Off-pump left ventricular assist device exchange via re-do left mini-thoracotomy with original outflow graft preservation.

Complications associated with long-term left ventricular assist device (LVAD) use may require pump exchange due to device thrombosis or thromboembolism. Minimally invasive off-pump procedures represent an advantageous alternative to standard full sternotomy exchanges and those performed with the use of cardiopulmonary bypass. By mitigating surgical invasion and trauma to the central chest, the potential for post-operative bleeding, transfusions and complications can be reduced. This case report describes the successful off-pump exchange of a HeartWare LVAD via left re-do-thoracotomy with the re-use of the original outflow graft.

Case Report: Disparate flow in HeartMate II patient with extensive left ventricle repair.

This case study reports the operative management of a 63-year-old male patient following implantation of the HeartMate II (HMII) left ventricular assist device (LVAD), with a non-compliant left ventricle (LV) and a reduced right ventricular (RV) end-diastolic volume. Intraoperatively, the patient had a thin, fragile LV wall with laminated clot; a ventricular septal defect was encountered during removal of the clot. Along with an aortic valve repair, the LV and the septum were reconstructed with multiple bovine pericardium patches, thus, moderately reducing the RV and LV stroke volume. A difference in cardiac output via a Swan-Ganz catheter (approximately 1.5 l/min) was observed as opposed to the HMII's estimated flow. The result was later replicated and verified ITALIC! in vitrovia the Donovan Mock Circulation System (DMCS), where about 2 l/min lower flow on the HMII system was observed. In conclusion, the HMII flow rate displayed can be inaccurate and should only be used for trending.

Populations of the gall midge Dasineura oxycoccana on cranberry and blueberry produce and respond to different sex pheromones.

We identified and field-tested the sex pheromones of Dasineura oxycoccana (Johnson) (Diptera: Cecidomyiidae) midges collected from cranberry, Vaccinium macrocarpon Aiton, and from highbush blueberry, Vaccinium corymbosum L., commonly named cranberry tipworm (CTW) and blueberry gall midge (BGM), respectively. Coupled gas chromatographic-electroantennographic detection (GC-EAD) analyses of pheromone gland extract from the ovipositor of calling CTW females revealed one component (<10 pg per ovipositor/pheromone gland) that elicited antennal responses from CTW males. Stepwise identification was based on its mass spectrum in a concentrated sample with 300 pheromone gland equivalents, retention indices (RI) on three GC columns (DB-5, DB-23, and DB 210), RI inter-column differentials, and RIs and double bond positions of other midge pheromones. These analyses indicated that (8Z)-2,14-diacetoxy-8-heptadecene (2,14-8Z-17) was the candidate pheromone of the CTW. GC-EAD analysis of pheromone gland extract from calling BGM females revealed two components that elicited antennal responses from BGM males. Retention times on the three GC columns were consistent with 2,14-8Z-17 and 2,14-17, indicating that these were candidate pheromone components of the BGM. The four stereoisomers of 2,14-8Z-17 were stereoselectively synthesized and field-tested in cranberry. Delta-type traps baited with SS-2,14-8Z-17 captured significantly more CTW males than did traps baited with any other single stereoisomer or with all four stereoisomers combined. In blueberry, delta-type traps baited with RR-2,14-8Z-17 captured significantly more BGM males than did traps baited with any other single stereoisomer or with all four stereoisomers combined. Subsequent field experiments demonstrated that RR-2,14-17 is the major pheromone component of BGM, and that RR-2,14-8Z-17 is a pheromone component that does not enhance attractiveness of RR-2,14-17. The BGM pheromone RR-2,14-17 has no antagonistic effect on the CTW pheromone SS-2,14-8Z-17 and vice versa. Our results substantiate the conclusion that populations of D. oxycoccana on cranberry and blueberry represent two cryptic species.

Neonatal-lethal dilated cardiomyopathy due to a homozygous LMOD2 donor splice-site variant.

