Left ventricular assist devices (LVADs) represent the final treatment for patients with end-stage heart failure (HF) not eligible for transplantation. Although LVAD design has been further improved ...in the last decade, their use is associated with different complications. Specifically, inflammation, fibrosis, bleeding events, right ventricular failure, and aortic valve regurgitation may occur. In addition, reverse remodeling is associated with substantial cellular and molecular changes of the failing myocardium during LVAD support with positive effects on patients' health. All these processes also lead to the identification of biomarkers identifying LVAD patients as having an augmented risk of developing associated adverse events, thus highlighting the possibility of identifying new therapeutic targets. Additionally, it has been reported that LVAD complications could cause or exacerbate a state of malnutrition, suggesting that, with an adjustment in nutrition, the general health of these patients could be improved.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The heart coordinates its functional parameters for optimal beat-to-beat mechanical activity. Reliable detection and quantification of these parameters still represent a hot topic in cardiovascular ...research. Nowadays, computer vision allows the development of open-source algorithms to measure cellular kinematics. However, the analysis software can vary based on analyzed specimens. In this study, we compared different software performances in in-silico model, in-vitro mouse adult ventricular cardiomyocytes and cardioids. We acquired in-vitro high-resolution videos during suprathreshold stimulation at 0.5-1-2 Hz, adapting the protocol for the cardioids. Moreover, we exposed the samples to inotropic and depolarizing substances. We analyzed in-silico and in-vitro videos by (i) MUSCLEMOTION, the gold standard among open-source software; (ii) CONTRACTIONWAVE, a recently developed tracking software; and (iii) ViKiE, an in-house customized video kinematic evaluation software. We enriched the study with three machine-learning algorithms to test the robustness of the motion-tracking approaches. Our results revealed that all software produced comparable estimations of cardiac mechanical parameters. For instance, in cardioids, beat duration measurements at 0.5 Hz were 1053.58 ms (MUSCLEMOTION), 1043.59 ms (CONTRACTIONWAVE), and 937.11 ms (ViKiE). ViKiE exhibited higher sensitivity in exposed samples due to its localized kinematic analysis, while MUSCLEMOTION and CONTRACTIONWAVE offered temporal correlation, combining global assessment with time-efficient analysis. Finally, machine learning reveals greater accuracy when trained with MUSCLEMOTION dataset in comparison with the other software (accuracy > 83%). In conclusion, our findings provide valuable insights for the accurate selection and integration of software tools into the kinematic analysis pipeline, tailored to the experimental protocol.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
One of the main goals of cardiopulmonary bypass (CPB) is targeting an adequate mean arterial pressure (MAP) during heart surgery, in order to maintain appropriate perfusion pressures in all ...end-organs. As inheritance of early studies, a value of 50-60 mmHg has been historically accepted as the "gold standard" MAP. However, in the last decades, the CPB management has remarkably changed, thanks to the evolution of technology and the availability of new biomaterials. Therefore, as highlighted by the latest European Guidelines, the current management of CPB can no longer refer to those pioneering studies. To date, only few single-centre studies have compared different strategies of MAP management during CPB, but with contradictory findings and without achieving a real consensus. Therefore, what should be the ideal strategy of MAP management during CPB is still on debate. This trial is the first multicentre, randomized, controlled study which compares three different strategies of MAP management during the CPB.
We described herein the methodology of a multicentre, randomized, controlled trial comparing three different approaches to MAP management during CPB in patients undergoing elective cardiac surgery: the historically accepted "standard MAP" (50-60 mmHg), the "high MAP" (70-80 mmHg) and the "patient-tailored MAP" (comparable to the patient's preoperative MAP). It is the aim of the study to find the most suitable management in order to obtain the most adequate perfusion of end-organs during cardiac surgery. For this purpose, the primary endpoint will be the peak of serum lactate (Lmax) released during CPB, as index of tissue hypoxia. The secondary outcomes will include all the intraoperative parameters of tissue oxygenation and major postoperative complications related to organ malperfusion.
