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.

Remote Optimization of Guideline-Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction.

Importance: Optimal treatment of heart failure with reduced ejection fraction (HFrEF) is scripted by treatment guidelines, but many eligible patients do not receive guideline-directed medical therapy (GDMT) in clinical practice. Objective: To determine whether a remote, algorithm-driven, navigator-administered medication optimization program could enhance implementation of GDMT in HFrEF. Design, Setting, and Participants: In this case-control study, a population-based sample of patients with HFrEF was offered participation in a quality improvement program directed at GDMT optimization. Treating clinicians in a tertiary academic medical center who were caring for patients with heart failure and an ejection fraction of 40% or less (identified through an electronic health record-based search) were approached for permission to adjust medical therapy according to a sequential titration algorithm modeled on the current American College of Cardiology/American Heart Association heart failure guidelines. Navigators contacted participants by telephone to direct medication adjustment and conduct longitudinal surveillance of laboratory tests, blood pressure, and symptoms under supervision of a pharmacist, nurse practitioner, and heart failure cardiologist. Patients and clinicians declining to participate served as a control group. Exposures: Navigator-led remote optimization of GDMT compared with usual care. Main Outcomes and Measures: Proportion of patients receiving GDMT in the intervention and control groups at 3 months. Results: Of 1028 eligible patients (mean [SD] values: age, 68 [14] years; ejection fraction, 32% [8%]; and systolic blood pressure, 122 [18] mm Hg; 305 women (30.0%); 892 individuals [86.8%] in New York Heart Association class I and II), 197 (19.2%) participated in the medication optimization program, and 831 (80.8%) continued with usual care as directed by their treating clinicians (585 [56.9%] general cardiologists; 443 [43.1%] heart failure specialists). At 3 months, patients participating in the remote intervention experienced significant increases from baseline in use of renin-angiotensin system antagonists (138 [70.1%] to 170 [86.3%]; P < .001) and ß-blockers (152 [77.2%] to 181 [91.9%]; P < .001) but not mineralocorticoid receptor antagonists (51 [25.9%] to 60 [30.5%]; P = .14). Doses for each category of GDMT also increased from baseline in the intervention group. Among the usual-care group, there were no changes from baseline in the proportion of patients receiving GDMT or the dose of GDMT in any category. Conclusions and Relevance: Remote titration of GDMT by navigators using encoded algorithms may represent an efficient, population-level strategy for rapidly closing the gap between guidelines and clinical practice in patients with HFrEF.

The NMDAR modulator NYX-2925 alleviates neuropathic pain via a Src-dependent mechanism in the mPFC.

Previous studies have shown that oral administration of the NMDAR modulator NYX-2925 alleviates pain in several animal models of neuropathic pain and this appears to be through mPFC, but not spinal, mediated mechanisms. While much is known about the impact of neuropathic pain on NMDAR-mediated signaling in the spinal cord, limited studies have focused on the brain. In the current study, we assess signaling changes associated with NMDAR-mediated plasticity in the mPFC and the impact of NYX-2925 administration on the normalization of these signaling changes. We found a decrease in activated Src levels in the mPFC of animals with chronic constriction injury (CCI) of the sciatic nerve. While Src mediated activation of NMDARs was also decreased in CCI animals, the main NMDAR phosphorylation site of CAMKII was not affected. This is in opposition to what has been found in the spinal cord, where both Src and CAMKII activation are increased. Oral administration of NYX-2925 restored levels of activated Src and Src phosphorylation sites on GluN2A and GluN2B in the mPFC, with no effect on activated CAMKII levels. The analgesic effect of NYX-2925 appears dependent on this restoration of Src activation in the mPFC, as co-administering Src activation inhibitors prevented the NYX-2925 analgesic effect. Overall, these data suggest that NMDAR-mediated signaling plays a key role in neuropathic pain, albeit in different directions in the spinal cord vs. the mPFC. Furthermore, the analgesic effect of NYX-2925 appears to involve a restoration of NMDAR-mediated signaling in the mPFC.

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.

Development of an entirely remote, non-physician led hypertension management program.

BACKGROUND: Hypertension remains poorly controlled on the population level. National rates of control, even when defined leniently by BP < 140/90 mm Hg, are only ~50%. As growing healthcare costs coincide with tighter blood pressure (BP) targets, innovative management programs are needed to maximize efficiency of care delivery and optimize control. HYPOTHESIS: We aimed to develop a remote, navigator-led hypertension innovation program that would leverage algorithmic care pathways, home BP measurements and patient coaching to allow rapid and complete medication titration. METHODS: A multidisciplinary group of clinical experts from subspecialties and primary care collaborated to develop an evidence-based clinical algorithm, designed to be automated and administered by non-licensed patient navigators. In the development stage, a prospective pilot cohort of 130 patients was managed by nurse practitioners and pharmacists to ensure efficacy and safety. Patients with clinic BP ≥ 140/90 mm Hg were enrolled and given a Bluetooth-enabled BP device. Home BPs were transmitted automatically into the electronic medical record. Medication titrations were performed by phone at biweekly intervals, based upon weekly average BP, until home BP was controlled at <135/85 mm Hg. RESULTS: Eighty-one percent of all enrolled, and 91% of those patients who regularly measured home BP achieved goal, in an average of 7 weeks. Control was reached similarly across races, genders, and ages. CONCLUSIONS: A home-based BP control program run by non-physicians can provide efficient, effective and rapid control, suggesting an innovative paradigm for hypertension management. This program is effective, sustainable, adaptable, and scalable to fit current and emerging national systems of healthcare.

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.