Cardiac RadiothErapy For hEart faiLure

The tolerable acute toxicity will be assessed by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) (U.S. Department of Health and Human Services 2017). It is defined as toxicity occurring within 30 days after the radiation treatment.

Death from any cause within 6 months after treatment. The Kaplan-Meier method will be used to estimate overall survival (OS).

The number and length of hospitalization related to HF after treatment and within 6 months after treatment. HF-related admissions are defined as a hospital admission lasting for more than 24 h, with signs or symptoms of congestion necessitating an increase of the dose of loop diuretics.

Late toxicity is defined as toxicity occurring after at least 30 days to 6 months after the radiation treatment and will be assessed by the CTCAE v5.0.

Health related quality-of-life (QOL) will be measured based on the SF-36. The 36-Item Short Form Survey (SF-36) is a set of generic, coherent, and easily administered quality of life measures that rely on patient self-reporting. The SF-36 evaluates 8 domains: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Scale values for each domain range from 0 to 100 where the higher score defines a more favorable health state.

Health related quality-of-life (QOL) will be measured based on the Minnesota Living with Heart Failure (MLWHF) questionnaire. The MLWHFis a valid and reliable instrument consisting of 21 items for measuring QOL in patients with HF. It covers various domains including physical, emotional, social, and mental aspects of living with heart failure. Each item is scored on a scale (usually 0 to 5 or 0 to 6), with higher scores indicating a greater impact.

N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) will be measured as a biomarker of cardiac stress and heart failure severity. Levels are determined using standardized immunoassays and reported in picograms per milliliter (pg/mL). Higher NT-proBNP values generally indicate worse cardiac function and are associated with increased risk of adverse outcomes, whereas lower values suggest improved cardiac status.

High-sensitivity cardiac troponin will be measured as a biomarker of myocardial injury. High-sensitivity troponin allow detection of very low concentrations and provide accurate quantification across a wide range. Elevated hs-cTn values are associated with acute or chronic myocardial injury and adverse cardiovascular outcomes, whereas stable or low levels indicate absence of significant myocardial damage.

High-sensitivity C-reactive protein (CRP) will be measured as a biomarker of systemic inflammation. High-sensitivity assays enable accurate detection of low CRP concentrations, reported in milligrams per liter (mg/L), which can reflect low-grade inflammation. Elevated hs-CRP levels are associated with increased cardiovascular risk and adverse outcomes, while lower levels indicate a more favorable inflammatory profile.

Left Ventricular End-Diastolic Volume (LVEDV) and End-Systolic Volume (LVESV) will be measured by transthoracic echocardiography using the Simpson's biplane method. These indices provide quantitative measures of left ventricular size and systolic function. Increased LVEDV and LVESV may reflect adverse remodeling and impaired function, whereas lower or normalized values indicate improved ventricular performance.

Ventricular arrhythmia burden will be measured by the cardiac implantable electronic device by assessing the Premature Ventricular Complexes (PVCs) burden; non-sustained Ventricular Tachycardia (nsVT), defined as ≥3 consecutive ventricular beats lasting <30 seconds; and sustainedventricular arrhythmia, defined as ≥30 seconds or requiring device intervention. Arrhythmia burden will be reported as the number of episodes detected during the specified follow-up period.