Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling.

In the clinic, most cases of congenital heart valve defects are thought to arise through errors that occur after the endothelial-mesenchymal transition (EndoMT) stage of valve development. Although mechanical forces caused by heartbeat are essential modulators of cardiovascular development, their role in these later developmental events is poorly understood. To address this question, we used the zebrafish superior atrioventricular valve (AV) as a model. We found that cellularized cushions of the superior atrioventricular canal (AVC) morph into valve leaflets via mesenchymal-endothelial transition (MEndoT) and tissue sheet delamination. Defects in delamination result in thickened, hyperplastic valves, and reduced heart function. Mechanical, chemical, and genetic perturbation of cardiac forces showed that mechanical stimuli are important regulators of valve delamination. Mechanistically, we show that forces modulate Nfatc activity to control delamination. Together, our results establish the cellular and molecular signature of cardiac valve delamination in vivo and demonstrate the continuous regulatory role of mechanical forces and blood flow during valve formation.

Feasibility of transradial coronary angiography and intervention using a single Ikari left guiding catheter for ST elevation myocardial infarction.

BACKGROUND: Transradial coronary intervention (TRI) has been widely adopted in ST elevation myocardial infarction (STEMI) patients but there is limited literature on the use of a single catheter for both diagnostic angiography and intervention. We aim to evaluate the feasibility and outcomes of TRI with a single Ikari left (IL) guiding catheter in STEMI patients. METHODS: This is a retrospective study of 362 consecutive STEMI patients from August 2007 to December 2008. We assessed the feasibility of TRI with a single IL and compared this strategy with conventional transfemoral intervention (TFI) on the following outcomes: (1) door to perfusion time, (2) total procedural duration, (3) total fluoroscopy duration, and (4) major adverse cardiac events (MACE) by intention to treat analysis. RESULTS: TRI was attempted in 185 patients. There were no failed radial cannulations. Overall success rate of primary TRI with a single IL was 96.9% and there were only 2 failures that required conversion to TFI. Compared to TFI, TRI with IL tended to a shorter median door to perfusion time, 90 (IQR 76.0 - 119.5) versus 98 (IQR 80.8 - 120.5) minutes (P = 0.07) and a shorter median procedure duration of 34 (IQR 27.0 - 45.0) versus 37 (IQR 28.0 - 49.3) minutes (P = 0.06). The median fluoroscopy duration was longer in the TRI group. MACE were comparable between the 2 groups. CONCLUSION: In experienced centers, TRI with a single IL catheter for STEMI is a feasible and effective approach and outcomes are comparable to conventional TFI.

Clinical and neurocognitive outcomes after transcatheter aortic valve implantation (TAVI) with cerebral protection: initial experience with a novel dual-filter device in Southeast Asia.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is increasingly performed in patients with severe aortic stenosis. A novel dual-filter system to reduce cerebral embolism during TAVI recently became available. We aimed to assess the feasibility, safety, and clinical and neurocognitive outcomes of TAVI with cerebral protection in Asian patients. METHODS: 40 consecutive patients undergoing TAVI with cerebral protection were enrolled. All procedures were performed via femoral access using the self-expanding Evolut R/PRO or Portico, or the balloon-expandable SAPIEN 3 bioprostheses. Baseline characteristics, procedural and clinical outcomes were recorded. Cognition was assessed at baseline and 30 days using the abbreviated mental test (AMT). RESULTS: The mean age of the patients (75% male) was 76.4 ± 8.4 years. TAVI was uncomplicated in all patients. The filter device was successfully deployed in 38 (95.0%) patients without safety issues. There was no stroke or death at 30 days, and the survival rate at nine months was 95.0%. There was no overall cognitive change (baseline vs. 30-day AMT: 9.2 ± 1.1 vs. 9.0 ± 1.5, p = 0.12), and only 1 (2.5%) patient developed impaired cognition at 30 days. Patients with a decreased AMT score at 30 days were significantly older than those without (82.1 ± 4.5 vs. 74.4 ± 7.7 years, p = 0.019). All patients with decreased AMT scores were aged ≥ 76 years. CONCLUSION: In this early Asian experience of TAVI under cerebral protection, the filter device was successfully deployed in 95% of patients, with 100% procedural success. There were no filter-related complications and no stroke or mortality at 30 days. Overall cognition was preserved, although increased age was associated with a decline in AMT score.

Comparison between glycoprotein IIb/IIIa blockade and distal protection device for the restoration of myocardial perfusion during percutaneous coronary intervention for acute myocardial infarction.

We compared the use of abciximab with a distal balloon occlusion device in preserving myocardial perfusion among patients undergoing acute percutaneous coronary intervention for ST-segment elevation myocardial infarction. Of 114 patients, 40 were treated with abciximab and 74 with distal protection. Although pre-treatment with abciximab resulted in marginally better myocardial perfusion at initial coronary angiography, distal protection emerged superior at the end of the procedure. The use of distal protection was associated with an adjusted odds of 4 (p = 0.017) for achieving normal myocardial perfusion and adjusted reduction of 11 corrected TIMI frame counts (p = 0.001) compared with abciximab.

Three-year experience of primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction in a hospital without on-site cardiac surgery.

INTRODUCTION: Primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in hospitals without on-site cardiac surgery capability, despite receiving only a class IIb recommendation in the ACC/AHA practice guidelines, can be performed effectively and safely. We reviewed the fi rst 3 years of our experience. MATERIALS AND METHODS: This is a retrospective single centre review of all patients receiving primary PCI for STEMI between 2003 and 2005. Demographic, procedural and outcome data were analysed. RESULTS: There were 259 patients who underwent primary PCI. The mean age was 55.3 +/- 12.3 years. Median door-to-balloon time was 97.5 minutes and 45.2% and 52.9% had anterior and inferior STEMI, respectively. The majority of patients presented with Killip class I (87.6%); however, 5.8% were in Killip class IV. Single vessel disease was found in 47.1%. Angiographic PCI success (defined as residual stenosis <50% with TIMI 3 fl ow) was achieved in 89.1%. Usage of stents, distal protection and aspiration devices were 97.2%, 27.8% and 34.1 %, respectively; 9.3% required intra-aortic balloon pump insertion. No patients required transfer for emergency coronary bypass surgery as a result of PCI complications. Post-PCI ST resolution >50% was achieved in 80.6%. The mean post-infarct left ventricular ejection fraction was 44.1%. In-hospital, 30-day, 6-month and 1-year mortality rates were 2%, 2.8%, 4.0% and 4.8%, respectively. Clinically driven target lesion revascularisation rate was 2.8% at 1 year. CONCLUSIONS: Our results are comparable to those from on-site surgical centres. This supports the feasibility and safety of primary PCI in cardiac centres without on-site cardiac surgery.