INVESTIGATION OF THE HEMODYNAMIC CARDIAC PROFILER IN ASSESSING CARDIAC INDICES AND CLINICAL PERFORMANCE DURING EXERCISE AND CARDIAC STRESS

The assessment of hemodynamic indices is of interest to evaluate performance in
athletes, changes in exercise capacity due to lifestyle interventions, and
medical therapies in patients with ischemic heart disease. Current non-invasive
options to measure cardiac output (CO) and stroke volume (SV) during exercise
and cardiac stress include exercise-transthoracic echocardiography (X-TTE) and
exercise-MRI. However, both these imaging modalities are expensive, highly
complex, and are not readily available in all clinical settings. The
Hemodynamic cardiac profiler device (HCP) has been shown to be reliably able to
non-invasively track changes in left ventricular stroke volume in rest by
producing left ventricle volume-time curves (LVVTC). However, the HCP has not
been validated during exercise or cardiac stress. Furthermore, it is not known
whether the measurements of HCP are related to other established (prognostic)
measurements of cardiopulmonary fitness, such as cardiopulmonary exercise
testing (CPX) (VO2peak and O2-pulse).

Primary Objective:
Phase 1: Reproducibility
To investigate the reproducibility of the LVVTCs of the HCP during exercise
(cardiopulmonary exercise testing, CPX).

Phase 2: Validation and association with physical fitness in healthy
volunteers.
To validate the HCP LVVTC during exercise against SV as measured during CPX in
healthy volunteers.
To investigate the association of the HCP LVVTC delta SV during exercise and
parameters for cardiopulmonary fitness (CPX; VO2peak and O2-pulse) in healthy
volunteers.

Phase 3:
To validate the HCP LVVTC during exercise against SV as measured during CPX in
patients with stable ischemic heart disease.
To investigate the association of the HCP LVVTC delta SV during exercise and
parameters for cardiopulmonary fitness (CPX; VO2peak and O2-pulse) in patients
with stable ischemic heart disease.

MRI Study:
To compare LVVTC parameters using HCP and MRI in healthy volunteers and in
patients with stable ischemic disease and to compare LVVTCs obtained using HCP
and MRI in healthy volunteers and in patients with stable ischemic disease.

Secondary Objectives:
- The reproducibility of LVVTC produced by HCP.
- Stroke volume variations in rest between HCP and MRI

The current study is a 3-phase, prospective reproducibility, validation and
measurement study

Phase 1:
Reproducibility of LVVTC during exercise in healthy volunteers.

Phase 2:
- Validation of LVVTC delta SV as measured by CPX in healthy volunteers.
- Association between LVVTC and physical fitness, as measured by VO2peak and
O2pulse (CPX) in healthy volunteers.

Phase 3:
- Validation of LVVTC delta SV as measured by CPX in individuals with stable
ischemic heart disease.
- Association between LVVTC and physical fitness, as measured by VO2peak and
O2pulse (CPX) in individuals with stable ischemic heart disease.

Between phases 2 and 3, an evaluation of phase 1 and 2 will take place. If
reproducibility and validity have been established in healthy volunteers, phase
3 will be initiated in patients. If these parameters have not been established,
evaluation will take place and problems preventing reproducibility and validity
will, if possible, be inventoried. If possible, software or hardware
modification of HCP will take place, and phase 1 will be re-initiated. If after
phase three results show an extra recalibration of HCP LVVTC is necessary, a
second MRI study with patients who are already included in phase 3 will be
executed.

An additional MRI study will be initiated to apply a modification of HCP
software and consequently establish a higher Intraclass correlation for
reproducibility and validity.

This additional MRI study consist of:
Calibration of HCP LVVTC with MRI. A detailed analysis of the different parts
of the LVVTC will be performed using established parameters, such as systolic
and diastolic times and slopes of the curve.

Phase 1a Reproducibility:

HCP during exercise (a total of 10 subjects)

4 conventional bike tests per subject
4 recumbent bike exercise tests per subject

Phase 1b Validity:( a total of 40 subjects)

Resting echo
During exercise:
1x HCP vs.
- Exercise echo
- Nexfin

Phase 2a Association with physical fitness in healthy volunteers (20 subjects)

During exercise:
HCP vs.
- Cardiopulmonary exercise test
- Nexfin

Resting:
- echo
- laboratory

2b Association with physical fitness in patients with ischemic heart disease
(20 subjects)

During exercise:
HCP vs.
- Cardiopulmonary exercise test
- Nexfin

Resting:
- echo
- laboratory

There will be no benefits for the participants. For patients with ischemic
heart disease the value in participating in the study will be that a new
noninvasive device is tested and validated for exercise testing. Exercise
testing is a standard clinical diagnostic procedure for this patient group. HCP
profiler may aid in diagnostics and facilitate early detection of problems and
may become a very useful addition to standard clinical tests. .