Can serial changes of diastolic dysfunction signal incremental risk of chemotherapy-induced heart failure missed by the timing of declining LV ejection fraction?

Cardiologists and oncologists are challenged to optimize safety and effectiveness of chemotherapy. The quest for therapeutic cancer cure is hampered by the risk of cardiotoxicity including potentially fatal clinical heart failure. Management of chemotherapy administration concordant with strategic baseline EF guideline recommendations for cumulative doxorubicin dose-related timing of accurate and precise radionuclide LVEF measurements, and recommendations for termination of therapy have been demonstrated in high-risk patients to change the natural history of heart failure associated with anthracycline cardiotoxicity.– Personalizing cardiooncologic care with specific chemotherapy regimens requires use of techniques and monitoring guidelines which have been proven effective by study of long term outcomes in high-risk patients who have abnormal baseline LVEF or those whose residual cancer risk requires consideration of ongoing chemotherapy. However, evidence of safe and effective management for timing and termination of chemotherapy by serial EF determinations without use of strategic baseline EF guidelines, use of other techniques such as echocardiographic EF and strain imaging, LV and RV volume indices, MIBG, biomarkers, and other novel markers remains undefined by prospective trials in high-risk patients receiving anthracycline and other types of chemotherapy. A potentially important set of novel risk markers of chemotherapy-induced heart failure includes measures of diastolic LV dysfunction which can precede systolic dysfunction in anthracycline and perhaps other chemotherapies and provide a more sensitive and specific predictor of long-term chemotherapy-induced heart failure. The importance of diastolic dysfunction and its progression to diastolic heart failure, now called ‘‘HFpEF’’ or ‘‘heart failure with preserved ejection fraction’’ in clinical cardiology, have been recognized for decades. Early studies identified a role for the negative inotropic and chronotropic therapies including the calcium channel blocker verapamil and beta blockers in the management of diastolic heart failure in hypertension or hypertrophic cardiomyopathy.– Radionuclide ventriculography identified a reduction in the diastolic peak filling rate and prolongation of the time to peak filling associated with HFpEF, and improvements in these dynamic filling characteristics and clinical heart failure with calcium and beta blockade therapy have been demonstrated.– Diastolic dysfunction was identified by Lee et al. with serial radionuclide angiography as an early marker of doxorubicin cardiotoxicity prior to reduction of LVEF in patients receiving doxorubicin. This observation was soon followed by reports of early diastolic dysfunction using Doppler echocardiography of LV filling dynamics during doxorubicin treatment. These observations suggested nearly three decades ago the potential to enhance the diagnostic and prognostic assessment of heart failure risk associated with progressive myocytolysis defined by serial endomyocardial biopsy during anthracycline Reprint requests: Ronald G. Schwartz, MD MS, Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester; ronald_schwartz@urmc.rochester.edu J Nucl Cardiol 2016;23:833–6. 1071-3581/$34.00 Copyright 2015 American Society of Nuclear Cardiology.