Studio longitudinale della funzione cardiaca materna nelle gravidanze gemellari

Obiettivo: studio longitudinale di una coorte di gravidanze gemellari e valutazione di eventuali correlazioni tra specifici parametri cardiaci materni ed esito sfavorevole della gravidanza. Metodi: Sono state arruolate in modo prospettico donne con gravidanze gemellari, sottoposte a controlli seriati della funzione cardiaca materna ( 20-23 settimane; 26-29 settimane e 30-33 settimane). Le pazienti in cui il parto si è verificato prima della 34°settimana compiuta di gestazione sono state escluse a priori dallo studio. Specifici parametri cardiaci campionati sono stati confrontati tra il gruppo di gravidanze con esito positivo ed il gruppo di pazienti che hanno sviluppato complicanze nel corso della gravidanza quali: preeclampsia o ipertensione gestazionale, basso peso alla nascita ( SGA: peso neonatale di uno o entrambi i feti < 5° centile per l’epoca di gestazione). Risultati: sono state incluse nello studio 28 gravidanze gemellari,di cui 8 complicate. Durante ogni visita abbiamo osservato un aumento significativo della gittata cardiaca ( CO ) e sistolica ( SV ) ed una caduta delle resistenze vascolari totali ( TVR ) nelle gravidanze gemellari normali vs complicate. Inoltre, CO, pressione arteriosa (BP), frequenza cardiaca ( HR ) e TVR son rimaste invariate nel corso dei controlli ambulatoriali per le gravidanze con esiti sfavorevole, mentre mostravano modificazioni significative ( CO, HR e BDP in aumento; TVR in diminuzione ) nel gruppo di pazienti con esito favorevole della gravidanza. Conclusioni: La valutazione longitudinale della funzione cardiaca materna sembra dimostrare una significativa differenza tra i valori dei parametri cardiaci materni delle gravidanze multiple non complicate, rispetto a quelle complicate da preeclampsia o neonati SGA.

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: experience of four years in a single centre

Background: Balloon pulmonary angioplasty (BPA) has recently been developed as an alternative and less- invasive treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH), but therapeutic efficacy and technical safety of the technique have to be established. Aim: effects of BPA on patients with inoperable disease or residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Methods: From June 2015 to September 2019 we enrolled symptomatic (NYHA ≥ II) inoperable CTEPH patients and patients with residual PH after PEA. At baseline, immediately before the first BPA session and 3-6 months after last BPA session all patients underwent clinical evaluation, six-minute walking distance and right heart catheterization. For comparisons Friedman test (with Bonferroni post-hoc pairwise analysis) was used. Survival curves were done with Kaplan Meier method. Results: Forty-seven patients [male 45%, median age 68 (51-74) years, 40 inoperable and 7 with residual PH after PEA] were treated for a total of 136 sessions (median number of sessions for each patient: 2); during each session we treated 2 (2-3) vessels; BPA significantly improved symptoms (NYHA III-IV from 85 to 42%), exercise capacity (from 425 to 446 m) and hemodynamic profile (reduction of mean pulmonary arterial pressure from 41 to 35 mmHg and of pulmonary vascular resistance from 7.1 to 4.7 WU). Five pulmonary artery dissection and 2 hemoptysis with clinical impairment were documented; 33 patients had lung injury (radiographic opacity with/without hemoptysis and/or hypoxemia), 7 patients had access site complications. Five patients died during follow-up (none within 30 days from the procedure) because of sepsis (1), heart failure (1), cancer (1), arrhythmic storm (1) and sudden death in a patient with severe coronary atherosclerosis (1). Conclusions: BPA is a safe and effective treatment able to improve symptoms and hemodynamic profile in inoperable CTEPH patients and in patients with residual PH after PEA.

Triple combination therapy in pulmonary arterial hypertension

Pulmonary arterial hypertension is a severe disease characterized by increasing in pulmonary vascular resistance leading to right ventricular failure and death. Currently available drugs for treatment of PAH act on three different pathways responsible of the pathogenesis of this disease: the endothelin pathway, the nitric oxide pathway and the prostacyclin pathway. The purpose of our study was to reassess our experience on the use of drugs that interact on the pathobiological line of prostacyclin so we retrospectively included all patients, referred to our center from February 1995 to December 2021, who received therapy with i.v. Epoprostenol, s.c. Treprostinil or oral Selexipag. Firstly, we observed that patients treated with Epoprostenol were significantly more compromised at baseline when compared to the two other groups and evaluating the effects of the three different drugs, it emerged that patients treated with Epoprostenol had significantly greater improvements in respect to those treated with Treprostinil and Selexipag. In the second part of our analysis we assessed the effects of these drugs when used as third line strategy in order to limit many confounding factors that could influence demographic, clinical and hemodynamic characteristics of patient populations. The differences emerged in exercise capacity and baseline hemodynamics reflect the fact that in our clinical practice, we add Epoprostenol as third line therapy in more compromised patients, Treprostinil in intermediate situations and Selexipag in less impaired conditions. Comparing the effects of treatments between baseline and first follow-up we noticed smaller benefits with Selexipag when compared with intravenous and subcutaneous strategies but it’s important to weight baseline patient’s differences. Our analysis confirmed clinical and functional benefits for the use of both prostacyclin analogues and prostacyclin receptor agonists in terms of improved functional class, six-minute walking distance and cardiopulmonary hemodynamics.

Effetto dell' ormone tiroideo (T3) durante ex vivo lung perfusion (EVLP) sul polmone di ratto: valutazione dell'azione protettiva nel danno da ischemia riperfusione.

