Cardiopulmonary and Right Ventricular Function in Health and Disease

For completion of specific aims 1-2, the protocol will be identical. Specific aim 1 involves analysis of patients with HFrEF as defined above; specific aim 2 involves analysis of patients with HFpEF as defined above. The protocol for specific aim 3 (analysis of endurance athletes) incorporates a different protocol than that described for specific aims 1-2.

For HFrEF and HFpEF patients (specific aims 1-2): There will be a single visit for testing. This visit will involve a baseline assessment of hemodynamics using a Swan-Ganz catheter, followed by invasive exercise testing with a high-fidelity conductance catheter, which provides the real-time RV PV loops. The Swan-Ganz catheter is a 7-French flexible catheter that is routinely used for hemodynamic assessment for clinical and research purposes (we are currently using this catheter for COMIRB #16-1635, and COMIRB #17-1042). The purpose of this catheter is to determine baseline hemodynamic parameters (in "layman's terms", to describe left and right-sided filling pressures, as well as pressures in the lungs), and to determine resting cardiac output. The Swan-Ganz catheter will be inserted and removed after obtaining these measurements - it is anticipated that this procedure will take 10-15 minutes. The primary investigator for this study, Dr. Cornwell, routinely performs these procedures in both clinical and research settings, and will use standard techniques for catheter insertion. Ultrasound guidance will be used to identify the right internal jugular vein, where the catheter is inserted, and fluoroscopy will be used to guide placement of the catheter for hemodynamic monitoring.

After completion of the baseline hemodynamic assessment, the Swan-Ganz catheter will be removed. Thereafter, the high-fidelity conductance catheter will be inserted into the RV using standard techniques. This catheter is also a 7-French flexible catheter (currently being used for COMIRB #17-1042) that has a pressure manometer on the tip, along with several conductance electrodes that continuously measure volume in the ventricle - by continuously recording changes in pressure and volume throughout the cardiac cycle, the catheter generates the "PV loop". These catheters provide information that is not available with standard Swan-Ganz catheters (refer to outcome measures listed above). Following insertion of the conductance catheter, an arterial line will be placed in either the left or right radial artery, using sterile technique and with ultrasound-guidance. The purpose of this catheter is two-fold: 1) to provide a gold-standard assessment of BP during exercise; and 2) to measure arterial oxygen saturation to calculate a cardiac output from the Fick equation. Baseline hemodynamic assessment will involve monitoring for approximately 5 minutes during spontaneous breathing, followed by approximately 6 minutes of breathing at a controlled respiratory rate (12 times per minute), which allows for determination of short-term blood pressure variability after controlling for the effect of respiratory variation, followed by Valsalva maneuver and vasomotor reactivity (inspiratory breath-hold for 30 seconds).

Following insertion of the conductance catheter, arterial catheter and acquisition of baseline data, the patient will be positioned on an upright cycle ergometer. In the event that the patient is not able to perform upright exercise, a supine ergometer will be used. The patient will then complete exercise at two submaximal workloads (below their ventilatory threshold) that simulate real-world scenarios/normal activities of daily living, followed by peak exercise. To obtain submaximal data, workload on the bicycle will begin at 0 Watts. Every 1-2 minutes, workload will be steadily increased, generally in 12.5-25 Watt-increments, until the patient indicates that the rate-of-perceived exertion (RPE) score is 7-9, on a 6-20 point scale.24 This workload will correspond to "mild" exercise, or steady-state 1. Workload will be held at this level for approximately 4-5 minutes, during which time hemodynamic data will be obtained. Thereafter, workload will again be increased in 12.5-25 Watt increments until the participate indicates that the RPE score is 11-13.24 This workload will correspond to a "moderate" exercise, or steady-state 2. Workload will be held at this level for approximately 4-5 minutes, during which time hemodynamic data will be obtained. The patient will then be allotted a 5-10 minute break. After the break, the patient will complete a symptom-limited cardiopulmonary exercise test, whereby workload will begin at 0 Watts, and generally increase every 1-2 minutes in 12.5-25 Watt increments until exhaustion. Hemodynamic data will be continuously recorded, and final data will be obtained at the peak workload achieved. This protocol will allow for acquisition of data at five different positions: 1) supine rest; 2) upright rest; 3) steady-state 1, or "mild" exercise; 4) steady-state 2, or "moderate" exercise; and 5) peak exercise. Blood samples will be collected at each of these stages: blood will be tested for arterial and venous oxygen saturation levels (to calculate a Fick cardiac output), as well as a venous/capillary lactic acid level by finger stick. Lactic acid levels will be used to assess the participant's work effort at each stage of exercise (as a "rule-of-thumb", submaximal levels of exercise have an associated lactic acid level of below 4mmol/L. A complete blood count will be obtained in the supine resting position to determine hemoglobin concentration, which will be used to calculate Fick cardiac output during all stages of exercise. Following completion of the study, the patient will be returned to a supine position and de-instrumented. This protocol is very similar to protocols used as part of COMIRB #16-1635 and #17-1042; based on our experience with these protocols, it is anticipated that this study will last approximately 4-5 hours.

For Endurance Athletes (specific aim 3): There will be two visits for this study: