Evaluation of the Usage and Dosing of Guideline-Directed Medical Therapy for Heart Failure With Reduced Ejection Fraction Patients in Clinical Practice.

BACKGROUND: Although strategies for optimization of pharmacologic therapy in patients with heart failure with reduced ejection fraction (HFrEF) are scripted by guidelines, data from HF registries suggests that guideline-directed medical therapies (GDMT) are underutilized among eligible patients. Whether this discrepancy reflects medication intolerance, contraindications, or a quality of care issue remains unclear. OBJECTIVE: The objective of this initiative was to identify reasons for underutilization and under-dosing of HFrEF therapy in patients at a large, academic medical center. METHODS: Among 500 patients with HFrEF enrolled in a quality improvement project at a tertiary center, we evaluated usage and dosing of 4 categories of GDMT: ACE inhibitors/Angiotensin Receptor Blockers (ACE-i/ARB), Angiotensin Receptor-Neprilysin Inhibitors (ARNi), beta blockers, and Mineralocorticoid Receptor Antagonists (MRA). Reasons for nonprescription and usage of suboptimal doses were abstracted from notes in the chart and from telephone review of previous medication trials with the patient. RESULTS: Of 500 patients identified, 472 subjects had complete data for analysis. Among eligible patients, ACE-i/ARB were prescribed in 81.4% (293 of 360) and beta blockers in 94.4% (442 of 468). Of these patients, 10.6% were prescribed target doses of ACE-i/ARB and 12.4% were prescribed target doses of beta blockers. Utilization of other categories of GDMT was lower, with 54% of eligible patients prescribed MRAs and 27% prescribed an ARNi. In most cases, the reasons for nonprescription or under-dosing of GDMT were not apparent on review of the health record or discussion with the patient. CONCLUSION: Clear rationale for nonprescription and under-dosing of GDMT often cannot be ascertained from detailed review and is only rarely related to documented medication intolerance or contraindications, suggesting an opportunity for quality improvement.

The VitMin Lab Sandwich-ELISA Assays for Iron and Inflammation Markers Compared Well with Clinical Analyzer Reference-Type Assays in Subsamples of the Nepal National Micronutrient Status Survey.

BACKGROUND: The low cost and small specimen volume of the VitMin Lab ELISA assays for serum ferritin (Fer), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) have allowed their application to micronutrient surveys conducted in low-resource countries for ∼2 decades. OBJECTIVES: We conducted a comparison between the ELISA and reference-type assays used in the US NHANES. METHODS: Using the Roche clinical analyzer as a reference, we measured random subsets of the 2016 Nepal National Micronutrient Status Survey (200 serum samples from children aged 6-59 mo; 100 serum samples from nonpregnant women) for Fer, sTfR, CRP, and AGP. We compared the combined data sets with the ELISA survey results using descriptive analyses. RESULTS: The Lin's concordance coefficients between the 2 assays were ≥0.89 except for sTfR (Lin's ρ = 0.58). The median relative difference to the reference was as follows: Fer, -8.5%; sTfR, 71.2%; CRP, -19.5%; and AGP, -8.2%. The percentage of VitMin samples agreeing within ±30% of the reference was as follows: Fer, 88.5%; sTfR, 1.70%; CRP, 74.9%; and AGP, 92.9%. The prevalence of abnormal results was comparable between the 2 assays for Fer, CRP, and AGP, and for sTfR after adjusting to the Roche assay. Continued biannual performance (2007-2019) of the VitMin assays in CDC's external quality assessment program (6 samples/y) demonstrated generally acceptable performance. CONCLUSIONS: Using samples from the Nepal survey, the VitMin ELISA assays produced mostly comparable results to the Roche reference-type assays for Fer, CRP, and AGP. The lack of sTfR assay standardization to a common reference material explains the large systematic difference observed for sTfR, which could be corrected by an adjustment equation pending further validation. This snapshot comparison together with the long-term external quality assessment links the survey data generated by the VitMin Lab to the Roche assays used in NHANES.

Rationale and design of a navigator-driven remote optimization of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

