Percutaneous mitral valve repair with the MitraClip: early results from the MitraClip Asia-Pacific Registry (MARS).

AIMS: Percutaneous MitraClip therapy has been shown to be safe and efficacious in mitral regurgitation (MR). Our aim was to describe early outcomes in patients from the Asia- Pacific region. METHODS AND RESULTS: The MitraClip Asia-Pacific Registry (MARS) includes data from eight different centres in five countries in the Asia-Pacific region. The primary efficacy outcome was reduction in MR to ≤2+ at 30 days. The safety outcome was 30-day freedom from major adverse events (MAE), defined as the composite of death, myocardial infarction, non-elective cardiac surgery, renal failure, transfusion of ≥2 units of blood, ventilation for >48 hours, septicaemia, and new onset atrial fibrillation. A total of 142 patients underwent the MitraClip procedure from February 2011 to October 2013. Fifty-three point five percent (76) of patients had functional MR, 45.8% (65) had degenerative MR and 0.7% (1) had mixed MR. The acute procedural success rate was 93.7% (133). Thirty-one point seven percent of the patients were in NYHA Class I-II at baseline, compared to 82.1% at 30 days (p<0.001). Zero percent (0) of the patients had ≤2+ MR at baseline compared to 76.8% (109) at 30 days (p<0.001). CONCLUSIONS: Results from the Asia-Pacific region show that the MitraClip procedure is effective in reducing mitral regurgitation and has favourable short-term safety outcomes.

Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes.

OBJECTIVES: Serum amyloid A (SAA) is a biomarker of inflammation. Elevated blood levels in cardiovascular disease and local deposition in atheroma implies a role of SAA as a mediator rather than just a marker of inflammation. This study explored SAA-induced cytokine production and secretion by mononuclear cells. METHODS AND RESULTS: RT-PCR showed that SAA time-dependently induced cytokine mRNAs in peripheral blood mononuclear cells (PBMC) and THP-1 monocytoid cells, and dramatically increased IL-1beta, MCP-1, IL-6, IL-8, IL-10, GM-CSF, TNF, and MIP-1alpha secretion by PBMC to levels 28 to 25,000 fold above baseline, as measured with Bio-Plex kits; monocytes were the principle source. SAA induction of cytokines in monocyte-derived macrophages (MDM) was significantly higher than from monocytes from the same donors. SAA time-dependently induced transient and significant upregulation of NF-kappaB1 mRNA; inhibitor studies indicate that activation of NF-kappaB through the ERK1/2, p38 and JNK MAPKs and the PI3K pathway was involved. PBMC from 10 patients with coronary artery disease (CAD) spontaneously secreted higher levels of IL-6 and MIP-1alpha after 24h incubation than PBMC from normal controls, whereas SAA-induced levels of all cytokines were similar to controls. Aortic and coronary sinus sampling in 23 CAD patients indicated significant SAA release into the coronary circulation, not evident in 11 controls. CONCLUSIONS: SAA can increase monocyte and macrophage cytokine production, possibly at sites of atherosclerosis, thereby contributing to the pro-inflammatory state in coronary artery disease.

Pleiotropic roles of S100A12 in coronary atherosclerotic plaque formation and rupture.

Macrophages, cytokines, and matrix metalloproteinases (MMP) play important roles in atherogenesis. The Ca(2+)-binding protein S100A12 regulates monocyte migration and may contribute to atherosclerosis by inducing proinflammatory cytokines in macrophages. We found significantly higher S100A12 levels in sera from patients with coronary artery disease than controls and levels correlated positively with C-reactive protein. S100A12 was released into the coronary circulation from ruptured plaque in acute coronary syndrome, and after mechanical disruption by percutaneous coronary intervention in stable coronary artery disease. In contrast to earlier studies, S100A12 did not stimulate proinflammatory cytokine production by human monocytes or macrophages. Similarly, no induction of MMP genes was found in macrophages stimulated with S100A12. Because S100A12 binds Zn(2+), we studied some functional aspects that could modulate atherogenesis. S100A12 formed a hexamer in the presence of Zn(2+); a novel Ab was generated that specifically recognized this complex. By chelating Zn(2+), S100A12 significantly inhibited MMP-2, MMP-9, and MMP-3, and the Zn(2+)-induced S100A12 complex colocalized with these in foam cells in human atheroma. S100A12 may represent a new marker of this disease and may protect advanced atherosclerotic lesions from rupture by inhibiting excessive MMP-2 and MMP-9 activities by sequestering Zn(2+).

Serum amyloid A may potentiate prothrombotic and proinflammatory events in acute coronary syndromes.

AIMS: Elevated serum amyloid A (SAA) levels, like C-reactive protein (CRP), predict coronary events. Both induce monocyte tissue factor (TF), and peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease (CAD) express higher TF in response to CRP. This study examined SAA induction of TF and tumour necrosis factor-alpha (TNF) in PBMC from patients with CAD and in monocytoid THP-1 cells. METHODS AND RESULTS: PBMC from 26 males with CAD (15 stable angina, SA, and 11 acute coronary syndromes, ACS) and 14 male controls were stimulated with SAA. SAA promoted up to six-fold increase in TF activity (recalcification assay) on PBMC from patients, associated with elevated TF mRNA and protein. PBMC responded optimally when monocytes were adherent. Unlike CRP, SAA induced TF and TNF in THP-1 cells. SAA-induced TNF was dose-dependently inhibited by HDL. PBMC from patients with ACS expressed more basal TF (257.4+/-46.8 mU/10(6) PBMC vs. 131.0+/-12.5 mU/10(6) PBMC, P=0.003), and greater SAA-induced TF than cells from controls, whereas no difference was found between SA and controls (ACS 2246+/-493, SA 1364+/-206, controls 1091+/-113 mU/10(6) PBMC, with SAA 250 ng/mL, P=0.002 ACS vs. controls across the dose range). Importantly, SAA-induced TNF levels (ELISA) were much higher in patients with ACS than SA or controls (ACS 211+/-41, SA 108+/-16, controls 73+/-11 pg/mL, with SAA 250 ng/mL, P=0.001 ACS vs. controls or P=0.013 ACS vs. SA across the dose range). SAA-induced TF and TNF correlated positively with serum SAA levels in CAD, but not controls. CONCLUSIONS: SAA is a prothrombotic and proinflammatory mediator in ACS which may contribute to atherogenesis and its complications.

Complex coronary sinus fistula in a 58-year-old female.

Coronary artery aneurysms and arterio-venous fistulae are uncommon malformations. We report the case of a 58-year-old woman with a large aneurysmal fistula arising from the left coronary tree and involving the entire coronary sinus venous system, resulting in significant left-to-right shunt. We discuss the management of aneurysmal fistulae of the coronary arteries, and the merits of prophylaxis for thrombotic complications of large aneurysms. We recommend consideration of warfarinisation in addition to aspirin of such patients post-operatively.