Phthalate exposure is associated with cardiovascular risk. Among the various phthalates, di-(2-ethylhexyl) phthalate (DEHP) is a deleterious plasticizer in our daily lives. This study investigated the association between DEHP exposure and the alteration of heart rate variability (HRV). During 2017–2019, we recruited 974 young adults to investigate the effects of living environments and dietary habits on cardiometabolic disorders in Taiwan. We quantitatively analyzed urinary metabolites of DHEP. A continuous electrocardiogram was recorded to obtain a 5-min ECG. Time-domain and frequency-domain HRV analyses were performed. Multiple linear regression showed that urinary oxidized DEHP metabolites MEHHP and MEOHP were associated with decreased HRV after controlling for associated cardiovascular risk factors. A higher MEHHP level was associated with a lower triangular interpolation of NN interval histogram (TINN), very low frequency (VLF), and low frequency/high frequency (LF/HF) ratio. A higher MEOHP level was associated with a decreased LF/HF ratio. In addition, trend analysis showed that higher MEHHP and MEOHP quantiles were significantly associated with a decreased LF/HF ratio. DEHP is a potentially harmful and invisible chemical. The urinary DEHP metabolites MEHHP and MEOHP are associated with decreased HRV, indicating an adverse effect on autonomic balance in young adults in Taiwan.

Objective To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. Materials and Methods A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm 2 (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). Results The number, area, and density of the subpleural small vessels increased after treatment by 35.7% ( P < 0.001), 13.3% ( P = 0.028), and 39.3% ( P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio ( P = 0.042). The BV5/TBV ratio was negatively correlated with PVR ( r = -0.26; P = 0.035) and positively correlated with CI ( r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP ( r = -0.56; P = 0.001), PVR ( r = -0.64; P < 0.001), and CI ( r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I–IV ( P = 0.004) and positively associated with 6MWD ( P = 0.013). Conclusion Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Pulmonary hypertension (PH) is a fatal disease even under state-of-the-art medical treatment. Non-invasive clinical tools for risk stratification are still lacking. The aim of this study was to investigate the clinical utility of heart rhythm complexity in risk stratification for PH patients. We prospectively enrolled 54 PH patients, including 20 high-risk patients (group A; defined as WHO functional class IV or class III with severely compromised hemodynamics), and 34 low-risk patients (group B). Both linear and non-linear heart rate variability (HRV) variables, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE) were analyzed. In linear and non-linear HRV analysis, low frequency and high frequency ratio, DFAα1, MSE slope 5, scale 5 and area 6–20 were significantly lower in group A. Among all HRV variables, MSE scale 5 (AUC: 0.758) had the best predictive power to discriminate the two groups. In multivariable analysis, MSE scale 5 (p = 0.010) was the only significantly predictor of severe PH in all HRV variables. In conclusion, the patients with severe PH had worse heart rhythm complexity. MSE parameters, especially scale 5, can help to identify high-risk PH patients.