Background: Chronic angiotensin II (AngII) infusion promotes ascending aortic dilation in C57BL/6J mice. Meanwhile, vasohibin-2 (VASH2) is an angiogenesis promoter in neovascularization under various pathologic conditions. The aim of this study was to investigate whether exogenous VASH2 influences chronic AngII-induced ascending aortic dilation.

Methods and Results: Eight–ten-week-old male C57BL/6J mice were injected with adenovirus (Ad) expressing either VASH2 or LacZ. One week after the injection, mice were infused with either AngII or saline s.c. for 3 weeks. Mice were divided into 4 groups: AngII+VASH2, AngII+LacZ, saline+VASH2, and saline+LacZ. Overexpression of VASH2 significantly increased AngII-induced intimal areas as well as the external diameter of the ascending aorta. In addition, VASH2 overexpression promoted ascending aortic medial elastin fragmentation in AngII-infused mice, which was associated with increased matrix metalloproteinase activity and medial smooth muscle cell (SMC) apoptosis. On western blot analysis, accumulation of apoptotic signaling proteins, p21 and p53 was increased in the AngII+VASH2 group. Furthermore, transfection of human aortic SMC with Ad VASH2 increased p21 and p53 protein abundance upon AngII stimulation. Positive TUNEL staining was also detected in the same group of the human aortic SMC.

Conclusions: Exogenous VASH2 exacerbates AngII-induced ascending aortic dilation in vivo, which is associated with increased medial apoptosis and elastin fragmentation.

Background: The concept of Clinical Scenario (CS) classification has been widely utilized to aid in choosing appropriate management strategies for acute decompensated heart failure (ADHF).

Methods and Results: The West Tokyo-Heart Failure (WET-HF) Registry is a multicenter, prospective cohort registry enrolling consecutive hospitalized ADHF patients. Based on systolic blood pressure (SBP) at admission, 4,000 patients enrolled between 2006 and 2017 were classified into 3 groups: CS1, SBP ≥140 mmHg; CS2, 100≤SBP<140 mmHg; and CS3, SBP <100 mmHg. The CS1 group had a high rate of fluid retention such as leg edema, and the largest reduction in body weight at discharge. In-hospital diuretics use was the most frequent in CS1. Although the primary endpoint of long-term all-cause death and/or ADHF re-hospitalization was more common in more advanced CS, there was no significant difference between the 3 CS groups in patients with HF with preserved ejection fraction (HFpEF; P=0.10). Although more advanced CS was associated with larger left ventricular (LV) chamber size in HF with reduced EF (HFrEF), it was associated with smaller LV size in HFpEF.

Conclusions: The long-term prognostic value of CS classification was limited in HFpEF. Whereas CS was closely associated with degree of LV remodeling in HFrEF, a smaller LV chamber might be associated with a lower cardiovascular functional reserve in HFpEF.

Background: Left ventricular reverse remodeling (LVRR) is a favorable response in non-ischemic, non-valvular cardiomyopathy (NICM) patients. Recently, 18-lead body surface electrocardiography (ECG), the standard 12-lead ECG with synthesized right-sided/posterior chest leads, has been developed, but its predictive value for LVRR has not been evaluated.

Methods and Results: Of 216 consecutive hospitalized NICM patients with LV ejection fraction (LVEF) ≤35%, we studied 125 who received optimization of their heart failure treatment and had 18-lead ECG and echocardiography data available for evaluating LVRR, defined as an absolute increase in LVEF ≥10% concomitant with LVEF ≥35% after 1-year optimized treatment. Most 18-lead ECG parameters in the NICM patients differed from those in 312 age- and body mass index-matched subjects with normal echocardiography. LVRR occurred in 59 NICM patients and they had a larger QRS amplitude in the limb leads (I, II, aVR, and aVF), precordial leads (V3–V6), and synthesized leads (syn-V4R–5R), decreased QRS axis and duration, and lower prevalence of fragmented QRS than those without LVRR. The ECG score using 3 selected parameters (QRS amplitude in aVR ≥675 µV; QRS duration <106 ms without fragmentation; and QRS axis <67°) was associated with the incidence of LVRR even after adjusting for optimized treatment.

Conclusions: The standard 12-lead ECG parameters are sufficiently predictive of LVRR in NICM patients.

Background: In heart failure (HF) management, early ambulation is recommended to prevent physical deconditioning. The effects of delayed ambulation on later clinical outcomes and the factors linked to delayed ambulation in hospitalized HF patients, however, remain unestablished.

Methods and Results: We retrospectively investigated 101 patients (mean age, 66±17 years) who were hospitalized for acute decompensated HF. During the mean follow-up of 244±15 days after hospital discharge, 34 patients had cardiovascular events leading to death or unplanned readmission. Patients with cardiovascular events had longer median days to acquire ambulation than those without cardiovascular events (11 days, IQR, 8–20 days vs. 7 days, IQR, 5–15 days, P<0.001). The optimal cut-off period until initiation of ambulation to discriminate cardiovascular events was 8 days, indicating that longer days (≥8 days) to acquire ambulation was associated with higher rates of cardiovascular events, even after adjustment of multiple confounders. On multivariate analysis, age >65 years (odds ratio [OR], 2.49; 95% confidence interval [CI]: 1.04–6.09) and increase in blood urea nitrogen (BUN; OR, 1.04; 95% CI: 1.01–1.08) were independent predictors of delayed ambulation.

Conclusions: Delayed ambulation is associated with older age and increased BUN in patients with acute HF. Time to ambulation in the recovery phase of acute HF is important, and delayed ambulation may increase the rate of cardiovascular events after hospital discharge.

Background: Despite advances in endovascular therapy (EVT), peripheral artery disease (PAD) is a public health problem associated with high cardiovascular mortality. Iron deficiency (ID) is associated with poor clinical outcome in patients with heart disease, but whether ID is associated with the severity and clinical outcome of PAD remains unclear.

Methods and Results: A total of 449 patients with PAD who received EVT and who had iron and red blood cell measurement were enrolled. ID was defined as transferrin saturation (TSAT) <20%, based on a previous report. TSAT and hemoglobin decreased with deteriorating Fontaine class. During a median follow-up period of 1,064 days, 71 major adverse cardiovascular and leg events (MACLE) and 47 major adverse cardiovascular events (MACE) were noted. All patients were divided into 2 groups based on the presence of ID. On Kaplan-Meier analysis, patients with ID had higher rates of MACE and MACLE than those without. On multivariate Cox proportional hazard regression analysis, TSAT and hemoglobin were independently associated with MACLE. Addition of TSAT to the known risk factors significantly improved the net reclassification index and integrated discrimination improvement.

Conclusions: ID, as assessed by TSAT, was associated with the severity and clinical outcome of PAD, indicating that it could be a therapeutic target.