Impact of Preexisting Heart Failure on Treatment and Outcomes in Older Patients With Hodgkin Lymphoma.

Background: Older patients with Hodgkin lymphoma (HL) often have comorbid cardiovascular disease; however, the impact of pre-existing heart failure (HF) on the management and outcomes of HL is unknown. Objectives: The aim of this study was to assess the prevalence of pre-existing HF in older patients with HL and its impact on treatment and outcomes. Methods: Linked Surveillance, Epidemiology, and End Results (SEER) and Medicare data from 1999 to 2016 were used to identify patients 65 years and older with newly diagnosed HL. Pre-existing HF, comorbidities, and cancer treatment were ascertained from billing codes and cause-specific mortality from SEER. The associations between pre-existing HF and cancer treatment were estimated using multivariable logistic regression. Cause-specific Cox proportional hazards models adjusted for comorbidities and cancer treatment were used to estimate the association between pre-existing HF and cause-specific mortality. Results: Among 3,348 patients (mean age 76 ± 7 years, 48.6% women) with newly diagnosed HL, pre-existing HF was present in 437 (13.1%). Pre-existing HF was associated with a lower likelihood of using anthracycline-based chemotherapy regimens (OR: 0.42; 95% CI: 0.29-0.60) and a higher likelihood of lymphoma mortality (HR: 1.25; 95% CI: 1.06-1.46) and cardiovascular mortality (HR: 2.57; 95% CI: 1.96-3.36) in models adjusted for comorbidities. One-year lymphoma mortality cumulative incidence was 37.4% (95% CI: 35.5%-39.5%) with pre-existing HF and 26.3% (95% CI: 25.0%-27.6%) without pre-existing HF. The cardioprotective medications dexrazoxane and liposomal doxorubicin were used in only 4.2% of patients. Conclusions: Pre-existing HF in older patients with newly diagnosed HL is common and associated with higher 1-year mortality. Strategies are needed to improve lymphoma and cardiovascular outcomes in this high-risk population.

Harnessing multi-source data for individualized care in Hodgkin Lymphoma.

Hodgkin lymphoma is a rare, but highly curative form of cancer, primarily afflicting adolescents and young adults. Despite multiple seminal trials over the past twenty years, there is no single consensus-based treatment approach beyond use of multi-agency chemotherapy with curative intent. The use of radiation continues to be debated in early-stage disease, as part of combined modality treatment, as well as in salvage, as an important form of consolidation. While short-term disease outcomes have varied little across these different approaches across both early and advanced stage disease, the potential risk of severe, longer-term risk has varied considerably. Over the past decade novel therapeutics have been employed in the retrieval setting in preparation to and as consolidation after autologous stem cell transplant. More recently, these novel therapeutics have moved to the frontline setting, initially compared to standard-of-care treatment and later in a direct head-to-head comparison combined with multi-agent chemotherapy. In 2018, we established the HoLISTIC Consortium, bringing together disease and methods experts to develop clinical decision models based on individual patient data to guide providers, patients, and caregivers in decision-making. In this review, we detail the steps we followed to create the master database of individual patient data from patients treated over the past 20 years, using principles of data science. We then describe different methodological approaches we are taking to clinical decision making, beginning with clinical prediction tools at the time of diagnosis, to multi-state models, incorporating treatments and their response. Finally, we describe how simulation modeling can be used to estimate risks of late effects, based on cumulative exposure from frontline and salvage treatment. The resultant database and tools employed are dynamic with the expectation that they will be updated as better and more complete information becomes available.

Atherosclerotic Cardiovascular Disease Risk and Longitudinal Risk Factor Management Among Patients With Breast Cancer.

