**7. Conclusions and future investigations**

Understanding of RV metabolism and mitochondrial function has lagged that of the left heart, and arguably even less is known about how RV mitochondria adapt to pathological stress. What little is known about the role of mitochondrial function and metabolism in the dysfunctional or failing RV (summarized in **Table 2**) has largely been extrapolated from studies of LV dysfunction, and there is a large need for more mechanistic studies of the failing RV to more successfully target therapies. In addition to a need for both pre-clinical and clinical investigations of the right heart, a reductionist approach may be needed to make significant strides in RV therapy. The heart (and the RV) is comprised of multiple different cell types. Due to the fact that cardiac myocytes are the work horses of the heart, heart failure studies have historically been myocyte-centric. However, emerging data from our group and others suggests that


Legend: Mitochondrial alterations in left and right heart failure. Assessment of mitochondrial content, function, dynamics, biogenesis, quality control, and non-energy production roles of mitochondria and changes in HF are summarized. Arrows indicate directional change with heart failure. NC: no consensus.

**Table 2.** Mitochondrial changes in left and right HF.

other cell types within the heart and within the dysfunctional RV may be causally involved in disease progression. Specifically, the cardiac fibroblast is emerging as a vital cell type in regulating cardiac function and pathophysiology [124]. Not only do these cells primarily regulate the extracellular matrix (and thus fibrosis, electrical remodeling, and inflammation), but it is becoming increasingly apparent that they communicate with other cell types such as myocytes to regulate cardiac function. Virtually nothing is known about RV fibroblast mitochondrial metabolism or biology, or how these cell types respond to cardiac stress. In conclusion, the RV is not a thinner, lower pressure LV. Significant physiological and pathophysiological differences separate the two ventricles, and RV-centric approaches are necessary for the identification, repurposing, or development of therapies for RHF.
