Palliative Care for Patients With Heart Failure: Results From a Heart Failure Society of America Survey.

BACKGROUND: Multiple guidelines recommend specialty palliative care (PC) for patients with heart failure (HF), including patients with left ventricular assist devices (LVADs). However, the degree of integration and clinicians' perceptions of PC in HF care remain incompletely characterized. METHODS AND RESULTS: A 36-item survey was sent to 2109 members of the Heart Failure Society of America. Eighty respondents (53% physicians), including 51 respondents from at least 42 medical centers, completed the survey, with the majority practicing in urban (76%) academic medical centers (62%) that implanted LVADs (81%). Among the 42 unique medical centers identified, respondents reported both independent (40%) and integrated (40%) outpatient PC clinic models, whereas 12% reported not having outpatient PC at their institutions. A minority (12%) reported that their institution used triggered PC referrals based on objective clinical data. Of respondents from LVAD sites, the majority reported that a clinician from the PC team was required to see all patients prior to implantation, but there was variability in practices. Among all respondents, the most common reasons for PC referral in HF were poor prognosis, consideration of advanced cardiac therapies or other high-risk procedures and advance-care planning or goals-of-care discussions. The most frequent perceived barriers to PC consultation included lack of PC clinicians, unpredictable HF clinical trajectories and limited understanding of how PC can complement traditional HF care. CONCLUSION: PC integration and clinician perceptions of services vary in HF care. More research and guidance regarding evidence-based models of PC delivery in HF are needed.

Phenyl Ether- and Aniline-Containing 2-Aminoquinolines as Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase.

Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.