Noninvasive device for fast cardiovascular condition assessment (NICVA) 1
Type of activity
AGAUR. Agència de Gestió d'Ajuts Universitaris i de Recerca
Funding entity code
2018 PROD 00092
Cardiovascular diseases (CVD) are a leading cause of deaths worldwide. Early diagnose and periodic monitoring of patients at risk can reduce mortality but current technology provides only partial solutions as extra-hospital devices can measure a limited number of physiological parameters, each of them needing a specific device and a skilled operator. Further, arterial blood pressure (ABP) cannot be continuously measured. A compact, affordable and self-administered device able to measure several cardiovascular signals anywhere there is access to a wireless communication network will be a major breakthrough in medical technology with a sizeable potential market and a major impact in health care as it will facilitate both periodic and continuous monitoring also in hospitals. We propose NICVA, a medical device able to monitor the performance of the cardiovascular system that relies on two complementary inventions. The first one is the detection of the ECG and an arterial pulse wave (APW) with information proximal to the heart by using only four dry electrodes, two for each hand or arm, and measuring, in addition to the ECG, changes in the limb-to-limb electrical impedance, the so-called Impedance plethysmogram (IPG). The limb-to-limb impedance depends on the tissues between the electrodes and its basal component is measured in some body composition analyzers. Blood ejection and arterial pulse wave propagation at each heart beat reduces that impedance and the amplitude of this change along the limb-to-limb path makes the IPG. Since the change starts during cardiac systole, that IPG provides information proximal to the heart. The second invention is the simultaneous detection of bilateral distal APWs using the same four-electrode set and measuring the electrical impedance between the two electrodes in the same limb. The time interval between the R-wave of the ECG and the foot of the limb-to-limb APW is the Pre-Ejection Period (PEP), a good indicator of myocardial contractility. The time interval between the proximal and each distal APW is the (brachial) Pulse Travel Time (PTT), a good indicator of arterial elasticity, which is correlated to ABP. Furthermore, respiratory information can be derived from the ECG (EDR: ECG-derived respiration) and also from the limb-to-limb IPG, as this includes the impedance pneumogram. Therefore, signals measured with only four electrodes provide a wealth of information about the electrical and mechanical condition of the heart and the mechanical status of the arteries that cannot be obtained by any other equivalent method, plus respiratory information. The technical simplicity of the measurements involved allow the system to be implemented in standalone handheld devices or in existing handheld devices, such as 1-lead ECG monitors and Body Composition Analyzers. A patent for the first invention (WO2013/017718A2) has already been granted in Spain, China, the United States and Japan, and is pending in Europe, India and South Korea. A laboratory prototype was built that measures the ECG and the limb-to-limb IPG, and was tested in 14 healthy subjects. Using paced respiration, which modulates PEP, an excellent correlation (r = 0.9) was found. A patent application for the second invention (WO2017/081353A1) has recently been completed in the same countries and region. The proof of concept was obtained in only 3 healthy young subjects, using as distal APW a photoplethysmogram (PPG). The results were encouraging and the aim is now to obtain two distal IPGs with the same electrode set used for the ECG and limb-to-limb IPG, and validate both inventions in a larger heterogeneous cohort, for example to determine whether PEP and PTT changes due to causes other than paced respiration are correctly detected. Replacing the PPG by local IPGs will overcome measurement problems during peripheral vasoconstriction and waveform dependence on sensor-contact force, two severe limitations of PTT-based ABP measurement devices. Algorithms used to estimate ABP changes from the PPG will be adapted to local IPGs, and limb-to-limb IPG is expected to contribute, in additional to proximal information, further information about arm arteries that will improve the repeatability of existing devices. The first aim of this project is to build a portable prototype for a pre-clinical study to obtain ECG lead I, PEP, PTT and ABP changes from four dry electrodes. This needs: 1) Improving the current laboratory prototype so that it can simultaneously measure three impedances, two of the very small; 2) Developing algorithms to automatically detect pre-defined fiducial points in the ECG and the three IPG signals obtained in quiet people; 3) Verifying that prototype in a significant group of people with no known cardiovascular disease; 4) 6 / 18 Validating the prototype in selected high-risk cohorts such as patients that are hypertensive or in risk of becoming hypertensive. The second aim of the project is to maintain and extend the IP in national phases in Europe to gain a competitive advantage in front of competitors and maximizing the R+D efforts. The third aim is to conceive a business plan to create a spin-off company.