BACKGROUND: Cardiovascular disease is the leading cause of noncancer mortality for breast cancer survivors. Data are limited regarding patient-level atherosclerotic cardiovascular disease (ASCVD) risk estimation and preventive medication use. This study aimed to characterize ASCVD risk and longitudinal preventive medication use for a cohort of patients with nonmetastatic breast cancer. PATIENTS AND METHODS: This retrospective cohort study included 326 patients at an academic medical center in Boston, Massachusetts diagnosed with nonmetastatic breast cancer or ductal carcinoma in situ from January 2009 through December 2015. Patient demographics, clinical characteristics, laboratory studies, medication exposure, and incident cardiovascular outcomes were collected. Estimated 10-year ASCVD risk was calculated for all patients from nonlaboratory clinical parameters. RESULTS: Median follow up time was 6.5 years (IQR 5.0, 8.1). At cancer diagnosis, 23 patients (7.1%) had established ASCVD. Among those without ASCVD, 10-year estimated ASCVD risk was ≥20% for 77 patients (25.4%) and 7.5% to <20% for 114 patients (37.6%). Two-hundred and sixteen patients (66.3%) had an indication for lipid-lowering therapy at cancer diagnosis, 123 of whom (57.0%) received a statin during the study. Among 100 patients with ASCVD or estimated 10-year ASCVD risk ≥20%, 92 (92.0%) received an antihypertensive medication during the study. Clinic blood pressure >140/90 mmHg was observed in 33.0% to 55.6% of these patients at each follow up assessment. CONCLUSION: A majority of patients in this breast cancer cohort had an elevated risk of ASCVD at the time of cancer diagnosis. Modifiable ASCVD risk factors were frequently untreated or uncontrolled in the years following cancer treatment.

Hodgkin lymphoma treatment for older persons in the modern era.

There has been a renewed effort globally in the study of older Hodgkin lymphoma (HL) patients, generating a multitude of new data. For prognostication, advancing age, comorbidities, altered functional status, Hispanic ethnicity, and lack of dose intensity (especially without anthracycline) portend inferior survival. Geriatric assessments (GA), including activities of daily living (ADL) and comorbidities, should be objectively measured in all patients. In addition, proactive multidisciplinary medical management is recommended (eg, geriatrics, cardiology, primary care), and pre-phase therapy should be considered for most patients. Treatment for fit older HL patients should be given with curative intent, including anthracyclines, and bleomycin should be minimized (or avoided). Brentuximab vedotin given sequentially before and after doxorubicin, vinblastine, dacarbazine (AVD) chemotherapy for untreated patients is tolerable and effective, and frontline checkpoint inhibitor/AVD platforms are rapidly emerging. Therapy for patients who are unfit or frail, whether due to comorbidities and/or ADL loss, is less clear and should be individualized with consideration of attenuated anthracycline-based therapy versus lower-intensity regimens with inclusion of brentuximab vedotin +/- checkpoint inhibitors. For all patients, there should be clinical vigilance with close monitoring for treatment-related toxicities, including neurotoxicity, cardiopulmonary, and infectious complications. Finally, active surveillance for "postacute" complications 1 to 10 years post therapy, especially cardiac disease, is needed for cured patients. Altogether, therapy for older HL patients should include anthracycline-based therapy in most cases, and novel targeted agents should continue to be integrated into treatment paradigms, with more research needed on how best to utilize GAs for treatment decisions.

Adverse Cardiovascular Events Associated With Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Metastatic Breast Cancer.

Background Cyclin-dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor-positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Methods and Results Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine-Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all-cause death was studied using Cox proportional hazard models. Propensity-weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person-years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines (P=0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased all-cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98-8.05]; and 5.88 [95% CI, 3.56-9.73], respectively). Conclusions CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.

Cardiac Cachexia in Left Ventricular Assist Device Recipients and the Implications of Weight Gain Early After Implantation.

Background Severe cardiac cachexia or malnutrition are commonly considered relative contraindications to left ventricular assist device (LVAD) implantation, but post-LVAD prognosis for patients with cachexia is uncertain. Methods and Results Intermacs (Interagency Registry for Mechanically Assisted Circulatory Support) 2006 to 2017 was queried for the preimplantation variable cachexia/malnutrition. Cox proportional hazards modeling examined the relationship between cachexia and LVAD outcomes. Of 20 332 primary LVAD recipients with available data, 516 (2.54%) were reported to have baseline cachexia and had higher risk baseline characteristics. Cachexia was associated with higher mortality during LVAD support (unadjusted hazard ratio [HR], 1.36 [95% CI, 1.18-1.56]; P<0.0001), persisting after adjustment for baseline characteristics (adjusted HR, 1.23 [95% CI, 1.0-1.42]; P=0.005). Mean weight change at 12 months was +3.9±9.4 kg. Across the cohort, weight gain ≥5% during the first 3 months of LVAD support was associated with lower mortality (unadjusted HR, 0.90 [95% CI, 0.84-0.98]; P=0.012; adjusted HR, 0.89 [95% CI, 0.82-0.97]; P=0.006). Conclusions The proportion of LVAD recipients recognized to have cachexia preimplantation was low at 2.5%. Recognized cachexia was independently associated with higher mortality during LVAD support. Early weight gain ≥5% was independently associated with lower mortality during subsequent LVAD support.

