Calcific aortic valve stenosis: hard disease in the heart (Peeters et al.)
Calcific aortic valve stenosis (CAVS) is common in the ageing population and set to become an increasing economic and health burden. Once present, it inevitably progresses and has a poor prognosis in symptomatic patients. No medical therapies are proven to be effective in holding or reducing disease progression. Therefore, aortic valve replacement remains the only available treatment option.
However, improved knowledge of the mechanisms underlying disease progression has provided us with insights that CAVS is not a passive disease. Rather, CAVS is regulated by numerous mechanisms with a key role for calcification. Aortic valve calcification (AVC) is actively regulated involving cellular and humoral factors that may offer targets for diagnosis and intervention. The discovery that the vitamin K-dependent proteins are involved in the inhibition of AVC has boosted our mechanistic understanding of this process and has opened up novel avenues in disease exploration. To that end, researchers have published a review in the European Heart Journal that discusses processes involved in CAVS progression, with an emphasis on recent insights into calcification, methods for imaging calcification activity, and potential therapeutic options.
According to researchers, once symptomatic severe CAVS has developed, the prognosis without intervention is dismal. Currently the only treatment for (symptomatic) severe CAVS is surgical or trans catheter aortic valve replacement (AVR), to which not all patients are suited. While multiple trials have attempted to repurpose commonly used pharmacological interventions to slow CAVS progression, pharmacological interventions have thus far failed to alter the course of CAVS. The review paper notes that studies have demonstrated that statins, widely used for lipid lowering in atherosclerosis and inflammation, have no effect on CAVS progression or clinical outcomes, and might actually exacerbate the condition.
However, the researchers noted promise with Vitamin K2, specifically the long-chain menaquinones (MK7), as they are transported efficiently beyond the liver. “Vitamin K supplementation is an attractive option to replenish vascular vitamin K stores to ensure optimal calcification inhibition,” the researchers wrote.
The review paper concluded: “The pathophysiological mechanisms involved in CAVS initiation and progression are being rapidly elucidated and include inflammation, fibrosis, and calcification. With this advancing knowledge, we have identified novel therapeutic targets like vitamin K and new imaging techniques that can be used to test the efficacy of novel agents and further inform our pathophysiological understanding.”
Peeters FECM, et al. Calcific aortic valve stenosis: hard disease in the heart. Euro Heart J (2017) 0,1-8.