Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab-based therapy

Abstract

BackgroundTrastuzumab (T) and anthracycline (A)-based chemotherapy is considered the standard of care in human epidermal growth factor receptor-2+ overexpressing breast cancer, but requires monitoring for known cardiotoxicity using left ventricular (LV) ejection fraction (EF) every 3–4 months during treatment. It is not conclusively established whether diastolic dysfunction (DD) precedes LVEF decrease in patients developing trastuzumab-induced cardiotoxicity (TIC).ObjectiveThe aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC.Patients and methodsPatients treated with T±A-based chemotherapy who had undergone multigated acquisition were selected by date range (January 2006–September 2015). Up to four scans were analyzed per patient: (a) pre-A therapy, (b) pre-T therapy, (c) 4 months into T therapy, and (d) at end of T therapy. Baseline referred to the first scan of each patient (i.e. pre-A or pre-T). LV systolic and DD were defined as follows: EF less than 50% or a 10-point decrease from baseline and LV peak filling rate (PFR) less than 2.5 end-diastolic volume/s and time to peak LV filling rates (TPFR) greater than 180 ms, respectively.ResultsA total of 202 patients were screened for this study, of whom 153 had received A therapy (5.1±4.1 months duration) before T, 192 had 4 months of follow-up data, and 146 had 4 months of follow-up data and beyond (10.5±5.0 months). LVEF decreased with A and T therapy (P<0.005), but remained stable between 4 months and the final exam (P=0.26). In patients with normal diastolic function at baseline (45.5%), PFR decreased with A and T, and DD preceded SD by 73 days on average. In the remaining patients, with abnormal diastolic function at baseline (54.5%), PFR did not change over the course of treatment (P>0.1), nor did TPFR (P>0.3).ConclusionPatients with normal diastolic function at baseline receiving trastuzumab±anthracycline adjuvant therapy may develop DD before SD, therefore offering an opportunity for early referral to cardiologists to optimize cardiovascular risk factors and manage cardiotoxicity.

Diastolic assessment by CZT-SPECT: Could it be the next best thing for the detection of subclinical chemotherapy-induced cardiotoxicity?

“…26,27 More recently, in their study of 202 patients, Klein et al showed that, following exposure to trastuzumab (with or without anthracyclines), patients who have normal diastolic function at baseline may develop diastolic dysfunction prior to evident drop in their LVEF. 28 These findings solidify the potential role for the new CZT-SPECT technology in the evaluation of patients at risk for CTRCD by a timelier risk stratification of the subset of patients who would benefit from earlier referral to Cardiology, more intensive monitoring, and more aggressive optimization of their risk factors to avoid development of complications.…”

Diastolic function as an early marker for systolic dysfunction and all‐cause mortality among cancer patients

“…Although the development of diastolic dysfunction in cancer patients has been previously suggested to occur and to precede systolic dysfunction, 13,25,26 other studies have contradicted such results 27,28 . Such discrepancy in evidence has led the current Expert Consensus for Multimodality Imaging Evaluation of the American Society of Echocardiography 16 to conclude that diastolic parameters have not been found to have a prognostic value in relation to systolic dysfunction development.…”

Predictors of Early or Delayed Diastolic Dysfunction After Anthracycline-Based or Nonanthracycline Chemotherapy: A Pharmacological Appraisal

“…Asymptomatic diastolic dysfunction (DD) has long been suspected to represent an early manifestation of cardiotoxicity induced by cancer drugs. DD preceded systolic dysfunction in breast cancer patients treated with anthracyclines, with or without subsequent treatment with the anti-ErbB2 monoclonal antibody, trastuzumab (Klein et al, 2019). DD was also shown to precede, or to accompany with heart failure (HF) and other cardiac events that occurred years or decades after anthracycline treatment of childhood or adult cancer (Carver et al, 2007;Armstrong et al, 2015).…”