Innate immunity has a dual effect on vascular healing: Suppression and aggravation of neointimal formation and remodeling post-endotoxin challenge

BACKGROUND: Inflammation is important to vascular repair following injury, modulating neointimal proliferation and remodeling. Previously, we have shown that a low-intensity inflammatory response aggravates neointimal formation following balloon and stent injury. The present study examined whether modulation of the extent and timing of nonspecific inflammation mediates the local vascular response in an additive unidirectional or rather a bidirectional fashion. METHODS AND RESULTS: Rabbits subjected to denudation and balloon injury of the iliac artery were treated with low(1 µg/kg) or high (100µg/kg) doses of bacterial endotoxin (LPS) immediately after injury, or with early high-dose LPS administered 3 days prior to injury (preconditioning). Neointimal formation at 28 days was significantly increased in the low-dose group (0.537 ± 0.059mm(2)) as compared with controls (0.3 ± 0.03mm(2)). High-dose LPS did not significantly affect neointimal formation while early high dose significantly reduced neointima (0.296 ± 0.033 and 0.194 ± 0.025mm(2), respectively, n = 12–14/group). Arterial wall and systemically circulating interleukin-1β levels, and monocyte CD14 activation correlated with neointimal formation. Vascular remodeling was accelerated in animals treated with low- or high-dose LPS while not affected in the preconditioned group. Remodeling index inversely correlated with arterial matrix metalloproteinase-2 levels 6 days after injury. CONCLUSIONS: The extent and timing of nonspecific inflammation that is concurrent with vascular injury can determine different and opposite vascular repair patterns

MitraClip therapy in patients with acute severe mitral regurgitation

Abstract Background There is a lack of data to support the optimal management of high-risk patients with acute severe mitral regurgitation (MR). The role of the MitraClip implantation in treatment of acute severe mitral regurgitation (MR) is undetermined. Methods We screened all patients who underwent MitraClip implantation at the Hadassah Medical Center between October 2015 and December 2019. We evaluated immediate, 30-day and 1-year outcomes after the procedure. We evaluated patients with severe MR due to ruptured cord because of degenerative disease and acute-on-chronic functional MR due to ischemic (after a recent myocardial infarction (MI)) or non-ischemic etiology (secondary to decompensated HF). Results From a cohort of 151 patients, who underwent MitraClip implantation in our center, we identified 35 patients (23.2%) with acute severe mitral regurgitation (4+) and decompensated refractory heart failure. Patients' mean age was 74.15 years, 66.9% - were males. One, 2, or 3 clips were implanted. Reduction of MR from 4+ to 1+ was achieved in 34 patients (66.7%). Twenty-eight patients (80%) had acute-on-chronic severe MR and refractory heart failure including 6 cases after recent MI, other 7 patients presented with heart failure and acute severe MR secondary to ruptured cord due to degenerative disease. After MitraClip implantation, reduction of MR severity was achieved in all patients. Seven patients were withdrawn from intravenous therapy and intra-aortic balloon pump 2–3 days after the procedure. Four patients died during hospitalization, three of them due to sepsis. 30-day follow-up showed improvement of NYHA functional class and a tendency toward improvement in left ventricle systolic function with signs of reverse remodeling. Nevertheless, we observed high 30-day and 1-year mortality rate (11.4 and 23.8% respectively). Conclusions MitraClip therapy could be an alternative option for treatment of patients with acute and acute-on-chronic severe MR of ischemic and non-ischemic etiology. Funding Acknowledgement Type of funding source: None </jats:sec

Echocardiographic and clinical outcomes of MitraClip therapy in patients with severe mitral regurgitation

Abstract Background MitraClip implantation improves mitral regurgitation (MR), however its impact on pulmonary hypertension (PHT) is not fully elucidated. Our hypothesis was that changes in pulmonary pressure after MitraClip implantation might predict outcomes. Methods We studied a cohort of 149 consecutive patients who underwent MitraClip implantation between August 2015 and September 2019. We compared echocardiographic and clinical variables between a group with not-severe PHT and a group with severe PHT according to Pulmonary artery systolic pressure (PASP) &amp;gt;55 mmHg. Results Mean age of the cohort was 73±10 years, 75% were men, and 80% had functional MR. There are no differences in baseline characteristics between the two groups. There was a significant reduction of 13.6 mmHg in PASP at the severe PHT group from 68.2±10.9 mmHg before the procedure to 54.6±14.9 after (P=0.001) compared to the absence of a significant change in the second group. This reduction was maintained in the 6 months follow-up. Although PHT is considered a poor prognostic measure, and the severe PHT group had a baseline PASP higher than the not-severe group (P&amp;lt;0.001), however the Kaplan Meier curve did not show any significant difference in overall survival (p=0.468), and there is also no difference in one-year survival. Conclusions MitraClip therapy improves PASP in patients with severe MR and severe PHT. These patients showed the same survival as patients with not-severe PHT. MitraClip is a safety and effective procedure even for patients with severe PHT, that should not be excluded. Funding Acknowledgement Type of funding source: None </jats:sec