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Giant cardiac lesion in anaplastic thyroid cancer
Full text linkCardiac metastases of ATC arerare. Benefits of cardiac surgery on early postoperative survival are very limited
Nonischemic Donor Heart Preservation: New Milestone in Heart Transplantation History
Full text linkHeart transplantation is considered the gold standard for the treatment of advanced end-stage heart failure. However, standard donors after brain death are decreasing, whereas patients on the heart transplant waitlist are constantly rising. The introduction of the ex vivo machine perfusion device has been a turning point; in fact, these systems are able to significantly reduce ischemic times and have a potential effect on ischemia-related damage reduction. From a clinical standpoint, these machines show emerging results in terms of heart donor pool expansion, making marginal donors and donor grafts after circulatory death suitable for donation. This article aims to review mechanisms and preclinical and clinical outcomes of currently available ex vivo perfusion systems, and to explore the future fields of application of these technologies
Preliminary Computational Analysis of Three Configurations for an Innovative Ventricular Chamber
Full text link(1) Background: shape, dimension, hemodynamics, and hemocompatibility are just a few
of the several challenging key points that must be addressed in designing any suitable solution for
the ventricular chamber of mechanical circulatory support devices. A preliminary evaluation of
different geometries of bellow‐like ventricular chambers is herein proposed. The chambers were
made with a polycarbonate urethane that is acknowledged to be a hemocompatible polymer. (2)
Methods: an explicit dynamic computational analysis was performed. The actuation of the three
chambers was simulated without the presence of an internal fluid. Maximum stress and strain
values were identified, as well as the most critical regions. Geometric changes were checked during
simulated motion to verify that the dimensional constraints were satisfied. (3) Results: one chamber
appeared to be the best solution compared to the others, since its dimensional variations were
negligible, and effective stresses and strains did not reach critical values. (4) Conclusions: the
identification of the best geometric solution will allow proceeding with further experimental
studies. Fluid–structure interactions and fatigue analyses were investigated
A step-by-step problem-solving strategy in a patient with heart failure and cerebral aneurysm
Full text linkLeft ventricular assist devices (LVAD) implantation is an established treatment for patients with end-stage heart failure. HeartMate 3 (HM3) is a continuous-flow centrifugal pump, recently introduced in the clinic, which has shown greater hemocompatibility compared to similar devices of previous generations. Nevertheless, anticoagulation is still required after HM3 implant to avoid pump dysfunction. Hereafter, we describe the case of a patient candidate to LVAD implantation for end-stage heart failure presenting a concomitant cerebrovascular lesion, accidentally found during pre-operative assessment, which would have contraindicated the procedure (for the prohibitive risk of cerebral hemorrhage), unless a step by step problem-solving approach was adopted
Exploring new frontiers for pediatric and grown-up congenital patients with heart disease (GUCH): tergitol-based strategies to improve performances of pulmonary xenografts
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MSC-EVs role in myocardial protection after prolonged warm ischemia: preliminary data and creation of an effective protocol for ex-vivo heart perfusion
No full textreservedBackground: To date, Donation after Brain and Circulatory Death (DBD and DCD) represent available sources of organs suitable for transplantation in humans. Heart donation and transplant, however, are not possible in Italy after DCD, as great concerns still exist regarding injury following the prolonged and inevitable warm ischemic time – Italian legislation requires at least 20 minutes of no-touch period – and further damage due to cold static storage and subsequent reperfusion, a damage known as Ischemia-Reperfusion Injury (IRI). Therefore, the development of effective strategies for myocardial protection during organ procurement, ex-vivo perfusion and implantation becomes crucial for an appropriate clinical translation.
Aim of the study: To develop an effective protocol for ex-vivo heart perfusion, which will also enable organ rescuing and its function assessment during perfusion. Moreover, the protocol will include the administration of cellular particles, known as exosomes or extracellular vesicles (EVs), which for their properties have the potential to improve organ function.
