Citations

Introduction: At the forefront of post-heart transplant care is early detection of transplant rejection. However, the current gold standard for detecting acute cellular transplant rejection is recurrent invasive endomyocardial biopsies (EMB). We aimed at developing a non-invasive biomarker for acute cellular heart transplant rejection (ACR) using a plasma extracellular vesicle (EV) platform. Methods: Peripheral and coronary sinus plasma samples were prospectively collected from 183 (31.7% female) patients from 2020 to 2023 during routine surveillance EMB. A discovery cohort comprised five patients who displayed ISHLT 0-1R biopsy followed by an ISHLT 2R grade rejection event. Plasma EVs were isolated from the baseline (0-1R) and rejection (2R) time points. Subsequently, integrative analysis of plasma EV proteomic, miRNomic, and metabolomics was performed pairwise with the samples. Results: The study collected 943 sample time points from 183 patients. Of these sample collections, 43 (4.5%) cases were 2R rejections. Our proteomic analysis of the plasma EVs identified 28 proteins found explicitly during a grade 2R rejection and 87 differentially expressed proteins during a 2R rejection event. An Ingenuity Pathway Analysis (IPA) analysis of the upregulated proteins highlighted EVs mediated mTOR signaling and antigen presentation as central to rejection events. Although all patients in the discovery cohort were negative for antibody-mediated rejection (AMR), the proteomic findings also revealed increased B-cell receptor signaling, implying a mechanistic intersection of ACR and AMR. Conclusions: A distinct set of proteins were found in plasma EVs during ACR events, providing potentially specific and sensitive biomarkers to reduce the need for EMB that could be exploited for ACR diagnosis. The proteins identified formed an immune signaling network that suggests a novel role for EVs in ACR pathogenesis.

Introduction: Left ventricular assist devices (LVAD) with magnetically levitated impellers have become standard due to hemocompatibility and survival profile. To optimize LVAD speeds, we previously introduced simultaneous right and left heart (RH/LH) catheterization during ramp studies. Here, we report pairing of this approach with pressure-volume (PV) assessment in a patient with a HeartMate 3 LVAD with mitral regurgitation (MR). The combined approach evaluated left ventricular (LV) hemodynamics and right ventricular (RV) PV-relationships during ramp testing. Methods: A 68-year-old male with ischemic cardiomyopathy, two years following HeartMate3 implantation, presented with NYHA class III symptoms. To evaluate for dyspnea, he underwent a RH/LH catheterization ramp study. RV PV-loops were created by use of a conductance catheter system, allowing creation of PV loops. Results: At the baseline LVAD speed of 5300 rotations per minute (RPM), right atrial pressure was elevated at 16 mmHg and pulmonary artery (PA) pressure of 26 mmHg. Left-end diastolic pressure (LVEDP) was elevated (16mmHg). Baseline cardiac index (CI) was 2.01 L/min/m 2 . Ramp testing was performed, increasing speeds from 5300 to 5800 RPM. Progressive LV unloading was observed with a 5 mmHg drop in LVEDP and a 3 mmHg drop in PA pressure. However, RV PV loop monitoring revealed a negative impact on RV contractility with the maximal elastance (Emax) slope demonstrating a 22% reduction. Furthermore, a 17% reduction in RV stroke volume was documented, while diastolic function remained unchanged. Thus, despite excellent LV offloading and diminishment of RV afterload, the significant negative impact on Emax resulted in no net increase in CI (+0.04 L/min/m 2 ) during the ramp evaluation. Inotrope therapy was initiated for RV function with increased LVAD RPM to outcompete MR. Conclusions: While RH/LH catheterization provides a real-time perspective of the interventricular relationship during ramp, the impact of increasing LVAD speeds on RV function has yet to be directly measured. Here, the RV PV loop relationship during LVAD ramp showed that although LVAD speed increases in the setting of MR may facilitate LV unloading, a drop in RV afterload did not compensate for reduction in RV contractility.

Coronary angiography is the gold standard for the diagnosis and treatment of epicardial coronary artery disease. Further, it is an essential tool for conduction of translational cardiac research on large animal models, in the development of novel cardiac therapies. While in humans coronary angiography has an exceedingly low mortality rate; in pigs, procedural mortality has been reported as high as 15%, likely due to unsuitable variations in angiographic techniques. Porcine models are used due to the resemblance of cardiac function and anatomy to humans. However, procedural guidelines delineating proper equipment to be used for angiography in this model has yet to be systematically assessed. Aims: To evaluate clinically common catheters for their utility in the safe engagement of the coronary vessels in pigs. Establish optimal workflow and fluoroscopy views for safe coronary artery engagement and angiography. Method/Results: Percutaneous superficial femoral artery access was acquired via ultrasound guidance and subsequent cardiac catheterization was performed in sus domesticus weighing 35-50 kg. Catheters that were tested included the JL 2.5, JL3.0, JR 3.0, AR1, AL1, MPA1, Champ1, 3DRC, hockey stick and RCB (5-7 french) operated over a standard .035 J tip wire. AP views were optimum to engage both the left and right coronary vessels. Only AR1, 3DRC, and hockey stick catheters successfully engaged the RCA, while all catheters tested could successfully engage the LCA. AR1 was noted to be the best for RCA engagement and AL1 for Left system engagement. AR1 was also the most succesful in engagement of both LM and RCA in same pig. AL1 provided the most stable engagement for Left coronary system. AR1/JL were better for LAD intervensions. AL1 is best for LCX intervensions Conclusion: We present a systematic description of percutaneous coronary angiographic procedures highlighting that AL for the LCA and AR for the RCA are the best choice of catheters for fastest and safest engagement of the coronary arteries limiting both radiation time and contrast use. While variations in anatomy can mandate changes in angiographic angles and catheter techniques, AP visualization and use of AL and AR catheters provided the most consistent and effective approach for porcine angiography.

For patients in cardiogenic shock, percutaneous mechanical circulatory support devices (MCSD) have emerged as critical tool to improve hemodynamics and optimize end-organ perfusion; successfully bridging patients to recovery, decision or transplantation. The most commonly utilized MCSD is the femoral intra-aortic balloon pump (IABP). However, femoral access hampers the patient's mobility, quality of life, and capacity to participate in rehabilitation. The advent of the axillary artery approach has served to circumvent limitations associated with the femoral artery approach. However, optimum anatomical placement of IABP within the axillary artery (axIABP) is a topic of debate considering its proximity to the brachial plexus. Here, we report our experince with percutaneous access of the third poriton of the axillary artery which showed promising results with minimal device related complications or adverse events. Methods/Results: Between 2017-2023, a total of 89 patients in cardiogenic shock underwent percutaneous axIABP placement at the Mayo Clinic, MN. All demographic, clinical, and periprocedural data were obtained from hospital chart review and recorded in a database under IRB approval. Indications for axIABP support was determined by multidisciplinary assessment. Complications encountered in the cohort included infection at site 6.7% (n=6), device malfunction [rupture, fracture, leak] 8.98%(n=8), and balloon migration 5.61% (n=5). One patient developed local erythema, 4 (4.49%) patients developed significant vascular complications, including access site bleeding in two patients 2.24%, arterial thrombosis in three patients 3.37%, and self-limited intracranial bleeding in one patient 1.12%. Of note, no nerve injury or damage was observed in the entire patient cohort. Conclusion: Our study highlights the feasibility of percutaneous axIABP in the third portion of the axillary artery, while assessing safety profile and ease of removal. Notably in our review, we did not encounter any brachial nerve damage. Ultrasound was pivotal in identifying and avoiding nerves and nerve bundles during initial access. In conclusion, this approach of axIABP insertion is feasible and can be leveraged for delivery of future innovation in MCSD

