Maciej Kaźmierski

Circulating Very Small Embryonic-Like Stem Cells in Cardiovascular Disease

Very small embryonic-like cells (VSELs) are a population of stem cells residing in the bone marrow (BM) and several organs, which undergo mobilization into peripheral blood (PB) following acute myocardial infarction and stroke. These cells express markers of pluripotent stem cells (PSCs), such as Oct-4, Nanog, and SSEA-1, as well as early cardiac, endothelial, and neural tissue developmental markers. VSELs can be effectively isolated from the BM, umbilical cord blood, and PB. Peripheral blood and BM-derived VSELs can be expanded in co-culture with C2C12 myoblast feeder layer and undergo differentiation into cells from all three germ layers, including cardiomyocytes and vascular endothelial cells. Isolation of VSLEs using fluorescence-activated cell sorting multiparameter live cell sorting system is dependent on gating strategy based on their small size and expression of PSC and absence of hematopoietic lineage markers. VSELs express early cardiac and endothelial lineages markers (GATA-4, Nkx2.5/Csx, VE-cadherin, and von Willebrand factor), SDF-1 chemokine receptor CXCR4, and undergo rapid mobilization in acute MI and ischemic stroke. Experiments in mice showed differentiation of BM-derived VSELs into cardiac myocytes and effectiveness of expanded and pre-differentiated VSLEs in improvement of left ventricular ejection fraction after myocardial infarction.

Exercise-induced mobilisation of endothelial progenitor cells in patients with premature coronary heart disease

BACKGROUND Endothelial progenitor cells (EPC) derive from bone marrow and participate in both endothelial regeneration and development of new blood vessels. EPC also play a role in the atherosclerotic process, and their number correlates negatively with the presence of classical risk factors. AIM To evaluate circulating EPC count and their exercise-induced mobilisation in patients with premature coronary artery disease (CAD). METHODS The study group included 60 patients with stable CAD diagnosed before 45 years of age. The control group consisted of 33 healthy age- and gender-matched volunteers. Venous blood was sampled 3 times in order to assess circulating EPC count immediately before an exercise test (EPC 0) and at 15 min (EPC 15) and 60 min (EPC 60) after the exercise test. RESULTS Circulating EPC count in the study group at rest and at 15 min after exercise was comparable (2.1 vs. 2.1 cell/μL, p = 0.35) and increased significantly at 60 min after exercise in comparison to resting values (2.1 vs. 3.2 cell/μL, p < 0.00001). In the control group, circulating EPC count increased significantly at 15 min after exercise (2.0 vs. 3.5 cell/μL, p < 0.0001) but later decreased at 60 min after exercise, although it remained greater than at rest (2.7 vs. 2.0 cell/μL, p < 0.0002). Circulating EPC count at rest and at 60 min after exercise was comparable in the two groups (2.1 vs. 2.0 cell/μL, p = 0.96; and 3.2 vs. 2.7 cell/μL, p = 0.13, respectively) but it was significantly lower in the study group compared to the control group at 15 min after exercise (2.1 vs. 3.5 cell/μL, p < 0.00001). Circulating EPC count at rest and at 15 min after exercise did not correlate with the number of stenosed coronary arteries but at 60 min after exercise it was greater in patients with one-vessel disease compared to those with two- or three-vessel disease (4.2 vs. 3.4 cell/μL, p = 0.01; and 4.2 vs. 2.3 cell/μL, p = 0.00003). However, no difference in circulating EPC count was seen at 60 min after exercise between patients with two- or three-vessel disease (3.4 vs. 2.3 cell/μL, p = 0.3). CONCLUSIONS 1. Circulating EPC count at rest is comparable between subjects with premature atherosclerosis and healthy volunteers. 2. A single bout of physical exercise causes a significant increase in circulating EPC count in both groups, but the dynamics of exercise-induced EPC mobilisation is different, with delayed exercise-induced EPC mobilisation in subjects with premature CAD. 3. The extent of atherosclerotic coronary lesions does not influence circulating EPC count at rest.

Non-ST elevation myocardial infarction related to critical left main stenosis in a patient after transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) is an alternative treatment for high-risk patients with severe aortic stenosis. Approximately, 52–68% of these patients have coronary artery disease as well. That may have a negative impact on procedural and long-term outcome, thus revascularisation should be considered prior to TAVI because the presence of the valve may increase the complexity of percutaneous coronary intervention (PCI). With the following case report we presented PCI of the left main coronary artery (LMCA) post TAVI. A 79-year-old female was admitted to the emergency department because of non-ST elevation myocardial infarction (NSTEMI); the patient’s GRACE risk score was 147 points. Her medical history included a history of PCI of right coronary artery (RCA) with three drug-eluting stents (DES) (August 2012) and TAVI with CoreValve implantation (September 2012). Coronary angiography revealed a 99% stenosis of the proximal LMCA with a TIMI 1 flow (Fig. 1) and without any significant stenosis in the RCA. Hence, the strategy was to perform urgent PCI of the LMCA. A Judkins Left Catheter 6-Fr 4.0 (Cordis Corp., Johnson & Johnson, Miami Lakes, FL, USA) was used, and a hydrophilic guidewire (Pilot 50, Abbott Vascular, Santa Clara, CA, USA) passed the lesion to the distal left circumflex. Direct stenting of the LMCA was performed (4.0 × 12-mm DES, Promus, Boston Scientific, Natick, MA, USA) with good angiographic results; final TIMI 3 flow and no residual stenosis (Fig. 2). At 1-month follow-up the patient remained asymptomatic, and angiography showed a well-expanded stent without significant residual stenosis (Fig. 3). Myocardial infarction in patients with implanted TAVI is challenging to treat using PCI. Furthermore, in those cases the procedure is complex due to the presence of the self-expandable nitinol cage of the CoreValve covering the coronary ostia. The valve struts may pose a problem during the guide catheter engagement into the LMCA. In some cases it is easier to use the telescopic technique, which improves the backup force of the guiding catheter. Fortunately, in this particular patient we successfully used a 6 Fr JL 4.0, which gave proper backup. The relation of the valvular prosthesis to the NSTEMI in this case cannot be excluded, perhaps due to the presence of the calcified native leaflet pressed against the coronary sinus by the valve. This case shows that interventional cardiologists should expect to perform urgent PCI in patients with previously implanted transcatheter valves, which may increase the procedural complexity.