Dilated cardiomyopathy (DCM) is characterized by cardiac enlargement and impaired ventricular contractility leading to heart failure. A single report identified variants in leiomodin-2 (LMOD2) as a cause of neonatally-lethal DCM. Here, we describe two siblings with DCM who died shortly after birth due to heart failure. Exome sequencing identified a homozygous LMOD2 variant in both siblings, (GRCh38)chr7:g.123656237G > A; NM_207163.2:c.273 + 1G > A, ablating the donor 5' splice-site of intron-1. Pre-mRNA splicing studies and western blot analysis on cDNA derived from proband cardiac tissue, MyoD-transduced proband skin fibroblasts and HEK293 cells transfected with LMOD2 gene constructs established variant-associated absence of canonically spliced LMOD2 mRNA and full-length LMOD2 protein. Immunostaining of proband heart tissue unveiled abnormally short actin-thin filaments. Our data are consistent with LMOD2 c.273 + 1G > A abolishing/reducing LMOD2 transcript expression by: (1) variant-associated perturbation in initiation of transcription due to ablation of the intron-1 donor; and/or (2) degradation of aberrant LMOD2 transcripts (resulting from use of alternative transcription start-sites or cryptic splice-sites) by nonsense-mediated decay. LMOD2 expression is critical for life and the absence of LMOD2 is associated with thin filament shortening and severe cardiac contractile dysfunction. This study describes the first splice-site variant in LMOD2 and confirms the role of LMOD2 variants in DCM.

CAP2 is a regulator of actin pointed end dynamics and myofibrillogenesis in cardiac muscle.

The precise assembly of actin-based thin filaments is crucial for muscle contraction. Dysregulation of actin dynamics at thin filament pointed ends results in skeletal and cardiac myopathies. Here, we discovered adenylyl cyclase-associated protein 2 (CAP2) as a unique component of thin filament pointed ends in cardiac muscle. CAP2 has critical functions in cardiomyocytes as it depolymerizes and inhibits actin incorporation into thin filaments. Strikingly distinct from other pointed-end proteins, CAP2's function is not enhanced but inhibited by tropomyosin and it does not directly control thin filament lengths. Furthermore, CAP2 plays an essential role in cardiomyocyte maturation by modulating pre-sarcomeric actin assembly and regulating α-actin composition in mature thin filaments. Identification of CAP2's multifunctional roles provides missing links in our understanding of how thin filament architecture is regulated in striated muscle and it reveals there are additional factors, beyond Tmod1 and Lmod2, that modulate actin dynamics at thin filament pointed ends.

Redefining actin dynamics of the pointed-end complex in striated muscle.

Striated muscle is intricately designed to provide efficient and powerful muscle contractions. Recently, a long sought-after missing component of the thin filament pointed-end machinery was discovered: cyclase-associated protein 2 (CAP2). CAP2 was identified as a crucial contributor to actin polymerization, striated muscle development, and severe muscle disease when mutated.

Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells.

The pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been attributed to its ability to enter through the membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, it has been heavily speculated that angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may modulate SARS-CoV-2 infection. In this study, exposure of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and human endothelial cells (hECs) to SARS-CoV-2 identified significant differences in protein coding genes involved in immunity, viral response, and cardiomyocyte/endothelial structure. Specifically, transcriptome changes were identified in the tumor necrosis factor (TNF), interferon α/ß, and mitogen-activated protein kinase (MAPK) (hPSC-CMs) as well as nuclear factor kappa-B (NF-κB) (hECs) signaling pathways. However, pre-treatment of hPSC-CMs or hECs with two widely prescribed antihypertensive medications, losartan and lisinopril, did not affect the susceptibility of either cell type to SARS-CoV-2 infection. These findings demonstrate the toxic effects of SARS-CoV-2 in hPSC-CMs/hECs and, taken together with newly emerging multicenter trials, suggest that antihypertensive drug treatment alone does not alter SARS-CoV-2 infection.

Clinical outcomes meta-analysis: measuring subendocardial perfusion and efficacy of transmyocardial laser revascularization with nuclear imaging.

INTRODUCTION: Randomized and nonrandomized clinical trials have tried to assess whether or not TMR patients experience an increase in myocardial perfusion. However there have been inconsistencies reported in the literature due to the use of different nuclear imaging modalities to test this metric. The primary purpose of this meta-analysis was to determine whether SPECT, MUGA and PET scans demonstrate changes in myocardial perfusion between lased and non-lased subjects and whether laser type affects myocardial perfusion. The secondary purpose was to examine the overall effect of laser therapy on clinical outcomes including survival, hospital re-admission and angina reduction. METHODS: Sixteen studies were included in the primary endpoint analysis after excluding all other non-imaging TMR papers. Standardized mean difference was used as the effect size for all quantitative outcomes and log odds ratio was used as the effect size for all binary outcomes. RESULTS: Statistically significant improvements in myocardial perfusion were observed between control and treatment groups in myocardial perfusion at 6-month follow up using PET imaging with a porcine model. However non-significant differences were observed in patients at 3 and 12 months using SPECT, PET or MUGA scans. Both CO2 and Ho:YAG laser systems demonstrated an increase in myocardial perfusion however this effect was not statistically significant. In addition both laser types displayed statistically significant decreases in patient angina at 3, 6 and 12 months but non-significant increases in survival rates and decreases in hospital re-admissions. CONCLUSION: In order to properly assess myocardial perfusion in TMR subjects, subendocardial perfusion needs to be analyzed via nuclear imaging. PET scans can provide this level of sensitivity and should be utilized in future studies to monitor and detect perfusion changes in lased and non-lased subjects.

