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Simplifying jugular venous pressure (JVP), visibility of the right internal jugular vein above the right clavicle in the sitting position, has been proposed in the management of heart failure (HF) because of its convenience. However, this method may be undervalued for the detection of mildly to moderately increased JVP. Increased JVP on inspiration, known as Kussmaul sign, may be a useful physical finding in this condition. This study consisted of 138 patients who were admitted for the management of HF. Using this simple method, JVP was assessed at rest in the sitting position before discharge; its response to inspiration was also examined if no high JVP was noted at rest. The primary outcome was a composite of cardiac death and hospitalization for worsening HF. Among all the patients, 16 patients (12%) had high JVP at rest and another 16 patients (12%) had high JVP not at rest but on inspiration. During a follow-up period of 249 ± 182 days, a primary outcome event occurred in 63 patients (46%). The incidence of adverse cardiac events was higher in patients with a high JVP at rest (69%; hazard ratio 3.31, 95% confidence interval 1.64 to 6.67, p = 0.0009) and in patients with a high JVP on inspiration (56%; hazard ratio 2.18, 95% confidence interval 1.02 to 4.63, p = 0.043) than in patients without a high JVP in both conditions (41%). In conclusion, a high JVP not only at rest but also on inspiration was associated with a poor prognosis. The response of JVP to inspiration using this simple technique of physical examination may be a new approach in the management of HF.

Senescent vascular cells are detected in atherosclerotic lesion, and its involvement in the development of atherosclerosis has been revealed; however, whether and the mechanism by which endothelial cell (EC) senescence is causally implicated in atherosclerosis remains unclear. We here investigate a role of EC senescence in atherosclerosis by utilizing EC-specific progeroid mice that overexpress the dominant negative form of telomeric repeat-binding factor 2 under the control of the Tie2 or vascular endothelial cadherin promoter. EC-specific progeria accelerated atherosclerosis in mice with target deletion of ApoE. Mechanistically, senescent ECs were markedly sensitive for inflammation-mediated VCAM-1 induction, leading to enhanced monocyte adhesion. Inhibition of NF-κB signaling abolished the enhanced inflammatory responses in senescent ECs, while NF-κB nuclear translocation in response to TNF-α were similar between young and senescent ECs. We found a higher association of VCAM-1 gene with active histone H3 trimethylated on lysine 4, leading to increased NF-κB accessibility in senescent ECs. Our data revealed that EC cellular senescence causes endothelial hyper-inflammability through epigenetic alteration, which consequently accelerates atherosclerosis. Therefore, EC senescence is a promising therapeutic target for the prevention and/or treatment of atherosclerotic disease in elderly population.

Yamanaka R, Hoshino A, Fukai K, Urata R, Minami Y, Honda S, Fushimura Y, Hato D, Iwai-Kanai E, Matoba S. TIGAR reduces smooth muscle cell autophagy to prevent pulmonary hypertension. Am J Physiol Heart Circ Physiol 319: H1087-H1096, 2020. First published September 18, 2020; doi:10.1152/ajpheart.00314.2020.-Pulmonary arterial hypertension (PAH) is a refractory disease. Its prognosis remains poor; hence, establishment of novel therapeutic targets is urgent. TP53-induced glycolysis and apoptosis regulator (TIGAR) is a downstream target of p53 and exhibits functions inhibiting autophagy and reactive oxygen species (ROS). Recently, p53 was shown to suppress PAH progression. Because inhibition of autophagy and ROS is known to improve PAH, we examined the effect of TIGAR on PAH progression. We compared pulmonary hypertension (PH) development between TIGAR-deficient knockout (KO) and wild-type (WT) mice using a hypoxia-induced PH model. Human pulmonary artery smooth muscle cells (PASMCs) were used for in vitro experiments with small interfering RNA (siRNA) to investigate the possible molecular mechanisms. From the analysis of right ventricular pressure, right ventricular weight, and mortality rate, we concluded that the hypoxia-induced PH development was remarkably higher in TIGAR KO than in WT mice. Pathological investigation revealed that medial thickening of the pulmonary arterioles and cell proliferation were increased in TIGAR KO mice. Autophagy and ROS activity were also increased in TIGAR KO mice. TIGAR knockdown by siRNA increased cell proliferation and migration, exacerbated autophagy, and increased ROS generation during hypoxia. Autophagy inhibition by chloroquine and ROS inhibition by N-acetylcysteine attenuated the proliferation and migration of PASMCs caused by TIGAR knockdown and hypoxia exposure. TIGAR suppressed the proliferation and migration of PASMCs via inhibiting autophagy and ROS and, therefore, improved hypoxia-induced PH. Thus, TIGAR might be a promising therapeutic target for PAH.NEW & NOTEWORTHY Pulmonary arterial hypertension is a refractory disease. TP53-induced glycolysis and apoptosis regulator (TIGAR) is a downstream target of p53 and exhibits functions inhibiting autophagy and reactive oxygen species (ROS). By using TIGAR-deficient knockout mice and human pulmonary artery smooth muscle cells, we found that TIGAR suppressed the proliferation and migration of PASMCs via inhibiting autophagy and ROS and, therefore, improved hypoxia-induced PH. TIGAR will be a promising therapeutic target for PAH.

