Piotr Musialek

Coronary artery ectasias and aneurysms (CAEAs) are present in up to 5% of patients undergoing coronary angiography. Recent studies indicated an independent association between CAEA and the risk of myocardial infarction but the underlying mechanisms have not yet been elucidated. We evaluated the relationship between CAEA and fibrin clot properties in 60 consecutive CAEA subjects and 60 clinically/angiographically matched controls enrolled across three tertiary centers. Fibrin clot permeability coefficient (K_s), clot lysis time (CLT), and levels of 3-nitrotyrosine, an oxidative stress marker, were assessed. Among patients with CAEA, 52 (86.7%) were male, the median age was 66.0 (59.5–74.1) years, and 30 (50.0%) had concomitant coronary artery disease. Compared with controls, CAEA subjects had 14% lower K_s (p = 0.036), 25% longer CLT (p = 0.001), and 21% higher 3-nitrotyrosine levels (p = 0.002). Multivariable regression analysis showed an association of CAEA with lower K_s, longer CLT, and higher 3-nitrotyrosine levels (all p < 0.05). In CAEA patients, 3-nitrotyrosine levels correlated with K_s (r = −0.31, p = 0.016) and CLT (r = 0.27, p = 0.037). With increasing CAEA peak-to-reference diameter ratio, K_s decreased (p-trend = 0.017), and 3-nitrotyrosine levels increased (p-trend = 0.002). In conclusion, we found that CAEA is independently associated with unfavorably altered fibrin clot properties, reflected by denser clot structure and reduced susceptibility to fibrinolysis. Our findings suggest that oxidative stress may contribute to unfavorable modification of fibrin clot properties in CAEA. With an increase in CAEA size, there is an increase in oxidative stress and worsening of the fibrin clot phenotype (CARE-ANEURYSM, NCT05183373).

Chronic ischemic heart failure (CIHF), caused by myocardial injury and cell loss, is a growing public health concern. Despite substantial investments in pharmaco- and device therapies for acute myocardial infarction and CIHF over the past decades, long-term prognosis has shown little improvement. There is a clear need to develop novel therapeutic strategies capable of attenuating progression from acute to chronic myocardial damage, reducing adverse myocardial remodeling, and enhancing myocardial contractility. Cell-based approaches are an important direction in basic and clinical research. Nevertheless, candidate cell types tested to-date in experimental and human studies show several fundamental limitations, including insufficient quantities and potency, poor myocardial uptake, immunogenicity and/or risk of tumorigenicity. Human umbilical cord matrix is a rich source of mesenchymal stem cells (Wharton’s jelly mesenchymal stem cells, WJMSCs). WJMSCs are naturally low-immunogenic, demonstrate high plasticity and proliferation capacity, and exhibit an absence of tumorigenic potential. Moreover, by producing specific anti-inflammatory cytokines and chemokines, they reduce the inflammatory response (hence their use in graft-versus-host disease) and have pro-angiogenic, anti-apoptotic, and antifibrotic properties, making them a natural player in myocardial repair and regeneration. Furthermore, WJMSCs can be expanded ex vivo with high genomic stability and full clonogenic potential and can be standardized as an “off-the-shelf” next-generation advanced therapy medicinal product (ATMP). This review aggregates essential, contemporary information on the properties and fundamental mechanisms of WJMSCs addressing the process of infarct healing and chronic myocardial injury. It discusses outcomes from pre-clinical studies, demonstrating improvements in myocardial function and reductions in fibrosis in animal models, paving the way for human ATMP trials.

Background/Objective: Transcutaneous Doppler ultrasound is a fundamental tool in evaluating carotid stenosis cross-sectional severity (CS-CSS) in clinical practice because peak-systolic and end-diastolic velocities (PSV, EDV) increase with angiographic diameter stenosis. We tested the hypothesis that lesion length (LL) may affect PSV and EDV. Methods: CARUS (Carotid Artery IntravasculaR Ultrasound Study) prospectively enrolled 300 consecutive patients (age 47–83 years, 64.3% men, 63.3% symptomatic) with carotid stenosis ≥50% by Doppler ultrasound considered diagnostic (corelab analyst). We correlated stenosis LL (mm) and minimal lumen area (MLA, mm²) with PSV and EDV. Results: IVUS imaging (20 MHz Volcano/Philips) was uncomplicated. As IVUS probe forward/backward movement with systole/diastole (“jumping”-related artifact superimposed on motorized pullback) restrained LL (but not MLA) determination, LL measurement was angiographic. Final data set included 293 patients/stenoses (applicable to seven angiograms unsuitable for LL measurement). Irrespective of CS-CSS, a significant LL effect on PSV and EDV occurred with LL ≥ 7 mm (n = 224/293, i.e., 76.5% study patients/lesions; r = 0.38 and r = 0.35); for MLA irrespective of CS-CCS the coefficients were r = 0.49 (PSV) and r = 0.42 (EDV); p < 0.001 for all. For LL and MLA considered together, the correlations were stronger: r = 0.61 (PSV) and r = 0.54 (EDV); p < 0.0001 for both. Combined LL and MLA effect was represented by the following formulas: PSV = 0.31 × LL/MLA + 2.02 [m/s]; EDV = 0.12 × LL/MLA + 0.63 [m/s], enabling to correct the PSV (EDV)-based assessment of CS-CSS for the LL effect. Conclusions: This study provides, for the first time, systematic evidence that the length of carotid stenosis significantly affects lesional Doppler velocities. We established formulas incorporating the contribution of both stenosis length and its cross-sectional severity to PSV and EDV. We advocate including stenosis length measurement in duplex ultrasound reports when performing PSV (EDV)-based assessment of carotid cross-sectional stenosis severity.