Development of a minimally invasive technique to measure the interstitial fluid pressure for remote monitoring of heart failure

Abstract Background Heart failure (HF) induces fluid interstitial retention, leading to oedema and elevated interstitial fluid pressure (IFP).1-3 There is a clinical need for remotely assessing IFP and understanding its correlation with cardiopulmonary haemodynamics for early treatment optimization in HF. IFP can be measured from a preserved fluid pocket formed by a subcutaneous perforated capsule in animals.4 However, the structural understanding of tissue neovascularization within a perforated capsule and the temporal relationship between altered cardiopulmonary haemodynamics and IFP remains unknown. Purpose To determine the neovascularisation of the perforated capsule over time and demonstrate the relationship between haemodynamic metrics of congestion (CVP, PAP, and LVEDP) and IFP during HF development. Methods Ten 45-55kg swine were implanted with subcutaneous perforated capsules. Perforated capsule characterisation included MicroCT using MicroFil cast (Fig. 1A) and microscopy initially at 3 and 6 weeks. A perforated capsule containing a PTFE (polytetrafluoroethylene) membrane was subcutaneously implanted in animals and chronic stability was studied at 90 using MicroCT and microscopy. After 3 weeks of perforated capsule implantation, HF was induced under general anaesthesia with 12-16 mg/kg/hour of esmolol (i.v.) and 0.9% NaCl (10% body weight, i.v.) and fluid was removed to euvolemia via ultrafiltration (Fig 2A). Concurrent measurements of IFP from perforated capsules and haemodynamic metrics of congestion were made using interventional techniques. Results MicroCT and microscopy have demonstrated perforated capsule neovascularization containing a central fluid pocket at 3 weeks and loss at 6 weeks due to continued tissue growth (Fig 1B-E). The perforated capsule at 90 days demonstrated fluid pocket preservation due to the PTFE membrane on MicroCT and microscopy (Fig. 1F-G). During the development of HF and offloading, there is a strong correlation between IFP and haemodynamic metrics of congestion (Fig. 2B). Conclusion We have developed a minimally invasive technique for continuous IFP measurement demonstrating a relationship between IFP and cardiac filling pressure in HF. IFP assessment offers a direct measure of fluid status and an indirect measure of haemodynamics, facilitating early treatment optimisation.