Aneurysms of the sinus of Valsalva are characterized by dilatation of at least one of the three aortic sinuses. We experienced a case with unruptured aneurysm of the right sinus of Valsalva, in which serial imaging studies were useful in assessing a rare complication after surgical repair. An asymptomatic 75-year-old man underwent patch closure of the aneurysm orifice because of progressive enlargement of the aneurysm. The postoperative course was uneventful, and computed tomography (CT), performed a week after the patch repair, showed no leakage of contrast medium into the isolated aneurysm. Three months later, echocardiography showed decreased size of the aneurysm with heterogeneous echogenicity and possible blood flow in the aneurysm, findings suggestive of thrombus formation and a recurrent fistula. CT with contrast medium showed partial recanalization between the patched aneurysm and the right sinus of Valsalva. Follow-up echocardiography, performed 1 year after surgery, revealed neither definite aneurysm nor shunt flow of Valsalva. The present case highlights that non-invasive follow-up can be an alternative option when carried out with caution in selected patients with incomplete closure of Valsalva aneurysm.

BACKGROUND Patients with hypertrophic cardiomyopathy (HCM) sometimes develop myocardial fibrosis in association with adverse cardiovascular events. Electrocardiography (ECG) could provide helpful information on myocardial fibrosis in HCM, as in coronary artery disease. METHODS AND RESULTS A total of 60 patients with HCM without bundle branch block underwent cardiac magnetic resonance imaging (CMR). The extent or location of late gadolinium enhancement (LGE) was examined in relation to 12-lead ECG. A notch on QRS was defined as at least 2 consecutive spikes in the same polarity with a reversal of direction ≥90° and the initial negative deflection ≥0.05 mV. LGE was associated with notched QRS, leftward QRS axis, and prolonged QRS duration, but not with any other findings such as abnormal Q waves, R-wave amplitude, or ST-T changes. Notched QRS was most useful in determining the presence or absence of myocardial fibrosis, with a sensitivity of 70% and a specificity of 81% using a cut-off of the number of leads with notched QRS ≥2. The number of notched QRS leads was positively correlated with LGE volume (P