Methods: To achieve our goal, at first, a model of normothermic regional perfusion was created using a modified cardiopulmonary by-pass (CPB) circuit. Swine hearts are comparable for weight and anatomy to the humans one, and therefore, they were chosen for our tests. The circuit for ex-vivo heart perfusion resembled the features of other already available devices and it was composed by four peristaltic pumps, a heat exchanger and a membrane oxygenator, as for standard CPB. The heart was cannulated in a retrograde fashion with the aortic root to deliver solution into the coronary arteries and with the pulmonary trunk to get the blood back after perfusion. The whole system so made was then placed into a box where blood leaking from the heart was vented by further vent cannulas (one of them into the left ventricle to avoid distention). The circuit was primed with a solution consisting of half part animal blood and half part an extracellular crystalloid solution created ad hoc since perfusing the heart with whole blood optimal heart contraction was not achievable. The heart was then perfused with the priming and with a maintenance solution. Several attempts (n=8) were made, before finally reaching acceptable results. Cardiac function was assessed by the evidence of a beating heart. The capability of the system to maintain adequate perfusion of the organ (beating) over 2 hours and biochemical results (ions, lactate, and troponin) during perfusion were evaluated to verify the composition of the perfusate and to evaluate cardiac damage. Histological analyses were carried out to study microscopical changes into the myocardium. After standardizing the perfusion protocol 2 hearts underwent MSC-EVs administration.
Results: In total 2 hearts, so far, underwent enriched perfusion with MSC-EVs. Our preliminary results show that our ex-vivo heart perfusion system is valid for the purpose and can be applicated to other experimental settings since the heart recovered part of its function. Troponin levels tend to increase later in heart treated with MSC-EVs. Histological proves show that there is no change in oedema, hemorrhage, ischemic injuries and cellular infiltration levels even with MSC-EVs. A difference was evidenced only in caspase 3 activation levels in heart treated with MSC-EVs.
An important preliminary result is related to the morphological analysis of mitochondria, indeed TEM studies showed an increased preservation of these organelles, when the heart is treated with MSC-EVs.
Conclusions: We achieved very preliminary proof of concept of the efficacy of the system and of the administration of the MSC-EVs in rescuing ischemic hearts. Nevertheless, the experiments are still ongoing and further data are necessary to improve the perfusion modalities and organ function assessment, before confirming the current data
Is Heart Transplantation a Modifier of the Organ Biological Age? Exploring New Research Pathways
No full textreservedPresupposti: I continui miglioramenti delle terapie mediche e dei dispositivi di assistenza circolatoria meccanica consentono a un numero sempre crescente di pazienti di sopravvivere allo scompenso cardiaco e raggiungere lo stadio avanzato della malattia. Nonostante la disponibilità di dispositivi di assistenza ventricolare e del cuore artificiale totale, la terapia gold standard per l'insufficienza cardiaca avanzata rimane il trapianto di cuore perché offre i più alti tassi di sopravvivenza una la migliore qualità della vita. Purtroppo, mentre il numero di pazienti in lista d'attesa per il trapianto di cuore è in costante aumento, il numero di donatori è in diminuzione e non è sufficiente per soddisfare la domanda di organi. In uno studio precedente, il nostro gruppo di ricerca ha scoperto che l'età biologica del cuore dei donatori sani è significativamente più giovane della loro età cronologica, portando alla conclusione che l’applicazione di modelli di predizione dell'età biologica potrebbero contribuire a delineare un quadro migliore del reale stato biologico del cuore, migliorando l'approvvigionamento degli organi e contribuendo ad ampliare il pool di donatori, prendendo in considerazione anche donatori cronologicamente più anziani. Tuttavia, l'adozione nella pratica clinica di modelli di predizione dell'età biologica dell'età nella pratica clinica richiede ulteriori indagini sul loro ruolo nel trapianto di cuore.
Scopo dello studio: Lo scopo di questo studio è valutare l'età epigenetica del cuore durante il primo anno dopo il trapianto e di valutare potenziali fattori, inclusa la terapia immunosoppressiva, che potrebbero influenzarla.
Materiali e metodi: Ai fini di questo studio sono stati ottenuti campioni di tessuto da 32 pazienti trapiantati di cuore durante le biopsie endomiocardiche di routine a 15 giorni dopo il trapianto (T1) ed a 1 anno dopo il trapianto (T2). Quindi il DNA è stato estratto dai campioni in modo automatizzato, utilizzando il QIAamp DNA FFPE Tissue Kit (Qiagen, Milano, Italia). I livelli di metilazione di cinque loci CpG, determinati adottando la metodologia Pyrosequencing®, sono stati inclusi in un modello biologico di previsione dell'età sviluppato da Zbieć-Piekarska et al. e la DNA methylation Age (DNAmAge) è stata calcolata sia a T1 che a T2. Successivamente è stata valutata l'associazione tra DNAmAge e un insieme di variabili, adottando un approccio di regressione lineare univariata. Le analisi statistiche sono state eseguite in R Software.
