Background:Despite the beneficial effects ofBCR-ABL1tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), they may also cause adverse events (AEs), especially cardiovascular toxicity. The incidence of TKI-induced AEs may vary among ethnic groups, and there is little specific information for Japanese patients.

Methods and Results:Sixty-nine consecutive patients who were started on treatment with dasatinib (n=25) or imatinib (n=44) for CML or gastrointestinal stromal tumor (GIST) between December 2008 and December 2019 were retrospectively recruited to the study. We determined the prevalence of AEs through October 2020 and compared the incidence of AEs between the 2 drugs. Baseline characteristics were comparable between the 2 groups. However, compared with the imatinib-treated group, the dasatinib-treated group had a higher incidence of congestive heart failure (CHF; 20.0% vs. 2.3%; P=0.04), pleural effusion (48% vs. 20.5%; P=0.03), pericardial effusion (24% vs. 4.6%; P=0.02), QT prolongation (4 vs. 0 patients; P=0.02), and pulmonary hypertension (3 vs. 0 patients; P=0.04). In the dasatinib-treated group, CHF tended to be associated with tricuspid valve regurgitation pressure gradient, and pleural effusion was observed in all patients. All-cause mortality and other cardiovascular events did not differ significantly between the 2 groups.

Conclusions:Cardiotoxic AEs occurred more frequently in Japanese patients with CML and GIST treated with dasatinib than imatinib.

Background:Body mass index (BMI) and the waist-to-height ratio (WHtR) are widely used anthropometric indices of obesity to predict cardiovascular risks. However, the usefulness of combining WHtR and BMI values to predict hypertension risk by sex has not been well elucidated.

Methods and Results:This cohort study enrolled 45,921 participants (mean [±SD] age 53.8±10.5 years; 47.0% men) without hypertension from among those undergoing annual health checkups. Participants were divided into 4 categories based on median BMI and WHtR values, and the 5-year incidence of hypertension was assessed for both sexes using logistic regression analysis. Mean (±SD) BMI and WHtR values were 23.5±3.1 kg/m²and 0.50±0.05, respectively, in men and 22.4±3.3 kg/m²and 0.53±0.06, respectively, in women. Among the women, those with high BMI and low WHtR had an increased risk of hypertension compared with those with low BMI and low WHtR (odds ratio [OR] 1.37, P<0.001); however, the same result was not found in men (OR 1.14, P=0.080). In both sexes, the incidence of hypertension was higher among participants with low BMI and high WHtR than among those with low BMI and low WHtR (men: OR 1.26, P<0.001; women: OR 1.15, P=0.048).

Conclusions:Using WHtR and BMI together provides a better hypertension risk assessment. Among men, those with a high BMI had no increased hypertension risk when WHtR was low.

Background:Clinical outcomes of adaptive servo-ventilation (ASV) therapy have not been rigorously assessed. Optimal device settings ascertained by a pressure ramp test may increase the utility of ASV therapy.

Methods and Results:Patients with congestive heart failure (CHF) who underwent ASV therapy were prospectively included in the study. Patients in the ramp test group underwent a pressure ramp test, during which the end-expiratory pressure was optimized to maximize cardiac output (assessed using the AESCLONE mini). The control group consisted of age-matched patients who received ASV therapy with a default pressure 5 cmH₂O. The primary endpoint was a composite of all-cause death and heart failure recurrence, and was compared between the 2 groups. Of a total of 37 patients, 11 each were included in the ramp test and control groups. Median patient age was 73 years (interquartile range 59–75 years) and 16 were men. There were no significant differences in baseline characteristics between the 2 groups. In the ramp test group, end-expiratory pressure was optimized between 2 and 5 cmH₂O in each patient. The 2-year incidence of the primary endpoint tended to be lower in the ramp test than control group (0% vs. 59%; P=0.080).

Conclusions:Pressure ramp testing may be a promising strategy to optimize device pressure settings in patients with CHF undergoing ASV therapy. Larger-scale trials are needed to validate our findings.

Background:The relationship between body posture and lung fluid level has not been quantified thus far. Remote dielectric sensing (ReDS^TM) is a recently introduced non-invasive electromagnetic-based technology to quantify lung fluid percentage.

Methods and Results:ReDS values were measured at different body postures (i.e., sitting, supine, and supine with legs elevated) in a healthy volunteer cohort (n=16; median age 39 years, 69% men, median [interquartile range {IQR}] body mass index 23.3 kg/m²[21.0–26.2 kg/m²]). In the sitting position, the median ReDS value was 27% (IQR 25–29%). The ReDS value increased significantly in the supine position (median 28%; IQR 27–30%; P=0.009), and increased further upon leg elevation (median 29%; IQR 28–32%; P=0.001).

Conclusions:In this proof-of-concept study, the relationship between body posture and lung fluid level was quantitatively validated in a healthy cohort.

Background:The aim of this study was to evaluate optical coherence tomography (OCT)-detected lipid-rich coronary plaques (LRCPs) with coronary computed tomography angiography (CCTA) 10 months after optimal medical therapy (OMT).

