Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy
Paaladinesh ThavendiranathanTomoko NegishiEmily SomersetKazuaki NegishiMartin PěničkaJulie LemieuxSvend AakhusSakiko MiyazakiMitra ShiraziMaurizio GalderisiThomas H. MarwickKazuaki NegishiBen CostelloLeah WrightAndré La GerchePhilip M. MottramLiza ThomasMitra ShiraziMartin PěničkaTomáš OndrúšStéphanie SeldrumPaaladinesh ThavendiranathanEitan AmirBabitha ThampinathanJulie LemieuxMarc‐André CôtéJonathan DebloisManish BansalMaurizio GalderisiCiro SantoroKoji KurosawaNobuaki FukudaHirotsugu YamadaYoshihito SaijoSakiko MiyazakiMasaki IzumoTomomi SuzukiKazuko TajiriGoo‐Yeong ChoSvend AakhusKlaus MurbræchRichard J. MasseyWojciech KosmalaMaciej SińskiDragoş VinereanuDiana MihalceaBogdan A. PopescuAndreea CălinEvgeny ShkolnikJosé BanchsShelby Kutty
Why the study?
Does global longitudinal strain (GLS)-guided cardioprotective therapy prevent reduction in LVEF and the development of cancer therapy-related cardiac dysfunction in high-risk patients undergoing cardiotoxic chemotherapy compared to LVEF-guided therapy?
Study Design
Type
RCT (n=331)
Randomization
Randomized
Multicenter
Yes
Structured PICO
Does global longitudinal strain (GLS)-guided cardioprotective therapy prevent reduction in LVEF and the development of cancer therapy-related cardiac dysfunction in high-risk patients undergoing cardiotoxic chemotherapy compared to LVEF-guided therapy?
P
Population
331 anthracycline-treated patients with another heart failure risk factor (mean age 54, 94% women), mostly with breast cancer, followed for 1 year.
I
Intervention
Cardioprotective therapy (CPT) initiation guided by a ≥12% relative reduction in global longitudinal strain (GLS)
C
Comparator
Usual care: cardioprotective therapy (CPT) initiation guided by a >10% absolute reduction of LVEF
O
Outcome
Change in left ventricular ejection fraction (LVEF) over 1 yearsurrogate
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The study failed to meet its primary endpoint, with the difference in LVEF from baseline to 1 year being −3.0% in the LVEF-guided arm versus −2.7% in the GLS-guided arm (p = 0.69). The investigators instead highlighted the results of the secondary endpoint of "cancer therapy–related cardiac dysfunction" occurring at any point during follow-up, which occurred in 13.7% of patients in the LVEF-guided arm and 5.8% of patients in the GLS-guided arm. Importantly, another key secondary outcome, proportion of patients with LVEF <55% at 1 year, was no different between the 2 arms: 21% in the LVEF-guided arm versus 22% in the GLS-guided arm.”
“one of the weaknesses of the initial SUCCOUR trial was that the majority of patients had no significant changes in the GLS, thus did not need cardioprotection.”
THThomas H. MarwickCardiologist, Baker Heart and Diabetes Institute
“More global longitudinal strain–guided patients were identified as having subclinical left ventricular dysfunction, with consequent initiation of cardioprotective therapy, but unlike the correspondents, we were surprised and disappointed that this process did not provide a meaningful difference in outcome.”
Implication
While the overall change in LVEF was not significantly different, GLS-guided cardioprotective therapy significantly reduced the incidence of cancer therapy-related cardiac dysfunction compared to EF-guided management.
Abstract
Background In patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardioprotective therapy (CPT) is constrained by the low sensitivity of ejection fraction (EF) for minor changes in left ventricular (LV) function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT. Objectives This study sought to identify whether GLS-guided CPT prevents reduction in LVEF and development of CTRCD in high-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. Methods In this international, multicenter, prospective, randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n = 166) or >10% absolute reduction of LVEF (n = 165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction of >5% or >10% asymptomatic to <55%) over 1 year. Results Of 331 randomized patients, 2 died, and 22 withdrew consent or were lost to follow-up. Among 307 patients (age: 54 ± 12 years; 94% women; baseline LVEF: 59 ± 6%; GLS: -20.6 ± 2.4%) with a median (interquartile range) follow-up of 1.02 years (0.98 to 1.07 years), most (n = 278) had breast cancer. Heart failure risk factors were prevalent: 29% had hypertension, and 13% had diabetes mellitus. At the 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the 2 arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs. 13.7%; p = 0.02), and the 1-year EF was 57 ± 6% versus 55 ± 7% (p = 0.05). Patients who received CPT in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1 ± 10.9% vs. 2.9 ± 7.4%; p = 0.03). Conclusions Although the change in LVEF was not different between the 2 arms as a whole, when patients who received CPT were compared, those in the GLS-guided arm had a significantly lower reduction in LVEF at 1 year follow-up. Furthermore, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).
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Cite This Study
Thavendiranathan et al. (2020) conducted an RCT in Cancer therapy-related cardiac dysfunction (CTRCD) (n=331). GLS-guided cardioprotective therapy initiation vs. EF-guided cardioprotective therapy initiation (>10% absolute reduction of LVEF) was evaluated on change in LVEF.