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PIK3CA-related overgrowth spectrum (PROS) includes rare genetic conditions due to gain-of-function mutations in the PIK3CA gene. There is no approved medical therapy for patients with PROS, and alpelisib, an approved PIK3CA inhibitor in oncology, showed promising results in preclinical models and in patients. Here, we report for the first time the outcome of two infants with PROS having life-threatening conditions treated with alpelisib (25 mg) and monitored with pharmacokinetics. Patient 1 was an 8-mo-old girl with voluminous vascular malformation. Patient 2 was a 9-mo-old boy presenting with asymmetrical body overgrowth and right hemimegalencephaly with West syndrome. After 12 mo of follow-up, alpelisib treatment was associated with improvement in signs and symptoms, morphological lesions and vascular anomalies in the two patients. No adverse events were reported during the study. In this case series, pharmacological inhibition of PIK3CA with low-dose alpelisib was feasible and associated with clinical improvements, including a smaller size of associated complex tissue malformations and good tolerability.

Background Although recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient's physical rehabilitation and assess their cardiovascular prognosis. Design We aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection. Methods Patients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta. Results Among the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence. Conclusion CPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.

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Background: Objective assessment of maximal aerobic capacity using peak oxygen consumption (peak VO2) can be helpful in the management of patients with asymptomatic aortic stenosis (AS). The relationship between peak VO2 and AS severity criteria derived from rest and supine exercise echocardiography (SEE) has never been explored. Objectives: We aimed to determine whether low peak VO2 (b85% of predicted value) is associated with severity parameters in SEE, and poor clinical outcome. Methods: Fifty one asymptomatic patients (mean age of 54 ± 21 years) with moderate to severe aortic stenosis (Vmax N 3 m/s) and left ventricle ejection fraction N 50% prospectively underwent resting and SEE and cardiopulmonary exercise testing (CPX). Results: Peak VO2 was lower than expected (21.9 ± 7.4 mL/kg/min), i.e. b85% of predicted value in 57% patients, secondary to cardiac limitation in most of them (69%). In multiple regression analysis, age, BMI and female gender were the only independent determinants of peak VO2. Interestingly no parameter derived from SEE was associated with peak VO2. After 21 ± 7 month follow-up, no patient died, 20 underwent cardiac surgery. Peak VO2 b 85% of predicted value was associated with lower event free survival compared to normal peak VO2 (57% ± 11% vs 93 ± 6%, p = 0.036) whereas no exercise echocardiographic parameter could predict such events. Peak VO2 ≥ 85% had a negative predictive value of 97%. Conclusion: CPX detects a high proportion of false asymptomatic AS patients with poorer outcome that cannot be predicted by SEE markers of AS severity. Assessment of aerobic capacity should be part of current approach within a "watchful waiting" strategy.