Comparison of Del Nido and histidine-tryptophan-ketoglutarate cardioplegia solutions: an animal study with prolonged ischaemia.

Objective: Myocardial protection is important for a successful procedure cardiac surgery, and the key element of myocardial protection is cardioplegia. We compared Del Nido cardioplegia (DN) and Bretschneider histidine-tryptophan-ketoglutarate cardioplegia (HTK) regarding cardioprotective effects in a porcine model of prolonged ischaemia.

Methods: Landrace pigs weighing 50-60 kg were randomized to receive either DN ( = 9) or HTK ( = 9).

Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document.

Comparison of modified Del Nido and Custodiol® cardioplegia in minimally invasive mitral valve surgery.

Objectives: In this study, we evaluated if modified Del Nido cardioplegia delivers comparable cardiac protection in comparison to Custodiol® in patients undergoing isolated minimally invasive mitral valve repair.

Methods: From January 2018 to October 2021, all patients undergoing non-emergent isolated minimally invasive mitral valve repair were included in this study. The cardioplegia was chosen at the surgeons' discretion.

Pre-Implant Immune Status is Associated with Infection Risk After Left Ventricular Assist Device Implantation.

Purpose: Infection is the most common complication after left ventricular assist device (LVAD) implantation. The immune status of LVAD patients is relevant for the incidence and severity of infection, but it is unknown if there is a predisposing immune status prior to LVAD implantation that contributes to an increased risk for infection in the post-implant period. We analyzed the pre-LVAD immune status in patients with infection within 3 months after LVAD implantation in comparison to infection-free patients.

Left ventricular fibrosis and CMR tissue characterization of papillary muscles in mitral valve prolapse patients.

Purpose: Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies.

Methods: MVP patients with indication for surgery due to severe mitral regurgitation (n = 19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE).

Body mass index-dependent immunological profile changes after left ventricular assist device implantation.

Purpose: Infection is a common complication following left ventricular assist device (LVAD) implantation. Patients with obesity are particularly at risk due to their high percentage of adipose tissue and the resulting chronic inflammatory state and resulting immunological changes. This study investigated changes of immunological parameters in relation to body mass index (BMI) during the first year after LVAD implantation.

Health status analysis is comparable in HM3 patients with different preoperative grades of mitral regurgitation.

Background: The guidelines for mechanical circulatory support of the International Society for Heart and Lung Transplantation do not recommend the routine replacement or repair of the mitral valve at the time point of left ventricular assist device (LVAD) implantation. We investigated different parameters of health status including exercise capacity, anxiety and depression after LVAD implantation in patients with different preoperative grades of mitral regurgitation (MR).

Methods: A single-center analysis of health status was performed including 45 patients with HeartMate 3 (HM 3) implantation using the 12-items Short Form Health Survey (SF-12) and the Hospital Anxiety and Depression Score (HADS) questionnaires.

Left Ventricular Fibrosis and CMR Tissue Characterization of Papillary Muscles in Mitral Valve Prolapse Patients.

Purpose: Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies.

Methods: MVP patients with indication for surgery due to severe mitral regurgitation (n=19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE).

The Impact of Obesity on T and NK Cells after LVAD Implantation.

Introduction: Infections are a major problem after left ventricular assist device (LVAD) implantation that affects morbidity, mortality, and the quality of life. Obesity often increases the risk for infection. In the cohort of LVAD patients, it is unknown if obesity affects the immunological parameters involved in viral defense.

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months.

Non-surgical bleeding (NSB) remains the most critical complication in patients under left ventricular assist device (LVAD) support. It is well known that blood exposed to high shear stress results in platelet dysfunction. Compared to patients without NSB, decreased surface expression of platelet receptor GPIbα was observed in LVAD patients with NSB.

Histopathological insights into mitral valve prolapse-induced fibrosis.

Mitral valve prolapse (MVP) is a cardiac valve disease that not only affects the mitral valve (MV), provoking mitral regurgitation, but also leads to maladaptive structural changes in the heart. Such structural changes include the formation of left ventricular (LV) regionalized fibrosis, especially affecting the papillary muscles and inferobasal LV wall. The occurrence of regional fibrosis in MVP patients is hypothesized to be a consequence of increased mechanical stress on the papillary muscles and surrounding myocardium during systole and altered mitral annular motion.

Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy.

Disturbances in the ubiquitin proteasome system, and especially changes of the E3 ligases, are subjects of interest when searching for causes and therapies for cardiomyopathies. The aim of this study was to clarify whether the myostatin/AKT/forkhead box O (FOXO) pathway, which regulates the expression of the E3 ligases muscle atrophy F-box gene (MAFbx) and muscle ring-finger protein-1 (MuRF1), is changed in dilated cardiomyopathy of ischemic origin (IDCM) and dilated cardiomyopathy of non-ischemic origin (NIDCM). The mRNA and protein expression of myostatin, AKT, FOXO1, FOXO3, MAFbx and MuRF1 were quantified by real-time polymerase chain reaction and ELISA, respectively, in myocardial tissue from 26 IDCM and 23 NIDCM patients.

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation.

Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear.

Long-Term Follow-Up of Mechanical Circulatory Support in Peripartum Cardiomyopathy (PPCM) Refractory to Medical Management: A Multicenter Study.

