PGC-1α-mediated angiogenesis prevents pulmonary hypertension in mice.

Pulmonary hypertension (PH) is a life-threatening disease characterized by a progressive narrowing of pulmonary arterioles. Although VEGF is highly expressed in lung of patients with PH and in animal PH models, the involvement of angiogenesis remains elusive. To clarify the pathophysiological function of angiogenesis in PH, we compared the angiogenic response in hypoxia (Hx) and SU5416 (a VEGFR2 inhibitor) plus Hx (SuHx) mouse PH models using 3D imaging. The 3D imaging analysis revealed an angiogenic response in the lung of the Hx-PH, but not of the severer SuHx-PH model. Selective VEGFR2 inhibition with cabozantinib plus Hx in mice also suppressed angiogenic response and exacerbated Hx-PH to the same extent as SuHx. Expression of endothelial proliferator-activated receptor γ coactivator 1α (PGC-1α) increased along with angiogenesis in lung of Hx-PH but not SuHx mice. In pulmonary endothelial cell-specific Ppargc1a-KO mice, the Hx-induced angiogenesis was suppressed, and PH was exacerbated along with increased oxidative stress, cellular senescence, and DNA damage. By contrast, treatment with baicalin, a flavonoid enhancing PGC-1α activity in endothelial cells, ameliorated Hx-PH with increased Vegfa expression and angiogenesis. Pulmonary endothelial PGC-1α-mediated angiogenesis is essential for adaptive responses to Hx and might represent a potential therapeutic target for PH.

Successful Treatment with Letermovir in a Heart Transplant Recipient with UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Colitis and Viremia.

Currently available anti-cytomegalovirus (CMV) agents are sometimes poorly tolerated, owing to their side effects. Letermovir is a novel anti-CMV drug that is only approved for CMV prophylaxis in hematopoietic stem cell transplant recipients, with fewer side effects. We report the case of a heart transplant recipient with UL97 mutation (L595F) ganciclovir-resistant cytomegalovirus colitis who was successfully treated with off-label use of letermovir. In treating CMV infection or disease with letermovir, a transient rise or lag in the clearance of CMV-DNA polymerase chain reaction levels has been observed. Our case suggests that CMV-pp65 antigenemia can be an additional marker of treatment efficacy.

Impact of stent edge dissection detected by optical coherence tomography after current-generation drug-eluting stent implantation.

BACKGROUND: Stent edge dissection (SED) is a well-known predictor of worse clinical outcomes. However, impact of SED after current-generation drug-eluting stent (DES) implantation remains unknown since there was no study using only current-generation DES to assess impact of SED. This study aimed to investigate a relationship between SED detected by optical coherence tomography (OCT) and clinical outcomes after current-generation DES implantation. METHODS: This study enrolled 175 patients receiving OCT after current-generation DES implantation. The SED group was compared with the non-SED group in terms of the primary study endpoints which was the cumulative incidence of major adverse cardiac event (MACE) composed of cardiac death, target vessel myocardial infarction (TV-MI), and clinically-driven target lesion revascularization (CD-TLR). RESULTS: Of 175 patients, SED detected by OCT was observed in 32 patients, while 143 patients did not show SED. In the crude population, the SED group showed a significantly higher incidence of CD-TLR, definite stent thrombosis, TV-MI and cardiac death relative to the non-SED group. After adjustment by an inverse probability weighted methods, the SED group showed a significantly higher incidence of MACE compared with the non-SED group (hazard ratio 3.43, 95% confidence interval 1.09-10.81, p = 0.035). Fibrocalcific or lipidic plaques, greater lumen eccentricity, and stent-oversizing were the predictors of SED. CONCLUSIONS: SED detected by OCT after the current-generation DES implantation led to unfavorable outcomes. Aggressive post-dilatation around the stent edge might worse clinical outcomes due to SED, although achievement of optimal stent expansion is strongly encouraged to improve clinical outcomes.

Factors associated with temporary pacing insertion in patients with inferior ST-segment elevation myocardial infarction.

