Publications by authors named "Knosalla C"

Article Synopsis
  • Calcification in pulmonary hypertension associated with left heart disease appears to be influenced by the interaction between RUNX2 and TAZ, which are key regulators in osteogenic processes.
  • Significant vascular calcification was observed in both patients and rat models, with elevated levels of RUNX2 and TAZ.
  • Inhibiting TAZ or RUNX2 effectively reduced vascular calcification and the progression of pulmonary hypertension in the rat model, suggesting potential therapeutic targets.
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Article Synopsis
  • Scientists wanted to see if a new method called hypothermic oxygenated machine perfusion (HOPE) is better for keeping donor hearts alive before they are transplanted, compared to the traditional cold storage method.
  • They did a big study with 229 patients across 15 transplant centers in Europe to compare these two methods.
  • The main goal was to find out if using HOPE reduces serious problems after heart transplant surgery, like heart failure or rejection, within the first 30 days.
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Heart failure (HF) is a common disease associated with high morbidity and mortality rates despite advanced pharmacological therapies. Heart transplantation remains the gold standard therapy for end-stage heart failure; however, its application is curtailed by the persistent shortage of donor organs. Over the past two decades, mechanical circulatory support, notably Left Ventricular Assist Devices (LVADs), have been established as an option for patients waiting for a donor organ.

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Transplantation of the liver in combination with other organs is an increasingly performed procedure. Over the years, continuous improvement in survival could be realized through careful patient selection and refined organ preservation techniques, in spite of the challenges posed by aging recipients and donors, as well as the increased use of steatotic liver grafts. Herein, we revisit the epidemiology, allocation policies in different transplant zones, indications, and outcomes with regard to simultaneous organ transplants involving the liver, that is combined heart-liver, liver-lung, liver-kidney, and multivisceral transplantation.

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Speckle-tracking echocardiography (STE) parameters are an integral part of the assessment of left ventricular (LV) function. We aimed to evaluate established and novel STE parameters of LV diastolic function and their prognostic role in patients with LV anteroapical aneurysm undergoing surgical ventricular repair (SVR). We retrospectively examined the data of 137 patients with anteroapical LV aneurysm who underwent SVR.

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Background: Survival rates after heart transplantation (HTx) have significantly improved over the last decades. There is a growing need to understand the long-term psychological and somatic outcomes, which constitute quality of life (QoL), for these long-term survivors.

Methods: The QoL of patients (N = 75) living 20-31 years (M = 24.

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Temporary mechanical circulatory support (tMCS) is increasingly used in patients with cardiogenic shock as a bridge to further treatment. We present the case of a 52-year-old female patient with biventricular heart failure who was bridged to heart transplantation employing biventricular tMCS through a non-femoral access. The 'groin-free' tMCS concept facilitates pre-habilitation while awaiting heart transplantation.

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Background: Endothelial cell (EC) apoptosis and proliferation of apoptosis-resistant cells is a hallmark of pulmonary hypertension (PH). Yet, why some ECs die and others proliferate and how this contributes to vascular remodeling is unclear. We hypothesized that this differential response may: (1) relate to different EC subsets, namely pulmonary artery (PAECs) versus microvascular ECs (MVECs); (2) be attributable to autophagic activation in both EC subtypes; and (3) cause replacement of MVECs by PAECs with subsequent distal vessel muscularization.

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Introduction: Microvascular dysfunction (MVD) is a hallmark feature of chronic graft dysfunction in patients that underwent orthotopic heart transplantation (OHT) and is the main contributor to impaired long-term graft survival. The aim of this study was to determine the effect of MVD on functional and structural properties of cardiomyocytes isolated from ventricular biopsies of OHT patients.

Methods: We included 14 patients post-OHT, who had been transplanted for 8.

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Objectives: The aim of this study was to evaluate the outcomes of transposition of the omentum into the mediastinum to support the replacement of infected aortic grafts or to cover infected aortic grafts that are not amenable for surgical replacement.

Methods: All patients with thoracic aortic graft infections who underwent mediastinal transposition of the omentum at our institution between 2005 and 2023 were included in this study. Mediastinal transposition of the omentum was performed either after replacement of the infected graft ('curative concept') or solely as bailout procedure by wrapping the infected graft ('palliative concept').

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Article Synopsis
  • CD40L-CD40-TRAF signaling is implicated in the progression of atherosclerosis and the pathogenesis of coronary heart disease (CHD), especially in individuals with comorbid conditions like hyperlipidemia, diabetes, and hypertension.
  • In mouse models with diabetes and hypertension, treatment with a TRAF6 inhibitor showed promising results by normalizing oxidative stress and inflammation markers, suggesting that this signaling pathway could serve as a therapeutic target.
  • Analysis of plasma and vascular materials from CHD patients revealed a correlation between elevated inflammatory markers and comorbidities, indicating that addressing these inflammatory pathways could help reduce cardiovascular events in affected individuals.
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Objective: Acute kidney injury (AKI) requiring renal-replacement therapy (RRT) after heart transplantation (OHT) is common and impairs outcomes. This study aimed to identify independent donor and recipient risk factors associated with RRT after OHT.

