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Background: Coronary artery fluid dynamics may be altered because of the nonphysiological flow seen in continuous-flow left ventricular assist devices (CF-LVADs). Our aim was to study the structure and composition of coronary vessels after CF-LVAD. Methods and Results: Coronary arteries were collected from patients with heart failure (HF) at the time of transplantation, of whom 15 were supported with a CF-LVAD before transplant (HF+LVAD group) and 9 were not (HF non-LVAD group). In addition, coronary samples were obtained from 5 nonfailing age-matched donors (nonfailing group). Histological analysis was performed to quantify coronary morphology, composition, vascular fibrosis, and vasa vasorum density. The age and sex mix of the 3 groups were similar, and the mean duration of LVAD support was 213 days. Compared with patients with HF and nonfailing donors, the arteries from patients with HF+LVAD had expansion of the adventitia, breakdown of the internal elastic lamina, and increased adventitial collagen deposition and density of vasa vasorum. Conclusions: Among patients supported with CF-LVADs, the coronary arteries develop marked remodeling with increased adventitial fibrosis. The physiological consequences of these structural changes are unknown, but it is possible that arterial contractility may be impaired, thus limiting coronary flow reserve and promoting myocardial ischemia. This may contribute to CF-LVAD complications, such as ventricular arrhythmias and right ventricular failure. As more patients receive CF-LVADs and new pump technology attempts to modulate flow profiles and pulsatility, further research is needed to understand the mechanisms and long-term sequela of these changes in coronary arteries and other vascular beds. [ABSTRACT FROM AUTHOR]

Objective: Extracellular matrix proteinases are implicated in the pathogenesis of calcific aortic valve disease. The ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) enzyme is secreted, matrix-associated metalloendopeptidase, capable of degrading extracellular matrix proteins, particularly matrilin 2. We sought to determine the role of the ADAMTS5/matrilin 2 axis in mediating the phenotype transition of valvular interstitial cells (VICs) associated with calcific aortic valve disease., Approach and Results: Levels of ADAMTS5, matrilin 2, and α-SMA (α-smooth muscle actin) were evaluated in calcified and normal human aortic valve tissues and VICs. Calcified aortic valves have reduced levels of ADAMTS5 and higher levels of matrilin 2 and α-SMA. Treatment of normal VICs with soluble matrilin 2 caused an increase in α-SMA level through Toll-like receptors 2 and 4, which was accompanied by upregulation of runt-related transcription factor 2 and alkaline phosphatase. In addition, ADAMTS5 knockdown in normal VICs enhanced the effect of matrilin 2. Matrilin 2 activated nuclear factor (NF) κB and NF of activated T cells complex 1 and induced the interaction of these 2 NFs. Inhibition of either NF-κB or NF of activated T cells complex 1 suppressed matrilin 2's effect on VIC phenotype change. Knockdown of α-SMA reduced and overexpression of α-SMA enhanced the expression of pro-osteogenic factors and calcium deposit formation in human VICs., Conclusions: Matrilin 2 induces myofibroblastic transition and elevates pro-osteogenic activity in human VICs via activation of NF-κB and NF of activated T cells complex 1. Myofibroblastic transition in human VICs is an important mechanism of elevating the pro-osteogenic activity. Matrilin 2 accumulation associated with relative ADAMTS5 deficiency may contribute to the mechanism underlying calcific aortic valve disease progression., (© 2017 American Heart Association, Inc.)

Objective: To compare the outcomes of mitral repair and replacement in revascularized patients with ischemic mitral regurgitation., Summary Background Data: Combined coronary bypass (CABG) and mitral procedures have been associated with the highest mortality (>10%) in cardiac surgery. Recent studies have suggested that mitral valve replacement (MVR) with sparing of the subvalvular apparatus had comparable results to mitral repair when associated with CABG., Methods: Over the past 7 years, 54 patients had CABG/mitral repair versus 56 who had CABG/MVR with preservation of the subvalvular apparatus. The groups were similar in age at 69.2 years in the replacement group versus 67.0 in the repair group. We compared these 2 groups based on hospital mortality, incidence of complications including nosocomial infection, neurologic decompensation (stroke), pulmonary complication (pneumonia, atelectasis, and prolonged ventilation), and renal complications (acute renal failure or insufficiency)., Results: The mitral repair group had a hospital mortality of 1.9% versus 10.7% in the replacement group (P = 0.05). Infection occurred in 9% of repairs compared with 13% of replacements (P = 0.59). The incidence of stroke was no different between groups (2 of 54 repairs vs. 2 of 56 replacements, P = 1.00). Pulmonary complication rate was 39% in repairs versus 32% in replacements (P = 0.59). Worsening renal function occurred in 15% of repairs versus 18% of replacements (P = 0.67)., Conclusions: Mitral repair is superior to mitral replacement when associated with coronary artery disease in terms of perioperative morbidity and hospital mortality. Although preservation of the subvalvular apparatus with MVR has a theoretical advantage in terms of ventricular function, mitral repair clearly adds a survival benefit in patients with concomitant ischemic cardiac disease.