This trial will assess the best strategy to target the MAP during CPB, thus further improving the outcomes of cardiac surgery.
NCT05740397 (retrospectively registered; 22/02/2023).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Endothelial nitric oxide (NO) production is crucial in maintaining vascular homeostasis. However, in the context of ischemia–reperfusion (I/R) injury, uncoupled endothelial nitric oxide synthase ...(eNOS) can exacerbate reactive oxygen species (ROS) generation. Supplementation with S-nitroso human serum albumin (S-NO-HSA) offers a potential solution by mitigating eNOS uncoupling, thereby enhancing NO bioavailability. In a study conducted at the University of Verona, male rats underwent thoracotomy followed by 30 min left anterior descendant coronary (LAD) occlusion and subsequent reperfusion. Hemodynamic parameters were meticulously assessed using a conductance catheter inserted via the carotid artery. The rats were stratified into two main groups based on reperfusion duration and the timing of drug infusion, with the effects of S-NO-HSA evaluated after 2 or 24 h. Remarkably, intravenous administration of S-NO-HSA, initiated before or during ischemia, exhibited notable benefits. It significantly improved left ventricular function, safeguarded energetic substrates such as phosphocreatine and ATP, and sustained glutathione levels akin to basal conditions, indicative of diminished oxidative stress. The data from this study strongly suggest a protective role for S-NO-HSA in mitigating I/R injury induced by LAD artery occlusion, a phenomenon observed at both 2 and 24 h post-reperfusion. These findings underscore the promising therapeutic potential of NO supplementation in alleviating myocardial damage subsequent to ischemic insult.
ST2 is a member of interleukin 1 receptor family with soluble sST2 and transmembrane ST2L isoforms. The ligand of ST2 is IL-33, which determines the activation of numerous intracytoplasmic mediators ...following the binding with ST2L and IL-1RAcP, leading to nuclear signal and cardiovascular effect. Differently, sST2 is released in the blood and works as a decoy receptor, binding IL-33 and blocking IL-33/ST2L interaction. sST2 is mainly involved in maintaining homeostasis and/or alterations of different tissues, as counterbalance/activation of IL-33/ST2L axis is typically involved in the development of fibrosis, tissue damage, inflammation and remodeling. sST2 has been described in different clinical reports as a fundamental prognostic marker in patients with cardiovascular disease, as well as marker for the treatment monitoring of patients with heart failure; however, further studies are needed to better elucidate its role. In this review we reported the current knowledge about its role in coronary artery disease, heart failure, heart transplantation, heart valve disease, pulmonary arterial hypertension, and cardiovascular interventions.
Despite the withdrawal of the HeartWare Ventricular Assist Device (HVAD), hundreds of patients are still supported with this continuous-flow pump, and the long-term management of these patients is ...still under debate. This study aims to analyse 5 years survival and freedom from major adverse events in patients supported by HVAD and HeartMate3 (HM3). From 2010 to 2022, the MIRAMACS Italian Registry enrolled all-comer patients receiving a LVAD support at seven Cardiac Surgery Centres. Out of 447 LVAD implantation, 214 (47.9%) received HM3 and 233 (52.1%) received HVAD. Cox-regression analysis adjusted for major confounders showed an increased risk for mortality (HR 1.5 1.2–1.9;
p
= 0.031), for both ischemic stroke (HR 2.08 1.06–4.08;
p
= 0.033) and haemorrhagic stroke (HR 2.6 1.3–4.9;
p
= 0.005), and for pump thrombosis (HR 25.7 3.5–188.9;
p
< 0.001) in HVAD patients. The propensity-score matching analysis (130 pairs of HVAD vs. HM3) confirmed a significantly lower 5 years survival (41.7% vs. 64.1%;
p
0.02), freedom from haemorrhagic stroke (90.5% vs. 70.1%;
p
< 0.001) and from pump thrombosis (98.5% vs. 74.7%;
p
< 0.001) in HVAD cohort. Although similar perioperative outcome, patients implanted with HVAD developed a higher risk for mortality, haemorrhagic stroke and thrombosis during 5 years of follow-up compared to HM3 patients.
