Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS VI). Pulmonary function was studied in patients during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN-acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to 240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed as absolute volume in liters. FEV1 and FVC showed little change from baseline during the first 24 weeks of ERT, but after 96 weeks, these parameters increased over baseline by 11% and 17%, respectively. This positive trend compared with baseline continued beyond 96 weeks of treatment. Improvements from baseline in pulmonary function occurred along with gains in height in the younger group (5.5% change) and in the older patient group (2.4% change) at 96 weeks. Changes in MVV occurred earlier within 24 weeks of treatment to approximately 15% over baseline. Model results based on data from all trials showed significant improvements in the rate of change in pulmonary function during 96 weeks on ERT, whereas little or no improvement was observed for the same time period prior to ERT. Thus, analysis of mean percent change data and longitudinal modeling both indicate that long-term ERT resulted in improvement in pulmonary function in MPS VI patients

Vessel‐Specific Myocardial Mass in Patients With Stable Coronary Artery Disease

Background Assessing the myocardial mass at risk is essential in evaluating patients with coronary artery disease. This study aims to establish reference values for vessel‐specific myocardial mass derived from coronary computed tomography angiography, providing a quantitative assessment of the myocardial mass subtended by each epicardial vessel. Methods Left ventricular (LV) and vessel‐specific myocardial mass were calculated from coronary computed tomography angiography using the Voronoi method in patients with stable coronary artery disease. Myocardial mass was quantified for each epicardial coronary artery with a diameter &gt;1.5 mm. Results We included 948 patients with 9228 epicardial coronary artery branches. Mean age was 66±9 years. The cohort was predominantly male (77%); 66% had hypertension, and 22% had diabetes. Vessel‐specific myocardial mass was calculated for 2767 main epicardial arteries (948 left anterior descending, 948 left circumflex, and 871 right coronary artery) and 6461 side branches (1888 diagonals, 1208 septals, 1422 obtuse marginals, 247 ramus intermedius, 850 right posterior descending, and 846 posterolateral branches). Median LV mass was 141 grams (interquartile range 118–166); women had smaller LV mass than men (106 [93–123] grams versus 150 [132–173] grams, P<0.001). On average, the left anterior descending subtended 42.5% [37.9–48.1] of LV mass, the left circumflex artery 28.8% [21.9–5.7], and the right coronary artery 26.4% [20.9–31.9]. Median LV mass subtended by the first septal, first diagonal, and first obtuse marginal were 8.9% [6.4–11.1], 7.9% [4.52–2.0], and 10.2% [4.52–12.0], respectively. Conclusions This study quantified the myocardial mass subtended by each major artery in the coronary circulation. Understanding the vessel‐specific mass at risk has significant clinical implications for personalizing revascularization strategies. Registration This is a retrospective analysis of 5 prospectively conducted trials (P3: NCT03782688; P4: NCT05253677; PPG Global: NCT04789317; Euro‐CRAFT: NCT05805462; INSIGHTFUL‐FFR: NCT05437900). No additional registration was required