Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: a population-based study.

Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VO2peak), and prevent cardiac dysfunction.Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52). Functional measures were performed at baseline, at 4 weeks after AC (4 months), and at 12 months, comprising: (1) cardiopulmonary exercise testing to quantify VO2peak and functional disability (VO2peak ≤18.0 mL·kg-1·min-1); (2) cardiac reserve (response from rest to peak exercise), quantified with exercise cardiac magnetic resonance measures to determine changes in left and right ventricular ejection fraction, cardiac output, and stroke volume; (3) standard-of-care echocardiography-derived resting left ventricular ejection fraction and global longitudinal strain; and (4) biochemistry (troponin and BNP [B-type natriuretic peptide]).Among 104 participants randomized, greater study attrition was observed among UC participants (P=0.031), with 93 women assessed at 4 months (ExT, n=49; UC, n=44) and 87 women assessed at 12 months (ExT, n=49; UC, n=38). ExT attenuated functional disability at 4 months (odds ratio, 0.32 [95% CI, 0.11-0.94]; P=0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06-1.12]; P=0.07). In a per-protocol analysis, functional disability was prevented entirely at 12 months among participants adherent to ExT (ExT, 0% versus UC, 20%; P=0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg-1·min-1 improvement in VO2peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (P<0.001 for all). There was no effect of ExT on resting measures of left ventricular function. Postchemotherapy troponin increased less in ExT than in UC (8-fold versus 16-fold increase; P=0.002). There were no changes in BNP in either group.In women with early-stage breast cancer undergoing AC, 12 months of ExT did not attenuate functional disability, but provided large, clinically meaningful benefits on VO2peak and cardiac reserve.URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12617001408370. 

Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study

The development of various antitumor drugs has significantly improved the survival of patients with cancer. Many first-line chemotherapy drugs are cytotoxic and the cardiotoxicity is one of the most significant effects that could leads to poor prognosis and decreased survival rate. Cancer treatment include traditional anthracycline drugs, as well as some new targeted drugs such as trastuzumab and ICIs. These drugs may directly or indirectly cause cardiovascular injury through different mechanisms, and lead to increasing the risk of cardiovascular disease or accelerating the development of cardiovascular disease. Cardiotoxicity is clinically manifested by arrhythmia, decreased cardiac function, or even sudden death. The cardiotoxicity caused by traditional chemotherapy drugs such as anthracyclines are significantly known. The cardiotoxicity of some new antitumor drugs such like immune checkpoint inhibitors (ICIs) is also relatively clear and requiring further observation and verification. This review is focused on major three drugs with relatively high incidence of cardiotoxicity and poor prognosis and intended to provide an update on the clinical complications and outcomes of these drugs, and we innovatively summarize the monitoring status of survivors using these drugs and discuss the biomarkers and non-invasive imaging features to identify early cardiotoxicity. Finally, we summarize the prevention that decreasing antitumor drugs-induced cardiotoxicity.

/pdf/clinical-manifestations-monitoring-and-prognosis-a-review-of-jewya7l6.pdf

Clinical Manifestations, Monitoring, and Prognosis: A Review of Cardiotoxicity After Antitumor Strategy

Determinants of oxygen utilization in breast cancer: Similarities between heart failure with preserved ejection fraction.

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.22.00111?role=tab

Toward a Better Understanding of the Differential Impact of Heart Failure Phenotypes After Breast Cancer