Endomyocardial biopsy (EMB) is considered the gold standard for monitoring allograft rejection after heart transplantation. EMB is an invasive procedure that may be performed via a trans-jugular or a ...trans-femoral approach with a complication rate reported as less than 6%. The aim of this study was to evaluate the complication rate after EMBs in heart recipients and to compare the results of EMBs performed via a trans-jugular or a trans-femoral approach.
Medical records of heart recipients undergoing EMBs between January 2012 and December 2022 were retrospectively reviewed. EMB-related complications were classified as major (death, pericardial effusion, hemopericardium, cardiac tamponade requiring a pericardiocentesis or an urgent cardiac surgery, ventricular arrythmias, permanent atrio-ventricular block requiring permanent pacing, hemothorax, pneumothorax and retroperitoneal bleeding) and minor (de novo tricuspid regurgitation, arrhythmias, coronary artery fistula, vascular access site complications).
A total of 1698 EMBs were performed during the study period at our institution in 212 heart recipients. There were 927 (55%) EMBs performed through a trans-jugular approach (TJ group) and 771 (45%) EMBs performed through a trans-femoral approach (TF group). A total of 60 (3.5%) complications were recorded, including nine (0.5%) major complications (six cardiac tamponades, two pneumothorax and one retroperitoneal bleeding) and 51 (3%) minor complications (seven coronary fistulae, five de novo tricuspid regurgitation, four supraventricular arrythmias and thirty-five vascular access site complications). No difference was found in total (38 4% vs. 22 3%;
= 0.16) and major (6 1%} vs. 3 0.4%;
= 0.65) complications (32 3% vs. 19 2%;
= 0.23) between the TJ group and the TF group. No difference was found in male sex, age at time of EMB and time from HT between complicated and not complicated EMBs.
EMBs represent a safe procedure with a low risk of complications. In our experience, EMBs performed via a trans-jugular approach are as safe as the trans-femoral approach.
: To evaluate the early and long-term results of surgical treatment of isolated mitral native and prosthetic valve infective endocarditis.
: All patients undergoing mitral valve repair or replacement ...for infective endocarditis at our institution between January 2001 and December 2021 were included in the study. The preoperative and postoperative characteristics and mortality of patients were retrospectively reviewed.
A total of 130 patients, 85 males and 45 females, with a median age of 61 ± 14 years, underwent surgery for isolated mitral valve endocarditis during the study period. There were 111 (85%) native and 19 (15%) prosthetic valve endocarditis cases. Fifty-one (39%) patients died during the follow-up, and the overall mean patient survival time was 11.8 ± 0.9 years. The mean survival time was better in patients with mitral native valve endocarditis compared to patients with prosthetic valve endocarditis (12.3 ± 0.9 years vs. 8 ± 1.4 years;
= 0.1), but the difference was not statistically significant. Patients who underwent mitral valve repair had a better survival rate compared to patients who had mitral valve replacement (14.8 ± 1.6 vs. 11.3 ± 1 years;
= 0.06); however, the difference was not statistically significant. Patients who underwent mitral valve replacement with a mechanical prosthesis had a significantly better survival rate compared to patients who received a biological prosthesis (15.6 ± 1.6 vs. 8.2 ± 0.8 years;
< 0.001). Patients aged ≤60 years had significantly better survival compared to patients aged >60 years (17.1 ± 1.1 vs. 8.2 ± 0.9;
< 0.001). Multivariate analysis showed that the patient's age >60 years at the time of surgery was an independent risk factor for mortality, while mitral valve repair was a protective factor. Eight (7%) patients required reintervention. Freedom from reintervention was significantly higher in patients with mitral native valve endocarditis compared to patients with prosthetic valve endocarditis (19.3 ± 0.5 vs. 11.5 ± 1.7 years;
= 0.04).
: Surgery for mitral valve endocarditis is associated with considerable morbidity and mortality. The patient's age at the time of surgery represents an independent risk factor for mortality. Mitral valve repair should be the preferred choice whenever possible in suitable patients affected by infective endocarditis.