Acellular porcine heart matrices: whole organ decellularization with 3D-bioscaffold & vascular preservation.

Regenerative medicine, particularly decellularization-recellularization methods via whole-organ tissue engineering, has been increasingly studied due to the growing donor organ shortage. Though numerous decellularization protocols exist, the ideal decellularization protocol for optimal recellularization is unclear. This study was performed to optimize existing heart decellularization protocols and compare current methods using the detergents SDS (sodium dodecyl sulfate), Triton X-100, OGP (octyl ß-D-glucopyranoside), and CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate) through retrograde aortic perfusion via aortic cannulation of a whole porcine heart. The goal of decellularization is to preserve extracellular matrix integrity and architecture, which was analyzed in this study through histology, microscopy, DNA analysis, hydroxyproline content analysis, materials analysis and angiography. Effective decellularization was determined by analyzing the tissue organization, geometry, and biological properties of the resultant extracellular matrix scaffold. Using these parameters, optimal decellularization was achieved between 90 and 120 mmHg pressure with 3% SDS as a detergent. Relevance for patients: This study provides important information about whole heart decellularization, which will ultimately contribute to heart bioengineering.

Novel method using rotational thromboelastography analysis for intraoperative management of device patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disease in response to previous heparin exposure. Direct thrombin inhibitors are suitable candidates for the prophylaxis of thrombosis in patients with HIT. Currently activated clotting time and activated partial thromboplastin time are used to guide dosing and monitor anticoagulation. These assays provide a measure of clot initiation and only account for a small fraction of the coagulation pathway. In this case study we performed rotational thromboelastography (ROTEM) analysis on a patient with HIT implanted with a continuous-flow CentriMag device for left ventricular support. ROTEM evaluation confirmed a decline in activated clotting time values and provided further information regarding intrinsic and extrinsic clotting times. Monitoring ROTEM parameters aided in the detection of coagulopathies and the decision to administer platelet or fresh frozen plasma products. Utilizing ROTEM can guide clinical decisions in transfusions, particularly in patients with HIT, where platelet and fibrinogen levels can be safely maintained to prevent thrombosis.

Remodeling an infarcted heart: novel hybrid treatment with transmyocardial revascularization and stem cell therapy.

Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patients suffering from diffuse coronary artery disease (CAD), providing immediate angina relief. Recent studies indicate that the volume of surgical cases being performed with TMR have been steadily rising, utilizing TMR as an adjunctive therapy. Therefore the purpose of this review is to provide an up-to-date appreciation of the current state of TMR and its future developmental directions on CAD treatment. The current potential of this therapy focuses on the implementation of stem cells, in order to create a synergistic angiogenic effect while increasing myocardial repair and regeneration. Although TMR procedures provide increased vascularization within the myocardium, patients suffering from ischemic cardiomyopathy may not benefit from angiogenesis alone. Therefore, the goal of introducing stem cells is to restore the functional state of a failing heart by providing these cells with a favorable microenvironment that will enhance stem cell engraftment.

Minimally invasive approach for percutaneous CentriMag right ventricular assist device support using a single PROTEKDuo Cannula.

BACKGROUND: Right ventricular failure is a serious complication after left ventricular assist device placement. CASE PRESENTATION: A 70-year-old male in decompensated heart failure with right ventricular failure after the placement of a left ventricular assist device. A single dual-lumen PROTEKDuo cannula was inserted percutaneously via the internal jugular vein to draw blood from the right atrium and return into the pulmonary artery using the CentriMag system, by passing the failing ventricle. The patient was successfully weaned from right ventricular assist device. CONCLUSIONS: In comparison to two-cannula conventional procedures, this right ventrivular assist device system improves patient rehabilitation and minimizes blood loss and risk of infection, while shortening procedure time and improving clinical outcomes in right ventricular failure.