Background: Multiple effective treatments exist for correction of skin photoaging. Topical L-ascorbic acid (vitamin C), a well-known antioxidant and topical human platelet extract (HPE), is a novel off-the-shelf cosmetic ingredient that has shown positive results in recent clinical studies. HPE is a leukocyte-depleted allogeneic product derived from United States–sourced, pooled, apheresed platelets produced with consistent batch quality, purity, and effect. The authors sought to characterize the effect of topical HPE (plated) intense serum (Rion Aesthetics) compared with vitamin C (C E Ferulic with 15% L-ascorbic acid; SkinCeuticals) in skin rejuvenation of dorsal hands after 12 to 26 weeks of twice-daily use. Methods: This prospective, longitudinal study sought to compare the effectiveness of 2 known treatments for skin rejuvenation. Evaluations at baseline and 6, 12, and 26 weeks included photographic documentation to assess common skin concerns related to aging. Results: For age-related skin appearance on the dorsal hands, topical HPE was noninferior to topical vitamin C for improvement in brown spot fractional area, wrinkle fractional area, and improvement in luminosity at 12 weeks after twice-daily topical use. Conclusions: HPE performed as well as vitamin C to rejuvenate the skin on the dorsal hands after 12 to 26 weeks of twice-daily topical use. Both topical serums may yield similar or superior results versus invasive procedures, such as intense pulsed light, in reducing brown spots on the dorsal hands. These topical products work equally well in both sexes. Skin improvements lasted through 6 months. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Abstract Patients with heart failure experience limitations in daily activity and poor quality-of-life. Prospective surveillance of health-related quality-of-life supplemented traditional death and hospitalization outcomes in the multinational, randomized, double-blinded CHART-1 clinical trial that assessed cardiopoiesis-guided cell therapy in ischemic heart failure patients with reduced left ventricular ejection fraction. The Minnesota Living with Heart Failure Questionnaire (MLHFQ), a Food and Drug Administration qualified instrument for evaluating therapeutic effectiveness, was applied through the 1-year follow-up. Cell treated (n = 109) and sham procedure (n = 140) cohorts reported improved MLHFQ scores comparable between the 2 study arms (mean treatment difference with baseline adjustment −3.2 points, P = .107). Superiority of cell treatment over sham in betterment of the MLHFQ score was demonstrated in patients with pre-existing advanced left ventricular enlargement (baseline-adjusted mean treatment difference −6.4 points, P = .009). In this highly responsive subpopulation, benefit on the MLHFQ score paralleled reduction in death and hospitalization post-cell therapy (adjusted Mann-Whitney odds 1.43, 95% CI, 1.01-2.01; P = .039). The potential of cell therapy in addressing the quality-of-life dimension of heart failure requires further evaluation for disease relief.

AbstractPatients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease‐specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human‐platelet‐derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)‐like module‐containing mucin‐like hormone receptor‐like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll‐like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL‐1β), transforming growth factor‐beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7–9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T‐cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.

AbstractBackgroundFractional carbon dioxide (CO2) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising.AimsThe primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO2 ablative laser resurfacing treatment to the entire face versus standard of care.MethodsIn a single‐center, randomized, evaluator‐blinded pilot study, a total of 18 subjects were randomized into two groups, CO2 facial resurfacing followed by post‐procedural standard of care (Stratacel silicone gel) or CO2 facial resurfacing with the addition of HPE renewosomes in the CALM Serum.ResultsCALM Serum demonstrated statistically significant less crusting at Day 10 compared to the control group (p = 0.0193) with less downtime in the first 14 days (p = 0.03). Subjects treated with CALM Serum had statistically significant brighter appearing skin at 14 days (p = 0.007) and more youthful looking skin on Days 14 and 30 (p = 0.003 and 0.04, respectively).ConclusionsThis study demonstrates that Renewosome™ technology provides statistically significant post‐laser clinical recovery over silicone gel for reducing crusting, and downtime. Subjects reported less diary days of symptoms of pain/tenderness, redness, crusting/flaking, bruising, and itching in the first 14 days compared to the control group. CALM also demonstrated statistically significant improvements in brighter and more youthful appearing skin. CALM is safe and well tolerated.