Stem cells for treatment of cardiovascular diseases: An umbrella review of randomized controlled trials.

AIMS: Stem cells are a promising therapy for various medical conditions. The literature regarding their adoption for the clinical care of cardiovascular diseases (CVD) is still conflicting. Therefore, our aim is to assess the strength and credibility of the evidence on clinical outcomes and application of stem cells derived from systematic reviews and meta-analyses of intervention studies in CVD. METHODS AND RESULTS: Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For meta-analyses of RCTs, outcomes with a random-effect p-value <0.05, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment was used, classifying the evidence from very low to high. From 184 abstracts initially identified, 11 meta-analyses (for a total of 34 outcomes) were included. Half of the outcomes were statistically significant (p < 0.05), indicating that stem cells are more useful than placebo. High certainty of evidence supports the associations of the use of stem cells with a better left ventricular end systolic volume and left ventricular ejection fraction (LVEF) in acute myocardial infarction; improved exercise time in refractory angina; a significant lower risk of amputation rate in critical limb ischemia; a higher successful rate in complete healing in case of lower extremities ulcer; and better values of LVEF in systolic heart failure, as compared to placebo. CONCLUSION AND RELEVANCE: The adoption of stem cells in clinical practice is supported by a high certainty of strength in different CVD, with the highest strength in acute myocardial infarction and refractory angina.

A Low Rivaroxaban Plasma Level May Indicate Anticoagulation Undertreatment.

Few reports have been published on the correlation between plasma concentrations of rivaroxaban and clinical outcome in patients who have experienced venous thromboembolism. This article describes the case of a 44-year-old woman who experienced deep vein thrombosis during anticoagulation therapy with rivaroxaban, with evidence of repeated low plasma levels of the drug. We postulate that the determination of plasma rivaroxaban anti-Xa activity can be useful in the evaluation of anticoagulation therapy in selected cases. LEARNING POINTS: Some patients with deep vein thrombosis do not respond to rivaroxaban therapy.Accurate determination of rivaroxaban plasma concentrations is important in clinical practice.The clinical value of rivaroxaban plasma concentrations might be limited by intra- and inter-individual variations.

Impact of acute changes of left ventricular contractility on the transvalvular impedance: validation study by pressure-volume loop analysis in healthy pigs.

BACKGROUND: The real-time and continuous assessment of left ventricular (LV) myocardial contractility through an implanted device is a clinically relevant goal. Transvalvular impedance (TVI) is an impedentiometric signal detected in the right cardiac chambers that changes during stroke volume fluctuations in patients. However, the relationship between TVI signals and LV contractility has not been proven. We investigated whether TVI signals predict changes of LV inotropic state during clinically relevant loading and inotropic conditions in swine normal heart. METHODS: The assessment of RVTVI signals was performed in anesthetized adult healthy anesthetized pigs (n = 6) instrumented for measurement of aortic and LV pressure, dP/dtmax and LV volumes. Myocardial contractility was assessed with the slope (Ees) of the LV end systolic pressure-volume relationship. Effective arterial elastance (Ea) and stroke work (SW) were determined from the LV pressure-volume loops. Pigs were studied at rest (baseline), after transient mechanical preload reduction and afterload increase, after 10-min of low dose dobutamine infusion (LDDS, 10 ug/kg/min, i.v), and esmolol administration (ESMO, bolus of 500 µg and continuous infusion of 100 µg·kg-1·min-1). RESULTS: We detected a significant relationship between ESTVI and dP/dtmax during LDDS and ESMO administration. In addition, the fluctuations of ESTVI were significantly related to changes of the Ees during afterload increase, LDDS and ESMO infusion. CONCLUSIONS: ESTVI signal detected in right cardiac chamber is significantly affected by acute changes in cardiac mechanical activity and is able to predict acute changes of LV inotropic state in normal heart.

From cell phenotype to epigenetic mechanisms: new insights into regenerating myocardium.

The self-regenerating property of the adult myocardium is not a new discovery. Even though we could not confirm that the adult myocardium is a post-mitotic tissue, we should consider that its plasticity is extremely low. Studies are still in progress to decipher the mechanisms underlying the abovementioned potential fetal features of the adult heart. The modest results of several clinical trials based on the transplantation of millions of autologous stem cells into the dysfunctional heart have confirmed that the cross-talk of different signals, such as the microenvironment, promotes the regeneration of adult myocardium. Recent scientific evidence has revealed that cellular cross-talk does not depend on the action of a single cell phenotype. It is conceivable that the limited turnover of cardiomyocytes is ensured by the interplay of adult cardiac cells in response to environmental changes. The epigenetic state of a cell serves as a dynamic interface between the environment and phenotype. The epigenetic modulation of the adult cardiac cells by natural active compounds encourages further studies to improve myocardial plasticity. In this review, we will highlight the most relevant studies demonstrating the epigenetic modulation of myocardial regeneration without the use of stem cell transplantation.

Mechanical properties and biological interaction of aortic clamps: are these all minimally invasive?

OBJECTIVE: Although specifically designed aortic clamps are mainstay of minimally invasive cardiac surgery, so far, no comparative reports about their mechanical properties and interaction with the aortic wall have been reported. In this study, the generated force in the clamps' jaws and the biological response of the aorta after clamping are evaluated. METHODS: The jaw force of five commercially available clamps [Geister, Cygnet, Cardiovision (CV) 195.10, CV 195.40, and CV 195.83] was assessed by clamping a 2.2-mm compression load cell with a dedicated computer universal serial bus interface at the proximal, the middle, and the distal site from the fulcrum. Biological response of the aortic wall was assessed in five minipigs (weight, 38-40 kg) that underwent thoracic aorta clamping and leakage point test. Immunohistochemistry and morphometric analysis were carried out for each aortic segment tested. RESULTS: Force generation pattern is peculiar of each clamp, being higher in the proximal and the middle portion and lower in the distal part. One clamp (Cygnet) exhibited homogeneous maximal force generation at all three sites. All clamps exhibited peculiar crushing artifacts. A variable degree of endothelial layer disruption occurred in all clamping tests; three clamps (CV 195.10, Cygnet, and Geister) had the lower amount of intact endothelium. The clamping force was not associated with the degree of endothelial disruption (P value was not significant). CONCLUSIONS: The choice of a clamp that is not only minimally invasive in design but also least traumatic will help avoid complications of aortic manipulation.