Background The 4th heart sound (S4) is commonly heard in patients with hypertrophic cardiomyopathy (HCM). The 3rd heart sound (S3) is also audible in HCM patients regardless of the presence or absence of heart failure. These extra heart sounds may be associated with myocardial fibrosis because myocardial fibrosis has been suggested to affect left ventricular compliance.Methods and Results:The present retrospective study evaluated 53 consecutive HCM patients with sinus rhythm who had no symptoms of heart failure and underwent an initial assessment including phonocardiography, echocardiography, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI). S3 was detected on phonocardiography in 13% of all patients, and S4 was recorded in 75% of patients. Patients with S3 had a higher incidence of LGE and larger LGE volumes (86% and 11.5±2.4 g/cm, respectively) than patients without S3 (33% and 2.5±0.8 g/cm, respectively; P=0.02 and P=0.002). The presence of S4 was not associated with MRI findings, including the incidence of LGE and LGE volume. The diagnostic value of S3 for the detection of LGE was highly specific (97%), with a low sensitivity (29%). Conclusions Myocardial fibrosis, as assessed by LGE, was associated with S3 but not with S4 in patients with HCM. These results may contribute to the risk stratification of patients with HCM.

Rhabdomyolysis, which is a characteristic occurrence in associated with muscle cell necrosis, develops due to various causes. We herein report a rare case of a patient with rhabdomyolysis after high intensity resistance training, in which markedly elevated levels of serum creatine kinase (CK) and urine myoglobin were observed. A previously healthy 37-year-old man presented with severe myalgia and dark urine after performing high-intensity exercise. The patient's serum CK level was 95,100 U/L and his urine myoglobin level was 160,000 ng/mL. His symptoms and laboratory findings gradually improved with the intravenous administration of saline and no complications (including electrolyte imbalance and acute renal failure) developed.

A 75-year-old man was admitted with abrupt onset of dyspnea during sleep. On examination, his blood pressure was 222/165 mm Hg, pulse was 160 bpm, and oxygen saturation was 75% while breathing ambient air. Heart sounds were difficult to assess because of coarse crackles and his moaning. There was no edema in the extremities. An ECG showed sinus tachycardia with a QRS duration of 111 milliseconds, and a chest radiograph showed pulmonary edema without cardiomegaly. A presumed diagnosis of acute heart failure was made, and isosorbide dinitrate was administered intravenously with supplemental oxygen via a face mask. Cardiac auscultation after stabilization of vital signs showed a holosystolic murmur at the apex and an early systolic click at the left sternal border. Mitral regurgitation resulting from mitral valve prolapse (MVP) was most likely but was not confirmed by transthoracic echocardiography because of a lack of definitive evidence (Figure 1). Of note, another extra sound during early diastole was heard best at the third left sternal border. Figure 1. Apical 2-chamber views of the left ventricle (LV) on transthoracic echocardiography show insufficient coaptation of the mitral leaflets ( A , arrow) and …

Background Right bundle branch block (RBBB) is associated with ventricular septal fibrosis in patients with hypertrophic cardiomyopathy (HCM) after alcohol septal ablation, but little data are available in HCM patients without a history of septal ablation. Methods Magnetic resonance late gadolinium enhancement (LGE) was performed in 59 HCM patients with no history of alcohol septal ablation. The location and extent of LGE were examined in relation to electrocardiographic features including RBBB. Results LGE volume was higher in 7 HCM patients with RBBB (7.3 ± 7.4 g/cm) than in patients without RBBB (2.9 ± 7.4 g/cm, p = 0.016). LGE volume was positively correlated to QRS duration of RBBB (correlation coefficient = 0.93, p = 0.023). The diagnostic value of RBBB was highly specific for the detection of LGE in the ventricular septum, with sensitivity 21% and specificity 94%. Conclusions The presence of RBBB may be a simple marker for detecting ventricular septal fibrosis in HCM patients who had no history of alcohol septal ablation. Further studies are necessary to confirm our findings.

We report here six cases of malignant melanoma in which metastatic lesions were detected first. Of these, two cases showed some peculiar features: one exhibited widespread subcutaneous bleeding, probably due to venous rupture, and the other case had a rare primary lesion on the penis. In the Japanese literature, there have been 46 cases of malignant melanoma in which metastatic lesions were detected prior to the initial ones. The preferential site for metastasis was the lymph node (32 cases). The primary lesion was unknown in 35 patients. The outcomes were available for 36 of the 46 patients; 23 died, including 18 who died within two years.