Search

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficient galactosidase A enzyme and subsequent accumulation of glycosphingolipids throughout the body. The result is a multi-system disorder characterized by cutaneous, corneal, cardiac, renal, and neurological manifestations. Increased left ventricular wall thickness represents the predominant cardiac manifestation of FD. As the disease progresses, patients may develop arrhythmias, advanced conduction abnormalities, and heart failure. Cardiac biomarkers, point-of-care dried blood spot testing, and advanced imaging modalities including echocardiography with strain imaging and magnetic resonance imaging (MRI) with T1 mapping now allow us to detect Fabry cardiomyopathy much more effectively than in the past. While enzyme replacement therapy (ERT) has been the mainstay of treatment, several promising therapies are now in development, making early diagnosis of FD even more crucial. Ongoing initiatives involving artificial intelligence (AI)-empowered interpretation of echocardiographic images, point-of-care dried blood spot testing in the echocardiography laboratory, and widespread dissemination of point-of-care ultrasound devices to community practices to promote screening may lead to more timely diagnosis of FD. Fabry disease should no longer be considered a rare, untreatable disease, but one that can be effectively identified and treated at an early stage before the development of irreversible end-organ damage.

Background: Centralized care models are often used for rare diseases like pulmonary hypertension (PH). It is unknown how living in a rural or remote area influences outcomes. Methods: We identified all patients from our PH database who carried a diagnosis of WHO Group 1 or WHO Group 4 PH. Using Canadian postal code data, patients were classified as living in a rural area; or a small, medium or large community size. The commute time from patient residence to our clinic was determined using mapping software. We compared baseline catheterization data according to community size and commute time. At follow up, we evaluated the association between community size and commute time with prognostic parameters of functional class, walk distance and echocardiography. Results: Of the 342 patients identified, 72(21%) patients lived in rural areas, while 26(8%), 49(14%) and 195(57%) resided in small, medium and large population centres, respectively. The commute time was 3 h for 120(35%). There was no association seen for any catheterization parameter by either community size or commute time. At last follow up, there was no association between any prognostic parameter and community size or commute time. Conclusions: We found no association between community size or commute time with severity of illness at diagnosis, or markers of prognosis at follow up. This suggests that patients who reside in rural or remote environments are not experiencing deficiencies in care compared to urban patients.

Background Competitive swimmers incur shoulder pain and injury. Physical characteristics such as shoulder range of motion (ROM) and endurance and tissue adaptations such as posterior capsule thickness (PCT) may be risk factors in addition to high training volume. Hypothesis/Purpose 1) To identify the most provocative special test and prevalence of positive special tests for shoulder impingement tests in a group of collegiate swimmers, (2) to assess shoulder pain and disability, internal rotation (IR) and external rotation, and horizontal adduction (HADD) ROM and posterior shoulder endurance longitudinally over a competitive collegiate season, and (3) determine if there is a relationship between swimming yardage, supraspinatus tendon organization, and PCT. Methods Thirty Division III swimmers were tested poolside at the beginning (T1), middle (T2), and end (T3) of their season. Dependent variables included pain and disability, shoulder ROM, Posterior Shoulder Endurance Test (PSET) value, and PCT. Analyses of variance with follow-up t tests compared measures over time, and Pearson correlation coefficients were performed. Results Despite increased swimming yardage, disability was reduced from T1 to T3 (P = .003). There was a reduction in bilateral IR and HADD ROM from T1 to T3. PSET values increased on the right from T1 to T3 (P = .014). There was a significant positive correlation between swimming yardage at T1 and T2 and PCT at T3 (P = .034, P = .028). Conclusion A loss of shoulder IR and HADD was observed across the season concurrent with less swimming-related disability, which may indicate a favorable adaptation. Improved PSET scores over the season is consistent with prior research linking endurance and less pain and disability.

Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9. In contrast, GLUT4, VEGF, eNOS, HIF-1α, and PGC1-α were significantly decreased in expression. The top biological process clusters identified in Database for Annotation, Visualization and Integrated Discovery, ToppGene, and PANTHER were collagen metabolic process, cellular ion homeostasis, regulation of cell migration, and response to decreased oxygen levels. These data suggest refocusing understanding of the pathophysiology of HFpEF to pathways involved in collagen metabolism, cell migration likely for inflammatory cells, and responses to decreased oxygen levels. Abbreviations Inducible nitric oxide synthase (INOS), neutrophil cytosolic factor 1 (p47phox), adrenomedullin (ADM), atrial natriuretic peptide (ANP), osteopontin (OPN/SPP1), angiotensin converting enzyme (ACE), monocyte chemotactic protein 1 (MCP-1), cytochrome b-245 beta polypeptide (gp91phox), intercellular adhesion molecule 1 (ICAM-1), transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), endothelin-1 (ET-1), cytochrome B-245, alpha polypeptide (p22phox), endothelin receptor type B (ETB/EDNRB), brain natriuretic peptide (BNP), endothelin receptor type A (ETA/EDNRA), matrix metallopeptidase 13 (MMP13), type I collagen (Col1a1), matrix metallopeptidase 2 (MMP2), TIMP metallopeptidase inhibitor 1 (TIMP1), Type III collagen (Col3a1), interleukin 1 beta (IL-1β), beta myocin heavy chain (β-MHC), endothelin converting enzyme 1 (ECE1) matrix metallopeptidase 14 (MMP14), angiotensinogen (AGT), angiotensin II receptor Type 1 (AT1R), cytochrome C oxidase I (COX1), fms-like tyrosine kinase 1 (FLT1), TIMP metallopeptidase inhibitor 2 (TIMP2), phospholamban (PLN), vascular cell adhesion molecule 1 (VCAM1), extracellular matrix (ECM).

The objective was to improve the management of patients with hypertension (HTN) and coronary artery disease (CAD), utilizing a model which integrates 3 determinants of coronary blood flow (CBF)—CAD severity, diastolic blood pressure (DBP), and left ventricular (LV) mass. We validated non‐parametric equations for CBF estimation in a consecutive patient sample (N = 81) with HTN and CAD. There was a highly significant correlation (r = .565; P 70 mm Hg. Estimated changes in CBF at different DBP considering the severity of CAD and LV mass can be calculated. In summary, the severity of CAD from coronary CT or coronary angiography combined with LV mass from echocardiography permits clinicians to guide the extent of, or target for, DBP to avoid seriously compromising CBF.