Faculty Bibliography

BACKGROUND:Bruton's tyrosine kinase inhibitors (BTKis) are central to the medical management of chronic lymphocytic leukemia (CLL). However, accumulating data suggest an important association with cardiovascular (CV) adverse events (AEs), including arrhythmias, hypertension, and bleeding, in patients with CLL and other hematological malignancies treated with this therapeutic class. Data from comparative trials with BTKis suggest second-generation agents, eg, acalabrutinib and zanubrutinib, may be associated with fewer CV AEs than first-in-class BTKi ibrutinib. METHODS:PubMed and the proceedings of key hematology congresses were searched for relevant information using broad search terms including CLL, BTKi, and toxicity. RESULTS:When managing patients with CLL, screening before and during treatment to assess CV risk is suggested to guide decision-making. Due to the increased toxicity with ibrutinib, the second-generation BTKis are now preferred (per the NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines®]). For patients with a high CV-risk, the decision between second-generation BTKi or a time-limited alternative, like venetoclax plus an anti-CD20 monoclonal antibody, should be made on an individual basis after patient consultation and consideration of the presenting characteristics of CLL in any given patient. The management of anticoagulant/antiplatelet medication during BTKi treatment requires specific attention, with coexistent medications being carefully assessed before starting a BTKi to reduce the risk of bleeding. For patients with a new-onset or worsening CV events during BTKi therapy, management may involve temporarily stopping the BTKi or switching to another class of therapy. To ensure the best outcomes, a collaborative care approach is essential, and some patients may need to be referred to a cardiologist/cardio-oncologist for specialist management. CONCLUSION/CONCLUSIONS:Baseline and ongoing CV risk assessment, careful monitoring, management, and a multidisciplinary team approach are all critical to ensure optimal oncologic and CV outcomes for patients with CLL receiving BTKis.

BACKGROUND:Extrinsic compression of the pulmonary artery (PA) has been described with mediastinal and other thoracic masses. This compression can lead to acquired pulmonic stenosis and pulmonary hypertension. CASE SUMMARY/METHODS:A 27-year-old woman was diagnosed with Hodgkin lymphoma with a mediastinal mass compressing her PA leading to severe pulmonary hypertension, without hemodynamic compromise. She was treated with chemotherapy and had rapid resolution of the pulmonary artery compression on subsequent transthoracic echocardiogram 1 month after starting treatment. DISCUSSION/CONCLUSIONS:The current literature on the rare entity of extrinsic PA compression includes cases of surgical or percutaneous intervention to relieve compression and cases with resolution of compression based on changes in physical examination or transthoracic echocardiogram several months after initial diagnosis. This case is novel in reporting echocardiographic evidence of complete resolution of PA compression within 1 month of treatment without invasive intervention. TAKE-HOME MESSAGES/CONCLUSIONS:Pulmonary hypertension secondary to extrinsic PA compression from a mediastinal tumor is rare, but this case demonstrates that it may completely and rapidly resolve after initiation of chemotherapy. Short-interval follow-up echocardiography is helpful to reassess the degree of pulmonary hypertension after treatment.

BACKGROUND:Acute decompensated heart failure (HF) can progress to cardiogenic shock, and patients with cancer are at an increased risk of HF compared to patients without cancer. However, limited data exist on outcomes of patients admitted for HF-related cardiogenic shock (HF-CS) with cancer versus without cancer. METHODS:Adult patients admitted for HF-CS between 2014-2020 were identified using the National Readmission Database. Propensity score matching (PSM) was used to match 1 patient with cancer to 10 patients without cancer. Primary outcomes were in-hospital death, major bleeding, and thrombotic complications. Exploratory outcomes were 90-day readmission rates among patients who survived initial hospitalization. Temporal trends were also explored. RESULTS:Of 137,316 admissions for HF-CS, 7,306 (5.3%) had active cancer. After PSM, patients with cancer had increased odds of in-hospital death (OR 1.12, 95% CI 1.06 - 1.18), thrombotic complications (OR 1.12, 95% CI 1.03 - 1.21), and major bleeding (OR 1.23, 95% CI 1.17 - 1.31) compared to patients without cancer, with risks differing by cancer type. In exploratory analyses, rates of readmission were similar for patients with and without cancer. From 2014-2020, patients with cancer had no significant change in in-hospital mortality (ptrend = 0.43), while patients without cancer had decreased mortality over time (ptrend < 0.001). CONCLUSIONS:Among patients admitted for HF-CS, patients with cancer are at increased risk of in-hospital death, thrombotic complications, and major bleeding compared to patients without cancer. Future studies are needed to guide nuanced evaluation and management of this population to improve outcomes.

