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Objective: To explore the optimal content and design of a clinical trial of an end-of-life intervention for advanced heart disease with patients, carers and healthcare professionals. Design: Qualitative interview and focus group study. Setting: Community and hospital-based focus groups and interviews. Participants: Stable community-dwelling patients, informal carers (PC, n=15) and primary and secondary care based healthcare professionals (HCP, n=11). Results: PC highlighted fragmentation of services and difficulty in accessing specialist care as key barriers to good care. They felt that time for discussion with HCP was inadequate within current National Health Service (NHS) healthcare systems. HCP highlighted uncertainty of prognosis, explaining mortality risk to patients and switching from curative to palliative approaches as key challenges. Patient selection, nature of the intervention and relevance of trial outcomes were identified by HCP as key challenges in the design of a clinical trial. Conclusions: PC and HCP expressed a number of concerns relevant to the nature and content of an end-of-life intervention for patients with advanced heart disease. The findings of this study are being used to support a phase II randomised clinical trial of Future Care Planning in advanced heart disease. [ABSTRACT FROM AUTHOR]

Background: To examine whether augmentation index (AIx) is increased in Marfan syndrome (MFS) and associated with increased aortic root size, and whether a peripheral-to-central generalised transfer function (GTF) can be applied usefully in MFS. Methods: 10 MFS patients and 10 healthy controls (matched for sex, age and height) were studied before and after 400 µg sub-lingual GTN. Arterial waveforms were recorded using applanation tonometry. AIx and pulse pressure (PP) were determined for the radial and carotid arteries. Pulse wave velocity (PWV) was measured between carotid and femoral arteries. GTFs were generated to examine the relationship between radial and carotid waveforms. Results: AIx was greater in MFS compared to controls at radial (mean -31.4 (SD 14.3)% v - 50.2(15.6)%, p = 0.003) and carotid (-7.6(11.2)% v -23.7(12.7)%, p = 0.004) sites. Baseline PP at all measurement sites, and PWV, did not differ between subject groups. Multivariate analysis demonstrated that PWV and carotid AIx were positively correlated with aortic root size (p < 0.001 and p = 0.012 respectively), independent of the presence of MFS. PP was not associated with aortic root size. GTN caused similar decreases in AIx in both controls and patients. Significant differences were found in GTFs between MFS and control subjects, which changed following GTN administration. However, when an independent GTF was used to derive carotid waves from radial waves, no differences were found in the degree of error between MFS and controls. Conclusion: AIx is sensitive to the vascular abnormalities present in MFS, and may have a role as an adjunct to measurement of central PP and PWV. Differences between MFS and controls in the nature of the peripheral-to-central GTF are present, although have little effect on the pulse contour. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1[1−21]) is an extremely potent vasoconstrictor in the human skin microcirculation and is generated from larger precursor peptides. The aims of the present study were to assess the vasoactive effects of these precursors as well as endothelin blockade in the human skin microcirculation, in vivo. Six healthy volunteers received intradermal injections of a range of doses of big ET-1[1−38], ET-1[1−31], ET-1[1−21], BQ-123 (ETA receptor antagonist), BQ-788 (ETB receptor antagonist), phosphoramidon [endothelin converting enzyme (ECE) inhibitor] or saline control (0.9%). Skin blood flow (SBF) was measured using standard laser Doppler flowmetry. Big ET-1[1−38], ET-1[1−31] and ET-1[1−21] reduced SBF when compared with saline control ( P < 0.01 for all). Big ET-1[1−38] and ET-1[1−31] were less potent than ET-1[1−21] as defined by skin vasoconstriction. Phosphoramidon, BQ-123 and BQ-788, given alone, all caused vasodilatation in the human skin microcirculation ( P < 0.01 for all). In the human skin microcirculation, big ET-1[1−38] and ET-1[1−31] are less potent vasoconstrictors than ET-1[1−21]. The effects of big ET-1[1−38] and phosphoramidon suggest the presence of endogenous ECE activity in the skin. In contrast to skeletal muscle resistance vessels, ET-1[1−21] contributes to the maintenance of skin microvascular tone through both ETA and ETB receptor-mediated vasoconstriction. [ABSTRACT FROM AUTHOR]

Aims Recent guidelines recommend regular exercise in the management of patients with chronic heart failure (CHF). This study was designed to compare the safety and efficacy of conventional bicycle exercise and functional electrical stimulation (FES) of the legs as forms of home-based exercise training for patients with stable CHF.Methods and results Forty-six patients (38 male) with stable NYHA Class II/III heart failure underwent a 6-week training programme using either a bicycle ergometer or electrical stimulation of the quadriceps and gastrocnemius muscles. In the bike group, significant increases were seen in 6-min walk (44.6m, 95% confidence interval (CI) 29.3–60.9m), treadmill exercise time (110s, 95% CI 72.2–148.0s), maximum leg strength (5.32kg, 95% CI 3.18–7.45kg), and quadriceps fatigue index (0.08, 95% CI 0.04–0.12) following training. In the stimulator group, similar significant increases were seen following training for 6-min walk (40.6m, 95% CI 28.2–53.0m), treadmill exercise time (67s, 95% CI 11.8–121.8s), maximum leg strength (5.35kg, 95% CI 1.53–9.17kg), and quadriceps fatigue index (0.10, 95% CI 0.04–0.17). Peak VO2did not change in either group following training, indicating a low-intensity regime. Quality of life scores improved following training when the bicycle and stimulator groups were considered together, but not when considered separately (−0.43, 95% CI −8.13 to −0.56).Conclusions FES produces beneficial changes in muscle performance and exercise capacity in patients with CHF. Within this study, the benefits were similar to those observed following bicycle training. FES could be offered to patients with heart failure as an alternative to bicycle training as part of a home-based rehabilitation programme. [ABSTRACT FROM PUBLISHER]

Supplemental Digital Content is available in the text. Background: Patients with heart failure have significant symptom burden, care needs, and often a progressive course to end-stage disease. Palliative care referrals may be helpful but it is currently unclear when patients should be referred and by whom. We conducted a systematic review of the literature to examine referral criteria for palliative care among patients with heart failure. Methods: We searched Ovid, MEDLINE, Ovid Embase, and PubMed databases for articles in the English language from the inception of databases to January 17, 2019 related to palliative care referral in patients with heart failure. Two investigators independently reviewed each citation for inclusion and then extracted the referral criteria. Referral criteria were then categorized thematically. Results: Of the 1199 citations in our initial search, 102 articles were included in the final sample. We identified 18 categories of referral criteria, including 7 needs-based criteria and 10 disease-based criteria. The most commonly discussed criterion was physical or emotional symptoms (n=51 [50%]), followed by cardiac stage (n=46 [45%]), hospital utilization (n=38 [37%]), prognosis (n=37 [36%]), and advanced cardiac therapies (n=36 [35%]). Under cardiac stage, 31 (30%) articles suggested New York Heart Association functional class ≥III and 12 (12%) recommended New York Heart Association class ≥IV as cutoffs for referral. Prognosis of ≤1 year was mentioned in 21 (21%) articles as a potential trigger; few other criteria had specific cutoffs. Conclusions: This systematic review highlighted the lack of consensus regarding referral criteria for the involvement of palliative care in patients with heart failure. Further research is needed to identify appropriate and timely triggers for palliative care referral. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]