NT-proBNP and other blood biomarkers in patients after Fontan Surgery: Prognostic, diagnostic, and management implications

IntroductionThe Fontan procedure is one of the most important advancements in the treatment of congenital heart disease.This has greatly improved the long-term survival of patients with univentricular hearts.This procedure was first described in the early 1970s by Fontan & Baudet.The Fontan approach redirects the systemic venous circulation directly into the pulmonary arteries.This process bypasses the heart and eliminates the need for a subpulmonary ventricle.This approach has transformed a once-deadly illness into a manageable chronic condition [1-3] (see Tables 12345, Figs. 1 and2).The Fontan procedure has undergone major technical improvements.Early atriopulmonary connections (APC) can cause atrial enlargement, arrhythmia, and thrombosis.The lateral tunnel eventually replaced these methods, along with extracardiac total cavopulmonary connection (TCPC).These newer techniques have improved blood flow and reduced initial health risks.Staged palliative care and long-term monitoring before and after surgery have also contributed to higher survival rates in adulthood [4][5][6].Despite these improvements, Fontan circulation remains nonphysiological.Passive blood flow to the lungs is maintained by elevated systemic venous pressure rather than ventricular contraction.Patients with this condition consistently face high central venous pressure, reduced preload and cardiac output, and unstable pulmonary hemodynamics.These factors place Fontan patients at a high risk for ongoing circulatory dysfunction and various complications, known as Fontan Failure [7,8].Fontan failure differs from conventional systolic heart failure.It is a complex disorder characterised by venous congestion, impaired lymphatic function, chronic inflammation, vascular abnormalities, and ongoing damage to vital organs.The most common complication is Fontan failure, which includes arrhythmia, protein-losing enteropathy, plastic bronchitis, Fontan-associated liver disease(FALD), kidney problems, blood clots, and limited exercise and functional capacity [9,10].Epidemiological modelling across 11 countries estimated that 47,881 persons were living with a Fontan circulation in 2020, with this number projected to rise to 59,777 by 2030, corresponding to a prevalence increase from 66 to 79 people per million [11].The identification of Fontan failure is insufficient based on clinical evaluation.Symptoms may be mild or nonspecific, especially in children and adolescents.Standard imaging measurements, such as the ventricular ejection fraction, remain stable until the disease progresses to advanced stages, and invasive hemodynamic assessment is impractical for routine surveillance.This has led to a growing interest in blood biomarkers as additional tools for long-term monitoring and surveillance [12-14] [12-14].NT pro-BNP has emerged as the most studied cardiac biomarker among available biomarkers.However, the interpretation of its level can be challenging because of the unique physiology of the Fontan procedure and its various influencing factors.Many researchers now agree that no single biomarker can adequately reflect the complex multisystem nature of Fontan circulation.Instead, a multimarker approach for assessing cardiac stress, inflammation, fibrosis, blood vessel function, liver congestion, kidney damage, and metabolic issues may offer a comprehensive assessment [15-17] [15-17].This review provides an in-depth examination of NT pro-BNP and other blood markers in patients after Fontan surgery.It focuses on their biological bases, clinical importance, prognostic and diagnostic abilities, and potential impact on management strategies.