Risultati: Questo studio ha dimostrato che l'età biologica del cuore non cambia drasticamente da T1 (mediana = 34 anni, IQR = 22-38) a T2 (mediana = 34 anni, IQR = 23-39) e rimane significativamente inferiore all'età cronologica sia dei donatori (mediana età T1 = 52, IQR T1 = 24-63; mediana età T2 = 53, IQR T2 = 25-64) che dei riceventi (mediana età T1 = 61, IQR T1 = 54-64; mediana età T2 = 62, IQR T2 = 55-65). Inoltre, l’unico fattore che sembrava essere associato alla DNAmAge era l'età cronologica dei donatori (p < 0,0001), mentre le variabili che entrano in gioco nel contesto del trapianto cardiaco, inclusa la terapia immunosoppressiva, non hanno mostrato un'associazione statisticamente significativa. Infine, da questo studio è emerso che l'età biologica del cuore non è modificata dal trapianto cardiaco ma, al contrario, continua ad essere associata alle caratteristiche dei donatori anche dopo 1 anno dal trapianto.
Conclusioni: Questo studio ha portato nuove evidenze nell’ambito applicazione dell'età biologica nel campo del trapianto cardiaco che potrebbero contribuire all'introduzione dei modelli di predizione dell'età biologica nella pratica clinica.Background: Continuous improvements of medical therapies and mechanical circulatory assist devices allow an evergrowing number of patients to survive heart failure and reach the advanced stage of the disease. Despite the availability of ventricular assist devices and total artificial heart, the gold standard therapy for advanced heart failure remains heart transplantation because it offers the highest survival rates and a better quality of life. Unfortunately, whilst the number of patients on the waiting list for heart transplant is constantly increasing, the number of donor hearts available is steadily decreasing and insufficient to fulfill the demand. A previous study of our research group discovered that the biological age of healthy donors’ hearts was significantly younger than their chronological age, leading to the conclusion that biological age predictors could delineate a better picture of the real biological status of the heart, improving organ procurement and contributing to extend the donor pool by considering chronologically older donors for donation. Although adopting biological age predictors in clinical practice requires further investigations about their role in heart transplantation.
Aim of the study: The aim of this study is to evaluate the epigenetic age of the heart during the first year after transplantation and to assess potential factors, including immunosuppressive therapy, that could have an influence on it.
Materials and methods: For the purpose of this study tissue samples from 32 heart transplant recipients were obtained during routine endomyocardial biopsies at 15 days after transplantation (T1) and at 1 year after transplant (T2). Then DNA was extracted from the samples using the QIAamp DNA FFPE Tissue Kit (Qiagen, Milan, Italy). Methylation levels of five CpG loci, determined adopting Pyrosequencing® methodology, were included in a biological age prediction model developed by Zbieć-Piekarska et al. and DNA methylation age (DNAmAge) were calculated both at T1 and at T2. Subsequently, the association between DNAmAge and a set of variables was evaluated adopting a univariate linear regression approach. Statistical analyses were performed in R Software.
Results: This study demonstrated that the biological age of the heart did not drastically change from T1 (median = 34 years, IQR = 22-38) to T2 (median = 34 years, IQR = 23-39) and it is significantly lower than the chronological age of both donors (median age T1 = 52, IQR T1 = 24-63; median age T2 = 53, IQR T2 = 25-64 ) and recipients (median age T1 = 61, IQR T1 = 54-64; median age T2 = 62, IQR T2 = 55-65). Furthermore, the only factor that appeared to be associated with DNAmAge was donors’ chronological age (p < 0,0001), whereas the variables that come into play in the context of heart transplantation, including immunosuppressive therapy did not show a statistically significant association. Finally, from this study emerged that the biological age of the heart was not modified by heart transplantation but, on the contrary, continued to be associated with donors’ characteristics even at 1 year from transplantation.
Conclusion: This study brought new evidence on the application of biological age prediction in the field of heart transplantation that, hopefully, would contribute to the introduction of biological age predictors in clinical practice
In vitro development of tissue-preserving strategies to enhance long term performance of aortic valve substitutes
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