Development of a Cardio-Oncology Service in Lithuania: Prediction, Prevention, Monitoring and Treatment of Cancer Treatment-Induced Cardiotoxicity

Abstract

Background: Advances in cancer therapy have dramatically improved outcomes for cancer pa-tients. However, cancer treatment can cause several cardiovascular (CV) complications, increasing cardiac mortality and morbidity in cancer patients and survivors. As a result, a new cardiology subspecialty—cardio-oncology (CO)—has been developed. The goals of CO are to understand the mechanism of the cardiotoxicity (CTX) of cancer therapies and invent the best monitoring and treatment strategies to improve the survival of cancer patients. Methods: We performed a retro-spective observational study reporting on the 6-year experience of the first CO service in Vilnius, Lithuania. Cancer patients were consulted by a single part-time specialist at Vilnius University Hospital. All new patients underwent blood tests, including cardiac biomarkers and advanced transthoracic echocardiogram (TTE) with stress protocol if indicated. During a follow-up, we evaluated the association of patient survival with such variables as age, gender, reasons for re-ferral, cancer location and stage, cardiovascular (CV) risk factors (RF), and rates and stage of CTX and treatment strategies. Results: 447 patients were consulted (70% females), and the median age was 64 years. Cardiovascular (CV) RF was common: 38.5% of patients had hypertension, almost 38% had dyslipidemia, 29% were obese, 10% were smokers, and 9% had diabetes. Nearly 26% of patients had a history of HF. Early biochemical cardiotoxicity was determined in 27%, early functional cardiotoxicity was seen in 17%, and early mixed cardiotoxicity—in 45% of referred patients treated with cardiotoxic cancer therapies. In addition, reduced left ventricular ejection fraction (LVEF) was found in 7% of patients. Beta-blockers (BB) were administered to 61.1% of patients, while angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) to 54.1% of patients. In addition, 18.3% of patients received loop diuretics and almost 12% mineralocorticoid receptor antagonists (MRA), respectively. A total of 143 patients died during the 6-year follow-up period. The leading cause of death was primarily cancer (92.3%). Only in 5.6% of patients, cardiovascular complications were reported as the cause of death, and 2.1% of deaths were due to the COVID−19 infection. We found that age (HR 1.020 [95% CI: (1.005−1.036)] p = 0.009); LV diastolic dysfunction (HR 1.731 [95% CI: 1.115−2.689] p = 0.015; NYHA stage II (HR 2.016 [95% CI: 1.242−3.272] p = 0.005; NYHA stage III (HR 3.545 [95% CI: 1.948−6.450] p < 0.001; kidney dysfunction (HR 2.085 [95% CI: 1.377−3.159] p = 0.001; previous cancer (HR 2.004 [95% CI: 1.219−3.295] p = 0.006); tumor progression (HR 1.853 [95% CI: 1.217−2.823] p = 0.004) and lung cancer (HR 2.907 [95%CI: 1.826−4.627] p < 0.001) were statistically significantly associated with the increased risk of all-cause death. Conclusions: CO is a rapidly growing subspecialty of cardiology that aims to remove cardiac disease as a barrier to effective cancer treatment by preventing and reversing cardiac damage caused by cancer therapies. Establishing a CO service requires a cardiologist with an interest in oncology. Continuous education, medical training, and clinical research are crucial to success. Age, previous cancer, tumor progression, kidney dysfunction, left ventricular diastolic dysfunction, and NYHA stages were associated with increased mortality.

Keywords: cancer; cardio-oncology; cardio-oncology service; cardiotoxicity; survival.

Figure 1

Sex differences in cancer incidence.

Figure 2

Cardiovascular risk factors in cancer patients.

Figure 3

Cardiovascular cardiotoxicity risk factors in cancer patients prior to cardiotoxic cancer therapies. AH—arterial hypertension; CAD—coronary artery disease; HF—heart failure; LVEF—left ventricular ejection fraction; NP—natriuretic peptides; RT—radiotherapy; Tn—troponin.

Figure 4

The relationship between anticancer therapies and cardiac risk factors.

Figure 5

Myocardial damage markers in patients with normal and reduced LVEF. NP—natriuretic peptides; GLS—global longitudinal strain; LVEF—left ventricular ejection fraction, LVSD—left ventricular systolic dysfunction.

Figure 6

Treatment options. ACEI/ARB—angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; BB—beta-blocker; CCB—calcium channel blocker; DOAC—direct oral anticoagulant; LMWH—low molecular weight heparin; MRA—mineralocorticoid receptor antagonist.

Figure 7

The cardiovascular risk profile and cardiovascular death rates of patients with different cancer stages. CV—cardiovascular.