Therapeutic Efficacy

Late gadolinium enhancement images from a healthy
control (A) and patient treated with anthracycline (B),
with higher extracellular volume in the anthracycline
treated patient (D).

Quantitative non-invasive cardiovascular imaging can serve as a powerful surrogate to evaluate therapeutic efficacy. Program investigators have pursued a multi-modality approach including PET, MR, and CT.

Statins to Prevent Cardiotoxicity from Anthracyclines
There is an increased risk for heart failure after anthracycline-based chemotherapy. The increased risk of heart failure after anthracyclines is due to an increase in myocardial fibrosis and a reduction in the left ventricular ejection fraction. In animal studies and preliminary human data, statins have been associated with a reduction in myocardial fibrosis and a higher LVEF. STOP-CA will test, in a randomized, double-blind, multi-center, placebo-controlled clinical trial whether statins at the time of anthracycline-based chemotherapy is associated with a reduction in myocardial fibrosis and preservation of the left ventricular ejection fraction using cardiac MRI.

Neilan TG at al, Myocardial extracellular volume by cardiac magnetic resonance imaging in patients treated with anthracycline-based chemotherapy. Am J Cardiol 2013;111(5):717-22.

Neilan TG et al. Characterization of the Changes in Cardiac Structure and Function in Mice Treated With Anthracyclines Using Serial Cardiac Magnetic Resonance Imaging. Circ Cardiovasc Imaging. 2016 Dec;9(12).

Neilan TG et al. Myocardial extracellular volume fraction from T1 measurements in healthy volunteers and mice: relationship to aging and cardiac dimensions. JACC: Cardiovascular Imaging 2013;6(6):672-83.

A) Enrollment and B) 1 year followup CT of enlarging
coronary artery plaque (arrows).

Statins to prevent cardiovascular events and reduce coronary plaque in HIV
HIV infection doubles the risk of major adverse cardiovascular events, independent of traditional risk factors such as high cholesterol. Preliminary work by our group found that one year of atorvastatin can reduce coronary plaque as measured on CT in HIV. The ongoing REPRIEVE trial (n = 6,500) will test whether pitavastatin can prevent adverse cardiovascular events in HIV. REPRIEVE includes a mechanistic CT substudy (n = 800) which will determine the effect on coronary plaque using serial CT, and place these changes in the context of blood markers of immune activation and inflammation.

Lo J et al. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV 2015;2(2):e52-63.

PET/CT for arterial inflammation
FDG PET/CT has been used extensively to characterize atherosclerotic plaque metabolism (an index of inflammatory activity). Program investigators have studied dozens of drug classes in the context of double-blind, placebo-controlled multi-center trials. Thus far, for all of the 5 drug classes for which there is both PET/CT and clinical event data, there has been concordance between change in imaging and reductions in outcomes. Accordingly, relatively small and swift imaging studies may facilitate the identification of the most promising drugs.

 

 

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