PRospective REgistry of PAtients in REfractory cardiogenic shock-The PREPARE CardShock registry.

AIM: Cardiogenic shock (CS) is a hemodynamically complex multisystem syndrome associated with persistently high morbidity and mortality. As CS is characterized by progressive failure to provide adequate systemic perfusion, supporting end-organ perfusion using mechanical circulatory support (MCS) seems intriguing. Since most patients with CS present in the catheterization laboratory, percutaneously implantable systems have the widest adoption in the field. We evaluated feasibility, outcomes, and complications after the introduction of a full-percutaneous program for both the Impella CP device and venoarterial extracorporeal membrane oxygenator (VA-ECMO). METHODS: PREPARE CardShock (PRospective REgistry of PAtients in REfractory cardiogenic shock) is a prospective single-center registry, including 248 consecutive patients between May 2019 and April 2021, who underwent cardiac catheterization and displayed advanced cardiogenic shock. The median age was 70 (58-77) years and 28% were female. Sixty-five percent of the cases had cardiac arrest, of which 66% were out-of-hospital cardiac arrest. A local standard operating procedure (SOP) indicating indications as well as relative and absolute contraindications for different means of MCS (Impella CP or VA-ECMO) was used to guide MCS use. The primary endpoint was in-hospital death and secondary endpoints were spontaneous myocardial infarction and major bleedings during the hospital stay. RESULTS: Overall mortality was 50.4% with a median survival of 2 (0-6) days. Significant independent predictors of mortality were cardiac arrest during the index event (odds ratio [OR] with 95% confidence interval [CI]: 2.53 [1.43-4.51]; p = 0.001), age > 65 years (OR: 2.05 [1.03-4.09]; p = 0.036]), pH < 7.30 (OR: 2.69 [1.56-4.66]; p < 0.001), and lactate levels > 2 mmol/L (OR: 4.51 [2.37-8.65]; p < 0.001). CONCLUSIONS: Conclusive SOPs assist target-orientated MCS use in CS. This study provides guidance on the implementation, validation, and modification of newly established MCS programs to aid centers that are establishing such programs.

Hyperbaric oxygen in patients with ischemic stroke following cardiac surgery: a retrospective observational trial.

BACKGROUND: Hyperbaric oxygenation (HBO2) involves breathing 100% oxygen under elevated ambient pressure in a hyperbaric chamber, thereby dissolving oxygen in the plasma. This results in an increase of arterial partial pressure of oxygen (pO2). Though well established in experimental studies, HBO2 treatment for ischemic stroke is still under discussion. METHODS: From 2002-2014 HBO2 (2.2 bar, 90 minutes one/day; average number per patient: 4.7) was applied in 49 consecutive patients (32 males, 17 females, mean age: 68.8 years, range 31.2 - 83.9) with acute neurological deficit following cardiac surgery (CABG 15; combined surgery 14; valve surgery 11; aneurysm repair 8; malformation 1). Patients' history including TIA or stroke and carotid artery pathology were documented. Both degree and type of neurological deficit was evaluated by a scoring system (0-4) before and after HBO2 treatment. RESULTS: Before HBO2 therapy, the average motor deficit score was 2.45 and the average speech disorder score was 0.55, as compared with an average motor deficit of 1.12 and an average speech disorder of 0.27 afterward (α=0.0001, α=0.009). The majority of patients had an overall improvement of 2 score-points after HBO2 therapy (n=23 patients). Probit analysis showed that for a 50% response/probability (LC50) of having an overall outcome of ≥2 scoring points, an estimate of 4.3 HBO2 therapy sessions is necessary. CONCLUSIONS: HBO22 therapy was associated with significant improvement in patients with acute neurological deficits due to ischemic stroke following cardiac surgery. Though this fact suggests gas embolism as the most likely cause of stroke in this collective, other underlying pathologies cannot be ruled out. Randomized studies are needed for further evaluation.

Subclavian Impella 5.5 implant for perioperative left ventricular dysfunction.

