Malnutrition in heart failure with preserved ejection fraction.

BACKGROUND: Malnutrition may be an important geriatric condition in adults with heart failure with preserved ejection fraction (HFpEF), but studies on its prevalence and associated clinical outcomes are limited. The aim of this study was to determine if malnutrition is associated with short-term morbidity and mortality in ambulatory patients with HFpEF. METHODS: We examined 231 patients with a clinical diagnosis of HFpEF seen at two dedicated academic HFpEF programs (Weill Cornell Medicine and Michigan Medicine) from June 2018 to April 2022. Malnutrition was defined by Mini-Nutritional Assessment Short Form (MNA-SF) scores ≤11. The primary endpoint was a 6-month composite of all-cause mortality and all-cause hospitalization. A Cox proportional-hazard models was used to examine the association between malnutrition and the primary endpoint, adjusting for race, prior hospitalization history, and the validated Meta-Analysis Global Group in Chronic (MAGGIC) heart failure prognostic risk score. RESULTS: The median age of the cohort was 73 years (interquartile range 64-81). The most common comorbid conditions included hypertension (prevalence 81%), atrial fibrillation (43%), and obesity (63%). The prevalence of malnutrition was 42% (n = 97), and MNA-SF scores did not significantly correlate with body mass index (R = -0.02, p = 0.71). At the 6-month follow-up, 62 patients (26.8%) were hospitalized and four patients died (1.7%). In a fully-adjusted analysis, malnutrition was independently associated with the composite outcome of all-cause mortality and all-cause hospitalization (HR 1.94 [95% CI: 1.17-3.20], p = 0.01). CONCLUSION: Despite a high prevalence of obesity, two out of five ambulatory adults with HFpEF are malnourished. Malnutrition was independently associated with adverse outcomes at 6 months. Future work is necessary to develop interventions that can address malnutrition.

Geriatric Domains in Patients with Heart Failure with Preserved Ejection Fraction.

Because heart failure with preserved ejection fraction (HFpEF) is closely linked to aging processes and disproportionately affects older adults, consideration of geriatric domains is paramount to ensure high-quality care to older adults with HFpEF. Multimorbidity, polypharmacy, cognitive impairment, depressive symptoms, frailty, falls, and social isolation each have important implications on quality of life and clinical events including hospitalization and mortality. There are multiple strategies to screen for these conditions. This narrative review underscores the importance of screening for multiple geriatric conditions, integrating these conditions into decision making, and addressing these conditions when caring for older adults with HFpEF.

Imaging Utilization and Outcomes in Vulnerable Populations during COVID-19 in New York City.

BACKGROUND: Coronavirus disease 2019 (COVID-19) affects vulnerable populations (VP) adversely. PURPOSE: To evaluate overall imaging utilization in vulnerable subgroups (elderly, racial/ethnic minorities, socioeconomic status [SES] disadvantage) and determine if a particular subgroup has worse outcomes from COVID-19. MATERIALS/METHODS: Of 4110 patients who underwent COVID-19 testing from March 3-April 4, 2020 at NewYork-Presbyterian Hospital (NYP) health system, we included 1121 COVID-19 positive adults (mean age 59±18 years, 59% male) from two academic hospitals and evaluated imaging utilization rates and outcomes, including mortality. RESULTS: Of 897 (80%) VP, there were 465 (41%) elderly, 380 (34%) racial/ethnic minorities, and 479 (43%) SES disadvantage patients. Imaging was performed in 88% of patients and mostly portable/bedside studies, with 87% of patients receiving chest radiographs. There were 83% hospital admissions, 25% ICU admissions, 23% intubations, and 13% deaths. Elderly patients had greater imaging utilization, hospitalizations, ICU/intubation requirement, longer hospital stays, and >4-fold increase in mortality compared to non-elderlies (adjusted hazard ratio[aHR] 4.79, p<0.001). Self-reported minorities had fewer ICU admissions (p=0.03) and reduced hazard for mortality (aHR 0.53, p=0.004; complete case analysis: aHR 0.39, p<0.001 excluding "not reported"; sensitivity analysis: aHR 0.61, p=0.005 "not reported" classified as minorities) with similar imaging utilization, compared to non-minorities. SES disadvantage patients had similar imaging utilization and outcomes as compared to their counterparts. CONCLUSIONS: In a predominantly hospitalized New York City cohort, elderly patients are at highest mortality risk. Racial/ethnic minorities and SES disadvantage patients fare better or similarly to their counterparts, highlighting the critical role of access to inpatient medical care during the COVID-19 pandemic.

Caged Cyclopropenes with Improved Tetrazine Ligation Kinetics.

Activatable cyclopropenes are unreactive toward their inverse electron demand Diels-Alder reaction partner (e.g., s-tetrazines) until they are activated. The activation strategy is highly modular due to the cyclopropene's ability to be caged by various light- and enzyme-activatable groups. This work describes the next generation of activatable cyclopropenes with a new core scaffold that maintains the activation modularity of the first generation but improves upon the ligation kinetics with s-tetrazines by ≤270-fold.

Lipidated cyclopropenes via a stable 3-N spirocyclopropene scaffold.

Lipidated cyclopropenes serve as useful bioorthogonal reagents for imaging cell membranes due to the cyclopropene's small size and ability to ligate with pro-fluorescent tetrazines. Previously, the lipidation of cyclopropenes required modification at the C3 position because methods to append lipids at C1/C2 were not available. Herein, we describe C1/C2 lipidation with the biologically active lipid ceramide and a common phospholipid using a cyclopropene scaffold whose reactivity with 1,2,4,5-tetrazines has been caged.

Caged cyclopropenes for controlling bioorthogonal reactivity.

Bioorthogonal ligations have been designed and optimized to provide new experimental avenues for understanding biological systems. Generally, these optimizations have focused on improving reaction rates and orthogonality to both biology and other members of the bioorthogonal reaction repertoire. Less well explored are reactions that permit control of bioorthogonal reactivity in space and time. Here we describe a strategy that enables modular control of the cyclopropene-tetrazine ligation. We developed 3-N-substituted spirocyclopropenes that are designed to be unreactive towards 1,2,4,5-tetrazines when bulky N-protecting groups sterically prohibit the tetrazine's approach, and reactive once the groups are removed. We describe the synthesis of 3-N spirocyclopropenes with an appended electron withdrawing group to promote stability. Modification of the cyclopropene 3-N with a bulky, light-cleavable caging group was effective at stifling its reaction with tetrazine, and the caged cyclopropene was resistant to reaction with biological nucleophiles. As expected, upon removal of the light-labile group, the 3-N cyclopropene reacted with tetrazine to form the expected ligation product both in solution and on a tetrazine-modified protein. This reactivity caging strategy leverages the popular carbamate protecting group linkage, enabling the use of diverse caging groups to tailor the reaction's activation modality for specific applications.

Inexpensive multigram-scale synthesis of cyclic enamines and 3-N spirocyclopropyl systems.

Cyclic enamines are important synthons for many synthetic and pharmacological targets. Here, we report an inexpensive, catalyst-free, multigram-scale synthesis for cyclic enamines with exocyclic double bonds and four- to seven-membered rings. This strategy is more conducive to scale up, permissive of functionalization around the cyclic system, and less sensitive to the nature of the N-protecting group than previously-described methods for cyclic enamine synthesis. Further, we explore application of these enamines to the synthesis of highly-strained spirocyclic 3N-cyclopropyl scaffolds.