Background: Peripartum cardiomyopathy (PPCM) is a rare, life-threatening form of heart disease, frequently associated with gene alterations and, in some cases, presenting with advanced heart failure. Little is known about ventricular assist device (VAD) implantation in severe PPCM cases. We describe long-term follow-up of PPCM patients who were resistant to medical therapy and received mechanical circulatory support or heart transplant.

Differential Regulation of Myocardial E3 Ligases and Deubiquitinases in Ischemic Heart Failure.

The pathological changes of ubiquitination and deubiquitination following myocardial infarction (MI) and chronic heart failure (CHF) have been sparsely examined. We investigated the expression of muscle-specific E3 ubiquitin ligases and deubiquitinases in MI and CHF. Therefore, mice were assigned to coronary artery ligation for 3 days or 10 weeks as well as for sham operation (each = 10).

Everolimus-Induced Immune Effects after Heart Transplantation: A Possible Tool for Clinicians to Monitor Patients at Risk for Transplant Rejection.

Background: Patients treated with an inhibitor of the mechanistic target of rapamycin (mTORI) in a calcineurin inhibitor (CNI)-free immunosuppressive regimen after heart transplantation (HTx) show a higher risk for transplant rejection. We developed an immunological monitoring tool that may improve the identification of mTORI-treated patients at risk for rejection.

Methods: Circulating dendritic cells (DCs) and regulatory T cells (T) were analysed in 19 mTORI- and 20 CNI-treated HTx patients by flow cytometry.

Relevance and Recommendations for the Application of Cardioplegic Solutions in Cardiopulmonary Bypass Surgery in Pigs.

Cardioplegic solutions play a major role in cardiac surgery due to the fact that they create a silent operating field and protect the myocardium against ischemia and reperfusion injury. For studies on cardioplegic solutions, it is important to compare their effects and to have a valid platform for preclinical testing of new cardioplegic solutions and their additives. Due to the strong anatomical and physiological cardiovascular similarities between pigs and humans, porcine models are suitable for investigating the effects of cardioplegic solutions.

Immune Monitoring Assay for Extracorporeal Photopheresis Treatment Optimization After Heart Transplantation.

Background: Extracorporeal photopheresis (ECP) induces immunological changes that lead to a reduced risk of transplant rejection. The aim of the present study was to determine optimum conditions for ECP treatment by analyzing a variety of tolerance-inducing immune cells to optimize the treatment.

Methods: Ten ECP treatments were applied to each of 17 heart-transplant patients from month 3 to month 9 post-HTx.

Validation of mitral regurgitation reversibility in patients with HeartMate 3 LVAD implantation.

The resolution of functional mitral valve regurgitation (MR) in patients awaiting left ventricular assist device (LVAD) implantation is discussed controversially. The present study analyzed MR and echocardiographic parameters of the third-generation LVAD HeartMate 3 (HM3) over 3 years. Of 135 LVAD patients (with severe MR, n = 33; with none, mild, or moderate MR, n = 102), data of transthoracic echocardiography were included preoperatively to LVAD implantation, up to 1 month postoperatively, and at 1, 2, and 3 years after LVAD implantation.

Cyclosporine A-enhanced cardioplegia preserves mitochondrial basal respiration after ischemic arrest.

Background: Mitochondrial permeability transition pore (mPTP) opening plays a crucial role in cell death during ischemia-reperfusion injury (IRI). Cyclosporine A (CsA) inhibits mPTP opening. This study aimed to investigate the effects of CsA treatment during cardioplegia on the mitochondrial function and cardiac IRI.

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome.

Device-induced platelet dysfunction in patients after left ventricular assist device implantation.

Background: Non-surgical bleeding (NSB) is a major complication after left ventricular assist device (LVAD) implantation. It has been reported that non-physiological shear stress caused by LVADs could alter platelet receptor expression, which leads to bleeding disorders caused by coagulation dysfunctions.

Objectives: Because bleeding diathesis could be multifactorial, we focused on the combined characterization of platelet receptor expression patterns and oxidative stress to compare patients with NSB and patients without coagulation disorder in a monocentric, prospective study.

Benefit of Self-Managed Anticoagulation in Patients with Left Ventricular Assist Device.

Background:  The exact monitoring of the therapeutic-range international normalized ratio (INR) after left ventricular assist device (LVAD) implantation is an important aim to reduce the risk of thrombosis or bleeding complications. Service providers offer a telemedical anticoagulation service (CS).

Methods:  We compared LVAD patients using the CS ( = 15) to those who received regular medical care (RMC;  = 15) to investigate if telemedicine supervision increased the INR-specific time in the therapeutic range (TTR) during anticoagulation.

Impact of Custodiol-N cardioplegia on acute kidney injury after cardiopulmonary bypass.

Myocardial protection during cardiopulmonary bypass (CPB) can be achieved using cardioplegic solutions. Although, acute kidney injury (AKI) is a common complication following CPB, the effects of cardioplegic solutions on AKI have rarely been investigated. Within this study, the effects of the cardioplegic solutions histidine-tryptophan-ketoglutarate (HTK; Custodiol) and HTK-N (Custodiol-N) on AKI in a large animal model were compared.

The Ubiquitin Proteasome System in Ischemic and Dilated Cardiomyopathy.

Dilated (DCM) and ischemic cardiomyopathies (ICM) are associated with cardiac remodeling, where the ubiquitin-proteasome system (UPS) holds a central role. Little is known about the UPS and its alterations in patients suffering from DCM or ICM. The aim of this study is to characterize the UPS activity in human heart tissue from cardiomyopathy patients.