La perfusione polmonare extracorporea (EVLP) è una tecnica utilizzata dal 2010 per valutare e migliorare la qualità dell'organo da trapiantare e il danno da ischemia-ripefusione (IRI). Tale perfusione utilizza la soluzione di Steen, la cui composizione è solo parzialmente nota. Lo scopo è quello di identificare gli effetti di T3 su IRI polmonare ex vivo, in un modello di ratto di donatore a cuore non battente. Animali (40) randomizzati in otto gruppi e il protocollo EVLP sono stati standardizzati nel nostro centro. Sono state valutate la funzione polmonare, PEEP, la resistenza vascolare polmonare totale a 45, 60, 120 e 180 minuti di EVLP per eseguire analisi di gas, dosaggio del mediatore di infiammazione, mitocondriale libero DNA, freeT3 e freeT4. Alla fine dei campioni di tessuto polmonare sono stati congelati dal dosaggio ATP, espressione genica, DNA mitocondriale, T3. Non date le concentrazioni del produttore, abbiamo analizzato gli acidi grassi liberi, vitamine, ormoni e composizione della soluzione Steen. Risultati La soluzione di steen contiene albumina umana x2 nel siero umano (7,5-8 g/dl): le concentrazioni di ft4 e ft3 sono x2 quelle nel siero umano e vengono rilasciati dall'albumina. La concentrazione di ft4 e ft3 non è cambiata durante l'EVLP. La Steen ha alta fluorescenza per l'alta concentrazione delle molecole aromatiche (ormoni) mai descritto in precedenza. NADH e mtDNA nel perfused aumenta con danno ischemico e nel gruppo trattato con T3 Conclusione Il modello EVLP è già convalidato nella perfusione nel trapianto polmonare, ma è necessario approfondire l'effetto della Steen in termini di ormoni e analiti. L'effetto sull'IRI dell'EVLP sembra essere influenzato negativamente da un T3 troppo alto in Steen, cosa che descriviamo per la prima volta. L'ulteriore aggiunta di T3 provoca disfunzione mitocondriale e infiammazione.

Hypertensive disorders of pregnancy and long-term cardiovascular health and outcomes

Introduction The maternal vasculature undergoes significant adaptations during pregnancy to meet the increased metabolic demands of the developing fetus. These adaptations include increased cardiac output and blood volume, as well as reduced systemic vascular resistance. In Hypertensive disorders of pregnancy (HDP) there is an impaired cardiovascular adaptation to pregnancy with effects extending beyond pregnancy. In the present study we aimed to characterize long-term cardiovascular status of women who suffered from HDP. Methods Fifty-eight women who attended at least one post-partum visit and a follow-up visit after at least 5 years from delivery were enrolled in the study. Exclusion criteria included multiple pregnancy, fetal genetic or congenital abnormalities, maternal history of organ transplantation, or chronic renal failure (eGFR≤45ml/min/1.73m2). In the follow-up visit participants underwent a complete cardiovascular assessment including echocardiography and multiparametric vascular function assessment. Results and Discussion Two major cardiovascular events, one stroke and one myocardial infarction, occurred both in women with index-pregnancy complicated by preeclampsia (PE). While not statistically significant, women with HDP-non-PE and PE displayed a trend towards an increased risk of developing composite cardiovascular outcome, and women with PE tended to experience it sooner. Nearly half of the women with a history of HDP, whether PE or HDP-non-PE, developed chronic hypertension. Some women also developed hyperuricemia, chronic kidney disease (CKD), and type 2 diabetes at follow- up, most of them had a previous history of PE. Structural and functional cardiac changes were observed in a few cases, especially among women with PE, and vascular dysfunction was more common in women with a history of HDP compared to those with normotensive pregnancies. Results of the present study adds on literature on long-term cardiovascular impact of HDP and further emphasize the importance of a timely follow-up of women who suffered from HDP and particularly PE.

Cell-free cryopreserved arterial allografts from multiorgan donors: a new strategy to fabricate artificial blood vessels suited for peripheral vascular surgery

Critical lower limb ischemia is a severe disease. A common approach is infrainguinal bypass. Synthetic vascular prosthesis, are good conduits in high-flow low-resistance conditions but have difficulty in their performance as small diameter vessel grafts. A new approach is the use of native decellularized vascular tissues. Cell-free vessels are expected to have improved biocompatibility when compared to synthetic and are optimal natural 3D matrix templates for driving stem cell growth and tissue assembly in vivo. Decellularization of tissues represent a promising field for regenerative medicine, with the aim to develop a methodology to obtain small-diameter allografts to be used as a natural scaffold suited for in vivo cell growth and pseudo-tissue assembly, eliminating failure caused from immune response activation. Material and methods. Umbilical cord-derived mesenchymal cells isolated from human umbilical cord tissue were expanded in advanced DMEM. Immunofluorescence and molecular characterization revealed a stem cell profile. A non-enzymatic protocol, that associate hypotonic shock and low-concentration ionic detergent, was used to decellularize vessel segments. Cells were seeded cell-free scaffolds using a compound of fibrin and thrombin and incubated in DMEM, after 4 days of static culture they were placed for 2 weeks in a flow-bioreactor, mimicking the cardiovascular pulsatile flow. After dynamic culture, samples were processed for histological, biochemical and ultrastructural analysis. Discussion. Histology showed that the dynamic culture cells initiate to penetrate the extracellular matrix scaffold and to produce components of the ECM, as collagen fibres. Sirius Red staining showed layers of immature collagen type III and ultrastructural analysis revealed 30 nm thick collagen fibres, presumably corresponding to the immature collagen. These data confirm the ability of cord-derived cells to adhere and penetrate a natural decellularized tissue and to start to assembly into new tissue. This achievement makes natural 3D matrix templates prospectively valuable candidates for clinical bypass procedures