even after complete repair of tetralogy of Fallot (TOF). The progression rate of the aortic diameter is so slow, and the incidence of aortic dissection is so low that it is suspected that frequent imaging of the aorta may not be necessary. Case presentation We describe an asymptomatic 41-year-old man with hypertension in whom aortic dilatation was accidentally discovered 39 years after TOF repair. He underwent ambulatory follow-up without any difficulty for 21 years after the repair. Contrast-enhanced computed tomography revealed significant aortic dilatation (maximum diameter of 88 mm at the sinus of Valsalva), and echocardiography revealed severe aortic regurgitation, which seemed to progress during the last 18 years without any evaluation or follow-up. The Bentall procedure was successfully performed using a valved graft, under deep hypothermic circulatory arrest with antegrade cerebral perfusion, and his postoperative course was uneventful. Histopathological examination of ascending aorta specimens revealed severe cystic medial degeneration. Conclusions Keeping in mind that a patient with rapid progression of the aortic dilatation after TOF repair exist, periodic follow-up for evaluation of the aorta is essential in patients with TOF.

Post-myocardial infarction ventricular septal perforation （ VSP ） is one of the lethal complications of transmural myocardial infarction. Although the treatment of VSP mostly requires surgical procedures using heterologous pericardium, thromboembolism rarely occurs in patients who undergo VSP repair. Herein we report the case of a patient who died of sudden massive cerebral infarction two weeks after the surgery. The autopsy findings revealed concaved mural LV thrombus in the dissected heart. It is suspected that the patient died of extensive cerebral infarction due to thromboembolic occlusion of the carotid or central cerebral artery. In the postoperative period after VSP repair, several risk factors for thrombus formation may occur, such as postoperative hypercoagulability due to systemic inflammation by the high operative invasiveness, the presence of foreign material in the impaired left ventricle, or pericardial patch suturing methods. Our clinical experience indicates that meticulous postoperative management may be needed, keeping LV thrombus formation in mind after VSP repair. Jpn. J. Cardiovasc. Surg. 49 : 280 - 283 2020