Exercise rehabilitation in cardiac resynchronization: systematic review and a meta-analysis.

The benefit of exercise training in cardiac resynchronization therapy (CRT) recipients is not well established. We conducted a systematic review and meta-analysis to determine the effect of exercise training on clinical outcomes in CRT recipients.A comprehensive search until 2019 was conducted of MEDLINE, Epub, Embase, CINAHL and Cochrane databases as well as a bibliographic hand search to identify additional studies. We included all studies that compared aerobic exercise interventions in adults treated with CRT devices with adults treated with usual CRT care. These studies evaluated patient clinical characteristics, exercise testing measures, hemodynamic measures, echocardiography parameters, biomarkers and adverse events. Independent reviewers evaluated study eligibility, abstracted data and assessed risk of bias in duplicate. We used random-effect meta-analysis methods to estimate mean differences and odds ratios. Grades of Recommendation, Assessment, Development and Evaluation system were used to quantify absolute effects and quality of evidence. I2 was used to evaluate heterogeneity.We identified seven studies, six randomized control trials and one observational study, totaling 332 CRT patients in the exercise intervention and 534 patients receiving usual care. Peak VO2 was 2.4 ml/kg/min higher in the exercise group in comparison with the control group (pooled mean difference 2.26, 95% CI 1.38-3.13, I2 = 53%, high quality). AT-VO2 improved with exercise rehabilitation, and heterogeneity was considered low (pooled mean difference 3.96, 95% CI 2.68-5.24, I2 = 0.0%, moderate quality).Peak VO2 and AT-VO2 are increased with aerobic exercise in CRT recipients, demonstrating a significant improvement in functional capacity.

Longitudinal assessment of inflammation in recipients of continuous-flow left ventricular assist devices.

BACKGROUND: The long-term effects of continuous-flow left ventricular assist device (CF-LVAD) support on trends of inflammatory markers over time are unknown. We examined the hypothesis that the levels of inflammatory markers in CF-LVAD recipients are higher than in healthy controls and that these levels increase over time with long-term CF-LVAD support. METHODS: We examined the levels of inflammatory markers longitudinally at baseline before CF-LVAD implantation and at 3, 6, and 9 months after implantation. We then compared the levels of inflammatory markers to those in a healthy control group. RESULTS: Compared with baseline values before CF-LVAD implantation, left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) decreased significantly at 3, 6, and 9 months after CF-LVAD implantation. Brain natriuretic peptide (BNP) levels dropped significantly after CF-LVAD implantation but did not normalize. Improvements in ejection fraction at 3, 6, and 9 months after CF-LVAD implantation did not reach significance. Monocyte chemoattractant protein-1, interferon γ-induced protein, and C-reactive protein levels were higher in the CF-LVAD recipients at each of the time points (baseline before CF-LVAD implantation and 3, 6, and 9 months after implantation) compared with levels in healthy controls. In CF-LVAD recipients, serum interleukin-8, tumour necrosis factor-α, and macrophage inflammatory protein-ß increased significantly at 9 months, and macrophage-derived chemokine increased at 6 months after CF-LVAD implantation compared with baseline. CONCLUSIONS: Despite improvements in LV dimensions and BNP levels, markers of inflammation remained higher in CF-LVAD recipients. High levels of inflammation in CF-LVAD recipients may result from heart failure preconditioning or the long-term device support, or both. Because inflammation may be detrimental to CF-LVAD recipients, future studies should determine whether inflammatory pathways are reversible.

Epidermal growth factor-like domain 7 is a novel inhibitor of neutrophil adhesion to coronary artery endothelial cells injured by calcineurin inhibition.

BACKGROUND: We investigated the effect of epidermal growth factor-like domain 7 (Egfl7) on nuclear factor-κB activation, intercellular adhesion molecule-1 expression, and neutrophil adhesion to human coronary artery endothelial cells after calcineurin-inhibition-induced injury. METHODS AND RESULTS: Human coronary endothelial cells were incubated with cyclosporine (CyA) 10 µg/mL with or without Egfl7 (100 ng/mL) or the Notch receptor activator Jagged1 (200 ng/mL) for 6 to 48 hours. CyA upregulated nuclear factor-κB (p65) activity (128 ± 2% of control, P<0.001) in nuclear extracts, as determined with a DNA-binding activity ELISA. This activity was inhibited by Egfl7 (86 ± 3% of control; P<0.001 versus CyA alone). Jagged1 blocked Egfl7-induced nuclear factor-κB inhibition (105 ± 4% of control; P<0.05 versus CyA plus Egfl7). CyA upregulated cell-surface intercellular adhesion molecule-1 expression (215 ± 13% of control; P<0.001), as determined by flow cytometry. This expression was suppressed by Egfl7 (148 ± 5%; P<0.001 versus CyA alone). Jagged1 attenuated the intercellular adhesion molecule-1-suppressive effect of Egfl7 when administered with CyA (193 ± 3% versus 148 ± 5%; P<0.01). CyA increased neutrophil adhesion to human coronary endothelial cells (control 20 ± 5%, CyA 37 ± 3%; P<0.001 versus control) in a nonstatic neutrophil adhesion assay. This increase was attenuated by Egfl7 (22 ± 6%; P<0.001 versus CyA alone). Jagged 1 attenuated the effect of Egfl7 on neutrophil adhesion (31±3%; P<0.001 versus Egfl7 plus CyA). CONCLUSIONS: Our study reveals that Egfl7 is a potent inhibitor of neutrophil adhesion to human coronary endothelial cells subsequent to calcineurin-inhibition-induced injury. Mechanistically, Egfl7 blocked nuclear factor-κB pathway activation and intercellular adhesion molecule-1 expression, which suggests that it may have significant antiinflammatory properties. Because Jagged1 blocked the effect of Egfl7, Notch receptor antagonism may contribute to the mechanism of action of Egfl7.