Percutaneous trans-axilla transcatheter aortic valve replacement.

The left axillary artery is an attractive alternative access route for transcatheter aortic valve replacement (TAVR) and may provide better outcomes compared to other alternatives. Nevertheless, there remain concerns about vascular complications, lack of compressibility, and thorax-related complications. Between March 2019 and March 2021, 13 patients underwent transaxillary TAVR for severe aortic stenosis at the University Hospital Bonn. The puncture was performed with a puncture at the distal segment of the axillary artery through the axilla, with additional femoral access for applying a safety wire inside the axillary artery. Device success was defined according to the VARC 2 criteria. The study participants were advanced in age (77 ± 9 years old), and 54% were female, with an intermediate risk for surgery (STS risk score 4.7 ± 2.0%). The average diameter of the distal segment of the axillary artery was 5.8 ± 1.0 mm (i.e., the puncture site) and 7.6 ± 0.9 mm for the proximal axillary artery. Device success was achieved in all patients. 30-day major adverse cardiac and cerebrovascular events were 0%. With complete percutaneous management, stent-graft implantation was performed at the puncture site in 38.5% of patients. Minor bleeding was successfully managed with manual compression. Moreover, no thorax-related complications, hematomas, or nerve injuries were observed. Percutaneous trans-axilla TAVR was found to be feasible and safe. This modified approach may mitigate the risk of bleeding and serious complications in the thorax and be less invasive than surgical alternatives.

A novel scoring system to estimate chemotherapy-induced myocardial toxicity: Risk assessment prior to non-anthracycline chemotherapy regimens.

BACKGROUND: Myocardial toxicity is a common side effect of chemotherapy and is associated with adverse outcomes in cancer patients. Sufficient prediction of chemotherapy-induced myocardiotoxicity (CIMC) is desirable. Therefore, we sought to develop a feasible scoring system to predict CIMC in cancer patients undergoing non-anthracycline chemotherapy. METHODS: We determined a scoring system, the "Cardiotoxicitiy Score" (the CardTox-Score), by multivariable regression of the parameters considered relevant to the development of CIMC, based on previously published data and current guidelines. Variables of the risk model consist of clinical (age, presence of cardiovascular risk conditionsconditions), blood tests (NT-proBNP), and echocardiographic parameters (left ventricular (LV) ejection fraction, LV strain analysis). The CardTox-Score was examined in an internal validation cohort by use of ROC and regression analysis. RESULTS: We prospectively investigated 225 patients (58.21 ± 6.3 years, 52.8% female) who received non-anthracycline myocardiotoxic anticancer agent as a derivation cohort. All patients underwent echocardiography before, during and after anticancer therapy. The mean follow-up duration was 25 ± 4 months. We found the CardTox-Score (>6 points) to be a strong independent predictor (AUC: 0.983, OR: 6.38, 95% CI: 1.6 2.8, p < 0.001) for the development of CIMC with high sensitivity (100%) and specificity (84.2%) in the validation cohort (n = 30, 59.2 ± 6.5 years, 57% female). Moreover, the CardTox-Score appropriately predicted all-cause mortality with high specificity (93.7%) and sensitivity (92.9%) as well (OR: 4.85, AUC: 0.978, p = 0.01). CONCLUSION: The CardTox-Score offers a promising, feasible, and easy-to-handle scoring system for predicting CIMC in cancer patients undergoing non-anthracycline regimes, independent from the type of cancer.

Role of the multidrug resistance protein-1 (MRP1) for endothelial progenitor cell function and survival.

The multidrug resistance related protein-1 (MRP1) is a member of the ATP binding cassette (ABC) of cell surface transport proteins expressed in multiple cell lines and tissues including endothelial cells and haematopoietic stem cells. MRP1 blockade has been shown to prevent endothelial cell apoptosis and improve endothelial function. Besides mature endothelial cells vascular homing of endothelial progenitor cells (EPC) contributes to endothelial regeneration after vascular damage. Thus, we hypothesized that MRP1 influences number and function of EPCs and mechanisms of vascular repair. To test this, we investigated the effects of MRP1 inhibition in vitro and in vivo. MRP1 is abundantly expressed in cultured human early outgrowth EPCs. Pharmacological inhibition of MRP1 by MK571 increased intracellular glutathione levels and reduced intracellular reactive oxygen species levels. This stabilization of the intracellular redox homeostasis via inhibition of MRP1 prevented angiotensin II-induced apoptosis and increased the number of early outgrowth EPCs and colony forming units in vitro. To extend the observed cytoprotective effect of MRP1 blockade in EPCs to an in vivo situation, MRP1(-/-) knockout mice were investigated. MRP1(-/-) knockout mice showed significantly increased numbers of EPCs circulating in the peripheral blood and residing in the bone marrow. Consistently, colony forming unit formation was enhanced and rate of apoptosis reduced in early outgrowth EPCs derived from MRP1(-/-) knockout mice. In addition, MRP1(-/-) knockout mice showed improved reendothelialization after carotid artery injury, and transfusion of MNCs derived from MRP1(-/-) knockout mice into wild-type mice accelerated reendothelialization compared to transfusion of wild-type cells. These findings indicate that the enhanced function and survival of EPCs in MRP1(-/-) knockout mice resulted in improved reendothelialization. In conclusion, MRP1 negatively influences EPC function and survival via perturbation of the intracellular redox homeostasis which finally leads to increased cellular apoptosis. These results reveal novel mechanistic insights and may identify MRP1 as therapeutic target to improve reendothelialization after vascular damage.

Personalized cardiac regeneration by stem cells-Hype or hope?

Cardiac diseases are the leading cause of death and reach epidemic proportions with aging. Advanced heart disease results from an abrupt or progressive loss of contractile cardiomyocytes. Following percutaneous coronary intervention and revascularization regenerative medicine aims at effectively repair damaged tissue and replacement of lost cardiomyocytes. However, mixed results were obtained from trials using bone marrow-derived stem cells. Benefits were rather attributed to paracrine effects leading to inhibition or reverse of negative remodeling processes than to regeneration of viable cardiomyocytes. Thus the aim of regenerative medicine, in particular stem cell research, to generate viable cardiac muscle has so far not been achieved in humans, reflecting our incomplete understanding of underlying biological mechanisms. Moreover, there is growing evidence that substantial person-to-person differences in the outcome of stem cell therapy exists. We here review our present knowledge in evolving stem cell based cardiovascular medicine and highlight personalized aspects of stem cell interventions.