Running on Empty: Cardiovascular Reserve Capacity and Late Effects of Therapy in Cancer Survivorship

Seminal investigations by Frank 1 and Starling 2 provided thefirst evidence that the heart possesses inherent reserve capacity—a key principle that is a pillar of modern cardiology research and practice. After 150 years of research, we now understand that cardiovascular reserve capacity (CVRC) is determined by the integrative ability of cross-system mechanisms (eg, neurohormonal, central, and peripheral oxygen delivery 3 ), which collectively possess remarkable adaptive capacity. Sequential as well as concurrent pathologic perturbations to either one or more of these mechanisms are offset by initial compensatory adaptive responses in other component systems to maintain whole-body homeostatic regulation—a process termed coordinated adaptation. 4 Unfortunately, CVRC is finite, and continued insults ultimately lead to overt dysfunction (eg, acute coronary syndromes, left ventricular dysfunction). Pathologic impairments in CVRC are etiologicinmanychronicdiseaseconditionsandarethusanintegralconsiderationindailypractice.Thepurposeofthiscommentaryistoprovidean overviewoftheguidingprinciplesandapplicationofCVRCintheoncology setting using early breast cancer as an illustrative model. Measurement of CVRC