Effects of prosthetic heart valve-associated subclinical intravascular hemolysis on endothelium and cardiovascular system: a retrospective cohort study.

Mechanical prosthetic heart valve implantation is a widely used surgical treatment for severe symptomatic valvular heart disease, and regular follow-up of prosthetic valve function together with associated clinical and laboratory parameters is essential after implantation. Chronic subclinical intravascular hemolysis is frequently observed in this population; however, its long-term clinical implications remain incompletely defined. In this single-center, retrospective, non-randomized cohort study, 346 patients who underwent aortic and/or mitral mechanical valve replacement and met predefined inclusion and exclusion criteria were evaluated to investigate the association between subclinical hemolysis severity-assessed by follow-up serum lactate dehydrogenase (LDH) levels-and endothelial dysfunction-related clinical outcomes, includin pulmonary hypertension (PHT) and major adverse cardiovascular events (MACE). Mechanical intravascular hemolysis severity was stratified according to the median follow-up LDH (fLDH) value of 264.5 U/L, categorizing patients into non-/mild hemolysis (Group 1) and moderate hemolysis (Group 2). The mean age of the cohort was 57.5 ± 12.5 years, 65% were male, and traditional coronary artery disease risk factors were similarly distributed between groups. Over a mean follow-up duration of 9.4 ± 3.3 years 18 MACE events (5.2%) were observed, while new-onset PHT developed in 122 patients (35.3%). MACE occurred in 1 patient (0.6%) in Group 1 and in 17 patients (9.8%) in Group 2 (p < 0.001). In multivariable logistic regression analysis, an fLDH level ≥ 265 U/L and the presence of diabetes mellitus were associated with MACE, although effect size estimates were accompanied by wide confidence intervals due to the limited number of events. Overall, higher levels of subclinical intravascular hemolysis, reflected by elevated LDH, were associated with an increased occurrence of MACE and PHT in patients with mechanical prosthetic heart valves. Given the low eventcount and resulting statistical uncertainty, these findings should be interpreted as exploratory and hypothesis-generating rather than causal, and larger prospective studies are warranted to clarify the prognostic significance of subclinical hemolysis and its potential role in long-term risk stratification.