6 research outputs found
Efficacy of guideline-directed medical treatment in heart failure with mildly reduced ejection fraction.
Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline-directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, Ī²-blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple-drug therapy (TT) and non-triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Of the 906 patients enrolled in the matched cohort (TT group, nĀ =Ā 302; NTT group, NĀ =Ā 604), 653 (72.08%) were male, and mean age was 61.1Ā Ā±Ā 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all-cause mortality (HR 0.656, 95% CI 0.447-0.961, PĀ =Ā 0.030), cardiac death (HR 0.599, 95% CI 0.380-0.946, PĀ =Ā 0.028), any-cause rehospitalization (HR 0.687, 95% CI 0.541-0.872, PĀ =Ā 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565-0.948, PĀ =Ā 0.018). In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF. [Abstract copyright: Ā© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
Efficacy of guidelineādirected medical treatment in heart failure with mildly reduced ejection fraction
Aims: Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guidelineādirected medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, Ī²āblockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. Methods: This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving tripleādrug therapy (TT) and nonātriple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Results: Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 Ā± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of allācause mortality (HR 0.656, 95% CI 0.447ā0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380ā0.946, P = 0.028), anyācause rehospitalization (HR 0.687, 95% CI 0.541ā0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565ā0.948, P = 0.018). Conclusions: In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF
Highly Selective Targeting of Hepatic Stellate Cells for Liver Fibrosis Treatment Using a dāEnantiomeric Peptide Ligand of Fn14 Identified by Mirror-Image mRNA Display
Although
liver fibrosis is a major public health issue, there is
still no effective drug therapy in the clinic. Fibroblast growth factor-inducible
14 (Fn14), a membrane receptor highly specifically expressed in activated
hepatic stellate cells (HSCs), is the key driver of liver fibrosis,
and thus, it has a great potential as a novel target for the development
of effective treatment. Here, we identified a d-enantiomeric
peptide ligand of Fn14 through mirror-image mRNA display. This included
the chemical synthesis of a d-enantiomer of the target protein
(extracellular domain of Fn14), identification of an l-peptide
ligand of d-Fn14 using a constructed mRNA peptide library,
and identification of a d-enantiomer of the l-peptide,
which is a ligand of the natural Fn14 for reasons of symmetry. The
obtained d-peptide ligand showed strong binding to Fn14 while
maintaining high proteolytic resistance. As a targeting moiety, this d-peptide successfully mediated high selectivity of activated
HSCs for liposomal vehicles compared to that of other major cell types
in the liver and significantly enhanced the accumulation of liposomes
in the liver fibrosis region of a carbon tetrachloride-induced mouse
model. Moreover, in combination with curcumin as an encapsulated load,
a liposomal formulation conjugated with this d-peptide showed
powerful inhibition of the proliferation of activated HSCs and reduced
the liver fibrosis to a significant extent in vivo. This Fn14-targeting
strategy may represent a promising approach to targeted drug delivery
for liver fibrosis treatment. Meanwhile, the mirror-image mRNA display
can provide a new arsenal for the development of d-peptide-based
therapeutics against a variety of human diseases
Highly Selective Targeting of Hepatic Stellate Cells for Liver Fibrosis Treatment Using a dāEnantiomeric Peptide Ligand of Fn14 Identified by Mirror-Image mRNA Display
Although
liver fibrosis is a major public health issue, there is
still no effective drug therapy in the clinic. Fibroblast growth factor-inducible
14 (Fn14), a membrane receptor highly specifically expressed in activated
hepatic stellate cells (HSCs), is the key driver of liver fibrosis,
and thus, it has a great potential as a novel target for the development
of effective treatment. Here, we identified a d-enantiomeric
peptide ligand of Fn14 through mirror-image mRNA display. This included
the chemical synthesis of a d-enantiomer of the target protein
(extracellular domain of Fn14), identification of an l-peptide
ligand of d-Fn14 using a constructed mRNA peptide library,
and identification of a d-enantiomer of the l-peptide,
which is a ligand of the natural Fn14 for reasons of symmetry. The
obtained d-peptide ligand showed strong binding to Fn14 while
maintaining high proteolytic resistance. As a targeting moiety, this d-peptide successfully mediated high selectivity of activated
HSCs for liposomal vehicles compared to that of other major cell types
in the liver and significantly enhanced the accumulation of liposomes
in the liver fibrosis region of a carbon tetrachloride-induced mouse
model. Moreover, in combination with curcumin as an encapsulated load,
a liposomal formulation conjugated with this d-peptide showed
powerful inhibition of the proliferation of activated HSCs and reduced
the liver fibrosis to a significant extent in vivo. This Fn14-targeting
strategy may represent a promising approach to targeted drug delivery
for liver fibrosis treatment. Meanwhile, the mirror-image mRNA display
can provide a new arsenal for the development of d-peptide-based
therapeutics against a variety of human diseases