Radio-frequency sensing: non-invasive monitoring of heart failure progression

Heart failure is a major healthcare burden with high incidence and mortality
(Groenewegen et al., 2020). An important challenge in heart failure treatment
is monitoring the progression of chronic heart failure and therefore required
optimization of medication. If heart failure develops from a chronic to an
acute state and medication is not adjusted properly, patients need to be
admitted to the hospital with very severe symptoms such as lung oedema.
Currently more than 50% of all patients with heart failure gets readmitted to
the hospital within 6 months after treatment (Desai and Stevenson, 2012) when
heart failure transitions from chronic compensated to an acute decompensated
state. Associated with hospitalization are increased mortality rates up to 10%
(McDonagh et al., 2021), irreversible disease progression and high costs.
Hospitalization is the driving factor behind the enormous economic costs of
heart failure ($ 65 billion per year worldwide, (Urbich et al., 2020)).
Tracking heart failure progression requires repeated (home) monitoring of
cardiac contractile function and left ventricular filling pressure, which is
not possible with current non-invasive technology. Available non-invasive
methods such as MRI or TTE can only be used by expert and are not
cost-effective. Previously we developed RF sensing, a novel method that
non-invasively measures hemodynamic parameters such as stroke volume, ejection
fraction, ejection time with radio-antennas (Steensma et al., 2022) which
represent the contractile function of the heart.

The concept of RF Sensing has been tested and validated in healthy controls in
an experimental setting, but not yet in larger groups of healthy subjects or
patients with cardiovascular disease. The overall aims of this study are to
demonstrate that with RF Sensing, it is possible to measure hemodynamic
parameters with comparable precision and accuracy as TTE and MRI and to show
that differences in RFS signals are observable between compensated and
decompensated heart failure, as well as healthy controls.

Based on the expected correlation between RFS and ground truth TTE/MRI
measurements of hemodynamic parameters, we expect that it is necessary to
compare TTE and RFS in at least 50 subjects.

This study is initiated by the sponsor UMC Utrecht. In addition, the study is
co-funded by PrecorDx, a spinoff company of UMC Utrecht that aims to
commercialize the RF Sensing technology. Dr. Steensma, a sub-PI of the study,
is a co-founder and shareholder of PrecorDx. Dr. Tjong, a sub-PI of the study,
is the spouse of a co-founder and shareholder of PrecorDx.

Primary objective: Determine correlation between RFS parameters (5 independent
signal characteristics) and non-invasive hemodynamic parameters (estimated left
ventricular end diastolic pressure, left ventricular ejection fraction, left
ventricular stroke volume, right ventricular ejection fraction, right
ventricular stroke volume) in a group of cardiovascular patients and healthy
controls with a wide range of anatomical variation and pathological conditions.

Secondary objective 1: Determine the correlation between RFS parameters and
invasive hemodynamic parameters (atrial pressure, right ventricular pressure,
pulmonary capillary wedge pressure and pulmonary artery pressure,
diastolic/systolic/mean) in cardiovascular patients.

Secondary objective 2: Explore the sensitivity of RFS parameters to treatment
effects.

This is an interventional study. The study will take place between 1 December
2023 (target start date) and 30 November 2026 (total duration 36 months) at the
Cardiology and Radiology department of the University Medical Center Utrecht
and the Cardiology department of the Amsterdam University Medical Center. The
study is a multi-center study, to ensure sufficient patients can be included,
and to ensure that patients with various types of heart failure can be
included. Data collection will take place at these same centers. Analysis will
be performed by researchers from the UMC Utrecht Radiology and Cardiology
departments.

To achieve sufficient statistical power for our primary objective, we will
include 40 patients and 10 healthy controls.

Participants undergo the following measurements, outside of standard care:

- TTE and RF Sensing measurement.
- MRI and RF Sensing measurement.
- RF Sensing measurement during catheterization (only if catheterization is
part of standard care).
- During the RF Sensing measurement, ECG and arm cuff blood pressure is
measured.
- Patient fill out a short questionnaire about the comfort of RFS measurements.

Subjects participating in this study will derive no direct benefit from the
study. However, the outcome of this study will aid in improving diagnosis and
treatment of heart failure, which may improve consequent individual treatment
possibilities.

In case of unexpected findings during the TTE or MRI, the treating cardiologist
will be warned.