We sought to address the clinical significance and prognostic value of sinus tachycardia in cancer patients. This study shows that sinus tachycardia around the time of cancer treatment, independent of typical risk factors that affect patients with cancer, was associated with the development of ACVO and higher risk of all-cause mortality at 10 years of follow-up. To our knowledge, this is the first study to determine the prognostic impact of sinus tachycardia on cardiovascular outcomes and mortality in cancer patients.
Many patients with cancer undergoing chemo- and/or chest radiation therapy are at increased risk cardiovascular disease [9, 12]. It has been well documented that certain types of chemotherapy such as anthracyclines, tyrosine kinase inhibitors, and monoclonal antibodies are associated with adverse effects on the cardiovascular system such as the development of heart failure or arrhythmias [9,10,11,12,13]. Additionally, radiation therapy is associated with increased incidence of myocardial fibrosis and valvular disease [14,15,16]. High cardiac output states are frequently noted in patients with underlying cancer . The pathophysiology of high output states in this patient population is often related to underlying anemia, hyperthyroidism, shunting of blood through the tumors, or secretion of antidiuretic hormone . In patients undergoing therapy with multiple chemotherapeutic agents and radiation, these negative cardiovascular effects could be amplified [19,20]. As a result, identifying patients with higher risk for cardiotoxicity is a key strategy in reducing morbidity and mortality associated with cancer treatment.
The effects of elevated RHR at baseline on cardiovascular mortality and morbidity in cancer patients have been extensively studied and well documented in the literature [1,2,3,4,5,6]. Elevated RHR such as sinus tachycardia results in decreased diastolic filling, decreased myocardial perfusion, and increased left ventricular function. Over time, these effects may result in myocardial damage and congestive heart failure [21,22]. Similarly in the Framingham study, elevated RHR was directly associated with increased all-cause mortality in patients with baseline hypertension after 36 years of follow-up . Additionally, the prognostic effects of RHR on patients with CAD and left ventricular systolic dysfunction were studied in the randomized BEAUTIFUL (Morbidity-Mortality Evaluation of the I(f) Inhibitor Ivabradine in Patients with Coronary Disease and Left Ventricular Dysfunction) trial. The authors reported that patients with RHR ≥ 70 bpm had more frequent cardiovascular events including increased number of admissions for heart failure, myocardial infarction and cardiovascular related mortality during 19-months of follow-up . Given the substantial effects of HR on cardiovascular outcomes and survival, slowing the HR has been a target for management of patients with CAD and heart failure.
Similarly, our study demonstrated that baseline sinus tachycardia resulted in 3-fold increased incidence of HFrEF, 6-fold increase in AHFE, and almost 3-fold increase in mortality. This study, while uniquely focused on cancer patients, adds to the current evidence that elevated RHR is associated with increased mortality and morbidity. These findings raise the question of whether controlling a patient’s HR with medication could improve mortality and decrease the risk of ACVO and mortality in this population. Beta-blockers and Ivabradine are two types of drugs that result in substantial decrease in HR and increased survival in patients with underlying cardiovascular disease [25,26]. However, no randomized control trials have been performed to evaluate potential benefits of these medications in treating cancer patients with sinus tachycardia. It is possible that the presence of sinus tachycardia in these patients is a compensatory mechanism (and therefore, a marker) reflecting their body’s adjustment to a systemic and multi-organ inflammatory and hypermetabolic state in the setting of their underlying malignancy. This idea, however, raises another question as to whether medically controlling the HR could harm these patients by blunting their cardiovascular response to the underlying disease process. Additionally, there is no strong evidence to support treating isolated sinus tachycardia in the absence of underlying cardiovascular disease. Therapeutic considerations for these patients are largely focused on lifestyle modification including regular aerobic exercise, hydration, avoiding stimulants, and maintaining normal body weight.
Some limitations of our study include the retrospective nature of the study and the small number of patients in the study group. We compensated for the latter concern by using the 1:10 matched control group to increase the power of our study in order to detect differences between both groups. Furthermore, we could not determine if sinus tachycardia was present in these patients prior to their diagnoses of cancer because most of them were referred to our oncology clinic after cancer diagnosis. Additionally, we were not able to determine the exact cause of death in these patients. This is partly due to the fact that the clinical picture in advanced cancer is rather complex and varies greatly between cancer types. We should note that the majority of the patients included in this study were elderly (70±10 years). Additional research is required to evaluate the risk of adverse cardiac outcomes and mortality on a younger patient population.