Elevated plasma Lp-PLA2, PCSK9, and HOMA index linked to valve deterioration
Hemodynamic bioprosthetic valve deterioration was not uncommon after surgical aortic valve replacement (SAVR) in a prospective longitudinal study, and was linked to death and aortic reinterventions years down the line.
Of 137 patients who survived to get a complete assessment at a median of 6.7 years after SAVR, 25.6% had leaflet calcification detected on computed tomography imaging. By the time the patients had another evaluation 3 years later, 13.1% had developed hemodynamic valve deterioration on Doppler echocardiography, researchers reported in the Journal of the American College of Cardiology.
Subsequently, there were 22 deaths and 30 aortic reinterventions, for an event rate of 38.0% in a median of 3.8 years since that echocardiogram, Philippe Pibarot, DVM, PhD, of Québec Heart & Lung Institute of Laval University in Quebec City, and colleagues found. The aortic reintervention was a transcatheter valve-in-valve procedure in one-third of cases, with redo SAVR making up the rest.
The independent predictors of these adverse outcomes were leaflet calcification (HR 2.58, 95% CI 1.35-4.82) and hemodynamic valve deterioration (HR 5.12, 95% CI 2.57-9.71).
In turn, the development of hemodynamic valve deterioration was associated with leaflet calcification, insulin resistance from the homeostatic model assessment (HOMA), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, and high PCSK9 levels.
A “dyslipidemic/dysmetabolic profile characterized by elevated plasma Lp-PLA2, PCSK9, and HOMA index are associated with increased risk of HVD [hemodynamic valve deterioration] at mid-term follow-up in patients with aortic bioprostheses,” Pibarot’s group concluded.
Hemodynamic valve deterioration was defined as a change in mean transprosthetic gradient of at least 3 mm Hg per year and/or worsening of transprosthetic regurgitation by at least 1/3 class.
“These results suggest that leaflet calcification that develops within the first few years post-AVR [aortic valve replacement] identifies a high-risk group of individuals for adverse valve outcomes who may require more careful follow-up,” George Thanassoulis, MD, MSc, of McGill University Health Center in Montreal, wrote in an accompanying editorial.
“Furthermore, the results suggest that several specific metabolic pathways, as captured by several plasma biomarkers, may predispose individuals to adverse valve outcomes in the post-AVR setting and may need to be considered before bioprosthetic AVR.”
Pibarot and colleagues acknowledged that their study was subject to survivorship bias: “The baseline factors were measured at mid-term follow-up, and further studies are needed to confirm that their associations with outcomes reported in this study also hold if these factors are measured early after AVR. The results of this study can therefore not be directly transposed to the context of early structural/functional valve deterioration post-AVR.”
Even so, the editorial suggested that “it would be interesting to consider whether individuals with elevations in one or more of these biomarkers should be counseled to forego the use of a bioprosthesis and be offered a more durable mechanical valve. Or whether lifestyle interventions or drug therapy could be offered before AVR to improve these metabolic parameters with the hope of avoiding repeat AVR, if a bioprosthesis is required.
“Whether Lp-PLA2 is causal in valve calcification and/or prosthetic deterioration will need to be carefully evaluated to determine its value as a potential therapeutic target for HVD.”
Pibarot disclosed research grants from Edwards Lifesciences and Medtronic for echocardiography core lab analyses in transcatheter aortic valve replacement.
Thanassoulis is a clinical research scholar funded by the Fonds de Recherche Sante-Quebec; and disclosed relationships with Ionis, Amgen, Sanofi, Servier Canada, Boehringer Ingelheim, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, and the U.S. National Institutes of Health.
Journal of the American College of Cardiology
Salaun E, et al “Hemodynamic deterioration of surgically implanted bioprosthetic aortic valves” J Am Coll Cardiol 2018; DOI: 10.1016/j.jacc.2018.04.064.
Journal of the American College of Cardiology
Thanassoulis G “Precision medicine for prosthetic valve deterioration: a glimpse into the future?” J Am Coll Cardiol 2018; DOI: 10.1016/j.jacc.2018.04.065.
Read the original article on Medpage Today: Hemodynamic Valve Deterioration Noted in Bioprosthetic SAVR Valves