Using cultured canine cardiac slices to model the autophagic flux with doxorubicin.

Chemotherapy-induced impairment of autophagy is implicated in cardiac toxicity induced by anti-cancer drugs. Imperfect translation from rodent models and lack of in vitro models of toxicity has limited investigation of autophagic flux dysregulation, preventing design of novel cardioprotective strategies based on autophagy control. Development of an adult heart tissue culture technique from a translational model will improve investigation of cardiac toxicity. We aimed to optimize a canine cardiac slice culture system for exploration of cancer therapy impact on intact cardiac tissue, creating a translatable model that maintains autophagy in culture and is amenable to autophagy modulation. Canine cardiac tissue slices (350 µm) were generated from left ventricular free wall collected from euthanized client-owned dogs (n = 7) free of cardiovascular disease at the Foster Hospital for Small Animals at Tufts University. Cell viability and apoptosis were quantified with MTT assay and TUNEL staining. Cardiac slices were challenged with doxorubicin and an autophagy activator (rapamycin) or inhibitor (chloroquine). Autophagic flux components (LC3, p62) were quantified by western blot. Cardiac slices retained high cell viability for >7 days in culture and basal levels of autophagic markers remained unchanged. Doxorubicin treatment resulted in perturbation of the autophagic flux and cell death, while rapamycin co-treatment restored normal autophagic flux and maintained cell survival. We developed an adult canine cardiac slice culture system appropriate for studying the effects of autophagic flux that may be applicable to drug toxicity evaluations.

Association of Preexisting Heart Failure With Outcomes in Older Patients With Diffuse Large B-Cell Lymphoma.

Importance: Anthracycline-containing regimens are highly effective for diffuse large B-cell lymphoma (DLBCL); however, patients with preexisting heart failure (HF) may be less likely to receive anthracyclines and may be at higher risk of lymphoma mortality. Objective: To assess the prevalence of preexisting HF in older patients with DLBCL and its association with treatment patterns and outcomes. Design, Setting, and Participants: This longitudinal cohort study used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry from 1999 to 2016. The SEER registry is a system of population-based cancer registries, capturing more than 25% of the US population. Linkage to Medicare offers additional information from billing claims. This study included individuals 65 years and older with newly diagnosed DLBCL from 2000 to 2015 with Medicare Part A or B continuously in the year prior to lymphoma diagnosis. Data were analyzed from September 2020 to December 2022. Exposures: Preexisting HF in the year prior to DLBCL diagnosis ascertained from billing codes required one of the following: (1) 1 primary inpatient discharge diagnosis, (2) 2 outpatient diagnoses, (3) 3 secondary inpatient discharge diagnoses, (4) 3 emergency department diagnoses, or (5) 2 secondary inpatient discharge diagnoses plus 1 outpatient diagnosis. Main Outcomes and Measures: The primary outcome was anthracycline-based treatment. The secondary outcomes were (1) cardioprotective medications and (2) cause-specific mortality. The associations between preexisting HF and cancer treatment were estimated using multivariable logistic regression. The associations between preexisting HF and cause-specific mortality were evaluated using cause-specific Cox proportional hazards models with adjustment for comorbidities and cancer treatment. Results: Of 30 728 included patients with DLBCL, 15 474 (50.4%) were female, and the mean (SD) age was 77.8 (7.2) years. Preexisting HF at lymphoma diagnosis was present in 4266 patients (13.9%). Patients with preexisting HF were less likely to be treated with an anthracycline (odds ratio, 0.55; 95% CI, 0.49-0.61). Among patients with preexisting HF who received an anthracycline, dexrazoxane or liposomal doxorubicin were used in 78 of 1119 patients (7.0%). One-year lymphoma mortality was 41.8% (95% CI, 40.5-43.2) with preexisting HF and 29.6% (95% CI, 29.0%-30.1%) without preexisting HF. Preexisting HF was associated with higher lymphoma mortality in models adjusting for baseline and time-varying treatment factors (hazard ratio, 1.24; 95% CI, 1.18-1.31). Conclusions and Relevance: In this study, preexisting HF in patients with newly diagnosed DLBCL was common and was associated with lower use of anthracyclines and lower use of any chemotherapy. Trials are needed for this high-risk population.

The effect of tablet computer-based telemonitoring added to an established telephone disease management program on heart failure hospitalizations: The Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) III Randomized Controlled Trial.

BACKGROUND: Mobile health applications are becoming increasingly common. Prior work has demonstrated reduced heart failure (HF) hospitalizations with HF disease management programs; however, few of these programs have used tablet computer-based technology. METHODS: Participants with a diagnosis of HF and at least 1 high risk feature for hospitalization were randomized to either an established telephone-based disease management program or the same disease management program with the addition of remote monitoring of weight, blood pressure, heart rate and symptoms via a tablet computer for 90 days. The primary endpoint was the number of days hospitalized for HF assessed at 90 days. RESULTS: From August 2014 to April 2019, 212 participants from 3 hospitals in Massachusetts were randomized 3:1 to telemonitoring-based HF disease management (n = 159) or telephone-based HF disease management (n = 53) with 98% of individuals in both study groups completing the 90 days of follow-up. There was no significant difference in the number of days hospitalized for HF between the telemonitoring disease management group (0.88 ± 3.28 days per patient-90 days) and the telephone-based disease management group (1.00 ± 2.97 days per patient-90 days); incidence rate ratio 0.82 (95% confidence interval, 0.43-1.58; P = .442). CONCLUSIONS: The addition of tablet-based telemonitoring to an established HF telephone-based disease management program did not reduce HF hospitalizations; however, study power was limited.

Taking Care of Us© (TCU) study protocol: feasibility and acceptability of a dyadic intervention for couples living with heart failure.

BACKGROUND: There are more than 1 million hospital admissions and 3 million emergency visits for heart failure in the USA annually. Although spouse/partners make substantial contributions to the management of heart failure and experience poor health and high levels of care strain, they are rarely the focus of heart failure interventions. This protocol describes a pilot randomized controlled trial that tests the feasibility, acceptability, and preliminary change in outcomes of a seven-session couple-based intervention called Taking Care of Us© (TCU). The TCU© intervention is grounded in the theory of dyadic illness management and was developed to promote collaborative illness management and better physical and mental health of adults with heart failure and their partners. METHODS: A two-arm randomized controlled trial will be conducted. Eligible adults with heart failure and their co-residing spouse/partner will be recruited from a clinical site in the USA and community/social media outreach and randomized to either the TCU© intervention or to a control condition (SUPPORT©) that offers education around heart failure management. The target sample is 60 couples (30 per arm). TCU© couples will receive seven sessions over 2 months via Zoom; SUPPORT© couples will receive three sessions over 2 months via Zoom. All participants will complete self-report measures at baseline (T1), post-treatment (T2), and 3 months post-treatment (T3). Acceptability and feasibility of the intervention will be examined using both closed-ended and open-ended questions as well as enrollment, retention, completion, and satisfaction metrics. Preliminary exploration of change in outcomes of TCU© on dyadic health, dyadic appraisal, and collaborative management will also be conducted. DISCUSSION: Theoretically driven, evidence-based dyadic interventions are needed to optimize the health of both members of the couple living with heart failure. Results from this study will provide important information about recruitment and retention and benefits and drawbacks of the TCU© program to directly inform any needed refinements of the program and decision to move to a main trial. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04737759) registered on 27 January 2021.

The Advanced-Stage Hodgkin Lymphoma International Prognostic Index: Development and Validation of a Clinical Prediction Model From the HoLISTIC Consortium.

PURPOSE: The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource individual patient data from the Hodgkin Lymphoma International Study for Individual Care consortium, we developed and validated a modern clinical prediction model. METHODS: Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines was performed on 4,022 patients with newly diagnosed advanced-stage adult cHL from eight international phase III clinical trials, conducted from 1996 to 2014. External validation was performed on 1,431 contemporaneously treated patients from four real-world cHL registries. To consider association over a full range of continuous variables, we evaluated piecewise linear splines for potential nonlinear relationships. Five-year progression-free survival (PFS) and overall survival (OS) were estimated using Cox proportional hazard models. RESULTS: The median age in the development cohort was 33 (18-65) years; nodular sclerosis was the most common histology. Kaplan-Meier estimators were 0.77 for 5-year PFS and 0.92 for 5-year OS. Significant predictor variables included age, sex, stage, bulk, absolute lymphocyte count, hemoglobin, and albumin, with slight variation for PFS versus OS. Moreover, age and absolute lymphocyte count yielded nonlinear relationships with outcomes. Optimism-corrected c-statistics in the development model for 5-year PFS and OS were 0.590 and 0.720, respectively. There was good discrimination and calibration in external validation and consistent performance in internal-external validation. Compared with the IPS, there was superior discrimination for OS and enhanced calibration for PFS and OS. CONCLUSION: We rigorously developed and externally validated a clinical prediction model in > 5,000 patients with advanced-stage cHL. Furthermore, we identified several novel nonlinear relationships and improved the prediction of patient outcomes. An online calculator was created for individualized point-of-care use.

Association between postoperative hemodynamic metrics of pulmonary hypertension and right ventricular dysfunction and clinical outcomes after left ventricular assist device implantation.

BACKGROUND: While preoperative hemodynamic risk factors associated with early right heart failure (RHF) following left ventricular assist device (LVAD) surgery are well-established, the relationship between postoperative hemodynamic status and subsequent outcomes remains poorly defined. METHODS: We analyzed adult CF-LVAD patients from the STS-INTERMACS registry surviving at least 3 months without evidence of early RHF and with hemodynamic data available at 3 months after LVAD implant. The association between metrics of RV afterload and function and the subsequent risk of death, right heart failure (RHF), gastrointestinal bleeding (GIB), or stroke were assessed using multivariable Cox proportional hazards modeling. RESULTS: Among 1,050 patients with available 3-month hemodynamics, pulmonary hypertension was common, with 585 (55.7%) having mPAP ≥ 20 mm Hg and 164 (15.6%) having PVR ≥ 3 WU. Pulmonary artery pulsatility index (PAPi, HR 0.62 per log-increase for values < 3, 95% CI 0.43-0.89) and PVR (HR 1.19 per 1 WU-increase for values > 1.5 WU, 95% CI 1.03-1.38) were independently associated with the composite of death or RHF. Postoperative RAP (HR 1.18 per 5 mm Hg increase, 95% CI 1.04-1.33), RAP:PCWP (HR 1.46 per log-increase, 95% CI 1.12-1.91), and PAPi (HR 0.76 per log-increase, 95% CI 0.61-0.95) were each associated with GIB risk. Postoperative hemodynamics was not associated with stroke risk. CONCLUSIONS: Hemodynamic metrics of postoperative RV dysfunction and elevated RV afterload are independently associated with RHF, mortality and GIB. Whether strategies targeting postoperative optimization of RV function and afterload can reduce the burden of these adverse events requires prospective study.

Cardioprotection of High-Risk Individuals.

Targeting cardioprotective strategies to patients at the highest risk for cardiac events can help maximize therapeutic benefits. Dexrazoxane, liposomal formulations, continuous infusions, and neurohormonal antagonists may be useful for cardioprotection for anthracycline-treated patients at the highest risk for heart failure. Prevalent cardiovascular disease is a risk factor for cardiac events with many cancer therapies, including anthracyclines, anti-human-epidermal growth factor receptor-2 therapy, radiation, and BCR-Abl tyrosine kinase inhibitors, and may be a risk factor for cardiac events with other therapies. Although evidence for cardioprotective strategies is sparse for nonanthracycline therapies, optimizing cardiac risk factors and prevalent cardiovascular disease may improve outcomes.

In-hospital mortality, length of stay and hospital costs for hospitalized breast cancer patients with comorbid heart failure in the USA.

OBJECTIVES: Breast cancer and heart failure (HF) are frequently interconnected due to shared risk factors and the cardiotoxicity of breast cancer treatment. However, the association between HF and hospital outcomes among breast cancer patients has not been studied. This study examined the association between HF and hospital outcomes among hospitalized patients with breast cancer. METHODS: This cross-sectional study using the 2015-2018 Healthcare Cost and Utilization Project-National Inpatient Sample data included hospitalized women who were aged 18 years or older and had a primary diagnosis code for breast cancer. Logistic regression, negative binomial regression, and generalized linear models with log-link and gamma distribution were used to assess the associations of HF with in-hospital mortality, length of stay (LOS) and hospital costs. RESULTS: Among 17,335 hospitalized patients with breast cancer, 4.2% (n = 1021) had HF. Compared to breast cancer patients without HF, those with HF were more likely to die during hospitalization (odds ratio = 1.65, 95% CI = 1.27-2.16, p < .001), stay in the hospital longer (incidence rate ratio = 1.22, 95% CI = 1.15-1.30, p < .001) and have higher hospital costs (cost ratio = 1.09, 95% CI = 1.03-1.14, p = .003) during hospitalization, controlling for covariates. CONCLUSION: HF has a substantial negative impact on health outcomes among hospitalized breast cancer patients. Breast cancer and HF are often considered separate medical conditions, but promoting effective management of comorbid HF in breast cancer patients may help to improve hospital outcomes in this population.

The Role of Biomarkers to Evaluate Cardiotoxicity.

OPINION STATEMENT: Moderate-level evidence suggests that cardiac troponin and natriuretic peptides are useful for risk stratification and early identification of anthracycline cardiotoxicity; however, many of these studies used older chemotherapy regimens, and thus, the applicability to current anthracycline treatment regimens is uncertain. Further research is needed to determine optimal timing and thresholds for troponin and natriuretic peptides in anthracycline-treated patients and evaluate these and other promising biomarkers for anti-HER2 therapies, thoracic radiation, anti-VEGF therapy, and fluoropyrimidine therapy-related cardiotoxicity. Risk tools that combine cardiac risk factors, cancer treatment variables, biomarkers, and imaging parameters are most likely to accurately identify individuals at highest risk for cancer therapy cardiotoxicity. Clinical trials focusing cardioprotective strategies on high-risk individuals are more likely to result in clinically significant results compared with primary prevention cardioprotective approaches.

Physical activity during and after breast cancer therapy and associations of baseline physical activity with changes in cardiac function by echocardiography.

BACKGROUND: Observational studies suggest that regular physical activity may reduce cardiovascular morbidity and cancer recurrence in survivors of breast cancer. The association between physical activity and cardiac function with breast cancer therapy is unknown. METHODS: Self-reported physical activity was assessed using the Godin Leisure-Time Exercise Questionnaire at repeated intervals in a longitudinal cohort study of 603 breast cancer participants treated with doxorubicin and/or trastuzumab. Multivariable regression models estimated associations between clinical variables and physical activity. Generalized estimating equations adjusted for prespecified variables estimated associations between baseline physical activity and longitudinal echocardiographic measures of systolic and diastolic function. RESULTS: Physical activity was low at baseline, prior to cancer therapy initiation. More than half of participants reported no moderate-strenuous physical activity, and only 12.1% met guideline recommended levels of physical activity. Physical activity increased after chemotherapy completion; however, only 26.0% of individuals were sufficiently active 3 years after cancer diagnosis. Body mass index, hyperlipidemia and higher cancer stage were significantly associated with lower total physical activity at baseline. Higher baseline physical activity was very modestly associated with an attenuation in the absolute decline in left ventricular ejection fraction over time (ß 0.4%, 95% CI 0.1, 0.7, P = .02 for each 10-unit increase in total activity). There tended to be a cardioprotective association with cardiotoxicity risk, although this was not statistically significant (HR 0.83, 95% CI 0.66, 1.04, P = .097). CONCLUSIONS: A small proportion of breast cancer patients and survivors are engaged in regular moderate-strenuous physical activity. While only modest associations between self-reported physical activity and left ventricular systolic function were observed, our findings do not exclude a cardioprotective benefit of exercise.

Cardioprotective Strategies to Prevent Cancer Treatment-Related Cardiovascular Toxicity: a Review.

PURPOSE OF REVIEW: Patients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular risks of different cancer therapies and the evidence for cardioprotective strategies. RECENT FINDINGS: Recent studies have provided additional support for the safety and efficacy of dexrazoxane and liposomal anthracycline formulations in certain high-risk patients receiving anthracyclines and for neurohormonal antagonist therapy in patients with breast cancer receiving sequential anthracyclines and trastuzumab. Ongoing studies are exploring the benefit of: (1) statins for anthracycline cardioprotection; (2) strict blood pressure control during vascular endothelial growth factor inhibitor treatment and; (3) dexrazoxane on long-term cardiac outcomes in pediatric populations. To date, there are no evidence-based cardioprotective strategies specifically for radiation-related heart and vascular disease, immunotherapy myocarditis, fluoropyrimidine cardiotoxicity, vascular endothelial growth factor inhibitor-related hypertension, BCR-Abl multikinase inhibitor vascular disease, and other established and emerging cancer therapeutics with cardiovascular effects. Current evidence supports specific cardioprotective strategies for high risk patients receiving anthracyclines or sequential anthracycline-trastuzumab therapy; however, major evidence gaps exist.