We present the implant method and the postoperative management for an Impella 5.5 device via the right subclavian artery in a 72-year-old patient with severe left ventricular dysfunction upon weaning from cardiopulmonary bypass during a cardiac surgery procedure.

Cardiogenic shock and tumor resection due to cardiac synovial sarcoma: a case report.

BACKGROUND: Cardiac synovial sarcoma of the heart is a rare, aggressive mesenchymal tumor with poor prognosis, since complete resection is seldom feasible. CASE PRESENTATION: A 23-year-old man was referred in cardiogenic shock. Emergency computed tomography (CT) revealed a large tumor with obstruction of the right atrium (RA) and prolapse into the right ventricle (RV). Resection and pericardial patch plasty were performed. Histology confirmed a G-3 spindle-cell sarcoma. At 21 months postoperatively, CT and cardiac magnetic resonance (MR) angiography showed a tumor emerging from the lateral wall of the superior caval vein (SCV) and the RA. The RA and SCV were completely resected and replaced with a tailored Dacron tunnel prosthesis. Histology confirmed R0 resection of a G-3 spindle-cell sarcoma. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed a monophasic fibrous synovial sarcoma. Echocardiography upon discharge showed normal biventricular function. The heart was tumor-free upon PET-CT 24 months thereafter. A sudden progression with innumerable pulmonary nodules caused only minimal exertional dyspnea, and the patient received palliative monochemotherapy with ifosfamide. Thirty months after the first operation, he succumbed to hemorrhage from a brain metastasis. CONCLUSIONS: We report an unusually long postoperative period of 30 months in our patient after resection of a very large right atrial sarcoma. Early diagnosis, aggressive surgical treatment, adjunctive chemotherapy and radiotherapy affect survival. Systematic inclusion of patients in multicenter initiatives, including biobanking, is necessary. Better knowledge of genetic defects relevant to these cardiac tumors will promote accurate diagnoses and suggest novel and personalized gene-based therapies.

Gadofosveset-Trinatrium-Enhanced MR Angiography and MR Venography in the Diagnosis of Venous Thromboembolic Disease: A Single-Center Cohort Study.

BACKGROUND: The aim of this single-center combined prospective/retrospective cohort study was to analyze Gadolinium (Gd)-enhanced MRA (magnetic resonance angiography) and MRV (MR venography) for the diagnosis of pulmonary artery embolism and deep venous thrombosis. The gold standard methods result in major exposure to radiation and a high amount of nephrotoxic iodinated contrast media. This is the first larger contrast-enhanced MR imaging study of acute and chronic venous thromboembolic disease of various stages. METHODS: We prospectively examined 88 patients presenting clinical signs of deep vein thrombosis and/or pulmonary artery embolism. A single-session, one-stop shop Gd-enhanced MRA/MRV at 1.5 Tesla, using gradient echo sequences with very short repetition and echo times as well as low flip angles with subtraction and three-dimensional reconstruction, was performed. A diagnosis was made with the consensus of two experienced radiologists. RESULTS: We observed excellent MRA image quality in 87% and even higher diagnostic image quality of MRV in 90% of our examinations. Pulmonary artery embolism occurred with deep vein thrombosis in 22%. CONCLUSIONS: Gd-enhanced MRA/MRV provided excellent image quality for the diagnosis of venous thromboembolic disease in the majority of cases. It may be particularly useful to plan and follow-up filter implantation and retrieval in the inferior caval vein.

Identification of a rare subset of adipose tissue-resident progenitor cells, which express CD133 and TRPC3 as a VEGF-regulated Ca2+ entry channel.

VEGF-induced Ca2+ signalling was investigated in CD133+/VEGFR-2+ progenitor cells isolated from human adipose stroma. Colonies derived from CD133+ immunoselected cells displayed inhomogenous Ca2+ signals, with variable magnitude of VEGF-induced Ca2+ entry, which positively correlated with expression of the Ca2+ channel protein TRPC3. High levels of VEGF-induced Ca2+ entry and TRPC3 expression were preferentially detected in rim areas of expanding colonies. Dominant negative suppression of TRPC3 inhibited VEGF-induced Ca2+ entry into CD133+ cells. Our results identify TRPC3 as a key Ca2+ entry channel in a subset of CD133+ stem cells. We suggest TRPC3 as an essential determinant of cell fate in CD133+ progenitor-derived colonies.

