Regulation of Angiopoietin-2 Before and After Mechanical Circulatory Support Therapy

Abstract

Gastrointestinal bleeding (GIB) during mechanical circulatory support (MCS) is a major unsolved comorbidity. Inadequate activation of angiopoietin-2-related systems is considered as a major cause of GIB. However, the regulation of angiopoietin-2 remains unknown. Consecutive 20 patients who received continuous-flow MCS therapy (MCS group) and 12 with advanced heart failure (HF; HF group) were prospectively enrolled and their angiopoetin-2 levels were compared. Angiopoietin-2 level had a moderate correlation with log10 B-type natriuretic peptide (BNP; r = 0.39, p < 0.001). The MCS group had significantly higher angiopoietin-2 level divided by log10 BNP compared with the HF group (2.80 ± 0.20 vs. 1.88 ± 0.17, p < 0.001). Angiopoetin-2 had a moderate correlation with central venous pressure and C-reactive protein during the MCS support (r = 0.51 and r = 0.45, respectively). Higher angiopoietin-2 level divided by log10 BNP (> 4.3) was significantly associated with the occurrence of GIB with a hazard ratio of 296 (95% confidence interval 2.24–38620, p = 0.0224). Angiopoietin-2 was already elevated in the HF cohort and more elevated following MCS initiation. Among the MCS cohort, angiopoietin-2 was particularly elevated in patients with systemic congestion and inflammation and was associated with higher incidence of GIB.

Implication of Hemodynamic Assessment during Durable Left Ventricular Assist Device Support

“…This might be the most common cause of LVAD-related gastrointestinal bleeding, as opposed to polyps or gastrointestinal mucosal ulceration [27,28]. It is plausible that abnormal hemodynamics, particularly systemic congestion due to elevated central venous pressures, are associated with the activation of these systems ( Figure 3) [29]. Recently, therapies including omega-3 fatty acid and digoxin administration were found to be associated with fewer gastrointestinal bleeding events, possibly due to suppression of these maladaptive cascades [30][31][32].…”

“…Furthermore, abnormal hemodynamics, particularly right heart failure with elevated central venous pressure, may increase the risk of incident stroke (Figure 3) [13]. We postulate that an inflammatory cascade activates due to chronic and systemic congestion which may, in turn, increase cerebral vasculature vulnerability and the potential risk of stroke [29]. Another explanation may be a decrease in blood flow through the device because of impaired right ventricular function, contributing to increased stasis of flow and potentially increased risk of clot formation in the device [11].…”

Angiopoietin‐2 and hemocompatibility‐related adverse events during percutaneous left ventricular assist device supports

“…The inflammatory system has a considerable association with advanced heart failure: Ang-2 and BNP have a strong correlation in the heart failure cohort. 5 Our team recently demonstrated that Ang-2 was inappropriately elevated relative to the BNP level during LVAD supports compared to the heart failure cohort, 4 probably due to the stimulation of Ang-2 activity via hematological instability. 6 This is a rationale of why we used Ang-2/BNP as a variable instead of Ang-2 alone.…”

“…Furthermore, Ang-2 is inappropriately elevated relative to BNP levels in some LVAD patients. 4 However, its prognostic impact on HRAEs remains uninvestigated. In this study, we investigated the prognostic impact of Ang-2 level relative to BNP (Ang-2/BNP) obtained immediately after percutaneous LVAD implantation on future occurrences of HRAE.…”

Impact of comorbid malignancy on clinical courses following left ventricular assist device implantation

“…Data of biomarkers associating with the formation of arteriovenous malformation including angiotensin-2 might approach their findings. 3 Post-LVAD therapeutic data including antiplatelet and anticoagulant would also useful to establish an optimal strategy for those with malignancy.…”