Prognostic refinement for valvular heart surgery

Abstract

Valvular heart disease (VHD) is a prevalent condition associated with substantial morbidity and mortality. Valvular interventions, either open heart surgery or transcatheter procedure, are the only definitive treatment to improve symptoms and prognosis. However, their relatively poor long-term survival attests to persistent deficits in VHD management, in which individual risks remain incompletely characterized despite the wide availability of cardiac surgery risk-scoring systems. This work, therefore, aims to investigate the avenues of prognostic refinement in valvular heart surgery, presenting clinical, laboratory, and radiological markers that may act as complementary prognosticators in VHD. This work contains four sections. Sections 1 and 2 focus on the characteristics and outcome implications of echocardiographic phenotypes associated with tricuspid regurgitation (TR) and multiple valvular heart disease. Section 1, undertaken in 290 patients undergoing tricuspid annuloplasty, identified two phenotypes of TR based on the effective regurgitant orifice area (EROA) to right ventricular (RV) end-diastolic area (RVDA) ratio. Disproportionate TR, defined as an EROA/RVDA ratio >1.74, was independently associated with higher risks of adverse events compared with proportionate TR. TR proportionality outperformed guideline-based TR classification scales with additive value to the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and Society of Thoracic Surgeons (STS) scores for outcome prediction. Section 2, which included 152 patients undergoing double valve surgery, classified the RV into four remodelling patterns: normal RV size and systolic function (pattern 1), dilated RV (tricuspid annulus diameter >35mm) with normal systolic function (pattern 2), normal RV size with systolic dysfunction (percentage RV fractional area change <35%) (pattern 3), and dilated RV with systolic dysfunction (pattern 4). Results show that patterns 3 and 4 RV remodelling, at both baseline and one year after surgery, were associated with significantly higher rates of heart failure (HF) and mortality compared with pattern 1. This staging system also yielded incremental prognostic value to traditional risk markers and guideline-based surgical indications for predicting adverse events. Section 3 presents results related to biomarker testing in a prospective cohort of multiple valvular heart disease patients scheduled for concomitant aortic and mitral valve surgery. All participants underwent N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin-T, growth differentiation factor-15, and galectin-3 measurements, from which an integer-based biomarker score was developed. Each biomarker was differentially associated with cardiac structure and function, with elevated concentrations independently predicting a higher event risk. The biomarker risk score also noted a graded increase in the rates of HF hospitalizations and mortality across groups, significantly improving risk prediction when added to the EuroSCORE II and STS score. Section 4 explores the prognostic role of clinical risk factors in the general VHD population. In 909 patients undergoing valvular surgery, hepatorenal dysfunction and malnutrition were associated with excess HF and mortality, with a greater step-up in event risk for concomitant hepatorenal dysfunction and malnutrition than for either phenotype alone. Their evaluation additionally provided independent and incremental value for risk assessment over the EuroSCORE II and STS score. The persistence of hepatorenal dysfunction and malnutrition one year following surgery also denoted a worse long-term prognosis.