Although optimal pharmacological therapy for heart failure with reduced ejection fraction (HFrEF) is carefully scripted by treatment guidelines, many eligible patients are not treated with guideline-directed medical therapy (GDMT) in clinical practice. We designed a strategy for remote optimization of GDMT on a population scale in patients with HFrEF leveraging nonphysician providers. An electronic health record-based algorithm was used to identify a cohort of patients with a diagnosis of heart failure (HF) and ejection fraction (EF) ≤ 40% receiving longitudinal follow-up at our center. Those with end-stage HF requiring inotropic support, mechanical circulatory support, or transplantation and those enrolled in hospice or palliative care were excluded. Treating providers were approached for consent to adjust medical therapy according to a sequential, stepped titration algorithm modeled on the current American College of Cardiology (ACC)/American Heart Association (AHA) HF Guidelines within a collaborative care agreement. The program was approved by the institutional review board at Brigham and Women's Hospital with a waiver of written informed consent. All patients provided verbal consent to participate. A navigator then facilitated medication adjustments by telephone and conducted longitudinal surveillance of laboratories, blood pressure, and symptoms. Each titration step was reviewed by a pharmacist with supervision as needed from a nurse practitioner and HF cardiologist. Patients were discharged from the program to their primary cardiologist after achievement of an optimal or maximally tolerated regimen. A navigator-led remote management strategy for optimization of GDMT may represent a scalable population-level strategy for closing the gap between guidelines and clinical practice in patients with HFrEF.

Phenotyping to Facilitate Accrual for a Cardiovascular Intervention.

BACKGROUND: The conventional approach for clinical studies is to identify a cohort of potentially eligible patients and then screen for enrollment. In an effort to reduce the cost and manual effort involved in the screening process, several studies have leveraged electronic health records (EHR) to refine cohorts to better match the eligibility criteria, which is referred to as phenotyping. We extend this approach to dynamically identify a cohort by repeating phenotyping in alternation with manual screening. METHODS: Our approach consists of multiple screen cycles. At the start of each cycle, the phenotyping algorithm is used to identify eligible patients from the EHR, creating an ordered list such that patients that are most likely eligible are listed first. This list is then manually screened, and the results are analyzed to improve the phenotyping for the next cycle. We describe the preliminary results and challenges in the implementation of this approach for an intervention study on heart failure. RESULTS: A total of 1,022 patients were screened, with 223 (23%) of patients being found eligible for enrollment into the intervention study. The iterative approach improved the phenotyping in each screening cycle. Without an iterative approach, the positive screening rate (PSR) was expected to dip below the 20% measured in the first cycle; however, the cyclical approach increased the PSR to 23%. CONCLUSIONS: Our study demonstrates that dynamic phenotyping can facilitate recruitment for prospective clinical study. Future directions include improved informatics infrastructure and governance policies to enable real-time updates to research repositories, tooling for EHR annotation, and methodologies to reduce human annotation.

Extraction of Ejection Fraction from Echocardiography Notes for Constructing a Cohort of Patients having Heart Failure with reduced Ejection Fraction (HFrEF).

Left ventricular ejection fraction (LVEF) is an important prognostic indicator of cardiovascular outcomes. It is used clinically to determine the indication for several therapeutic interventions. LVEF is most commonly derived using in-line tools and some manual assessment by cardiologists from standardized echocardiographic views. LVEF is typically documented in free-text reports, and variation in LVEF documentation pose a challenge for the extraction and utilization of LVEF in computer-based clinical workflows. To address this problem, we developed a computerized algorithm to extract LVEF from echocardiography reports for the identification of patients having heart failure with reduced ejection fraction (HFrEF) for therapeutic intervention at a large healthcare system. We processed echocardiogram reports for 57,158 patients with coded diagnosis of Heart Failure that visited the healthcare system over a two-year period. Our algorithm identified a total of 3910 patients with reduced ejection fraction. Of the 46,634 echocardiography reports processed, 97% included a mention of LVEF. Of these reports, 85% contained numerical ejection fraction values, 9% contained ranges, and the remaining 6% contained qualitative descriptions. Overall, 18% of extracted numerical LVEFs were ≤ 40%. Furthermore, manual validation for a sample of 339 reports yielded an accuracy of 1.0. Our study demonstrates that a regular expression-based approach can accurately extract LVEF from echocardiograms, and is useful for delineating heart-failure patients with reduced ejection fraction.

An unlikely DNA cleaving agent: A photo-active trinuclear Cu(II) complex based on hexaazatriphenylene.

This paper describes the synthesis of a trinuclear Cu(II) complex (4) containing a central 1,4,5,8,9,12-hexaazatriphenylene-hexacarboxylate (hat) core (3). Low, micromolar concentrations of the negatively charged parent ligand 3 and the neutral trinuclear complex 4 were found to photocleave negatively charged pUC19 plasmid DNA with high efficiency at neutral pH (350nm, 50min, 22°C). The interactions of complex 4 with double-helical DNA were studied in detail. Scavenger and colorimetric assays pointed to the formation of Cu(I), superoxide anion radicals, hydrogen peroxide, and hydroxyl radicals during photocleavage reactions. UV-visible absorption, circular dichroism, DNA thermal denaturation, and fluorescence data suggested that the Cu(II) complex contacts double-stranded DNA in an external fashion. The persistent association of ligand 3 and complex 4 with Na(I) and/or other cations in aqueous solution might facilitate electrostatic DNA interactions.