Left ventricular assist device (LVAD) use in patients with dilated cardiomyopathy (DCM) can lead to a differential response in the LV and right ventricle (RV), and RV failure remains the most common complication post-LVAD insertion. We assessed transcriptomic signatures in end-stage DCM, and evaluated changes in gene expression (mRNA) and regulation (microRNA/miRNA) following LVAD. LV and RV free-wall tissues were collected from end-stage DCM hearts with (n = 8) and without LVAD (n = 8). Non-failing control tissues were collected from donated hearts (n = 6). Gene expression (for mRNAs/miRNAs) was determined using microarrays. Our results demonstrate that immune response, oxygen homeostasis, and cellular physiological processes were the most enriched pathways among differentially expressed genes in both ventricles of end-stage DCM hearts. LV genes involved in circadian rhythm, muscle contraction, cellular hypertrophy, and extracellular matrix (ECM) remodelling were differentially expressed. In the RV, genes related to the apelin signalling pathway were affected. Following LVAD use, immune response genes improved in both ventricles; oxygen homeostasis and ECM remodelling genes improved in the LV and, four miRNAs normalized. We conclude that LVAD reduced the expression and induced additional transcriptomic changes of various mRNAs and miRNAs as an integral component of the reverse ventricular remodelling in a chamber-specific manner.

Anderson-Fabry disease (AFD) is an X-linked recessive, multisystem disease of lysosomal storage. A mutation in the gene encoding the hydrolase enzyme α-galactosidase A results in its deficiency, or complete absence of activity. Subsequent progressive intracellular accumulation of glycosphingolipids, predominantly globotriaosylceramide, in various tissues, results in progressive organ dysfunction and failure, most commonly affecting the kidneys, nervous system, skin, eyes, vascular endothelium, and the heart. Cardiac involvement in AFD represents a leading cause of morbidity and mortality. Globotriaosylceramide accumulation affects cardiomyocytes, smooth muscle cells, vascular endothelial cells, and fibroblasts leading to various pathologies including valvular regurgitation, conduction disease and arrhythmias, coronary microvascular dysfunction, and right and left ventricular hypertrophy (LVH) leading to early diastolic dysfunction and late-stage systolic impairment. Diagnosis is on the basis of decreased plasma α-galactosidase activity in men and positive genetic testing in women. Contemporary large-scale screening studies have revealed a prevalence of 1%-5% in patients with unexplained LVH in multiple cohorts. Cardiac magnetic resonance imaging, with its unique tissue characterization capabilities, is the most important imaging modality to assess for cardiomyopathy in patients with AFD. Enzyme replacement therapy is indicated in AFD patients with significant organ involvement, and has been shown to clear sphingolipids from endothelial cells in other organs, as well as to reduce left ventricular mass as early as 6 months after starting treatment. There is increasing evidence that enzyme replacement therapy might be more effective if given at earlier stages of disease, before the development of LVH and myocardial fibrosis.

PURPOSE OF REVIEW:To provide an overview of the transplant component of the Canadian Organ Replacement Register (CORR).FINDINGS:CORR is the national registry of organ failure in Canada. It has existed in some form since 1972 and currently houses data on patients with end-stage renal disease and solid organ transplants (kidney and/or non-kidney). The transplant component of CORR receives data on a voluntary basis from individual transplant centres and organ procurement organizations across the country. Coverage for transplant procedures is comprehensive and complete. Long-term outcomes are tracked based on follow-up reports from participating transplant centres. The longitudinal nature of CORR provides an opportunity to observe the trajectory of a patient's journey with organ failure over their life span. Research studies conducted using CORR data inform both practitioners and health policy makers alike.IMPLICATIONS:The importance of registry data in monitoring and improving care for Canadian transplant candidates/recipients cannot be over-stated. This paper provides an overview of the transplant data in CORR including its history, data considerations, recent findings, new initiatives, and future directions.

Background Observational data suggest that the diffuse inflammatory nature of coronary disease may be expressed by the presence of unstable coronary lesions in multiple vessels in patients with acute myocardial infarction. The aim of our study was to investigate the existence of complex lesions in nonculprit vessels in patients with ST-elevation myocardial infarction and to assess their clinical and functional significance.Methods We evaluated 974 non-infarct-related arteries (nlRAs) in 439 patients presenting within 6 hours of acute ST-elevation myocardial infarction. Coronary angiograms and electrocardiograms (ECGs) were obtained 60 minutes after fibrinolysis and systematically analyzed in core angiographic and ECG laboratories. Complex lesions in nlRA were identified according to prior criteria, that is, stenosis > 50% with one of the following: overhanging edges, markedly irregular borders, ulceration, or thrombus.Results Complex lesions were identified in 85 (8.7%) of 974 nlRAs. Seventy-three (16.7%) of 439 patients had at least 1 complex lesion in a nlRA, with 10 of the 73 patients having > 1 nlRA affected. There were no differences in baseline total ST deviation on the qualifying ECG between patients with or without nlRA complex lesions. TIN 3 flow in nlRAs occurred less frequently in vessels with complex lesions (50.8% vs 81.5%, P <.001), a difference maintained when nlRAs with stenosis between 50% and 99% were analyzed (P <.006). Patients with nlRA complex lesions had a higher inhospital incidence of congestive heart failure (16.4% vs 6.3%, P =.007) and a trend toward more recurrent ischemia (13.7% vs 7.4%, P =.102).Conclusion These findings provide new evidence supportive of the concept that active coronary lesions occur simultaneously in > 1 vessel, while also attesting to their functional and clinical significance.

Background: The relevance of the atrial coronary anatomy in the pathogenesis of atrial arrhythmias and atrioventricular (AV) block complicating acute myocardial infarction (AMI) remains unclear.Objectives: We evaluated the location of the infarct-related coronary lesion relative to the principal atrial branches (ie, sinoatrial nodal, AV nodal, left atrial circumflex) in 454 patients with ST-elevation AMI in the CAPTORS II trial.Methods: Patients underwent systematic 60-minute postfibrinolytic angiograms, and coronary anatomy was correlated with evidence of atrial arrhythmias and AV block on sequential electrocardiograms.Results: Patients with either sinoatrial nodal or left atrial circumflex compromise (n = 34) had a higher incidence of "early" (ie, up to 90 minutes postfibrinolysis) atrial arrhythmias vs those without (23.5% vs 7.1%; P = .004). Patients with AV nodal compromise (n = 207) had a higher incidence of "early" AV block vs those without (12.1% vs 3.6%; P = .001).Conclusion: These findings support the etiological role of acute atrial ischemia in the development of early atrial arrhythmias and AV block complicating AMI. (c) 2005 Elsevier Inc. All rights reserved.