Exercise Right Ventricular Coupling in HFpEF

In this prospective, two-center study, the investigators will recruit 30 HFpEF-PH patients in whom a CardioMEMS device will be implanted because of clinical indication. Potential study candidates will be enrolled in the outpatient clinic or during hospitalization.

Subjects who sign the informed consent form and meet the eligibility criteria at the baseline visit will be eligible for the trial. Subjects will undergo the study-related procedures, including clinical laboratory measurements and body mass index (BMI) calculation.

Eligible subjects will be scheduled for the Implant procedure (PA sensor implant in conjunction with a RHC procedure).

Subjects must also have an appropriately sized (≥7mm diameter) pulmonary artery branch identified by a selective pulmonary angiogram prior to Sensor implant. Subjects who do not meet this inclusion criteria will be documented as consented not implanted.

After implantation of the CardioMEMS device, the patient will be asked to perform cardiopulmonary exercise testing (CPET) with continuous expiratory gas monitoring on an upright cycle ergometer (ER900 and Alpha, Jaeger, Germany), using a continuous ramp protocol until exhaustion.

During the next visit, exercise RVAC will be assessed using a hybrid approach of exercise CMR and PAP measurement using the CardioMEMS system (Figure 1). Firstly, subjects will perform supine bicycle exercise within the CMR bore using a cycle-ergometer with adjustable electronic resistance (Lode, Groningen, The Netherlands). Exercise workloads for the exercise CMR protocol will be determined as 25%, 50% and 66% of peak power (Pmax) achieved during previous CPET, as the investigators previously demonstrated that supine exercise at 66% of peak power closely corresponds to maximal sustainable exercise intensity in an upright position. After the exercise test in the CMR bore, a second exercise test will be repeated on a supine bicycle ergometer. The CardioMEMS transmit-receive coil will be put under the back of the supine patient. After waiting one minute for the patient to stabilize, the CardioMEMS measurement will be initiated at rest and subsequently at the same workloads as during the exercise CMR protocol. This second exercise test will be combined with a exercise echocardiography.

CMR imaging will be performed on a Philips 1.5T CMR (Philips Medical Systems, Best, The Netherlands). RV-arterial coupling will be evaluated using a combined approach of CardioMEMS-derived pulmonary artery pressure data and CMR-derived volume data, thereby enabling the calculation of RV end-systolic pressure volume relationships. In addition, RVEF will be assessed as surrogate measure of RV-arterial coupling.

Prior to hospital discharge, subjects will be trained on the home monitoring system and instructed to take pulmonary artery pressure measurements daily at approximately the same time each day in the morning or as directed by their physician. Subjects will be supplied with a patient implant identification card, a Patient System Manual, and a Helpline phone number.

After discharge, the subject will take PA pressure measurements at home, as directed by the investigator, utilizing the CardioMEMS HF System. These measurements will be transmitted via modem to a secure data base. Patient compliance will be monitored by the Investigator.

Follow-up study visits will be scheduled at Month 1, Month 6, and every 6 months thereafter for 2 years (± 14 days visit window). Follow-up visits will include a physical exam, evaluation of NYHA Class, heart failure medications review, quality of life assessment, and assessment of any hospitalizations (including HF hospitalizations), that may have occurred between visits. In addition, all contacts between site staff and study subjects post implant will be recorded on a log to capture frequency, purpose and outcome of each contact.

The hybrid exercise CMR-CardioMEMS-derived assessment of exercise RVAC will be repeated at Month 6 and after 1 year following the same exercise protocol as detailed above.

All subjects included in this trial meet the criteria to start a SGLT-2 inhibitor on clinical indication following the latest evidence. Those who currently lack a SGLT-2 inhibitor, this medication will be initiated after the run-in period and the baseline testing (6 weeks after implantation of de CardioMems device).

Biochemistry will involve traditional parameters, such as hemoglobin, hematocrit, ionogram, renal function, NTproBNP, hs-troponin hs-CRP, ferritin, transferrin and iron level. In addition, at each time point, samples (serum and whole blood) will be stored for future analyses at Biobank UZ Leuven.