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Background: Heart failure with mid-range ejection fraction (HFmrEF) has been proposed as a new phenotype of heart failure. We therefore investigated the pulsatile hemodynamic characteristics and outcomes in patients with HFmrEF, in comparison with those with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Methods: The study was composed of two cohorts of patients hospitalized due to acute heart failure. Pulsatile hemodynamic measures, including carotid-femoral pulse wave velocity (cf-PWV), carotid pulse pressure (cPP), amplitude of the backward pressure wave (Pb) and carotid augmentation index (cAIx), were recorded on admission and before discharge in Cohort A (n = 230, mean age 69.9 ±15.4 years), and long-term follow-up was performed in Cohort B (n = 2677, mean age 76.3 ± 33.4 years). Results: In Cohort A, patients with HFmrEF had persistently greater cf-PWV, cPP, Pb, and cAI than those with HFrEF, both on admission and before discharge. In contrast, patients with HFmrEF and HFpEF had similar pulsatile hemodynamic characteristics. In cohort B, patients with HFmrEF and HFrEF had similar three-year mortality rates and both were significantly higher than that in patients with HFpEF (both P values < 0.05). Conclusions: Patients with HFmrEF were characterized by a worse left ventricular systolic function than patients with HFpEF and excessive wave reflections than patients with HFrEF. Future studies are required to confirm that the unfavorable ventriculo-arterial coupling in HFmrEF might play a role in the pathogenesis of high long-term mortality in these patients. [ABSTRACT FROM AUTHOR]

Objective: The hepatitis B virus (HBV)-polymerase region overlaps pre-S/S genes with high epitope density and plays an essential role in viral replication. We investigated whether genetic variation in the polymerase region determined long-term dynamics of viral load and the risk of hepatitis B progression in a population-based cohort study. Methods: We sequenced the HBV-polymerase region using baseline plasma from treatment-naïve individuals with HBV-DNA levels≥1000 copies/mL in a longitudinal viral-load study of participants with chronic HBV infection followed-up for 17 years, and obtained sequences from 575 participants (80% with HBV genotype Ba and 17% with Ce). Results: Patterns of viral sequence diversity across phases (i.e., immune-tolerant, immune-clearance, non/low replicative, and hepatitis B e antigen (HBeAg)-negative hepatitis phases) of HBV-infection, which were associated with viral and clinical features at baseline and during follow-up, were similar between HBV genotypes, despite greater diversity for genotype Ce vs. Ba. Irrespective of genotypes, however, HBeAg-negative participants had 1.5-to-2-fold higher levels of sequence diversity than HBeAg-positive participants (P<0.0001). Furthermore, levels of viral genetic divergence from the population consensus sequence, estimated by numbers of nucleotide substitutions, were inversely associated with long-term viral load even in HBeAg-negative participants. A mixed model developed through analysis of the entire HBV-polymerase region identified 153 viral load-associated single nucleotide polymorphisms in overall and 136 in HBeAg-negative participants, with distinct profiles between HBV genotypes. These polymorphisms were most evident at sites within or flanking T-cell epitopes. Seven polymorphisms revealed associations with both enhanced viral load and a more than 4-fold increased risk of hepatocellular carcinoma and/or liver cirrhosis. Conclusions: The data highlight a role of viral genetic divergence in the natural course of HBV-infection. Interindividual differences in the long-term dynamics of viral load is not only associated with accumulation of mutations in HBV-polymerase region, but differences in specific viral polymorphisms which differ between genotypes. [ABSTRACT FROM AUTHOR]