The Future of the RV: From Diagnostics to Therapeutics
Presenter: Jane A. Leopold, MD
Individuals typically reside along a spectrum that encompasses health being at risk or having established disease, and they can move back and forth across this spectrum during their lifetime.
Looking at this from the perspective of the right ventricle (RV), typically the focus is on individuals who have a diseased RV.
Jane A. Leopold, MD, of Brigham and Women’s Hospital, said, “One of the concepts I think we’re going to be looking at in the future is that we’re going to be moving toward identifying RV disease inception and starting to focus more on prevention as well as learning more about taking care of patients with RV disease.”
Dr. Leopold explained that a second conceptual shift will also be occurring and said, “We’re going to start thinking about the RV in patients with pulmonary hypertension as more focused on the endophenotypes and phenotypes, as opposed to thinking about hypertension as the primary component,” she said.
Individuals who are typically grouped by their PH group often have a lot of dissimilarities with respect to RV structure and function. Using big data should allow a better understanding of the patients, which will allow clustering into different groups on the basis of their RV.
Diagnostics will be moving toward a liquid biopsy of the RV. RV tissue is difficult to obtain, but with increasing availability of “omics” platforms, researchers will be able to use blood specimens and circulating cells to get molecular signatures of the RV in both health and disease. The most notable weakness of this approach is that it is dependent on how rapidly there are advances in omics platforms.
Another diagnostic change that is occurring is early use of challenges in clinical testing to unmask RV dysfunction. This can be an exercise challenge or a pharmacologic challenge, but there is clear benefit to making a diagnosis of RV dysfunction early.
There will also be more focus on precision analysis of RV structure in diagnostics, especially with MRI, which has the potential for ultra-high resolution of RV structure and function, and can also tell us a lot about fibrosis and extracellular volume content, both of which change with the progression of RV disease. This will also allow movement toward newer methodologies such as 4D MRI that reveal flow patterns in the RV. The pathline visualization of blood flow in the RV can be determined and mapped to the RV structure to look at different aspects over time.
Dr. Leopold said this is important because it allows a measure of RV performance and said, “Changes here may turn out to be one of the earliest biomarkers of RV dysfunction.” She said it’s likely that PET imaging will also be used to understand RV dysfunction.
For therapeutics, big data will be used to identify patient-specific therapeutics for the RV, based on an understanding of their genomic and molecular profile, their clinical data, and their exposures. The data will be combined to form networks, which are basically a wiring diagram of a person, which can be looked at to see what is prominently expressed in a patient, and used to tailor therapy.
Another therapeutic change involves finding ways to treat the RV, or RV afterload, directly, to allow the RV to remodel itself. There is interest in both cell and gene therapies.
One more new approach in therapeutics is a device that is placed into the pulmonary artery that will unload the RV and decrease RV work. Early studies show an increase in CPA both at rest and during exercise with the device.1
In summary, Dr. Leopold said we’ll be moving from focusing on the RV in the disease state toward identifying early markers of disease inception to shift the focus to prevention. There will be identification of new RV phenotypes and endophenotypes as well as increased reliance on liquid biopsies. Challenges will be used to unmask RV dysfunction, MRI and PET imaging will improve assessment of RV structure and function, and therapeutics will be tailored to individual patients.
Niushen Zhang, MD, receives research funding from NHLBI, American Heart Association, and Astellas; is on a speaker bureau for United Therapeutics; and is a consultant for Abbott Vascular.
Reference
- Gerges C, Vollmers K, Pritzker MR, Gainor J, Scandurra J, Weir EK, Lang IM. Pulmonary Artery Endovascular Device Compensates for Loss of Vascular Compliance in Pulmonary Arterial Hypertension. J Am Coll Cardiol. 2020 Nov 10;76(19):2284-2286. doi: 10.1016/j.jacc.2020.08.080. PMID: 33153589.