Detoxification on top of enhanced, diamine-extended glutaraldehyde fixation significantly reduces bioprosthetic root calcification in the sheep model.

BACKGROUND AND AIM OF THE STUDY: Increased concentrations of glutaraldehyde (GA), diamine-extension (DA) of crosslinks and subsequent extraction of excess GA all reduce bioprosthetic calcification in the subdermal rat model. The study aim was to demonstrate the combined effect of all three treatments in a circulatory sheep model. METHODS: Two fixation treatments were used for GA detoxification (urazole in acetate buffer, 0.1 M; pH 4.5; 37 degrees C; 7 days): (i) conventional 0.2% GA fixation (4 degrees C; 7 days); and (ii) enhanced 3.0% GA fixation (4 degrees C; 2 days, followed by a DA interim step; 100 mM L-lysine; 37 degrees C; 2 days, followed by GA; 3.0%; 37 degrees C; 5 days). Entire porcine root prostheses were implanted in the distal aortic arch of young sheep for 12 weeks (n = 5 per group). Non-detoxified 0.2% GA-treated roots served as controls (n = 5). Calcium analysis was based on atomic absorption spectrophotometry; morphology was assessed using light and transmission electron microscopy. RESULTS: Detoxification alone resulted in an 83% reduction of leaflet calcification (p = 0.086), but achieved only 23% (p = 0.145) and 12% (p = 0.362) mitigation of calcification in aortic wall and sinus tissue, respectively. When combined with DA-enhanced 3% GA fixation, detoxification led to a 95% reduction in leaflet calcification (p = 0.057), followed by 79% in sinus (p = 0.003) and 79% in aortic wall tissue (p = 0.0003). Morphologically, detoxification primarily affected leaflets and the subadventitial layer of aortic wall tissue, whereas enhanced fixation seemed to affect all structures. CONCLUSION: It was shown in a circulatory sheep model that a combination of DA-enhanced fixation with an extraction process of excess GA leads to a distinct mitigation of leaflet and aortic wall calcification.

Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

OBJECTIVE: High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. METHODS AND RESULTS: Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, p<0.01) while ursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. CONCLUSIONS: High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

Nanopatterned polymer substrates promote endothelial proliferation by initiation of ß-catenin transcriptional signaling.

Control of endothelial phenotype involves a variety of signaling pathways and transcriptional regulators, including the junctional protein ß-catenin. This multifunctional signaling molecule is part of adhesion contacts in the endothelium and is able to translocate into the nucleus to activate genetic programs and control proliferation and the fate of the cells. We investigated the influence of laser-generated nanopatterns on polymeric cell culture substrates on endothelial tissue architecture, proliferation and ß-catenin signaling. For our experiments human microvascular endothelial cells or CD34(+) endothelial progenitor cells, isolated from human adipose tissue, were cultured on polyethylene terephthalate (PET) substrates with oriented nanostructures with lateral periodicities of 1.5 µm and 300 nm, respectively. The surface topography and chemistry of the PET substrates were characterized by electron microscopy, atomic force microscopy, water contact angle measurement and X-ray photoelectron spectroscopy. Analysis of cell phenotype markers as well as ß-catenin signaling revealed that short-term culture of endothelial cells on nanostructured substrates generates a proliferative cell phenotype associated with nuclear accumulation of ß-catenin and activation of specific ß-catenin target genes. The effects of the nanostructures were not directly correlated with nanostructure-induced alignment of cells and were also clearly distinguishable from the effects of altered PET surface chemistry due to photomodification. In summary, we present a novel mechanism of surface topology-dependent control of transcriptional programs in mature endothelium and endothelial progenitor cells.