Aerobic training as an adjunctive therapy to enzyme replacement in Pompe disease.

BACKGROUND: Aerobic exercise may be used in conjunction with enzyme replacement therapy (ERT) to attenuate cardiovascular deconditioning, skeletal muscle wasting, and loss of motor function in Pompe disease (glycogen storage disease type II; GSDII), but the effects on lysosomal glycogen content and macroautophagy have not been defined to date. PURPOSE: The main objectives of this study were to determine if acute aerobic exercise enhances 24-h uptake of recombinant human enzyme (rhGAA; Myozyme® [aim 1]) and if endurance training improves disease pathology when combined with ERT [aim 2] in Pompe mice. METHODS: For the first aim in our study, Pompe mutant mice (6(neo)/6(neo)) were grouped into ERT (Myozyme® injection only [40 mg/kg]) and ERT+EX (Myozyme® injection followed by 90 min treadmill exercise) cohorts, and enzyme uptake was assessed in the heart and quadriceps 24h post injection. For the second aim of our study, mutant mice were randomized into control, endurance-trained, enzyme-treated, or combination therapy groups. Exercised animals underwent 14 weeks of progressive treadmill training with or without biweekly Myozyme® injections (40 mg/kg) and tissues were harvested 1 week post last treatment. RESULTS: Myozyme® uptake (GAA activity) was not improved in ERT+EX over ERT alone at 24-h post injection. Endurance exercise training, with or without ERT, improved aerobic capacity and normalized grip strength, motor function, and lean mass (P<0.05), but did not reduce glycogen content or normalize macroautophagy beyond traditional enzyme replacement therapy. CONCLUSIONS: Endurance training is beneficial as an adjunctive therapy to ERT in Pompe disease, although it works by mechanisms independent of a reduction in glycogen content.

Incidence and Predictors of Adverse Events Among Initially Stable ST-Elevation Myocardial Infarction Patients Following Primary Percutaneous Coronary Intervention.

Background Cardiac intensive care units were originally created in the prerevascularization era for the early recognition of ventricular arrhythmias following a myocardial infarction. Many patients with stable ST-segment-elevation myocardial infarction (STEMI) are still routinely triaged to cardiac intensive care units after a primary percutaneous coronary intervention (pPCI), independent of clinical risk or the provision of critical care therapies. The aim of this study was to determine factors associated with in-hospital adverse events in a hemodynamically stable, postreperfusion population of patients with STEMI. Methods and Results Between April 2012 and November 2019, 2101 consecutive patients with STEMI who received pPCI in the Vancouver Coastal Health Authority were evaluated. Patients were stratified into those with and without subsequent adverse events, which were defined as cardiogenic shock, in-hospital cardiac arrest, stroke, re-infarction, and death. Multivariable logistic regression models were used to determine predictors of adverse events. After excluding patients presenting with cardiac arrest, cardiogenic shock, or heart failure, the final analysis cohort comprised 1770 stable patients with STEMI who had received pPCI. A total of 94 (5.3%) patients developed at least one adverse event: cardiogenic shock 55 (3.1%), in-hospital cardiac arrest 42 (2.4%), death 28 (1.6%), stroke 21 (1.2%), and re-infarction 5 (0.3%). Univariable predictors of adverse events were older age, female sex, prior stroke, chronic kidney disease, and atrial fibrillation. There was no significant difference in reperfusion times between those with and without adverse events. Following multivariable adjustment, moderate to severe chronic kidney disease (creatinine clearance <44 mL/min; 13% of cohort) was associated with adverse events (odds ratio 2.24 [95% CI, 1.12-4.48]) independent of reperfusion time, age, sex, smoking status, hypertension, diabetes, and prior myocardial infarction/PCI/coronary artery bypass grafting. Conclusions Only 1 in 20 initially stable patients with STEMI receiving pPCI developed an in-hospital adverse event. Moderate to severe chronic kidney disease independently predicted the risk of future adverse events. These results indicate that the majority of patients with STEMI who receive pPCI may not require routine admission to a cardiac intensive care unit following reperfusion.