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

Ran Klein, Doaa Nadouri, Erin Osler, Christopher Johnson, Susan Dent, Girish Dwivedi

Research output: Contribution to journalArticle

Abstract

Background Trastuzumab (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). Objective The aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC. Patients and methods Patients 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. Results A 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). Conclusion Patients 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.

Original languageEnglish
Pages (from-to)22-29
Number of pages8
JournalNuclear Medicine Communications
Volume40
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

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Neoplasms
Therapeutics
Drug Therapy
Trastuzumab
Anthracyclines
Standard of Care
Radioisotopes
Stroke Volume
Referral and Consultation
Breast Neoplasms
Cardiotoxicity

Cite this

Klein, Ran ; Nadouri, Doaa ; Osler, Erin ; Johnson, Christopher ; Dent, Susan ; Dwivedi, Girish. / Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab-based therapy. In: Nuclear Medicine Communications. 2019 ; Vol. 40, No. 1. pp. 22-29.
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title = "Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab-based therapy",
abstract = "Background Trastuzumab (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). Objective The aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC. Patients and methods Patients 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. Results A 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). Conclusion Patients 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.",
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Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab-based therapy. / Klein, Ran; Nadouri, Doaa; Osler, Erin; Johnson, Christopher; Dent, Susan; Dwivedi, Girish.

In: Nuclear Medicine Communications, Vol. 40, No. 1, 01.01.2019, p. 22-29.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab-based therapy

AU - Klein, Ran

AU - Nadouri, Doaa

AU - Osler, Erin

AU - Johnson, Christopher

AU - Dent, Susan

AU - Dwivedi, Girish

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background Trastuzumab (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). Objective The aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC. Patients and methods Patients 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. Results A 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). Conclusion Patients 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.

AB - Background Trastuzumab (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). Objective The aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC. Patients and methods Patients 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. Results A 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). Conclusion Patients 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.

KW - cardiotoxicity

KW - chemotherapy

KW - diastolic dysfunction

KW - early detection

KW - radionuclide angiography

KW - radionuclide multigated acquisition

KW - trastuzumab

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DO - 10.1097/MNM.0000000000000941

M3 - Article

VL - 40

SP - 22

EP - 29

JO - Nuclear Medicine Communications

JF - Nuclear Medicine Communications

SN - 0143-3636

IS - 1

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