Cardiotoxicity of FDA-approved immune checkpoint inhibitors: A rare but serious adverse event

Refractory cancer represents a challenge for oncologists in providing treatment options without excessive toxicity and has led to the investigation of immune mechanisms. Immune checkpoint inhibitors (ICIs) directly interfere with the tumor cells' ability to evade the innate and adaptive immune system by targeting specific proteins such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein-ligand 1 (PD-L1), which are involved as negative regulators of T-cell function. Their growing success has led to the investigation for frontline treatment in several types of cancers. Even though these ICIs have demonstrated efficacy in the treatment of a variety of cancers, their use has been associated with the development of rare but severe adverse events. These events are the result of targeting specific checkpoint proteins on normal cells of the body as well as secondary downstream off-target effects on normal tissue. Similar to combined conventional cancer treatment, treating with combined ICIs are also associated with a higher risk of adverse events. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant heart failure, hemodynamic instability, and cardiac arrest. Oncologists must carefully weigh the risk versus the therapeutic benefit of these agents in determining the best option for improving overall survival and minimizing morbidity and mortality of their patients. Our review focuses on the approved ICIs, their mechanism of action, their oncologic efficacy, and the associated potential for cardiovascular toxicity

The Onco-cardiologist Dilemma: to Implant, to Defer, or to Avoid Transcatheter Aortic Valve Replacement in Cancer Patients with Aortic Stenosis?

Aging is associated with an increased prevalence of both cancer and heart disease. The progression of aortic valve calcification to aortic stenosis may be accelerated by both cardiovascular risk factors and cancer treatments, such as radiotherapy with mediastinal involvement. Symptomatic aortic stenosis is occasionally diagnosed in cancer patients undergoing cardiovascular evaluation; likewise, cancer is often recognized during assessment preceding aortic valve interventions. In these complex cases, physicians face difficult treatment decisions. Due to a myriad of clinical presentations of cancer and valve disease, specific guidelines for this patient population are not currently in place. Management is currently based on clinical judgment, on an individual basis.Patients with cancer in remission or with a favorable prognosis should be treated according to current cardiovascular guidelines. In these patients, aortic valve replacement can be performed either by surgery or transcatheter. Significant challenges arise in patients with active cancer, especially those receiving anti-cancer treatment. Recent data suggests that these patients can be offered aortic valve replacement, with a trend of favoring the transcatheter route in order to minimize perioperative risk and complications associated with major surgery. Patients with advanced cancer and severe aortic stenosis should be offered palliative care and can benefit from aortic balloon valvuloplasty if indicated. Modern cancer treatments associated with improved long-term prognosis may allow the appropriate cure of aortic stenosis. We discuss the protocol, outcomes, and evolving recommendations of aortic valve replacement in cancer patients with aortic stenosis

Interventional Cardio-Oncology: Adding a New Dimension to the Cardio-Oncology Field

The management of cardiovascular disease in patients with active cancer presents a unique challenge in interventional cardiology. Cancer patients often suffer from significant comorbidities such as thrombocytopenia and coagulopathic and/or hypercoagulable states, which complicates invasive evaluation and can specifically be associated with an increased risk for vascular access complications. Furthermore, anticancer therapies cause injury to the vascular endothelium as well as the myocardium. Meanwhile, improvements in diagnosis and treatment of various cancers have contributed to an increase in overall survival rates in cancer patients. Proper management of this patient population is unclear, as cancer patients are largely excluded from randomized clinical trials on percutaneous coronary intervention (PCI) and national PCI registries. In this review, we will discuss the role of different safety measures that can be applied prior to and during these invasive cardiovascular procedures as well as the role of intravascular imaging techniques in managing these high risk patients

Trigger related outcomes of takotsubo syndrome in a cancer population.

Takotsubo syndrome (TTS) occurs more frequently in cancer patients than in the general population, but the effect of specific TTS triggers on outcomes in cancer patients is not well studied.The study sought to determine whether triggering event (chemotherapy, immune-modulators vs. procedural or emotional stress) modifies outcomes in a cancer patient population with TTS.All cancer patients presenting with acute coronary syndrome (ACS) between December 2008 and December 2020 at our institution were enrolled in the catheterization laboratory registry. Demographic and clinical data of the identified patients with TTS were retrospective collected and further classified according to the TTS trigger. The groups were compared with regards to major adverse cardiac events, overall survival and recovery of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) after TTS presentation.Eighty one of the 373 cancer patients who presented with ACS met the Mayo criteria for TTS. The triggering event was determined to be "cancer specific triggers" (use of chemotherapy in 23, immunomodulators use in 7, and radiation in 4), and "traditional triggers" (medical triggers 22, and procedural 18 and emotional stress in 7). Of the 81 patients, 47 died, all from cancer-related causes (no cardiovascular mortality). Median survival was 11.9 months. Immunomodulator (IM) related TTS and radiation related TTS were associated with higher mortality during the follow-up. Patients with medical triggers showed the least recovery in LVEF and GLS while patients with emotional and chemotherapy triggers, showed the most improvement in LVEF and GLS, respectively.Cancer patients presenting with ACS picture have a high prevalence of TTS due to presence of traditional and cancer specific triggers. Survival and improvement in left ventricular systolic function seem to be related to the initial trigger for TTS