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Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

ABSTRACT: Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods and Results: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with left ventricular ejection fraction (LVEF) ≤50% were excluded. CTRCD was defined as a ≥10% decline in LVEF and LVEF <50% after chemotherapy. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. CTRCD was observed in 36 patients (22%). Mean LVEF and global longitudinal strain (GLS) were lower, left ventricular mass index was higher, and ASA was smaller in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (hazard ratio [HR] per 1% decrease 1.20; 95% confidence interval [CI] 1.07-1.35) and ASA (HR per 1° increase 0.97; 95% CI 0.95-0.99) were identified as independent determinants of CTRCD. An integrated discrimination improvement evaluation confirmed the significant incremental value of ASA for developing CTRCD. Conclusions: Smaller ASA was an independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.

SUBMITTER: Nakayama T

PROVIDER: S-EPMC8977195 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

Nakayama Takafumi T Oshima Yoshiko Y Shintani Yasuhiro Y Yamamoto Junki J Yokoi Masashi M Ito Tsuyoshi T Wakami Kazuaki K Kitada Shuichi S Goto Toshihiko T Hashimoto Hiroya H Kusumoto Shigeru S Sugiura Tomonori T Iida Shinsuke S Seo Yoshihiro Y

Circulation reports 20220326 4

Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods and Results: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echo ...[more]

PMID: 35434414

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Project description:ObjectivesThis study sought to determine the relationships between echocardiography-derived measures of myocardial mechanics and cancer therapeutics-related cardiac dysfunction (CTRCD).BackgroundDoxorubicin and trastuzumab are highly effective breast cancer therapies, but have a substantial risk of CTRCD. There is a critical need for the early detection of patients at increased risk of toxicity.MethodsWe performed a prospective, longitudinal cohort study of breast cancer participants undergoing doxorubicin and/or trastuzumab therapy. Echocardiography was performed prior to therapy initiation (baseline) and at standardized follow-up intervals during and after completion of therapy. Ejection fraction (EF), strain, strain rate, and ventricular-arterial coupling (effective arterial elastance [Ea]/end-systolic elastance [Eessb]) were quantitated. CTRCD was defined as a ≥10% reduction in EF from baseline to <50%. Multivariable logistic regression models were used to determine the associations between baseline levels and changes from baseline in echocardiographic measures and CTRCD. Receiver-operating characteristic curves were used to evaluate the predictive ability of these measures.ResultsIn total, 135 participants contributed 517 echocardiograms to the analysis. Over a median follow-up time of 1.9 years (interquartile range: 0.9 to 2.4 years), 21 participants (15%) developed CTRCD. In adjusted models, baseline levels and changes in Ea/Eessb, circumferential strain, and circumferential strain rate were associated with 21% to 38% increased odds of CTRCD (p < 0.001). Changes in longitudinal strain (p = 0.037), radial strain (p = 0.015), and radial strain rate (p = 0.006) were also associated with CTRCD. Ea/Eessb (area under the curve: 0.703; 95% confidence interval: 0.583 to 0.807) and circumferential strain (area under the curve: 0.655; 95% confidence interval: 0.517 to 0.767) demonstrated the greatest predictive utility. Sensitivity analyses using an alternative CTRCD definition did not impact our results.ConclusionsOver an extended follow-up time, ventricular-arterial coupling and circumferential strain were strongly predictive of CTRCD. Our findings suggest a noninvasive strategy to identify high-risk patients prior to, during, and after cardiotoxic cancer therapy.

Project description:ImportanceAnthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use.ObjectiveTo test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.Design, setting, and participantsDouble-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022.InterventionsParticipants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months.Main outcomes and measuresThe primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months.ResultsOf the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups.Conclusions and relevanceAmong patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.Trial registrationClinicalTrials.gov Identifier: NCT02943590.

Dataset Information

Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

Publications

Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

Similar Datasets

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