Effect of Active Cancer on the Cardiac Phenotype: A Cardiac Magnetic Resonance Imaging‐Based Study of Myocardial Tissue Health and Deformation in Patients With Chemotherapy‐Naïve Cancer

Abstract

Background The overlap between cancer and cardiovascular care continues to expand, with intersections emerging before, during, and following cancer therapies. To date, emphasis has been placed on how cancer therapeutics influence downstream cardiac health. However, whether active malignancy itself influences chamber volumes, function, or overall myocardial tissue health remains uncertain. We sought to perform a comprehensive cardiovascular magnetic resonance‐based evaluation of cardiac health in patients with chemotherapy‐naïve cancer with comparison with a healthy volunteer population. Methods and Results Three‐hundred and eighty‐one patients with active breast cancer or lymphoma before cardiotoxic chemotherapy exposure were recruited in addition to 102 healthy volunteers. Both cohorts underwent standardized cardiovascular magnetic resonance imaging with quantification of chamber volumes, ejection fraction, and native myocardial T1. Left ventricular mechanics were incrementally assessed using three‐dimensional myocardial deformation analysis, providing global longitudinal, circumferential, radial, and principal peak‐systolic strain amplitude and systolic strain rate. The mean age of patients with cancer was 53.8±13.4 years; 79% being women. Despite similar left ventricular ejection fraction, patients with cancer showed smaller chambers, increased strain amplitude, and systolic strain rate in both conventional and principal directions, and elevated native T1 versus sex‐matched healthy volunteers. Adjusting for age, sex, hypertension, and diabetes mellitus, the presence of cancer remained associated with these cardiovascular magnetic resonance parameters. Conclusions The presence of cancer is independently associated with alterations in cardiac chamber size, function, and objective markers of tissue health. Dedicated research is warranted to elucidate pathophysiologic mechanisms underlying these findings and to explore their relevance to the management of patients with cancer referred for cardiotoxic therapies.

Doxorubicin Paradoxically Ameliorates Tumor-Induced Inflammation in Young Mice

“…Most previously conducted animal studies emphasize how cancer therapeutics promote inflammation or cardiac dysfunction, while the effects of cancer development are not well researched. Intriguingly, cancer itself can affect cardiovascular health through independent signaling pathways other than those triggered by cancer treatment [58]. In a recent clinical study, chemotherapy-naive patients with newly diagnosed lymphoma demonstrated reduced cardiac chamber volumes compared to healthy volunteers [58].…”

“…Intriguingly, cancer itself can affect cardiovascular health through independent signaling pathways other than those triggered by cancer treatment [58]. In a recent clinical study, chemotherapy-naive patients with newly diagnosed lymphoma demonstrated reduced cardiac chamber volumes compared to healthy volunteers [58]. One of the suggested pathways in which cancer could affect the heart is through cancer-induced inflammation [59].…”

Cardiac Cachexia: Unaddressed Aspect in Cancer Patients

“…In a prospective study during follow up with cancer patients, Pavo et al [77] demonstrated that myocardial damage indicated the augmented expression of cardiovascular functional peptides and morphological markers might be responsible for disease progression and lead to increased mortality in cancer patients [77]. A multicomponent cardiovascular resonance imaging study revealed that cancer itself could modulate the morphology and function of the heart (chamber volume, ejection fraction and native T1 mapping) in naïve breast cancer or lymphoma patients [78]. A study based on the data collected from 7.5 million cancer patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program revealed that cancer patients are more prone to develop fatal heart disease with a standardized mortality ratio (SMR) of 2.4.…”

Cardiovascular Safety Assessment in Cancer Drug Development

“…In addition, recent evidence suggests that already at the time of diagnosis, patients with de novo cancers have abnormal cardiovascular imaging characteristics, as defined by cardiac magnetic resonance imaging, including smaller chamber sizes, increased strain amplitude, and systolic strain rate, and therefore various cardiovascular phenotypes will invariably exist in a given cohort of cancer patients. 72 Second, narrow eligibility criteria compound the evaluation of drug‐drug and drug‐disease interactions, which is vital to the development of safe pharmacologic treatment practices. For example, epidermal growth factor receptor inhibitors are a cornerstone in the treatment of patients with advanced lung adenocarcinoma who harbor epidermal growth factor receptor mutations but may prolong the QT interval.…”