DASH-HF Study: A Pragmatic Quality Improvement Randomized Implementation Trial for Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure is a prevailing diagnosis of hospitalization and readmission within 6 months, and nearly a quarter of these patients die within a year. Guideline-directed medication therapies reduce risk of mortality by 73% over 2 years; however, the implementation of these therapies to their target dose in clinical practice continues to be challenging. In 2020, the Veterans Affairs (VA) Health Care System developed a HF dashboard to monitor and improve outpatient HF management. The DASH-HF (Dashboard Activated Services and Telehealth for Heart Failure) study is a randomized, pragmatic clinical trial to evaluate proactive dashboard-directed telehealth clinics to improve the use and dosing of guideline-directed medication therapy for patients with heart failure with reduced ejection fraction not on optimal guideline-directed medication therapy within the VA. METHODS: Three hundred veterans with heart failure with reduced ejection fraction met inclusion criteria with an optimization potential score (OPS) of 5 or less out of 10, representing nonoptimal guideline-directed medication therapy. The primary outcome was a composite score of guideline-directed medical therapy, the OPS, 6 months after the end of the intervention. Secondary outcomes included active prescriptions for each individual guideline-directed medical therapy class, HF-related hospitalizations, deaths, and clinician time per patient during the intervention clinics. RESULTS: There was no significant difference between the intervention arm and usual care group in the primary outcome (OPS, 2.9; SD=2.1 versus OPS, 2.6, SD=2.1); adjusted mean difference 0.3 (95% CI, -0.1 to 0.7) or in the prespecified secondary outcomes for hospitalization and all-cause mortality for the intervention of proactive dashboard-based clinics. CONCLUSIONS: A dashboard-based clinic intervention did not improve the OPS or secondary outcomes of hospitalization and all-cause mortality. There remains a larger opportunity to better target patients and provide more intensive follow-up to further evaluate the utility of proactive dashboard-based clinics for HF management and quality improvement. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05001165.

The design of the Dashboard Activated Services and Telehealth for Heart Failure (DASH-HF) study: A pragmatic quality improvement randomized implementation trial for patients with heart failure with reduced ejection fraction.

BACKGROUND: Gaps in the receipt and dosing of guideline-directed medical therapy (GDMT) persist for patients with heart failure with reduced ejection fraction (HFrEF) [1]. In 2020, the Veterans Affairs (VA) developed a heart failure (HF) specific population dashboard to monitor care quality and performance on standard HFrEF performance measures [2]. METHODS: The Dashboard Activated Services and Telehealth for HF (DASH-HF) study is a pragmatic randomized quality improvement study designed to evaluate the utility of proactive population management clinics using the VA's HF dashboard to optimize GDMT for patients with HFrEF. Panel management telemedicine clinics incorporated multidisciplinary clinicians to perform chart review and impromptu telephone encounters to evaluate current HFrEF management and opportunities to optimize GDMT. The study will evaluate the efficacy of proactive panel management to usual care at 6 months as quantified by the GDMT optimization potential score. Secondary outcomes include hospitalizations, mortality, and clinician time per intervention. The study completed enrollment and randomization of 300 participants. The intervention was performed from September to December 2021. CONCLUSION: DASH-HF will contribute to the literature by evaluating use of the existing VA dashboard to identify HF patients with the lowest adherence to GDMT and proactively target this group for the intervention. REGISTRATION: https://clinicaltrials.gov/. Unique identifier: NCT05001165.

Conformational changes of trialanine induced by direct interactions between alanine residues and alcohols in binary mixtures of water with glycerol and ethanol.

Despite the increasing relevance of characterizing local conformational distributions in the unfolded state, an unambiguous description of the role that solvation and the addition of certain cosolvents play in altering this ensemble has yet to emerge. Alcohol cosolvents, and specifically glycerol, are known to act as protein stabilizers. The underlying mechanism of this effect is, however, still debated. Short alanine-based peptides provide a suitable model system for exploring the influence of cosolvents on backbone conformations, as ample experimental evidence now indicates that alanine does not exhibit a true statistical coil behavior but rather shows strong preference for sampling the polyproline II (PPII) region of the Ramachadran map when solvated in water. To explore the effect glycerol and ethanol cosolvents have on the conformational distribution of trialanine, we combined UV-CD and H NMR spectroscopies. The temperature dependence of the conformationally sensitive maximum dichroism (Δε) and (3)J(H(α)H(N)) coupling constants of two amide protons (N- and C-terminal) was subjected to a global thermodynamic analysis based on simple two-state PPIIâ†”ß models. Interestingly, our results show that even small admixtures of alcohol (5% v/v) considerably change the spectral parameters, Δε(PPII) and Δε(ß), as well as the enthalpic and entropic differences between the two states. For the central residue of trialanine in 5% glycerol, we obtained a gain in enthalpy favoring PPII of ΔΔH(n) = -4.80 kJ/mol and a compensating increase in entropy favoring the ß-strand of ΔΔS(n) = -13.53[J/mol K]. This causes increases in -ΔG and slight increases in PPII content. Further addition of alcohol, however, reverses the trend in that it causes a destabilization of the hydration shell and a shift toward ß-strand conformations. The combined manifold of ΔH and ΔS values obtained for the investigated binary mixtures and the pure aqueous solvent exhibits an excellent linear correlation, which reflects enthalpy-entropy compensation and a common transition temperature. The latter can be considered an indication of a weak binding between cosolvent and peptide. A comparison of infrared and Raman spectra of trialanine in water and in water-alcohol mixtures indeed reveals a close proximity between aliphatic side chains of alanine residues and alcohol molecules even for 5% (v/v) alcohol-water mixtures. Hence, our results provide the first experimental evidence for direct interactions between, e.g., glycerol and peptides in aqueous solutions, in line with the result of recent calculations by Vagenende et al. (Biochemistry 2009, 48, 11084-11096) but at variance with preferential exclusion theories.