Breast cancer (BC) survivors experience an increased burden of long-term comorbidities, including heart failure (HF). However, there is limited understanding of the risk for the development of HF subtypes, such as HF with preserved ejection fraction (HFpEF), in BC survivors.This study sought to estimate the incidence of HFpEF and HF with reduced ejection fraction (HFrEF) in postmenopausal BC survivors and to identify lifestyle and cardiovascular risk factors associated with HF subtypes.Within the Women's Health Initiative, participants with an adjudicated diagnosis of invasive BC were followed to determine the incidence of hospitalized HF, for which adjudication procedures determined left ventricular ejection fraction. We calculated cumulative incidences of HF, HFpEF, and HFrEF. We estimated HRs for risk factors in relation to HF, HFpEF, and HFrEF using Cox proportional hazards survival models.In 2,272 BC survivors (28.6% Black and 64.9% White), the cumulative incidences of hospitalized HFpEF and HFrEF were 6.68% and 3.96%, respectively, over a median of 7.2 years (IQR: 3.6-12.3 years). For HFpEF, prior myocardial infarction (HR: 2.83; 95% CI: 1.28-6.28), greater waist circumference (HR: 1.99; 95% CI: 1.14-3.49), and smoking history (HR: 1.65; 95% CI: 1.01-2.67) were the strongest risk factors in multivariable models. With the exception of waist circumference, similar patterns were observed for HFrEF, although none were significant. In relation to those without HF, the risk of overall mortality in BC survivors with hospitalized HFpEF was 5.65 (95% CI: 4.11-7.76), and in those with hospitalized HFrEF, it was 3.77 (95% CI: 2.51-5.66).In this population of older, racially diverse BC survivors, the incidence of HFpEF, as defined by HF hospitalizations, was higher than HFrEF. HF was also associated with an increased mortality risk. Risk factors for HF were largely similar to the general population with the exception of prior myocardial infarction for HFpEF. Notably, both waist circumference and smoking represent potentially modifiable factors. 

https://doi.org/10.1016/j.jaccao.2022.01.099

Lifestyle and Cardiovascular Risk Factors Associated With Heart Failure Subtypes in Postmenopausal Breast Cancer Survivors

Checkpoint-inhibitor immunotherapies have had a profound effect in the treatment of cancer by inhibiting down-regulation of T-cell response to malignancy. The cardiotoxic potential of these agents was first described in murine models and, more recently, in numerous clinical case reports of pericarditis, myocarditis, pericardial effusion, cardiomyopathy, and new arrhythmias. The objective of our study was to determine the frequency of and associated risk factors for cardiotoxic events in patients treated with immune checkpoint inhibitors.Medical records of patients who underwent immunotherapy with durvalumab, ipilimumab, nivolumab, and pembrolizumab at Wake Forest Baptist Health were reviewed. We collected retrospective data regarding sex, cancer type, age, and cardiovascular disease risk factors and medications. We aimed to identify new diagnoses of heart failure, atrial fibrillation, ventricular fibrillation/tachycardia, myocarditis, and pericarditis after therapy onset. To assess the relationship between CVD risk factors and the number of cardiac events, a multivariate model was applied using generalized linear regression. Incidence rate ratios were calculated for every covariate along with the adjusted P-value. We applied a multivariate model using logistic regression to assess the relationship between CVD risk factors and mortality. Odds ratios were calculated for every covariate along with the adjusted P-value. Adjusted P-values were calculated using multivariable regression adjusting for other covariates.Review of 538 medical records revealed the following events: 3 ventricular fibrillation/tachycardia, 12 pericarditis, 11 atrial fibrillation with rapid ventricular rate, 0 myocarditis, 8 heart failure. Significant risk factors included female gender, African American race, and tobacco use with IRR 3.34 (95% CI 1.421, 7.849; P = 0.006), IRR 3.39 (95% CI 1.141, 10.055; P = 0.028), and IRR 4.21 (95% CI 1.289, 13.763; P = 0.017) respectively.Our study revealed 34 significant events, most frequent being pericarditis (2.2%) and atrial fibrillation (2.0%) with strongest risk factors being female gender, African American race, and tobacco use. Patients who meet this demographic, particularly those with planned pembrolizumab treatment, may benefit from early referral to a cardio-oncologist. Further investigation is warranted on the relationship between CTLA-4 and PD-L1 expression and cardiac adverse events with ICIs, particularly for these subpopulations. 

/pdf/cardiotoxicity-risk-factors-with-immune-checkpoint-191o5exa.pdf

Cardiotoxicity risk factors with immune checkpoint inhibitors

https://escholarship.org/content/qt43v9k54m/qt43v9k54m.pdf?t=rdsob8

Training and Career Development in Cardio-Oncology Translational and Implementation Science.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

/pdf/correction-to-cardio-oncology-preventative-care-racial-and-1uo1ar1f.pdf

Mary Branch

Papers

Lifestyle and Cardiovascular Risk Factors Associated With Heart Failure Subtypes in Postmenopausal Breast Cancer Survivors

Cardiotoxicity risk factors with immune checkpoint inhibitors

Training and Career Development in Cardio-Oncology Translational and Implementation Science.

Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

Correction to: Cardio-oncology Preventative Care: Racial and Ethnic Disparities