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The Trifecta valve (St Jude Medical, Inc, St Paul, Minn) was approved for commercial use by the US Food and Drug Administration in 2011. Several isolated cases have been reported since then, describing early structural valve deterioration. We report a case series of 8 Trifecta valve failures, describing patients' clinical substrate and management, and the pathologic characteristics of the explanted valves.Trifecta valve failure occurred in 7 patients (8 valves) receiving 19-mm (n = 2), 21-mm (n = 3), 23-mm (n = 1), and 25-mm (n = 2) valves. The mean duration of valve durability was 32 ± 21 months, and the most common lesion was prosthetic regurgitation. The mean Society of Thoracic Surgeons risk score for perioperative mortality at the time of reintervention was 9.75% ± 8.1%. Heart failure exacerbation was the most common presenting symptom.Five patients underwent surgical aortic valve replacement, 2 patients received valve-in-valve transcatheter aortic valve replacement, and 1 patient died of cardiogenic shock before reintervention. The most common pathologic finding in the explanted valves was a tan-yellow fibrofatty circumferential pannus adherent to the inflow portion of the Trifecta valve.Our findings provide further insights into the pathologic mechanisms leading to early Trifecta valve failure. In addition to tear of the noncoronary cusp of the Trifecta prosthesis described as the most common mechanism in the literature for its failure, circumferential pannus formation composed of fibrofatty tissue in the inflow portion and leaflet calcification concentrated around the posts in the outflow portion are important mechanisms contributing toward early Trifecta valve failure.