Design: A retrospective data analysis.

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Acute type A aortic dissection (ATAAD) is a dramatic emergency exhibiting a mortality of 50% within the first 48 hours if not operated. This study found an absolute value of cosine-like seasonal variation pattern for Germany with significantly fewer ATAAD events (Wilcoxon test) for the warm months of June, July, and August from 2005 to 2015. Many studies suspect a connection between ATAAD events and weather conditions.

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Pulmonary and systemic congestion as a consequence of heart failure are clinically recognized as alarm signals for clinical outcome and mortality. Although signs and symptoms of congestion are well detectable in patients, monitoring of congestion in small animals with heart failure lacks adequate noninvasive methodology yet. Here, we developed a novel ultrasonography-based scoring system to assess pulmonary and systemic congestion in experimental heart failure, by using lung ultrasound (LUS) and imaging of the inferior vena cava (Cava), termed CavaLUS.

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Background: Disturbance in bodily experience (BE) is a potential adverse consequence of ventricular assist device (VAD) implantation. The concept BE encompasses all cognitive and affective processes related to the subjective experience of one's own body.

Methods: A cross-sectional, multicenter study was performed, involving 365 VAD patients (85% male; time postimplant: 3-36 months).

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Article Synopsis
  • Machine perfusion (EVMP) is a new method used for preserving solid organs, particularly in organ transplants, that improves upon traditional cold preservation by allowing for better monitoring and reducing damage during preservation.
  • This technique has broadened the donor pool by including organs from expanded criteria donors, such as those from circulatory death cases, and shows potential for treating and modifying diseased organs.
  • The review discusses key differences in EVMP applications for various organs (kidney, liver, lung, heart) and explores both the benefits and limitations of this technique, highlighting the need for interdisciplinary approaches in its development.
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Pulmonary hypertension worsens outcome in left heart disease. Stiffening of the pulmonary artery may drive this pathology by increasing right ventricular dysfunction and lung vascular remodeling. Here we show increased stiffness of pulmonary arteries from patients with left heart disease that correlates with impaired pulmonary hemodynamics.

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The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles.

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Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls.

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Pulmonary hypertension (PH) is a progressive disease that arises from multiple etiologies and ultimately leads to right heart failure as the predominant cause of morbidity and mortality. In patients, distinct inflammatory responses are a prominent feature in different types of PH, and various immunomodulatory interventions have been shown to modulate disease development and progression in animal models. Specifically, PH-associated inflammation comprises infiltration of both innate and adaptive immune cells into the vascular wall of the pulmonary vasculature-specifically in pulmonary vascular lesions-as well as increased levels of cytokines and chemokines in circulating blood and in the perivascular tissue of pulmonary arteries (PAs).

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Animal studies show a pivotal role of dihydrotestosterone (DHT) in pressure overload-induced myocardial hypertrophy and dysfunction. The aim of our study was to evaluate the role of DHT levels and myocardial hypertrophy and myocardial protein expression in patients with severe aortic valve stenosis (AS). Forty-three patients [median age 68 (41-80) yr] with severe AS and indication for surgical aortic valve replacement (SAVR) were prospectively enrolled.

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Purpose Of Review: Ex-situ machine perfusion for both heart (HTx) and lung transplantation (LuTx) reduces ischemia-reperfusion injury (IRI), allows for greater flexibility in geographical donor management, continuous monitoring, organ assessment for extended evaluation, and potential reconditioning of marginal organs. In this review, we will delineate the impact of machine perfusion, characterize novel opportunities, and outline potential challenges lying ahead to improve further implementation.

Recent Findings: Due to the success of several randomized controlled trials (RCT), comparing cold storage to machine perfusion in HTx and LuTx, implementation and innovation continues.

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Background: Cardiac computed tomography (CCT) based computational fluid dynamics (CFD) allows to assess intracardiac flow features, which are hypothesized as an early predictor for heart diseases and may support treatment decisions. However, the understanding of intracardiac flow is challenging due to high variability in heart shapes and contractility. Using statistical shape modeling (SSM) in combination with CFD facilitates an intracardiac flow analysis.

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Background: Although the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan started a new era in heart failure (HF) treatment, less is known about the tissue-level effects of the drug on the atrial myocardial functional reserve and arrhythmogenesis.

Methods And Results: Right atrial (RA) biopsies were retrieved from patients ( = 42) undergoing open-heart surgery, and functional experiments were conducted in muscle strips ( = 101). B-type natriuretic peptide (BNP) did not modulate systolic developed force in human myocardium during β-adrenergic stimulation, but it significantly reduced diastolic tension ( < 0.

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