Methods and Results:Baseline OCT detected 28 LRCPs in non-culprit lesions. High-risk plaque features (HRPFs), such as positive remodeling, very low attenuation plaques, napkin-ring sign, and spotty calcification, were observed in 67.9%, 67.9%, 21.4%, and 64.3% of LRCPs, respectively, at the 10-month follow-up CCTA. Lesions with ≥3 HRPFs were defined as high-risk LRCPs (n=12); the remaining were defined as low-risk LRCPs (n=16). The maximum lipid arc on baseline OCT was larger in high- than low-risk LRCPs (221±62° vs. 179±44°, respectively; P=0.04). Receiver operating characteristic curve analysis indicated that a maximum lipid arc >154° on baseline OCT was the optimal cut-off value to predict high-risk LRCPs 10 months after OMT. Patients with high-risk LRCPs had worse clinical outcomes, defined as a composite of cardiac death, target lesion-related myocardial infarction, and target lesion-related revascularization, during follow-up than those with low-risk LRCPs (33.3% vs. 0%; P=0.01).

Conclusions:A high-risk LRCP at follow-up CCTA was correlated with a larger maximum lipid arc on baseline OCT. Further aggressive treatment for patients with large LRCPs may reduce vulnerable plaque features and prevent future cardiac events.

Background:Previous studies showed that hydroxyapatite electret (HAE) accelerates the regeneration of vascular endothelial cells and angiogenesis. This study investigated the effects of HAE in myocardial infarction (MI) model mice.

Methods and Results:MI was induced in mice by ligating the left anterior descending artery. Immediately after ligation, HAE, non-polarized hydroxyapatite (HAN), or water (control) was injected into the infarct border myocardium. Functional and histological analyses were performed 2 weeks later. Echocardiography revealed that HAE injection preserved left ventricular systolic function and the wall thickness of the scar, whereas HAN-injected mice had impaired cardiac function and thinning of the wall, similar to control mice. Histological assessment showed that HAE injection significantly attenuated the length of the scar lesion. There was significant accumulation of CD31-positive cells and increased expression of vascular endothelial growth factor (Vegf), intercellular adhesion molecule-1 (Icam1), vascular cell adhesion molecule-1 (Vcam1), hypoxia-inducible factor-1α (Hif1a), and C-X-C motif chemokine ligand 12 (Cxcl12) genes in the infarct border zone of HAE-injected mice. These effects were not induced by HAN injection. Anti-VEGFR2 antibody canceled the beneficial effect of HAE. In vitro experiments in a human cardiovascular endothelial cell line showed that HAE dose-dependently increasedVEGFAexpression.

Conclusions:Local injection of HAE attenuated infarct size and improved cardiac function after MI, probably due to angiogenesis. The electric charge of HAE may stimulate angiogenesis via HIF1α-CXCL12/VEGF signaling.

Background:Left ventricular ejection fraction (LVEF) is a basic clinical index that determines the heart failure (HF) treatment strategy. We aimed to evaluate the association between hospitalization costs for HF patient and LVEF in an advanced aging society in a region in Japan.

Methods and Results:Consecutive HF patients admitted to Miyazaki Prefectural Nobeoka Hospital between January 2015 and March 2018 were included in the study. The 346 HF patients (mean age 78 years) were divided into 2 groups: HF with reduced ejection fraction (HFrEF; LVEF <40%; n=129) and HF with preserved ejection fraction (HFpEF; LVEF ≥40%; n=217). Median hospitalization costs (in 2017 US dollars) were higher in the HFrEF than HFpEF group, but the difference was not statistically significant (&#36;7,128 vs. &#36;6,580; P=0.189). However, in older adults (age ≥75 years; n=252), median hospitalization costs were significantly higher in the HFrEF than HFpEF group (&#36;7,240 vs. &#36;6,471; P=0.014), and LVEF was an independent factor of hospitalization costs (β=−0.0301, P=0.006). Median hospitalization costs were significantly lower in the older than younger HFpEF group (&#36;6,471 vs. &#36;7,250; P=0.011), but there was no significant difference in costs between the older and younger HFrEF groups (&#36;7,240 vs. &#36;6,760; P=0.351).

Conclusions:The relationship between LVEF and hospitalization costs became more pronounced with age, and LVEF was a negative independent factor for hospitalization costs in the older population.

Background:Various issues, such as gender diversity and overwork, need to be considered in cardiovascular workplaces. Here, we report the results of 2 questionnaire surveys conducted among members of the Chugoku branch of the Japanese Circulation Society.

Methods and Results:The first questionnaire was posted to all 194 female members in 2018. Of the 73 respondents, 61.6% reported feeling that it would be difficult to continue in cardiovascular care. The second questionnaire was completed by participants of the Chugoku Regional Meeting in 2019. Of the 133 respondents, 42.4% reported difficulties continuing in cardiovascular care. Respondents reporting difficulties had a significantly lower mean age, a higher frequency of day and night shifts, and a higher rate of working >80 h/week than respondents who did not report such difficulties. In logistic regression analysis, working >80 h/week was the only independent factor associated with difficulties continuing in cardiovascular care (odds ratio 4.16; 95% confidence interval 1.46–11.9; P=0.008). Although 47.4% of respondents worked >960 h overtime per year (considered a risk factor for death from overwork), 59.6% of these respondents reported being satisfied with their current situation.

Conclusions:In the Chugoku region, the work-life balance of medical personnel engaged in cardiovascular care has not been sufficiently secured. In order to promote diverse human resources, we need to recognize the current situation and continue to take countermeasures.