Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry.

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection. OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)]. METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF ≤ 57% (i.e. median). We defined reduced EF/PARADIGM-HF as EF < 40%, mildly reduced EF/PARAGON-HF ≤ median as EF 40-49%, and normal EF/PARAGON-HF > median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario). RESULTS: Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes. CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered.

Amino acid ferrocene conjugates using sulfonamide linkages.

This report presents the synthesis and characterization of mono- and bis(amino acid ester) ferrocene complexes generated using a sulfonamide linking strategy as an alternative to the more heavily explored amide linking strategy. These compounds were investigated to test their ability to form hydrogen bonding interactions both in the solid state and in solution, and were compared to the previously observed intramolecular interstrand crosslinking seen in amide-linked ferrocene constructs. Synthesized compounds also included controls that do not exhibit sulfonamide N-H bonds and thus cannot engage in hydrogen bonding. In the solid state, we observe both S=O⋯H-N and C=O⋯H-N intermolecular interactions, but we do not observe any intramolecular interstrand hydrogen bonding. In the solution phase, we also do not see any intramolecular hydrogen bonding interactions in these compounds as measured by titration of d6-DMSO as a competitive hydrogen bonding reagent. We also collected CD spectra on these compounds, which revealed that the chiral peptides can induce dichroism in the dd transition of the ferrocene units. Our results indicate that the peptide-ferrocene linking group governs whether intermolecular hydrogen bonding interactions can occur between the amino acids adjacent to the cyclopentadienyl groups.

The predictive value of different equations for estimation of glomerular filtration rate in patients with coronary artery disease - Results from the AtheroGene study.

BACKGROUND: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients. METHODS: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years. RESULTS: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23. CONCLUSION: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD.