Table 3.

Key Knowledge Gaps and Approaches to Improve Methodology to Assess Right Ventricular Function in Acute and Chronic Conditions in Preclinical Models, Human Studies, and Clinical Trials

Key knowledge gaps

• What is the definition of “normal” and “abnormal” RV structure and function? How do key demographic characteristics such as age, sex, race/ethnicity, and socioeconomic status affect the definitions of “normal” and “abnormal”?

• How do aspects of RV development throughout the life span as well as cardiopulmonary interactions under stress and in response to critical exposures affect the definition of “normal” vs. “abnormal” RV function?

• What is the exact impact of existing and novel PAH therapies on RV function?

• Better animal and in vitro models are needed that allow study of RV function in all groups of PH.

• What are the mechanisms of RV dysfunction in acute PE and ARDS? Which interventions improve RV function in these settings?

Solution approaches/pathways forward

• After the identification of a critical set of RV biomarkers, a joint global effort is needed to replicate and validate prior findings and to determine effects of age, sex, race/ethnicity, exercise, and other exposures on these biomarkers in animal studies and human cohorts.

• Human RV specimens should be studied to improve understanding of human disease and determine to what extent experimental models may or may not recapitulate human disease.

• A small but unique set of biomarkers of RV function should be defined that can be used to quantify load-independent effects of medical and nonmedical PH treatment in clinical studies.

• While acknowledging that a single model reflecting RV function in all aspects and types of PH is unlikely to be developed, novel models (in vivo, in vitro [e.g., “heart on a chip,” iPSCs], and in silico) should be developed that replicate critical aspects of RVF in all groups of PH.

• Determine mechanisms of RVF in patient cohorts and in animal models of acute (and chronic) PE and ARDS. The effect of novel RV-directed therapies (e.g., prone positioning in ARDS) on RV function in these settings should be prospectively studied.

Definition of abbreviations: ARDS = acute respiratory distress syndrome; iPSCs = induced pluripotent stem cells; PAH = pulmonary arterial hypertension; PE = pulmonary embolism; PH = pulmonary hypertension; RV = right ventricle; RVF = right ventricular failure.