Background/Objectives: Dermal interstitial fluid (dISF) is probably the most interesting biofluid for biomarker analysis as an alternative to blood, enabling higher patient comfort and closer or even continuous biomarker monitoring. The prerequisite for dISF-based analysis tools is having convenient access to dISF, as well as a better knowledge of the presence, concentration, and dynamics of biomarkers in dISF. Hollow microneedles represent one of the most promising platforms for access to pure dISF, enabling the mining of biomarker information. Methods and Results: Here, a microneedle-based method for dISF sampling is presented, where a combination of hollow microneedles and sub-pressure is used to optimize both penetration depth in skin and dermal interstitial fluid sampling volumes, and the design of an open, prospective, exploratory, and interventional study to examine the detectability of inflammatory and cardiocirculatory biomarkers in the dISF of heart failure patients, the relationship between dISF-derived and blood-derived biomarker levels, and their kinetics during a cardiopulmonary exercise test (CPET) is introduced. Conclusions: The dISF sampling method and study presented here will foster research on biomarkers in dISF in general and in heart failure patients in particular. The study is part of the European project DIGIPREDICT—Digital Edge AI-deployed DIGItal Twins for PREDICTing disease progression and the need for early intervention in infectious and cardiovascular diseases beyond COVID-19.

Background: Despite the risk for complications, allograft surveillance after orthotopic heart transplantation (OHT) is performed by cardiac catheterization and biopsies. We investigated the diagnostic and prognostic value of a TDI-derived systolic wall motion analysis of the posterobasal wall of the left ventricle (Sm) as a screening modality in OHT aftercare. Methods: We examined data of 210 eligible patients who underwent OHT between 2010 and 2020. Forty-four patients who had died within the initial hospital stay were excluded. For 166 patients, baseline and follow-up data were analyzed. The mean age at OHT was 46.2 (±11.4) years; 76.5% were male. Results: Within the observational period, 22 (13.3%) patients died. In total, 170 episodes of acute cellular or humoral rejections occurred (84 ISHLT1R; 13 ISHLT2R; 8 ISHLT3R; 65 AMR), and 29 catheterizations revealed cardiac allograft vasculopathy (5 CAV1; 4 CAV2; 20 CAV3). Individual Sm radial/longitudinal remained stable within the follow-up period (11.5 ± 2.2 cm/s; 10.9 ± 2.1 cm/s). Patients with acute rejections and CAV3 showed significant Sm radial/longitudinal reductions (AMR1: 1.6 ± 1.9 cm/s, confidence interval (CI) 0.77–0.243, p < 0.001; 1.8 ± 2.0 cm/s, CI 0.92–0.267, p < 0.001. ISHLT1R: 1.7 ± 1.8 cm/s, CI 1.32–2.08, p < 0.001; 2.0 ± 1.6 cm/s, CI 1.66–2.34, p < 0.001. CAV3: 1.3 ± 2.5 cm/s, CI 0.23–2.43, p < 0.017; 1.4 ± 2.8 cm/s, CI 0.21–2.66, p < 0.021). Lower Sm was associated with a threefold increase in all-cause mortality (hazard ratio (HR) 3.24, CI 1.2–8.76, p = 0.020; HR 2.92, CI 1.19–7.18, p = 0.019). Overall, Sm-triggered surveillance led to 0.75 invasive diagnostics per patient post-OHT year. Conclusions: Sm remained stable in the post-OHT course. Reductions indicated ISHLT1R, AMR1 and CAV3 and were associated with higher all-cause mortality. Sm-triggered surveillance may be referred to as a safe, high-yield screening modality in OHT aftercare.

Background: Frailty is a potential reversible state, which affects the prognosis of advanced heart failure patients. This study aimed to examine the influence of continuous-flow ventricular assist device (cf-VAD) implantation on frailty. Method: We evaluated frailty in 64 patients prior to and 6 months after surgery via bioelectrical impedance analysis (BIA), 6-minute-walk test (6MWT) and grip strength measurement. Results: Postoperative phase angle increased (4.25° [IQR 3.30, 5.03] to 5.00° [IQR 4.57, 5.90]; p < 0.001) with a mean difference of 0.8°. 34 (53%) patients had a postoperative phase angle within the normal range (≥5.0°), whereas preoperative only 18 (28%) patients had a normal phase angle. Further analysis showed a significant postoperative increase in body cell mass (28.45 kg [IQR 24.60, 34.55] to 30.60 kg [IQR 26.80, 35.23]; p = 0.008) with a mean increase of 2.28 kg, while body water decreased (51.70 L [IQR: 45.25, 57.37] to 47.55 L [IQR 42.88, 52.28]; p = 0.003). Physical performance improved, evaluated by grip strength (28.50 kg [IQR 19.00, 39.00] to 33.50 kg [IQR 24.00, 43.00]; p = 0.001) and walking distance (145.00 m [IQR 0.00, 322.75] to 382.50 m [IQR 270.75, 471.00]; p < 0.001) with a mean difference of 6.5 kg resp. 192 m. Conclusion: After cf-VAD implantation, frailty state represented by phase angle improved significantly. Further analysis of BIA parameters and physical performance confirmed that the increase of phase angle originated from increase in muscle mass and cardiac recompensation. Analysis of changes in frailty status after efficient heart failure treatment could help develop a frailty assessment, which is able to distinguish disease dependent from disease independent frailty. Early cf-VAD implantation might be able to reverse both frailty and heart failure. It should be further evaluated against stabilization of heart failure with medical therapy/short-term mechanical circulatory support in combination with prehabilitation efforts prior to cf-VAD implantation. Publication Date: 03 February 2022 (online) © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany