Publications

Assessing cardiac risk prior to initiating breast cancer treatment, monitoring cardiac function during treatment, and implementing appropriate follow-up strategies are essential components of managing cardiotoxicity in breast cancer patients. A comprehensive cardiovascular evaluation should be conducted before treatment, including a detailed medical history, physical examination, and baseline cardiac imaging. Risk stratification tools can aid in determining the individual patient's risk profile. Close monitoring of cardiac function, including regular assessment of left ventricular ejection fraction (LVEF) and monitoring for signs and symptoms of cardiac dysfunction, is crucial during treatment. Prompt action should be taken if an adverse cardiovascular event is detected, including considering discontinuing or modifying the treatment regimen. Appropriate follow-up care is essential to monitor for long-term cardiac effects and optimize cardiovascular health in breast cancer survivors. Regular cardiovascular assessments, lifestyle modifications, and collaboration between healthcare professionals are important in managing cardiotoxicity effectively.

Heart failure and cancer remain 2 of the leading causes of morbidity and mortality, and the 2 disease entities are linked in a complex manner. Patients with cancer are at increased risk of cardiovascular complications related to the cancer therapies. The presence of cardiomyopathy or heart failure in a patient with new cancer diagnosis portends a high risk for adverse oncology and cardiovascular outcomes. With the rapid growth of cancer therapies, many of which interfere with cardiovascular homeostasis, heart failure practitioners need to be familiar with prevention, risk stratification, diagnosis, and management strategies in cardio-oncology. This Heart Failure Society of America statement addresses the complexities of heart failure care among patients with active cancer diagnoses and cancer survivors. Risk stratification, monitoring and management of cardiotoxicity are presented across stages A through D heart failure, with focused discussion on heart failure with preserved ejection fraction and special populations, such as survivors of childhood and young-adulthood cancers. We provide an overview of the shared risk factors between cancer and heart failure, highlighting heart failure as a form of cardiotoxicity associated with many different cancer therapeutics. Finally, we discuss disparities in the care of patients with cancer and cardiac disease and present a framework for a multidisciplinary-team approach and critical collaboration among heart failure, oncology, palliative care, pharmacy, and nursing teams in the management of these complex patients.

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.

BACKGROUND: Diuretic responsiveness is associated with heart failure disease progression. Among patients with advanced heart failure, we hypothesized that decreased diuretic responsiveness and higher diuretic requirement are correlates of progressive right ventricular dysfunction and may help to risk stratify patients undergoing left ventricular assist device (LVAD) evaluation.

METHODS: We performed a single-center, retrospective analysis of 147 patients undergoing LVAD implantation between 2014 and 2018. The primary outcome was early right heart failure (RHF) or death during the index hospital stay. Patients were stratified by tertiles of preoperative 24-hour diuretic dose within 72 hours of surgery.

RESULTS: The incidence of early RHF was higher in the highest-dose group (66.0%) compared to the medium- (41.3%) and low-dose groups (23.5%) (p < 0.001). Each 40 mg increase in intravenous furosemide dose was associated with a 6% increase in the risk of RHF, after adjusting for other known risk factors. The median ICU length of stay was 2 days longer for patients in the highest compared to low-dose group (7 vs 5 days, p = 0.02). Mortality within 14 days post-op was numerically higher although not significantly different between the highest-dose group and the low-dose group (12.0% vs 5.9%, p = 0.55). Six-month survival across diuretic dose tertiles was also not statistically different (p = 0.40).

CONCLUSIONS: We concluded that higher preoperative diuretic dose is associated with risk of early RHF following LVAD surgery. These data furthermore support the role of progressive right ventricular dysfunction on the development of cardiorenal disease and diuretic resistance.

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.

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.

Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer survival but are associated with treatment-limiting hypertension, often attributed to endothelial cell (EC) dysfunction. Using phosphoproteomic profiling of VEGFRi-treated ECs, drugs were screened for mitigators of VEGFRi-induced EC dysfunction and validated in primary aortic ECs, mice, and canine cancer patients. VEGFRi treatment significantly raised systolic blood pressure (SBP) and increased markers of endothelial and renal dysfunction in mice and canine cancer patients. α-Adrenergic-antagonists were identified as drugs that most oppose the VEGFRi proteomic signature. Doxazosin, one such α-antagonist, prevented EC dysfunction in murine, canine, and human aortic ECs. In mice with sorafenib-induced-hypertension, doxazosin mitigated EC dysfunction but not hypertension or glomerular endotheliosis, while lisinopril mitigated hypertension and glomerular endotheliosis without impacting EC function. Hence, reversing EC dysfunction was insufficient to mitigate VEGFRi-induced-hypertension in this mouse model. Canine cancer patients with VEGFRi-induced-hypertension were randomized to doxazosin or lisinopril and both agents significantly decreased SBP. The canine clinical trial supports safety and efficacy of doxazosin and lisinopril as antihypertensives for VEGFRi-induced-hypertension and the potential of trials in canines with spontaneous cancer to accelerate translation. The overall findings demonstrate the utility of phosphoproteomics to identify EC-protective agents to mitigate cardio-oncology side effects.

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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.