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Essentials: High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. Summary: Background: Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives: To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods: Males aged 12-50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results: Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, - 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus - 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions: Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible. (Less)

It has been shown that the echographic motion of the posterior aortic wall in diastole is closely related to the underlying left atrial events, possibly due to the anatomical proximity of the two structures. We observed that the pulmonary artery shares a similar close anatomical relationship with the left atrium. The present study in 55 consecutive patients with adequate echocardiographic recordings of the aortic root and the pulmonary valve demonstrates that the diastolic waveforms of the pulmonary valve and the posterior aortic wall are nearly identical in early diastole. The pulmonary valve e-f slope correlated with the posterior aortic wall O-R slope (r = 0.95) and the S2-f interval (second heart sound to f on the pulmonary valve) correlated closely with the S2-R interval (second heart sound to R on the posterior aortic root) (r = 0.94)). No significant correlation was found between the pulmonary valve e-f slope and the pulmonary artery pressures. The presence and amplitude of the maximum "a dip," on the other hand, correlated with the presence of pulmonary hypertension, with some notable exceptions. In addition, the "a dip" on the pulmonary valve and the depth of the A wave on the posterior aortic wall were significantly correlated (r = 0.85). It appears that the "a dip" on the pulmonary valve is influenced by dual mechanisms: pressure differences between the pulmonary artery and the right ventricle in late diastole and the left atrial events. Thus, the early diastolic waveform of the pulmonary valve, like the posterior aortic wall waveform, may primarily reflect underlying left atrial events and is not a measure of pulmonary artery pressure. The late diastolic waveform "a dip" has a dual mechanism, related in part to the underlying left atrial events, and also reflecting the instantaneous pressure differences across the pulmonary valve following atrial systole.