Impact case study database

Background

Heart failure affects 26 million people worldwide and accounts for 1 million inpatient bed days per year (2% of the NHS total) and 5% of emergency medical admissions, costing ~£2 billion (2% of the total NHS budget). Optimisation of medical therapy requires careful alterations in medications based on patient symptoms and key physiological parameters that are typically measured in a hospital setting. With commercial collaborators, Rothman and Swift conducted research to design and develop a novel heart failure management system that enables remote continuous monitoring of key physiological parameters; a central part of the research was the design of a sensor implanted in the pulmonary artery that wirelessly transmits arterial pressure measurements to a reader device held on the patient's chest (Figure 1).

Procedure and Device Development: Proof-of-concept

Rothman developed acute [R1] and chronic [R2] models of increased pulmonary artery pressure and heart failure in large animals to demonstrate the safety and accuracy of the pressure monitor and to develop techniques to be used to implant the device in patients. [Text removed for publication] using these models, it was demonstrated, for the first time, the safe delivery of the pressure monitor to the desired implant location, device stability at the implant location, accurate measurement of pulmonary artery pressure over a range observed in patients, stability and accuracy of the readings over prolonged time periods, and safe interactions of the device with tissue at the implantation site (at a histological level) [R3]. [Text removed for publication] the development of a technique that facilitated percutaneous catheterisation lab-based implantation that critically contributed to securing funding and conducting the first-in-human study (the SIRONA study [R4]).

Procedure and device development: Imaging the pulmonary arteries

The size and shape of the pulmonary artery in humans are not uniform. To ensure that a single pulmonary artery pressure sensor would be appropriately sized for the majority of patients, it was necessary to understand the relevant 3-D anatomy in a representative population. Based on research by Swift [R5], 3-D reconstructions of pulmonary arteries were made from a cohort of patients with heart failure from the UK (Sheffield) and the USA to evaluate the size distribution of the pulmonary arteries at the site of implant. Based on this work, the device anchors were sized in advance of the first-in-human study. For each patient enrolled the pulmonary arteries were reconstructed to identify the implant zone, optimise angiographic views and to measure vessel diameter and length and distance from the implant site to the location of the reader (Figure 2). This pre-procedure planning ensured device compatibility, readability and procedural safety.

Figure 2: A - 3-D reconstruction of the pulmonary arteries of a patient with heart failure. Labels 1 to 5 represent angulated planes for measurement of size and curvature of the pressure monitor implant site. Multiple scans were analysed for determination of population mean and variance to size the pressure monitor. B-D – CT scans from individual patients enrolled in SIRONA were reconstructed to determine implant site dimensions (B), distal wire/catheter capacity (C) and reader area (D).

Procedure and device development: design iteration

Rothman led the first-in-human study undertaken at independent centres with staff without experience of interventional pulmonary procedures. [Text removed for publication]. In proctoring cases, Dr Rothman was scrubbed in the catheterisation lab when all implantations were undertaken, advising and training operators for independent implantation.

Two specific changes were made based on the anatomical [R5] and cath lab-based research [R3, R4]: 1- A change of nitinol anchors was made during the study to accommodate a broader range of patient and vessel sizes and to improve stability of the device. The imaging and 3-D reconstruction of the pulmonary arteries [R5] enabled iteration of the device, lengthening and angulating the distal anchor to stabilize the device on the inferior‐posterior inflection of the pulmonary artery (Figure 3). 2- A device adjustment was initiated to make radio-opaque markers on the sensor asymmetric allowing the implanting physician to check orientation quickly (the device must face forward) and accurately during the procedure (Figure 3).