BACKGROUND: High-degree atrioventricular block (HAVB) is a prognostic factor for survival in patients with inferior ST-segment elevation myocardial infarction (STEMI). However, there is little information about factors associated with temporary pacing (TP). The aim of this study was to find factors associated with TP in patients with inferior STEMI. METHODS: We included 232 inferior STEMI patients, and divided those into the TP group (n = 46) and the non-TP group (n = 186). Factors associated with TP were retrospectively investigated using multivariate logistic regression model. RESULTS: The incidence of right ventricular (RV) infarction was significantly higher in the TP group (19.6%) than in the non-TP group (7.5%) (p = 0.024), but the incidence of in-hospital death was similar between the 2 groups (4.3% vs. 4.8%, p = 1.000). Long-term major adverse cardiovascular events (MACE), which were defined as a composite of all-cause death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and readmission for heart failure, were not different between the 2 groups (p = 0.100). In the multivariate logistic regression analysis, statin at admission [odds ratio (OR) 0.230, 95% confidence interval (CI) 0.062-0.860, p = 0.029], HAVB at admission (OR 9.950, 95% CI 4.099-24.152, p<0.001), and TIMI-thrombus grade ≥3 (OR 10.762, 95% CI 1.385-83.635, p = 0.023) were significantly associated with TP. CONCLUSION: Statin at admission, HAVB at admission, and TIMI-thrombus grade ≥3 were associated with TP in patients with inferior STEMI. Although the patients with TP had the higher incidence of RV infarction, the incidence of in-hospital death and long-term MACE was not different between patients with TP and those without.

Comparison of Clinical Characteristics of Acute Myocardial Infarction Between Young (< 55 Years) and Older (55 to < 70 Years) Patients.

Although the incidence of acute myocardial infarction (AMI) has been decreasing in the elderly, it has been increasing in the young, especially in Japan. A social impact of AMI would be greater in the young, because loss of the young directly influences social activities such as business, child-raising, and tax payment. The aim of this study was to identify the specific characteristics of young AMI patients. We retrospectively included 408 consecutive AMI patients < 70 years of age, divided into a young group (< 55 years: n = 136) and an older group (55 to < 70 years: n = 272). The prevalence of overweight was greater in the young group (58.5%) than in the older group (40.7%) (P = 0.001). The frequency of current smokers was higher in the young group (67.6%) than in the older group (44.9%) (P < 0.001). Although the prevalence of hypertension was lower in the young group (66.7%) than in the older group (77.2%) (P = 0.017), that of untreated hypertension was greater in the young group (40.4%) than in the older group (27.2%) (P = 0.007). Furthermore, the prevalence of untreated dyslipidemia was greater in the young group (45.0%) than in the older group (26.6%) (P < 0.001). In conclusion, the young AMI patients had more modifiable risk factors such as obesity, smoking, untreated hypertension, and untreated dyslipidemia than the older patients. There is an unmet medical need for the prevention of AMI in the young generation.

Endomyocardial fibrosis and calcification in an elderly patient.

Endomyocardial fibrosis (EMF) is a rare restrictive cardiomyopathy in developed countries. The prognosis of EMF depends on severity of heart failure, and it is generally poor as there is no proven specific effective therapy. We have experienced a rare case of EMF in an elderly Japanese man.

The first report of human meningitis and pyogenic ventriculitis caused by Streptococcus suis: A case report.

Streptococcus suis, a gram-positive facultative anaerobe commonly found in pigs, is an emerging zoonotic pathogen. Herein, we describe a case of a 45-year-old male Japanese meat wholesaler with S. suis meningitis and pyogenic ventriculitis. S. suis was isolated from his blood and cerebrospinal fluid culture, and sequence type (ST) and serotype were confirmed to be ST1 and serotype 2, respectively, by multilocus sequence typing and the Quellung reaction. Magnetic resonance imaging (MRI) revealed right labyrinthitis and pyogenic ventriculitis. The patient was treated with ceftriaxone and ampicillin for 24 days; the treatment was deemed successful based on negative blood cultures on day 4. However, the patient experienced hearing loss and a vestibular nerve disorder. S. suis is a rare pathogen in Japan but can cause severe infection and sequelae. To the best of our knowledge, this is the first report of a human case of pyogenic ventriculitis caused by S. suis. Our findings suggest that S. suis infection should be considered when hearing impairment is present in a patient with bacterial infection and that MRI can help detect ventriculitis, which can necessitate a prolonged treatment duration.