BackgroundMetabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).Methods and ResultsWe identified HFpEF cases, HFrEF controls, and no‐HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No‐HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no‐HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.ConclusionsWe identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.

Background More than 1 in 4 Americans report difficulty paying medical bills. Cost-reducing strategies discussed during outpatient physician visits remain poorly characterized. Objective We sought to determine how often patients and physicians discuss healthcare costs during outpatient visits and what strategies, if any, they discussed to lower patient out-of-pocket costs. Design Retrospective analysis of dialogue from 1,755 outpatient visits in community-based practices nationwide from 2010–2014. The study population included 677 patients with breast cancer, 422 with depression, and 656 with rheumatoid arthritis visiting 56 oncologists, 36 psychiatrists, and 26 rheumatologists, respectively. Results Thirty percent of visits contained cost conversations (95% confidence interval [CI], 28 to 32). Forty-four percent of cost conversations involved discussion of cost-saving strategies (95% CI, 40 to 48; median duration, 68 seconds). We identified 4 strategies to lower costs without changing the care plan – in order of overall frequency, (1) Changing logistics of care; (2) Facilitating copay assistance; (3) Providing free samples; (4) Changing/adding insurance plans – and 4 strategies to reduce costs by changing the care plan – (1) Switching to lower-cost alternative therapy/diagnostic; (2) Switching from brand name to generic; (3) Changing dosage/frequency; (4) Stopping/withholding interventions. Strategies were relatively consistent across health conditions, except for switching to lower-cost alternative (more common in breast oncology), and providing free samples (more common in depression). Limitation Focus on three conditions with potentially high out-of-pocket costs. Conclusions Despite price opacity, physicians and patients discuss a variety of out-of-pocket cost reduction strategies during clinic visits. Almost half of cost discussions mention one or more cost-saving strategies, with more frequent mention of those not requiring care-plan changes.

BackgroundNearly one in three Americans are financially burdened by their medical expenses. To mitigate financial distress, experts recommend routine physician-patient cost conversations. However, the content and incidence of these conversations are unclear, and rigorous definitions are lacking. We sought to develop a novel set of cost conversation definitions, and determine the impact of definitional variation on cost conversation incidence in three clinical settings.MethodsRetrospective, mixed-methods analysis of transcribed dialogue from 1,755 outpatient encounters for routine clinical management of breast cancer, rheumatoid arthritis, and depression, occurring between 2010–2014. We developed cost conversation definitions using summative content analysis. Transcripts were evaluated independently by at least two members of our multi-disciplinary team to determine cost conversation incidence using each definition. Incidence estimates were compared using Pearson’s Chi-Square Tests.ResultsThree cost conversation definitions emerged from our analysis: (a) Out-of-Pocket (OoP) Cost -- discussion of the patient’s OoP costs for a healthcare service; (b) Cost/Coverage -- discussion of the patient’s OoP costs or insurance coverage; (c) Cost of Illness-- discussion of financial costs or insurance coverage related to health or healthcare. These definitions were hierarchical; OoP Cost was a subset of Cost/Coverage, which was a subset of Cost of Illness. In each clinical setting, we observed significant variation in the incidence of cost conversations when using different definitions; breast oncology: 16, 22, 24 % of clinic visits contained cost conversation (OOP Cost, Cost/Coverage, Cost of Illness, respectively; P < 0.001); depression: 30, 38, 43 %, (P < 0.001); and rheumatoid arthritis, 26, 33, 35 %, (P < 0.001).ConclusionsThe estimated incidence of physician-patient cost conversation varied significantly depending on the definition used. Our findings and proposed definitions may assist in retrospective interpretation and prospective design of investigations on this topic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1353-2) contains supplementary material, which is available to authorized users.

Metabolic impairment is an intrinsic component of heart failure (HF) pathophysiology. Although initially conceived as a myocardial defect, metabolic dysfunction is now recognized as a systemic process with complex interplay between the myocardium and peripheral tissues and organs. Specifically, HF-associated metabolic dysfunction includes alterations in substrate utilization, insulin resistance, defects in energy production, and imbalanced anabolic-catabolic signaling leading to cachexia. Each of these metabolic abnormalities is associated with significant morbidity and mortality in patients with HF; however, their detection and therapeutic management remains challenging. Given the difficulty in obtaining human cardiac tissue for research purposes, peripheral blood metabolomic profiling, a well-established approach for characterizing small-molecule metabolite intermediates from canonical biochemical pathways, may be a useful technology for dissecting biomarkers and mechanisms of metabolic impairment in HF. In this review, metabolic abnormalities in HF will be discussed with particular emphasis on the application of metabolomic profiling to detecting, risk stratifying, and identifying novel targets for metabolic therapy in this heterogeneous population.

We identified cost conversations in approximately one in five breast cancer visits. Cost conversations were mostly oncologist initiated, lasted < 1 minute, and dealt with a wide range of health care expenses. Cost-reducing strategies were mentioned in more than one third of cost conversations and often involved switching antineoplastic agents for lower-cost alternatives or altering logistics of diagnostic tests.

Some experts contend that requiring patients to pay out of pocket for a portion of their care will bring consumer discipline to health care markets. But are physicians prepared to help patients factor out-of-pocket expenses into medical decisions? In this qualitative study of audiorecorded clinical encounters, we identified physician behaviors that stand in the way of helping patients navigate out-of-pocket spending. Some behaviors reflected a failure to fully engage with patients’ financial concerns, from never acknowledging such concerns to dismissing them too quickly. Other behaviors reflected a failure to resolve uncertainty about out-of-pocket expenses or reliance on temporary solutions without making long-term plans to reduce spending. Many of these failures resulted from systemic barriers to health care spending conversations, such as a lack of price transparency. For consumer health care markets to work as intended, physicians need to be prepared to help patients navigate out-of-pocket expenses when financial concerns arise during clinical encounters.

Endocardial cells form the inner endothelial layer of the heart tube, surrounded by the myocardium. Signaling pathways that regulate endocardial cell specification and differentiation are largely unknown and the origin of endocardial progenitors is still being debated. To study pathways that regulate endocardial differentiation in a zebrafish model system, we isolated zebrafish NFATc1 homolog which is expressed in endocardial but not vascular endothelial cells. We further demonstrate that Hedgehog (Hh) but not VegfA or Notch signaling is required for early endocardial morphogenesis. Pharmacological inhibition of Hh signaling with cyclopamine treatment resulted in nearly complete loss of the endocardial marker expression. Simultaneous knockdown of the two zebrafish sonic hedgehog homologs, shh and twhh or Hh co-receptor smoothened (smo) resulted in similar defects in endocardial morphogenesis. Inhibition of Hh signaling resulted in the loss of fibronectin (fn1) expression in the presumptive endocardial progenitors as early as the 10-somite stage which suggests that Hh signaling is required for the earliest stages of endocardial specification. We further show that the endoderm plays a critical role in migration but not specification or differentiation of the endocardial progenitors while notochord-derived Hh is a likely source for the specification and differentiation signal. Mosaic analysis using cell transplantation shows that Smo function is required cell-autonomously within endocardial progenitor cells. Our results argue that Hh provides a critical signal to induce the specification and differentiation of endocardial progenitors.

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