Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Renal Outcomes in Patients Bridged to Heart Transplant With a Left Ventricular Assist Device

BACKGROUND: Patients with end stage heart failure are increasingly being bridged to heart transplant (BTT) with mechanical circulatory support (MCS), however the association between a left ventricular assist device (LVAD) BTT strategy and post-transplant renal outcomes is unclear. The aim of this study was to analyze the association of LVAD BTT with the development of post-transplant renal failure using a large national registry. METHODS: We queried the 2009-2018 United Network for Organ Sharing (UNOS) registry for all adults undergoing first-time heart or heart-kidney transplantation and stratified patients by use of pre-transplant durable LVAD. The primary outcome of interest was post-transplant renal failure, which was evaluated with multivariable logistic regression. RESULTS: 18,307 patients met inclusion criteria including 7,887 (43%) and 10,420 (57%) that were and were not bridged to transplant with an LVAD, respectively. BTT patients had slightly better baseline renal function (eGFR 68.7 vs 65.8 mL/min, p<0.001) and were less likely to receive a heart-kidney transplant (2.7% vs 4.8%, p<0.001). On multivariable logistic regression, LVAD BTT strategy was not independently associated with post-transplant renal failure (OR 1.13, 95% CI 0.86-1.49). Similarly, LVAD BTT among patients with preoperative renal dysfunction was not associated with post-transplant renal failure (AOR 1.40, 95% CI 0.91-2.18). CONCLUSIONS: BTT with an LVAD does not appear to be associated with worse renal outcomes regardless of baseline renal function. Furthermore, an LVAD BTT strategy in patients with chronic kidney disease may enable clinicians to identify candidates suitable for isolated heart transplantation without increasing their risk for post-transplant renal failure