Patients with myeloproliferative neoplasms (MPNs) are at increased risk for cardiovascular disease. Although thrombosis is a well-recognized complication, emerging evidence indicates that nonthrombotic conditions, including heart failure (HF) and pulmonary hypertension (PH), are also prevalent and associated with adverse cardiovascular and hematologic outcomes. Clinical and preclinical data suggest a shared pathophysiology linking MPNs to the development and progression of cardiomyopathy, HF, and both precapillary and postcapillary PH. Recent studies further support a bidirectional relationship, in which HF and PH are associated with hematologic progression and vice versa. Elucidating the mechanisms underlying these interactions may uncover novel therapeutic targets and inform clinical management. Here, the authors review the pathophysiology and impact of HF and PH in patients with MPNs.

The optimal treatment of patients with diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) with preexisting cardiomyopathy is uncertain. An anonymous, electronic survey was distributed by e-mail to three US lymphoma cooperative groups, two community hospitals, and twelve academic medical systems, and distributed at one international lymphoma meeting. Fifty hematology-oncology providers caring for patients with lymphoma were included. In response to a vignette of a 67-yo with Stage III DLBCL with LVEF of 40-45%, 15 (30%) would use non-anthracycline regimens, 13 (26%) R-CHOP with liposomal doxorubicin instead of doxorubicin, 11 (22%) R-CHOP without modification and 6 (12%) R-CHOP with a continuous doxorubicin infusion. In a second vignette of a patient with HL in remission after frontline treatment with doxorubicin cumulative dose 300 mg/m², 16 (32%) would order an echocardiogram after treatment. There was substantial variability in preferred treatment regimens with preexisting cardiomyopathy and in cardiac monitoring after anthracycline.

The organization of a cardio-oncology clinic and overall program is designed to provide comprehensive cardiovascular care to patients who are at risk of or have developed cardiovascular sequelae during or following cancer treatments. In this article, we summarize the core components of a contemporary cardio-oncology program, including its core members (cardiologists, oncologists, clinical pharmacists, advanced practice providers, nurses, and coordinators), key services (risk assessment, treatment planning, cardiac imaging, intervention, and management), and practical integration within the health care system.

Heart failure and cancer remain two of the leading causes of morbidity and mortality and the two 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 diagnosis 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 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 between heart failure, oncology, palliative care, pharmacy, and nursing teams in the management of these complex patients.

INTRODUCTION/BACKGROUND:Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated. METHODS:Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. T primary outcome was a composite outcome of PTM or death due to malignancy. Multivariable Fine-Gray competing-risk regression was used to estimate the subhazard ratio (SHR) of primary and secondary outcomes. RESULTS:Of the total of 29717 patients with HT were included, 1017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with a higher risk of the primary outcome (SHR 1.43, 95% CI 1.15-1.80). Among patients who developed PTM, the median time to diagnosis of first PTM (median 36 vs. 46 months, p = 0.027) was shorter in patients with CHD. Among patients with CHD, survival after PTM was significantly lower compared with patients without malignancy (HR 3.32, 95% CI 2.03-5.43). CONCLUSIONS:Among adult patients with HT, CHD was associated with an increased risk of PTM. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout the course and following completion of cancer therapy. Here we utilize a case to summarize aspects of the ESC guideline relevant to HF clinicians, with a focus on risk stratification, early detection, prevention of CM and HF, and the role for guideline directed medical therapy in patients with cancer.