Zellers, Thomas M.

AbstractObjectiveWe compared 5‐year outcomes of transcatheter pulmonary valve (TPV) replacement with the Melody TPV in the post‐approval study (PAS) and the investigational device exemption (IDE) trial.BackgroundAs a condition of approval of the Melody TPV after the IDE trial, the Food and Drug Administration required that a PAS be conducted to evaluate outcomes of TPV replacement in a “real‐world” environment. The 5‐year outcomes of the PAS have not been published, and the IDE and PAS trials have not been compared.MethodsThe cohorts comprised all patients catheterized and implanted at 5 IDE sites and 10 PAS sites. Differences in trial protocols were detailed. Time‐related outcomes and valve‐related adverse events were compared between the two trials with Kaplan–Meier curves and log‐rank testing.Results167 patients (median age, 19 years) were catheterized and 150 underwent TPV replacement in the IDE trial; 121 were catheterized (median age, 17 years) and 100 implanted in the PAS. Freedom from hemodynamic dysfunction (p = .61) or any reintervention (p = .74) over time did not differ between trials. Freedom from stent fracture (p = .003) and transcatheter reintervention (p = .010) were longer in PAS, whereas freedom from explant (p = .020) and TPV endocarditis (p = .007) were shorter. Clinically important adverse events (AEs) were reported in 14% of PAS and 7.2% of IDE patients (p = .056); the incidence of any particular event was low in both.ConclusionsHemodynamic and time‐related outcomes in the PAS and IDE trials were generally similar, confirming the effectiveness of the Melody TPV with real‐world providers. There were few significant complications and limited power to identify important differences in AEs. The lack of major differences in outcomes between the two studies questions the usefulness of mandated costly post‐approval studies as part of the regulatory process for Class III medical devices.

Experiments were designed to determine the endothelium-dependent and endothelium-independent responses to aggregating platelets in porcine pulmonary arteries. Isolated rings with and without endothelium from large (5-7-mm-diameter) and small (2-3-mm-diameter) pulmonary arteries were suspended in modified Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2 in the presence of indomethacin. Aggregating platelets caused relaxations in rings with endothelium but contractions in rings without endothelium, both of which were significantly larger in small versus large pulmonary artery rings. Serotonin and ADP caused concentration-dependent endothelium-augmented relaxations that were unaffected by ketanserin. Methiothepin, but not apyrase, significantly decreased the platelet-induced endothelium-dependent relaxations; the residual relaxation was abolished when rings were incubated with methiothepin, apyrase, and theophylline but was unaffected if apyrase was absent, indicating that ADP is responsible for the residual relaxation caused by aggregating platelets. Quiescent rings, with and without endothelium, contracted in a dose-dependent manner to norepinephrine and histamine but not to serotonin or vasopressin. The contraction to aggregating platelets was blocked by methiothepin, pyrilamine, and diphenhydramine but was unaffected by phentolamine, ketanserin, or incubation of the platelets with dazoxiben. These data indicate that, in large and small porcine pulmonary arteries, serotonin and ADP are the major contributors to the endothelium-dependent relaxation caused by aggregating platelets, while histamine appears to be responsible for the contraction that platelets cause in rings without endothelium.