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Decreased serum zinc levels are associated with high mortality, accompanied by impaired exercise capacity.

Sub-hypo might be associated with adverse prognosis, accompanied by impaired exercise capacity and higher pulmonary arterial pressure, in HF patients.

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Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2V617F) mice, as well as recipient mice transplanted with JAK2V617F bone marrow cells. JAK2V617F progressively upregulates Acvrl1 (encoding ALK1) during the differentiation from bone marrow stem/progenitor cells peripherally into mature neutrophils of pulmonary arterial regions. JAK2V617F-mediated STAT3 phosphorylation upregulates ALK1-Smad1/5/8 signaling. ALK1/2 inhibition completely prevents the development of PH in JAK2V617F mice. Finally, our prospective clinical study identified JAK2V617F-positive clonal hematopoiesis is more common in PH patients than in healthy subjects. These findings indicate that clonal hematopoiesis with JAK2V617F causally leads to PH development associated with ALK1 upregulation.

Background The prognostic impact of benzodiazepines has been unclear in patients with heart failure (HF). Methods and Results This was a historical observational cohort study. A total of 826 patients who had been hospitalized for HF and were being treated for insomnia with either benzodiazepines or Z‐drugs (zolpidem, zopiclone, or eszopiclone), were enrolled and divided on the basis of their hypnotics: benzodiazepine group (n=488 [59.1%]) and Z group (n=338 [40.9%]). We compared the patient characteristics and postdischarge prognosis between the groups. The primary end points were rehospitalization for HF and cardiac death. The benzodiazepine group was older (age, 72.0 versus 69.0 years; P =0.010), had a higher prevalence of depression (17.4% versus 8.9%; P <0.001), and showed a higher use of loop diuretics (77.9% versus 67.8%; P =0.001). In the laboratory data, the benzodiazepine group demonstrated lower levels of hemoglobin (12.3 versus 13.0 g/ dL ; P =0.001), sodium (139.0 versus 140.0 mE q/L; P =0.018), and albumin (3.7 versus 3.9 g/ dL ; P =0.003). Kaplan‐Meier analysis showed that both end points were higher in the benzodiazepine group (rehospitalization for HF , log‐rank P =0.001; cardiac death, log‐rank P =0.043). Multiple Cox proportional hazard analysis revealed that the use of benzodiazepines was an independent predictor of rehospitalization for HF (hazard ratio, 1.530; 95% CI, 1.025–2.284; P =0.038). Furthermore, rehospitalization for HF was higher in the benzodiazepine group after propensity score matching (log‐rank P =0.036). Conclusions Benzodiazepine is associated with higher risk of rehospitalization for HF compared with Z‐drugs in patients with HF .

Background: Sleep-disordered breathing (SDB) and blood pressure variability (BPV) are strongly associated with cardiovascular diseases. Recently, pulse transit time (PTT) has enabled the monitoring of beat-to-beat BP; however, little is known about its clinical utility. The present study aimed to clarify the impact of SDB on very short-term BPV determined by PTT-based BP monitoring (PTT-BP). Methods: We analyzed 242 patients with suspected SDB. PTT-BP was continuously recorded overnight together with a portable sleep monitor. PTT index was defined as the average number of transient rises in PTT-BP (≥12 mmHg) within 30 s/h. We compared PTT-BP values with each SDB parameter, and examined the association between BPV and subclinical organ damage. Results: Standard deviation (SD) of systolic, mean or diastolic PTT-BP, which indicates very short-term BPV, was significantly correlated with apnea--hypopnea index (AHI) and oxygen desaturation index (ODI). PTT index was positively associated with AHI, ODI, and minimal SpO2. Regression analyses showed that AHI and ODI were significant variables to determine systolic, mean, or diastolic PTT-BP SD and PTT index. Logistic regression analyses demonstrated that diastolic PTT-BP SD significantly influenced the presence of chronic kidney disease and left ventricular hypertrophy. Conclusion: SDB severity was closely associated with very short-term BP variability, and diastolic PTT-BP SD might be an important factor linked to subclinical organ damage. PTT-BP measurement may be useful to evaluate very short-term BPV during the night.

Background: It has been reported that the pattern of hepatic vein (HV) waveforms determined by abdominal ultrasonography is useful for the diagnosis of hepatic fibrosis in patients with chronic liver disease. We aim to clarify the clinical implications of HV waveform patterns in patients with heart failure (HF). Methods: We measured HV waveforms in 350 HF patients, who were then classified into 3 categories based on their waveforms: those with a continuous pattern (C group); those whose V wave ran under the R ESUM E